Diabetes Mellitus

What is diabetes?

Diabetes mellitus is a group of metabolic diseases characterized by high blood sugar (glucose) levels, that result from defects in insulin secretion, or action, or both. Diabetes mellitus, commonly referred to as diabetes (as it will be in this article) was first identified as a disease associated with "sweet urine," and excessive muscle loss in the ancient world. Elevated levels of blood glucose (hyperglycemia) lead to spillage of glucose into the urine, hence the term sweet urine.
Normally, blood glucose levels are tightly controlled by insulin, a hormone produced by the pancreas. Insulin lowers the blood glucose level. When the blood glucose elevates (for example, after eating food), insulin is released from the pancreas to normalize the glucose level. In patients with diabetes, the absence or insufficient production of insulin causes hyperglycemia. Diabetes is a chronic medical condition, meaning that although it can be controlled, it lasts a lifetime.

What is the impact of diabetes?

Over time, diabetes can lead to blindness, kidney failure, and nerve damage. These types of damage are the result of damage to small vessels, referred to as microvascular disease. Diabetes is also an important factor in accelerating the hardening and narrowing of the arteries (atherosclerosis), leading to strokes, coronary heart disease, and other large blood vessel diseases. This is referred to as macrovascular disease. Diabetes affects approximately 17 million people (about 8% of the population) in the United States. In addition, an estimated additional 12 million people in the United States have diabetes and don't even know it.
From an economic perspective, the total annual cost of diabetes in 1997 was estimated to be 98 billion dollars in the United States. The per capita cost resulting from diabetes in 1997 amounted to $10,071.00; while healthcare costs for people without diabetes incurred a per capita cost of $2,699.00. During this same year, 13.9 million days of hospital stay were attributed to diabetes, while 30.3 million physician office visits were diabetes related. Remember, these numbers reflect only the population in the United States. Globally, the statistics are staggering.
Diabetes is the third leading cause of death in the United States after heart disease and cancer.

What causes diabetes?

Insufficient production of insulin (either absolutely or relative to the body's needs), production of defective insulin (which is uncommon), or the inability of cells to use insulin properly and efficiently leads to hyperglycemia and diabetes. This latter condition affects mostly the cells of muscle and fat tissues, and results in a condition known as "insulin resistance." This is the primary problem in type 2 diabetes. The absolute lack of insulin, usually secondary to a destructive process affecting the insulin producing beta cells in the pancreas, is the main disorder in type 1 diabetes. In type 2 diabetes, there also is a steady decline of beta cells that adds to the process of elevated blood sugars. Essentially, if someone is resistant to insulin, the body can, to some degree, increase production of insulin and overcome the level of resistance. After time, if production decreases and insulin cannot be released as vigorously, hyperglycemia develops.
Glucose is a simple sugar found in food. Glucose is an essential nutrient that provides energy for the proper functioning of the body cells. Carbohydrates are broken down in the small intestine and the glucose in digested food is then absorbed by the intestinal cells into the bloodstream, and is carried by the bloodstream to all the cells in the body where it is utilized. However, glucose cannot enter the cells alone and needs insulin to aid in its transport into the cells. Without insulin, the cells become starved of glucose energy despite the presence of abundant glucose in the bloodstream. In certain types of diabetes, the cells' inability to utilize glucose gives rise to the ironic situation of "starvation in the midst of plenty". The abundant, unutilized glucose is wastefully excreted in the urine.
Insulin is a hormone that is produced by specialized cells (beta cells) of the pancreas. (The pancreas is a deep-seated organ in the abdomen located behind the stomach.) In addition to helping glucose enter the cells, insulin is also important in tightly regulating the level of glucose in the blood. After a meal, the blood glucose level rises. In response to the increased glucose level, the pancreas normally releases more insulin into the bloodstream to help glucose enter the cells and lower blood glucose levels after a meal. When the blood glucose levels are lowered, the insulin release from the pancreas is turned down. It is important to note that even in the fasting state there is a low steady release of insulin than fluctuates a bit and helps to maintain a steady blood sugar level during fasting. In normal individuals, such a regulatory system helps to keep blood glucose levels in a tightly controlled range. As outlined above, in patients with diabetes, the insulin is either absent, relatively insufficient for the body's needs, or not used properly by the body. All of these factors cause elevated levels of blood glucose (hyperglycemia).

What are the different types of diabetes?

There are two major types of diabetes, called type 1 and type 2. Type 1 diabetes was also called insulin dependent diabetes mellitus (IDDM), or juvenile onset diabetes mellitus. In type 1 diabetes, the pancreas undergoes an autoimmune attack by the body itself, and is rendered incapable of making insulin. Abnormal antibodies have been found in the majority of patients with type 1 diabetes. Antibodies are proteins in the blood that are part of the body's immune system. The patient with type 1 diabetes must rely on insulin medication for survival.
In autoimmune diseases, such as type 1 diabetes, the immune system mistakenly manufactures antibodies and inflammatory cells that are directed against and cause damage to patients' own body tissues. In persons with type 1 diabetes, the beta cells of the pancreas, which are responsible for insulin production, are attacked by the misdirected immune system. It is believed that the tendency to develop abnormal antibodies in type 1 diabetes is, in part, genetically inherited, though the details are not fully understood.
Exposure to certain viral infections (mumps and Coxsackie viruses) or other environmental toxins may serve to trigger abnormal antibody responses that cause damage to the pancreas cells where insulin is made. Some of the antibodies seen in type 1 diabetes include anti-islet cell antibodies, anti-insulin antibodies and anti-glutamic decarboxylase antibodies. These antibodies can be measured in the majority of patients, and may help determine which individuals are at risk for developing type 1 diabetes.
At present, the American Diabetes Association does not recommend general screening of the population for type 1 diabetes, though screening of high risk individuals, such as those with a first degree relative (sibling or parent) with type 1 diabetes should be encouraged. Type 1 diabetes tends to occur in young, lean individuals, usually before 30 years of age, however, older patients do present with this form of diabetes on occasion. This subgroup is referred to as latent autoimmune diabetes in adults (LADA). LADA is a slow, progressive form of type 1 diabetes. Of all the patients with diabetes, only approximately 10% of the patients have type 1 diabetes and the remaining 90% have type 2 diabetes.
Type 2 diabetes was also referred to as non-insulin dependent diabetes mellitus (NIDDM), or adult onset diabetes mellitus (AODM). In type 2 diabetes, patients can still produce insulin, but do so relatively inadequately for their body's needs, particularly in the face of insulin resistance as discussed above. In many cases this actually means the pancreas produces larger than normal quantities of insulin. A major feature of type 2 diabetes is a lack of sensitivity to insulin by the cells of the body (particularly fat and muscle cells).
In addition to the problems with an increase in insulin resistance, the release of insulin by the pancreas may also be defective and suboptimal. In fact, there is a known steady decline in beta cell production of insulin in type 2 diabetes that contributes to worsening glucose control. (This is a major factor for many patients with type 2 diabetes who ultimately require insulin therapy.) Finally, the liver in these patients continues to produce glucose through a process called gluconeogenesis despite elevated glucose levels. The control of gluconeogenesis becomes compromised.
While it is said that type 2 diabetes occurs mostly in individuals over 30 years old and the incidence increases with age, we are seeing an alarming number patients with type 2 diabetes who are barely in their teen years. In fact, for the first time in the history of humans, type 2 diabetes is now more common than type 1 diabetes in childhood. Most of these cases are a direct result of poor eating habits, higher body weight, and lack of exercise.
While there is a strong genetic component to developing this form of diabetes, there are other risk factors - the most significant of which is obesity. There is a direct relationship between the degree of obesity and the risk of developing type 2 diabetes, and this holds true in children as well as adults. It is estimated that the chance to develop diabetes doubles for every 20% increase over desirable body weight.
Regarding age, data shows that for each decade after 40 years of age regardless of weight there is an increase in incidence of diabetes. The prevalence of diabetes in persons 65 to 74 years of age is nearly 20%. Type 2 diabetes is also more common in certain ethnic groups. Compared with a 6% prevalence in Caucasians, the prevalence in African Americans and Asian Americans is estimated to be 10%, in Hispanics 15%, and in certain Native American communities 20% to 50%. Finally, diabetes occurs much more frequently in women with a prior history of diabetes that develops during pregnancy (gestational diabetes - see below).
Diabetes can occur temporarily during pregnancy. Significant hormonal changes during pregnancy can lead to blood sugar elevation in genetically predisposed individuals. Blood sugar elevation during pregnancy is called gestational diabetes. Gestational diabetes usually resolves once the baby is born. However, 25%-50% of women with gestational diabetes will eventually develop type 2 diabetes later in life, especially in those who require insulin during pregnancy and those who remain overweight after their delivery. Patients with gestational diabetes are usually asked to undergo an oral glucose tolerance test about six weeks after giving birth to determine if their diabetes has persisted beyond the pregnancy, or if any evidence (such as impaired glucose tolerance) is present that may be a clue to the patient's future risk for developing diabetes.
"Secondary" diabetes refers to elevated blood sugar levels from another medical condition. Secondary diabetes may develop when the pancreatic tissue responsible for the production of insulin is destroyed by disease, such as chronic pancreatitis (inflammation of the pancreas by toxins like excessive alcohol), trauma, or surgical removal of the pancreas.
Diabetes can also result from other hormonal disturbances, such as excessive growth hormone production (acromegaly) and Cushing's syndrome. In acromegaly, a pituitary gland tumor at the base of the brain causes excessive production of growth hormone, leading to hyperglycemia. In Cushing's syndrome, the adrenal glands produce an excess of cortisol, which promotes blood sugar elevation.
In addition, certain medications may worsen diabetes control, or "unmask" latent diabetes. This is seen most commonly when steroid medications (such as prednisone) are taken and also with medications used in the treatment of HIV infection (AIDS).

What are diabetes symptoms?

• The early symptoms of untreated diabetes are related to elevated blood sugar levels, and loss of glucose in the urine. High amounts of glucose in the urine can cause increased urine output and lead to dehydration. Dehydration causes increased thirst and water consumption.
  
• The inability of insulin to perform normally has effects on protein, fat and carbohydrate metabolism. Insulin is an anabolic hormone, that is, one that encourages storage of fat and protein.
  
• A relative or absolute insulin deficiency eventually leads to weight loss despite an increase in appetite.
  
• Some untreated diabetes patients also complain of fatigue, nausea and vomiting.
  
• Patients with diabetes are prone to developing infections of the bladder, skin, and vaginal areas.
  
• Fluctuations in blood glucose levels can lead to blurred vision. Extremely elevated glucose levels can lead to lethargy and coma.

How is diabetes diagnosed?

The fasting blood glucose (sugar) test is the preferred way to diagnose diabetes. It is easy to perform and convenient. After the person has fasted overnight (at least 8 hours), a single sample of blood is drawn and sent to the laboratory for analysis. This can also be done accurately in a doctor's office using a glucose meter.

• Normal fasting plasma glucose levels are less than 100 milligrams per deciliter (mg/dl).
  
• Fasting plasma glucose levels of more than 126 mg/dl on two or more tests on different days indicate diabetes.
  
• A random blood glucose test can also be used to diagnose diabetes. A blood glucose level of 200 mg/dl or higher indicates diabetes.

When fasting blood glucose stays above 100mg/dl, but in the range of 100-126mg/dl, this is known as impaired fasting glucose (IFG). While patients with IFG do not have the diagnosis of diabetes, this condition carries with it its own risks and concerns, and is addressed elsewhere.
The oral glucose tolerance test
Though not routinely used anymore, the oral glucose tolerance test (OGTT) is a gold standard for making the diagnosis of type 2 diabetes. It is still commonly used for diagnosing gestational diabetes and in conditions of pre-diabetes, such as polycystic ovary syndrome. With an oral glucose tolerance test, the person fasts overnight (at least eight but not more than 16 hours). Then first, the fasting plasma glucose is tested. After this test, the person receives 75 grams of glucose (100 grams for pregnant women). There are several methods employed by obstetricians to do this test, but the one described here is standard. Usually, the glucose is in a sweet-tasting liquid that the person drinks. Blood samples are taken at specific intervals to measure the blood glucose.
For the test to give reliable results:

• the person must be in good health (not have any other illnesses, not even a cold).
  
• the person should be normally active (not lying down, for example, as an inpatient in a hospital), and
  
• the person should not be taking medicines that could affect the blood glucose.
  
• For three days before the test, the person should have eaten a diet high in carbohydrates (200-300 grams per day).
  
• The morning of the test, the person should not smoke or drink coffee.

The classic oral glucose tolerance test measures blood glucose levels five times over a period of three hours. Some physicians simply get a baseline blood sample followed by a sample two hours after drinking the glucose solution. In a person without diabetes, the glucose levels rise and then fall quickly. In someone with diabetes, glucose levels rise higher than normal and fail to come back down as fast.
People with glucose levels between normal and diabetic have impaired glucose tolerance (IGT). People with impaired glucose tolerance do not have diabetes, but are at high risk for progressing to diabetes. Each year, 1%-5% of people whose test results show impaired glucose tolerance actually eventually develop diabetes. Weight loss and exercise may help people with impaired glucose tolerance return their glucose levels to normal. In addition, some physicians advocate the use of medications, such as metformin (Glucophage), to help prevent/delay the onset of overt diabetes.
Recent studies have shown that impaired glucose tolerance itself may be a risk factor for the development of heart disease. In the medical community, most physicians are now understanding that impaired glucose tolerance is nor simply a precursor of diabetes, but is its own clinical disease entity that requires treatment and monitoring.
Evaluating the results of the oral glucose tolerance test
Glucose tolerance tests may lead to one of the following diagnoses:

• Normal response: A person is said to have a normal response when the 2-hour glucose level is less than 140 mg/dl, and all values between 0 and 2 hours are less than 200 mg/dl.
  
• Impaired glucose tolerance: A person is said to have impaired glucose tolerance when the fasting plasma glucose is less than 126 mg/dl and the 2-hour glucose level is between 140 and 199 mg/dl.
  
• Diabetes: A person has diabetes when two diagnostic tests done on different days show that the blood glucose level is high.
  
• Gestational diabetes: A woman has gestational diabetes when she has any two of the following: a 100g OGTT, a fasting plasma glucose of more than 95 mg/dl, a 1-hour glucose level of more than 180 mg/dl, a 2-hour glucose level of more than 155 mg/dl, or a 3-hour glucose level of more than 140 mg/dl.

  Why is blood sugar checked at home?

  Home blood sugar (glucose) testing is an important part of controlling blood sugar. One important goal of diabetes treatment is to keep the blood glucose levels near the normal range of 70 to 120 mg/dl before meals and under 140 mg/dl at two hours after eating. Blood glucose levels are usually tested before and after meals, and at bedtime. The blood sugar level is typically determined by pricking a fingertip with a lancing device and applying the blood to a glucose meter, which reads the value. There are many meters on the market, for example, Accu-Check Advantage, One Touch Ultra, Sure Step and Freestyle. Each meter has its own advantages and disadvantages (some use less blood, some have a larger digital readout, some take a shorter time to give you results, etc). The test results are then used to help patients make adjustments in medications, diets, and physical activities.
  There are some interesting developments in blood glucose monitoring. Currently, at least three continuous glucose sensors are approved in the United States (Dexcom, Medtronic and Navigator). The new continuous glucose sensor systems involve an implantable cannula placed just under the skin in the abdomen or in the arm. This cannula allows for frequent sampling of blood glucose levels. Attached to this is a transmitter that sends the data to a pager-like device. This device has a visual screen that allows the wearer to see, not only the current glucose reading, but also the graphic trends. In some devices, the rate of change of blood sugar is also shown. There are alarms for low and high sugar levels. Certain models will alarm if the rate of change indicates the wearer is at risk for dropping or rising blood glucose too rapidly. The Medtronic version is specifically designed to interface with their insulin pumps. However, at this time the patient still must manually approve any insulin dose (the pump cannot blindly respond to the glucose information it receives, it can only give a calculated suggestion as to whether the wearer should give insulin, and if so, how much). All of these devices need to be correlated to fingersticks for a few hours before they can function independently. The devices can then provide readings for 3-5 days.
  Diabetes experts feel that these blood glucose monitoring devices give patients a significant amount of independence to manage their disease process; and they are a great tool for education as well. It is also important to remember that these devices can be used intermittently with fingersticks. For example, a well-controlled patient with diabetes can rely on fingerstick glucose checks a few times a day and do well. If they become ill, if they decide to embark on a new exercise regimen, if they change their diet and so on, they can use the sensor to supplement their fingerstick regimen, providing more information on how they are responding to new lifestyle changes or stressors. This kind of system takes us one step closer to closing the loop, and to the development of an artifical pancreas that senses insulin requirements based on glucose levels and the body's needs and releases insulin accordingly - the ultimate goal.
  Hemoglobin A1c (A1c)
  To explain what an hemoglobin A1c is, think in simple terms. Sugar sticks, and when it's around for a long time, it's harder to get it off. In the body, sugar sticks too, particularly to proteins. The red blood cells that circulate in the body live for about three months before they die off. When sugar sticks to these cells, it gives us an idea of how much sugar is around for the preceding three months. In most labs, the normal range is 4%-5.9 %. In poorly controlled diabetes, its 8.0% or above, and in well controlled patients it's less than 7.0% (optimal is <6.5%). The benefits of measuring A1c is that is gives a more reasonable and stable view of what's happening over the course of time (three months), and the value does not bounce as much as finger stick blood sugar measurements. There is a direct correlation between A1c levels and average blood sugar levels as follows.
  While there are no guidelines to use A1c as a screening tool, it gives a physician a good idea that someone is diabetic if the value is elevated. Right now, it is used as a standard tool to determine blood sugar control in patients known to have diabetes.
  
  
  

  A1c(%)	Mean blood sugar (mg/dl)
  6	135
  7	170
  8	205
  9	240
  10	275
  11	310
  12	345

  The American Diabetes Association currently recommends an A1c goal of less than 7.0%. Other Groups such as the American Association of Clinical Endocrinologists feel that an A1c of <6.5% should be the goal.
  Of interest, studies have shown that there is about a 10% decrease in relative risk for microvascular disease for every 1% reduction in A1c. So, if a patient starts off with an A1c of 10.7 and drops to 8.2, though there are not yet at goal, they have managed to decrease their risk of microvascular complications by about 20%. The closer to normal the A1c, the lower the absolute risk for microvascular complications. Data also suggests that the risk of macrovascular disease decreases by about 24% for every 1% reduction in A1c values.
  It should be mentioned here that there are a number of conditions in which an A1c value may not be accurate. For example, with significant anemia, the red blood cell count is low, and thus the A1c is altered. This may also be the case in sickle cell disease and other hemoglobinopathies.
  

  What are the acute complications of diabetes?

• Severely elevated blood sugar levels due to an actual lack of insulin or a relative deficiency of insulin.
  
• Abnormally low blood sugar levels due to too much insulin or other glucose-lowering medications.

Insulin is vital to patients with type 1 diabetes - they cannot live with out a source of exogenous insulin. Without insulin, patients with type 1 diabetes develop severely elevated blood sugar levels. This leads to increased urine glucose, which in turn leads to excessive loss of fluid and electrolytes in the urine. Lack of insulin also causes the inability to store fat and protein along with breakdown of existing fat and protein stores. This dysregulation, results in the process of ketosis and the release of ketones into the blood. Ketones turn the blood acidic, a condition called diabetic ketoacidosis (DKA). Symptoms of diabetic ketoacidosis include nausea, vomiting, and abdominal pain. Without prompt medical treatment, patients with diabetic ketoacidosis can rapidly go into shock, coma, and even death.
Diabetic ketoacidosis can be caused by infections, stress, or trauma all which may increase insulin requirements. In addition, missing doses of insulin is also an obvious risk factor for developing diabetic ketoacidosis. Urgent treatment of diabetic ketoacidosis involves the intravenous administration of fluid, electrolytes, and insulin, usually in a hospital intensive care unit. Dehydration can be very severe, and it is not unusual to need to replace 6-7 liters of fluid when a person presents in diabetic ketoacidosis. Antibiotics are given for infections. With treatment, abnormal blood sugar levels, ketone production, acidosis, and dehydration can be reversed rapidly, and patients can recover remarkably well.
In patients with type 2 diabetes, stress, infection, and medications (such as corticosteroids) can also lead to severely elevated blood sugar levels. Accompanied by dehydration, severe blood sugar elevation in patients with type 2 diabetes can lead to an increase in blood osmolality (hyperosmolar state). This condition can lead to coma (hyperosmolar coma). A hyperosmolar coma usually occurs in elderly patients with type 2 diabetes. Like diabetic ketoacidosis, a hyperosmolar coma is a medical emergency. Immediate treatment with intravenous fluid and insulin is important in reversing the hyperosmolar state. Unlike patients with type 1 diabetes, patients with type 2 diabetes do not generally develop ketoacidosis solely on the basis of their diabetes. Since in general, type 2 diabetes occurs in an older population, concomitant medical conditions are more likely to exist, and these patients may actually be sicker overall. The complication and death rates from hyperosmolar coma is thus higher than in DKA.
Hypoglycemia means abnormally low blood sugar (glucose). In patients with diabetes, the most common cause of low blood sugar is excessive use of insulin or other glucose-lowering medications, to lower the blood sugar level in diabetic patients in the presence of a delayed or absent meal. When low blood sugar levels occur because of too much insulin, it is called an insulin reaction. Sometimes, low blood sugar can be the result of an insufficient caloric intake or sudden excessive physical exertion.
Blood glucose is essential for the proper functioning of brain cells. Therefore, low blood sugar can lead to central nervous system symptoms such as:

• dizziness,
  
• confusion,
  
• weakness, and
  
• tremors.

The actual level of blood sugar at which these symptoms occur varies with each person, but usually it occurs when blood sugars are less than 65 mg/dl. Untreated, severely low blood sugar levels can lead to coma, seizures, and, in the worse case scenario, irreversible brain death. At this point, the brain is suffering from a lack of sugar, and this usually occurs somewhere around levels of <40 mg/dl.
The treatment of low blood sugar consists of administering a quickly absorbed glucose source. These include glucose containing drinks, such as orange juice, soft drinks (not sugar-free), or glucose tablets in doses of 15-20 grams at a time (for example, the equivalent of half a glass of juice). Even cake frosting applied inside the cheeks can work in a pinch if patient cooperation is difficult. If the individual becomes unconscious, glucagon can be given by intramuscular injection.
Glucagon causes the release of glucose from the liver (for example, it promotes gluconeogenesis). Glucagon can be lifesaving and every patient with diabetes who has a history of hypoglycemia (particularly those on insulin) should have a glucagon kit. Families and friends of those with diabetes need to be taught how to administer glucagon, since obviously the patients will not be able to do it themselves in an emergency situation. Another lifesaving device that should be mentioned is very simple; a medic alert bracelet should be worn by all patients with diabetes.

What are the chronic complications of diabetes?

These diabetes complications are related to blood vessel diseases and are generally classified into small vessel disease, such as those involving the eyes, kidneys and nerves (microvascular disease), and large vessel disease involving the heart and blood vessels (macrovascular disease). Diabetes accelerates hardening of the arteries (atherosclerosis) of the larger blood vessels, leading to coronary heart disease (angina or heart attack), strokes, and pain in the lower extremities because of lack of blood supply (claudication).
Eye Complications
The major eye complication of diabetes is called diabetic retinopathy. Diabetic retinopathy occurs in patients who have had diabetes for at least five years. Diseased small blood vessels in the back of the eye cause the leakage of protein and blood in the retina. Disease in these blood vessels also causes the formation of small aneurysms (microaneurysms), and new but brittle blood vessels (neovascularization). Spontaneous bleeding from the new and brittle blood vessels can lead to retinal scarring and retinal detachment, thus impairing vision.
To treat diabetic retinopathy a laser is used to destroy and prevent the recurrence of the development of these small aneurysms and brittle blood vessels. Approximately 50% of patients with diabetes will develop some degree of diabetic retinopathy after 10 years of diabetes, and 80% of diabetics have retinopathy after 15 years of the disease. Poor control of blood sugar and blood pressure further aggravates eye disease in diabetes.
Cataracts and glaucoma are also more common among diabetics. It is also important to note that since the lens of the eye lets water through, if blood sugar concentrations vary a lot, the lens of the eye will shrink and swell with fluid accordingly. As a result, blurry vision is very common in poorly controlled diabetes. Patients are usually discouraged from getting a new eyeglass prescription until their blood sugar is controlled. This allows for a more accurate assessment of what kind of glasses prescription is required.
Kidney damage
Kidney damage from diabetes is called diabetic nephropathy. The onset of kidney disease and its progression is extremely variable. Initially, diseased small blood vessels in the kidneys cause the leakage of protein in the urine. Later on, the kidneys lose their ability to cleanse and filter blood. The accumulation of toxic waste products in the blood leads to the need for dialysis. Dialysis involves using a machine that serves the function of the kidney by filtering and cleaning the blood. In patients who do not want to undergo chronic dialysis, kidney transplantation can be considered.
The progression of nephropathy in patients can be significantly slowed by controlling high blood pressure, and by aggressively treating high blood sugar levels. Angiotensin converting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARBs) used in treating high blood pressure may also benefit kidney disease in diabetic patients.
Nerve damage
Nerve damage from diabetes is called diabetic neuropathy and is also caused by disease of small blood vessels. In essence, the blood flow to the nerves is limited, leaving the nerves without blood flow, and they get damaged or die as a result (a term known as ischemia). Symptoms of diabetic nerve damage include numbness, burning, and aching of the feet and lower extremities. When the nerve disease causes a complete loss of sensation in the feet, patients may not be aware of injuries to the feet, and fail to properly protect them. Shoes or other protection should be worn as much as possible. Seemingly minor skin injuries should be attended to promptly to avoid serious infections. Because of poor blood circulation, diabetic foot injuries may not heal. Sometimes, minor foot injuries can lead to serious infection, ulcers, and even gangrene, necessitating surgical amputation of toes, feet, and other infected parts.
Diabetic nerve damage can affect the nerves that are important for penile erection, causing erectile dysfunction (ED, impotence). Erectile dysfunction can also be caused by poor blood flow to the penis from diabetic blood vessel disease.
Diabetic neuropathy can also affect nerves to the stomach and intestines, causing nausea, weight loss, diarrhea, and other symptoms of gastroparesis (delayed emptying of food contents from the stomach into the intestines, due to ineffective contraction of the stomach muscles).
The pain of diabetic nerve damage may respond to traditional treatments with:

• gabapentin (Neurontin),
  
• phenytoin (Dilantin),
  
• carbamazepine (Tegretol),
  
• desipramine (Norpraminine),
  
• amitriptyline (Elavil), or
  
• with topically-applied capsaicin (an extract of pepper).

Gabapentin (Neurontin), phenytoin (Dilantin), and carbamazepine (Tegretol) are medications that are traditionally used in the treatment of seizure disorders. Amitriptyline (Elavil) and desipramine (Norpraminine) are medications that are traditionally used for depression. While many of these medications are not FDA indicated specifically for the treatment of diabetes related nerve pain, they are used by physicians commonly.
The pain of diabetic nerve damage may also improve with better blood sugar control, though unfortunately blood glucose control and the course of neuropathy do not always go hand in hand. Newer medications for nerve pain have recently come to market in the US. Pregabalin (Lyrica) which has an indication for diabetic neuropathic pain and  duloxetine (Cymbalta) are newer agents used in the treatment of diabetic neuropathy.

What can be done to slow diabetes complications?

Findings from the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) have clearly shown that aggressive and intensive control of elevated levels of blood sugar in patients with type 1 and type 2 diabetes decreases the complications of nephropathy, neuropathy, retinopathy, and may reduce the occurrence and severity of large blood vessel diseases. Aggressive control with intensive therapy means achieving fasting glucose levels between 70-120 mg/dl; glucose levels of less than 160 mg/dl after meals; and a near normal hemoglobin A1C levels (see below).
Studies in type 1 patients have shown that in intensively treated patients, diabetic eye disease decreased by 76%, kidney disease decreased by 54%, and nerve disease decreased by 60%. More recently the EDIC trial has shown that type 1 diabetes is also associated with increased heart disease, similar to type 2 diabetes. However, the price for aggressive blood sugar control is a two to three fold increase in the incidence of abnormally low blood sugar levels (caused by the diabetes medications). For this reason, tight control of diabetes to achieve glucose levels between 70-120 mg/dl is not recommended for children under 13 years of age, patients with severe recurrent hypoglycemia, patients unaware of their hypoglycemia, and patients with far advanced diabetes complications. To achieve optimal glucose control without an undue risk of abnormally lowering blood sugar levels, patients with type 1 diabetes must monitor their blood glucose at least four times a day and administer insulin at least three times per day. In patients with type 2 diabetes, aggressive blood sugar control has similar beneficial effects on the eyes, kidneys, nerves and blood vessels.

Diabetes At A Glance

• Diabetes is a chronic condition associated with abnormally high levels of sugar (glucose) in the blood.
  
• Insulin produced by the pancreas lowers blood glucose.
  
• Absence or insufficient production of insulin causes diabetes.
  
• The two types of diabetes are referred to as type 1 (insulin dependent) and type 2 (non-insulin dependent).
  
• Symptoms of diabetes include increased urine output, thirst and hunger as well as fatigue.
  
• Diabetes is diagnosed by blood sugar (glucose) testing.
  
• The major complications of diabetes are both acute and chronic.
  
  
  • Acutely: dangerously elevated blood sugar, abnormally low blood sugar due to diabetes medications may occur.
    
  • Chronically: disease of the blood vessels (both small and large) which can damage the eye, kidneys, nerves, and heart may occur
• Diabetes treatment depends on the type and severity of the diabetes. Type 1 diabetes is treated with insulin, exercise, and a diabetic diet. Type 2 diabetes is first treated with weight reduction, a diabetic diet, and exercise. When these measures fail to control the elevated blood sugars, oral medications are used. If oral medications are still insufficient, insulin medications are considered.

Blood Clots

What are blood clots?

Blood is a liquid that flows within blood vessels. It is constantly in motion as the heart pumps blood through arteries to the different organs and cells of the body. The blood is returned back to the heart by the veins. Veins are squeezed when muscles in the body contract and push the blood back to the heart.
Blood clotting is an important mechanism to help the body repair injured blood vessels. Blood consists of:

• red blood cells containing hemoglobin that carry oxygen to cells and remove carbon dioxide (the waste product of metabolism),
  
• white blood cells that fight infection,
  
• platelets that are part of the clotting process of the body, and
  
• blood plasma, which contains fluid, chemicals and proteins that are important for bodily functions.

Complex mechanisms exist in the bloodstream to form clots where they are needed. If the lining of the blood vessels becomes damaged, platelets are recruited to the injured area to form an initial plug. These activated platelets release chemicals that start the clotting cascade, using a series of clotting factors produced by the body. Ultimately, fibrin is formed, the protein that crosslinks with itself to form a mesh that makes up the final blood clot.
The medical term for a blood clot is a thrombus (plural= thrombi). When a thrombus is formed as part of a normal repair process of the body, there is little consequence. Unfortunately, there are times when a thrombus (blood clot) will form when it is not needed, and this can have potentially significant consequences.

What does a blood clot look like?

Picture of a how blood clot is formed

What causes blood clots?

Blood clots form when there is damage to the lining of a blood vessel, either an artery or a vein. The damage may be obvious, such as a laceration, or may occur on the microscopic level. As well, blood will begin to clot if it stops moving and becomes stagnant.
Venous thrombosis or blood clots in a vein occur when a person becomes immobilized and muscles are not contracting to push blood back to the heart. This stagnant blood begins to form small clots along the walls of the vein. This initial clot can gradually grow to partially or completely occlude or block the vein and prevent blood from returning to the heart. An analogy to this process is a slow moving river. Over time, weeds and algae start to accumulate along the banks of the river where the water flows more slowly. Gradually, as the weeds start to grow, they begin to invade the center of the river because they can withstand the pressure of the oncoming water flow.
Arterial thrombi (blood clots in an artery) occur by a different mechanism. For those with atherosclerotic disease, plaque deposits form along the lining of the artery and grow to cause narrowing of the vessel. This is the disease process that may cause heart attack, stroke, or peripheral artery disease. If a plaque ruptures, a blood clot can form at the site of that rupture and can completely or partially occlude the blood flow at that point.
Blood clots in the heart. In atrial fibrillation, the atrium or upper chamber of the heart does not beat in an organized manner. Instead, it jiggles, and blood tends to become stagnant along the walls of the atrium. Over time, this may cause small blood clots to form. Clots can also form in the ventricle after a heart attack when part of the heart muscle is injured and unable to contract normally. Since the damaged area doesn't contract with the rest of the heart, blood can start to pool or stagnate, leading to clot formation.
Blood leaking out of a blood vessel.  Blood clots can form when blood leaks out of a blood vessel. This is very beneficial when a person gets a cut or scrape wound, because the clot helps stop further bleeding at the wound site. The clotting mechanism works well following trauma as well. Broken bones, sprains and strains, and nosebleeds all result in bleeding that is controlled by the body's clotting mechanism.
Blood clots causing other medical problems. Sometimes, normal blood clotting can cause medical problems because of its location. For example, if bleeding occurs in the urine from any of a variety of reasons (such as infection, trauma, or tumor) clots may form and prevent the bladder from emptying, causing urinary retention. Clot formation in the uterus may cause pain when the clots are passed through the cervix and can lead to vaginal bleeding, either as part of menstruation or as abnormal vaginal bleeding (menorrhagia, dysmenorrhea).

What are the risk factors for blood clots?

The risk factors for arterial clots are those that are common to all diseases that cause narrowing of blood vessels, cholesterol plaque formation, and plaque rupture.

• High blood pressure
  
• High cholesterol levels
  
• Diabetes
  
• Smoking
  
• Family history

Venous clots are formed due to one of two main reasons: 1) immobility, and 2) genetic errors in the clotting mechanism.

1. Immobility: Most commonly, when the body stops moving, the risk of blood clots increases, since muscle movement is required to pump blood towards the heart. Stagnant blood in a vein is prone to clot.

• This may occur when a person is hospitalized or bedridden after illness or surgery.
  
• It may also occur with long trips (such as in a car, train, or plane) where hours may pass without a person getting up to walk or stretch.
  
• Orthopedic injuries and casting also put the person at risk.
  
• Pregnancy is a risk factor for forming blood clots in the legs and pelvis, since the growing uterus may slow blood flow back to the heart to a sufficient extent that blood clots may form.

2. Genetic errors in the clotting mechanism: There may be a genetic or inborn error in the clotting mechanism, making a person hypercoagulable (hyper=more + coagulation= clotting) and at greater risk for forming clots.

   What types of conditions are caused by blood clots?

   Blood clots may cause life-threatening medical conditions, and are always considered in the differential diagnosis of any symptoms or signs. Differential diagnosis is the list of potential causes of a patient's condition, that is considered by the health care practitioner when caring for a patient.
   Deep venous thrombosis and pulmonary embolism
   Deep venous thrombosis may lead to a pulmonary embolism. If there is a blood clot or thrombus in a deep vein, it has the potential to break off (embolize) and flow through the veins back through the heart, and into the lung where it can become lodged in a small blood vessel, which prevents the lung from functioning. Pulmonary embolism is a medical emergency and can cause serious illness or death.
   An embolus is the medical term for a blood clot that has moved with the bloodstream to a different location. With pulmonary embolus (pulmonary embolism), two issues occur.
   
3. The lungs' blood supply is comprised and the affected area of lung tissue may infarct, or die.
   
4. Because of the blockage, the ability of the lung to provide oxygen to the body is decreased and hypoxia (decreased levels of oxygen in the blood and throughout the body) may occur.

Even if venous blood clots do not embolize, they may cause significant local problems with swelling and pain. Since blood cannot return to the heart if a vein is blocked by a clot, the limbs may chronically swell and have decreased function in a condition called chronic thrombophlebitis.
Arterial thrombus
An arterial thrombus stops the blood supply to the tissues beyond the blockage, depriving cells of oxygen and nutrients. This quickly leads to tissue death. Arterial thrombus is the mechanism that causes:

• heart attack (when it occurs in the coronary arteries that supply blood to the heart)
  
• stroke (when it occurs in arteries within the brain), or
  
• peripheral vascular disease (occurring in the arteries of the legs).

Atrial fibrillation
In atrial fibrillation, small clots may form along the walls of the atrium or the upper chambers of the heart. Should one of these clots break off, it may embolize, or travel in the bloodstream to the brain, blocking an artery and causing a stroke. Other arteries may also be involved by this process, including those that supply the bowel. This can cause mesenteric ischemia (mesentery=lining of the bowel + ischemia=loss of blood supply) and potential necrosis (tissue death) of the intestine. Clots can also affect blood supply to fingers and toes.
Blood should clot anytime it becomes stagnant. This also means that clots will form when blood leaks out of blood vessels.
Examples include some of the following:

• With bleeding peptic ulcers, patients may vomit liquid blood mixed with clot.
  
• Patients with rectal bleeding may also have clot mixed with the bloody stool if there has been time for the clot to form.
  
• Sometimes patients with urinary tract or bladder infections develop associated bleeding in their urine, and small clots can form. On occasion these clots may be so big that they cannot be passed and block the urethra, preventing urination and causing urinary retention.
  
• Vaginal bleeding is a normal event for most women in the reproductive years and occasionally, blood can pool in the vagina and form clots before being expelled. If clots form in the uterus, they may cause significant pain and pressure as they pass through the cervix while being expelled.

  What are the symptoms of blood clots?

  Venous clots do not allow blood to return to the heart and symptoms occur because of this damming effect. Most often occurring in the legs or the arms, symptoms include:
  
• swelling,
  
• warmth,
  
• redness, and
  
• pain.

Arterial clots do not allow blood get to the affected area. Body tissue that is deprived of blood and oxygen begins to die and becomes ischemic (isch=to restrain + emia = blood)

• Pain is the initial symptom of the ischemia, or oxygen deprivation due to loss of blood supply.
  
• Other symptoms depend upon the location of the clot, and often the effect will be a loss of function. Heart attack and stroke are self-explanatory.
  
• In an arm or leg, in addition to pain, the limb may appear white, and weakness, loss of sensation, or paralysis may occur.
  
• If the blood supply is lost to an area of the bowel, in addition to intense pain, there may be bloody diarrhea.

How are blood clots diagnosed?

The initial step in making the diagnosis of a blood clot is obtaining a patient history. The blood clot itself does not cause a problem. It's the location of the blood clot and its effect on blood flow that causes symptoms and signs. If a blood clot or thrombus is a consideration, the history may expand to explore risk factors or situations that might put the patient at risk for forming a clot.
Venous blood clots often develop slowly with a gradual onset of swelling, pain, and discoloration. Symptoms of a venous thrombus will often progress over hours.
Arterial thrombi occur as an acute event. Tissues need oxygen immediately, and the loss of blood supply creates a situation in which symptoms begin immediately.
There may be symptoms that precede the acute artery blockage, that may be warning signs of the potential future complete occlusion of the blood vessel.

• Patients with an acute heart attack (myocardial infarction) may experience angina in the days and weeks prior to the heart attack.
• Patients with peripheral artery disease may have pain with walking (claudication), and a TIA (transient ischemia attack, mini-stroke) may precede a stroke.

Physical examination can assist in providing additional information that may increase the suspicion for a blood clot.

• Venous thrombi may cause swelling of an extremity. It may be red, warm, and tender; sometimes the appearance is difficult to distinguish from cellulitis or an infection of the extremity. If there is concern about a pulmonary embolus, the clinician may examine the lungs, listening for abnormal sounds caused by an area of inflamed lung tissue.
  
• Arterial thrombus symptoms are much more dramatic. If a leg or arm is involved, the tissue may be white because of the lack of blood supply. As well, it may be cool to touch and there may be loss of sensation and movement. The patient may be writhing in pain.

Arterial thrombus is also the cause of heart attack (myocardial infarction) and stroke (cerebrovascular accident) and their associated symptoms.
Testing for venous blood clots
Venous blood clots may be detected in a variety of ways, though ultrasound is most commonly used. Occasionally, the patient's size and shape limit the ability for ultrasound to provide a definitive answer.
Venography is an alternative test to look for a clot. In this test, a radiologist injects contrast dye into a small vein in the hand or foot and using fluoroscopy (video X-ray), watches the dye fill the veins in the extremity as it travels back to the heart. The area of clot or obstruction can thus be visualized.
Sometimes, a blood test is used to screen for blood clots. D-Dimer is a breakdown product of a blood clot, and its levels in the bloodstream may be measured. Blood clots are not stagnant; the body tries to dissolve them at the same time as new clot is being formed. D-Dimer is not specific for a blood clot in a given area and cannot distinguish a "good” or needed blood clot, one that forms after surgery or due to bruising from a fall, from one that is causing medical problems. It is used as a screening test with hopes that the result will be negative and show that there is no need to look further for blood clots.
The D-dimer blood test is usually ordered with the expectation that it will be negative. It is a useful test in patients who have a low probability of having a blood clot, and the health care practitioner usually counsels the patient that a positive blood test will likely require additional tests being ordered.
Should a blood clot embolize to the lung, this may be a medical emergency. There are a variety of tests to look for pulmonary emboli. A plain chest X-ray will not show blood clots, but it may be done to look for other conditions that can cause chest pain and shortness of breath, which are the symptoms of a pulmonary embolus. An electrocardiogram (EKG) may show abnormalities suggestive of a pulmonary embolus and also may reveal other causes of chest pain.
Computerized tomography (CT scan) is often the test of choice when suspicion of pulmonary embolus is high. Contrast material is injected intravenously, and the radiologist can determine whether a clot is present in the pulmonary vessels. The contrast material injected into the body can be irritating to the kidney(s) and should not be used in patients who have impaired kidney function. In older patients, screening blood tests (serum creatinine) to check kidney function may be required before a dye study is considered.
On occasion, a ventilation perfusion (V/Q) scan is performed to look for pulmonary emboli. This test uses labeled chemicals to identify inhaled air into the lungs and match it with blood flow in the arteries. If a mismatch occurs, meaning that there is lung tissue that has good air entry but no blood flow, it may be indicative of a pulmonary embolus. It is less accurate and more subjective than a CT scan, and requires the skill and experience of a radiologist to interpret. Two radiologist may interpret a VQ scan differently and come to different conclusions.
Testing for arterial blood clots
Arterial thrombosis is an emergency, since tissue cannot survive long without blood supply before there is irreversible damage. When this occurs in an arm or leg, often a surgeon is consulted on an emergency basis. Arteriography may be considered, a test in which contrast material is injected into the artery in question to look for blockage on imaging studies. Sometimes, if there is a large artery that is occluded, this test is done in the operating room with the presumption that a surgical procedure will be needed to open the vessel and restore blood flow.
For a heart attack (acute myocardial infarction, MI), the EKG may establish the diagnosis, although blood tests may be used to look for enzymes (troponin, myoglobin, CPK) that leak into the bloodstream from irritated heart muscle. In an acute heart attack, the diagnostic and therapeutic procedure of choice is a heart catheterization.
For an acute stroke (cerebrovascular accident, CVA), the test of choice is a computerized tomography (CT) scan of the head to look for bleeding or tumor as the cause of stroke symptoms. If the symptoms resolve, the diagnosis is a transient ischemic attack (TIA, mini-stroke), and further tests may include carotid ultrasound to look for blockages in the major arteries of the neck and echocardiography to look for blood clots in the heart that may embolize to the brain.

How are blood clots treated?

Depending upon their location, blood clots may be aggressively treated or may need nothing more than symptomatic care.
Venous blood clots
Venous thrombosis in the leg may occur in the superficial or deep systems of veins.
Clots in the superficial system are often treated symptomatically with warm compresses and acetaminophen or ibuprofen since there is no risk for clots in the superficial veins to embolize to the lung. They are connected to the deep system by perforator veins that have valves that act like a sieve to strain and prevent any clots form getting to the lung.
Deep venous thrombosis usually requires anticoagulation to prevent the clot from growing and causing a pulmonary embolus. Initial therapy with injectable enoxaparin (Lovenox) is used to immediately "thin" the blood. Meanwhile, warfarin (Coumadin) is prescribed as an anti-coagulation pill. It takes a few days for warfarin to reach therapeutic levels and in this time frame, both the injectable and oral medications are used. Most often, patients with DVTs are treated as an outpatient and taught how to give themselves enoxaparin (Lovenox) injections. Occasionally, depending upon circumstances, patients may be admitted to the hospital for an unfractionated heparin intravenous (IV) injection.
Blood clots below the knee are at lower risk for embolization to the lung, and an alternative to anti-coagulation treatment is serial ultrasound examinations to monitor the clot to see if it is growing or being resorbed by the body.
Pulmonary emboli are treated similarly to deep venous thrombosis, but depending on the severity of the symptoms, amount of clot formation, and the underlying health of the patient, admission to the hospital for treatment and observation may be needed. This is especially the case if lung function is compromised and the patient is short of breath or is experiencing hypoxia, or low oxygen levels in the blood.
Arterial blood clots
Arterial blood clots are often managed more aggressively. Surgery may be attempted to remove the clot, or medication may be administered directly into the clot to try to dissolve it. Alteplase (Activase, TPA) or tenecteplase (TNKase) are examples of medications that may be used in peripheral arteries to try to restore blood supply.
This is the same approach that is used for heart attack. If possible, cardiac catheterization is performed to locate the blocked blood vessel and a balloon is used to open the occluded area, restore blood flow, and place a stent to keep it open. This is a time-sensitive procedure and if a hospital is not available to do the procedure emergently, TPA or TNK is used intravenously to try to dissolve the thrombus and minimize heart damage.
Stroke is also treated with TPA if the patient is an appropriate candidate for this therapy.

What are the complications of blood clots?

Blood clots prevent proper circulation of blood.
Deep vein thrombosis of the leg or arm may cause permanent damage to the veins themselves and cause persistent swelling of the extremity. The life-threatening issue that may arise from deep venous clots is a clot that breaks off and embolizes to the lungs (pulmonary embolus), causing problems with lung function and oxygenation of the blood.
Arterial thrombus often is a life- or limb threatening event, since organs and cells do not get enough oxygen.

How can blood clots be prevented?

Prevention is key in thrombosis or clot formation.
Arterial thrombosis

• For arterial thrombosis, the most likely precipitating event is a plaque rupture with clot formation in the artery.
  
• Minimizing the risk of vascular disease requires life-long attention to the risk factors that lead to plaque buildup and "hardening" of the arteries.
  
• Blood pressure and cholesterol control, diabetes management, and refraining from smoking all minimize the risk of arterial disease.
  
• Although family history is an important risk factor, one needs to be even more vigilant about the other risk factors if there is a family history of early heart attack or stroke.

Deep vein thrombosis
The main risk factor for deep vein thrombosis risks is immobilization. It is important to move around routinely so that blood can circulate in the venous system. On long trips, it is recommended to get out of the car every couple of hours and in an airplane routinely get up and stretch.
Physicians and nurses work hard at getting people moving after surgery or while in the hospital for medical conditions. Enoxaparin (Lovenox) can also be used in low doses to prevent clot formation. Patients are often given tight stockings to promote blood return from the legs and prevent pooling of blood.
In patients with atrial fibrillation, warfarin (Coumadin) is used to prevent clot formation and minimize the risk of embolus and stroke.

Blood Clots At A Glance

• Blood clots form when blood fails to circulate adequately.
  
• Arterial thrombi form when a plaque ruptures and promotes an acute clot formation.
  
• Venous thrombosis occurs when prolonged immobilization allows blood to pool in an extremity and then clot.
  
• The diagnosis is suggested by the history and physical examination and often confirmed with a radiologic test.
  
• Treatment may require surgery, anti-coagulation medications, or a combination of the two.
  
• Prevention of blood clots involves attention to the risk factors for vascular disease.
  
• Serious complications can arise from blood clots, and individuals should seek medical care if they believe a blood clot exists.

REFERENCE:

eMedicine.com. Deep Vein Thrombosis and Thrombophlebitis.
<http://emedicine.medscape.com/article/758140-overview.>

Fauci, Anthony S., et al. Harrison's Principles of Internal Medicine. 17th ed. United States: McGraw-Hill Professional, 2008.

Hematoma

Definition

By definition, a hematoma is a collection of blood outside of a blood vessel. It occurs because the wall of a blood vessel wall, artery, vein or capillary, has been damaged and blood has leaked into tissues where it does not belong. The hematoma may be tiny, with just a dot of blood or it can be large and cause significant swelling.
The blood vessels in the body are under constant repair. Minor injuries occur routinely and the body is usually able to repair the damaged vessel wall by activating the blood clotting cascade and forming fibrin patches. Sometimes the repair fails if the damage is extensive and the large defect allows for continued bleeding. As well, if there is great pressure within the blood vessel, for example a major artery, the blood will continue to leak and the hematoma will expand.
Blood that escapes from the blood stream is very irritating and may cause symptoms of inflammation including pain, swelling and redness. Symptoms of a hematoma depend upon their location, their size and whether they cause associated swelling or edema.

articlekey=3682Bruises and contusions
The medical term ecchymosis is what most people would recognize as a bruise, or blood that has leaked out of a broken blood vessel under the skin that is caused by an injury. Another word for this injury is a contusion. An ecchymosis tends to be flat while a hematoma has more of a three dimensional character to it. As well, hematomas may occur in any organ and not just under the skin.
Hemorrhage
Hemorrhage is the term used to describe active bleeding. The term hematoma describes blood that has already clotted.

What causes a hematoma?

Trauma is the most common cause of a hematoma. When people think of trauma, they generally think of car accidents, falls, head injuries, broken bones, and gunshot wounds, etc.. Trauma to tissue may also be caused by an aggressive sneeze or an unexpected twist of a limb. When a blood vessel is damaged blood leaks into the surrounding tissue; this blood tends to coagulate or clot. The greater the amount of bleeding that occurs, the larger the amount of clot formation.
Blood vessels that are fragile may contribute to hematoma formation. For example, an aneurysm or weakening in a blood vessel wall may spontaneously leak.
There are many people who take blood thinners (anti-coagulation) medications. Examples include warfarin (Coumadin), aspirin, clopidogrel (Plavix) and prasugrel (Effient). These medications increase the potential for spontaneous bleeding and for hematomas to expand because the body cannot efficiently repair blood vessels and blood continues to leak through the damaged areas.
Occasionally, diseases may occur that decrease the number of platelets in the blood stream (thrombocytopenia) or their ability to function. The platelets are the cells that help initiate blood clot and fibrin formation.
All of the above situations may exist independently to cause a hematoma or they may occur together.

What are the types of hematomas?

Hematomas are often described based upon their location.
The most dangerous hematomas are those that occur inside the skull. Because the skull is an enclosed box, anything that takes up space increases pressure within that box and potentially impairs the ability of the brain to function.
Epidural hematomas occur because of trauma, often to the temple, where the middle meningeal artery is located. Bleeding accumulates in the epidural space, outside the 'dura' which is the lining of the brain. Because of the way the dura is attached to the skull, small hematomas can cause significant pressure and brain injury.
Subdural hematomas also occur because of trauma but the injury is usually to the veins in the brain. This causes a slower leak of blood, which enters the 'subdural' space below the dura. The space below the dura has much more room for blood to accumulate before brain function suffers. As people age, they lose some brain tissue and the subdural space is relatively larger. Bleeding into the subdural space may be very slow, gradually stop, and not cause acute symptoms. These 'chronic' subdural hematomas are often found incidentally on computerized tomography (CT) scans as part of a patient evaluation for confusion or because another traumatic incident occurred.
Intracerebral hematomas occur within the brain tissue itself. Intracerebral (intra= within + cerebrum=brain) hematomas may be due to bleeding from uncontrolled high blood pressure, an aneurysm leak or rupture, trauma, tumor or stroke.

Scalp hematomas occur on the outside of the skull and often can be felt as a bump on the head. Because the injury is to the skin and muscle layers outside of the skull, the hematoma itself cannot press on the brain. However, a scalp hematoma signals that there has been a head injury and it is important to assure that internal bleeding has not occurred within the skull. There are a variety of guidelines available to the health care practitioner to assist in accessing whether a patient will require further testing to explore any bleeding in the brain.
Aural or ear hematomas may occur if an injury causes bleeding to the outside helix or cartilage structure of the ear. Often called boxer's, wrestler's ear, or cauliflower ear, blood gets trapped between the thin layer of skin and the cartilage itself. Since the ear cartilage gets its blood supply directly from the overlying skin, a hematoma can decrease blood flow causing parts of the cartilage to shrivel and die. This scenario results in a bumpy, deformed outer ear.
Septal hematomas occur with nasal trauma. A septal hematoma may form associated with a broken nose. If not recognized and treated, the cartilage can break down and cause a perforation of the septum.
Orthopedic injuries are often associated with hematoma formation. Bones are very vascular structures since the marrow is where blood cells are made. Fractures are always associated with hematomas at the fracture site. Fractures of long bones such as the thigh (femur) and upper arm (humerus) can be associated with a significant amount of bleeding, sometimes up to one unit of blood or 10% of the body's blood supply.
Pelvic bone fractures can also bleed significantly since it takes a large amount of force to break these bones and it is very difficult to compress the area to decrease the amount of bleeding. Pelvic hematomas are hidden and the amount of blood loss may be difficult to assess.
Intramuscular hematomas can be very painful due to the amount of swelling and inflammation. Some muscles are surrounded by tough bands of tissues. If enough bleeding occurs, the pressure within these compartments can increase to the point that a 'compartment syndrome' can occur. In this situation, the blood supply of the muscle is compromised and the muscle and other structures such as nerves can be permanently damaged. This is most commonly seen in the lower leg and forearm.
Subungual hematomas are the result of rush injuries to the fingers or toes. Bleeding occurs under the fingernail or toenail and since it is trapped, pressure builds causing pain. Trephination, or drilling a hole through the nail to remove the blood clot, relieves the pressure and resolves the injury. A new nail grows over time.

Bruises and contusions of the skin (ecchymosis) are terms that describe subcutaneous hematomas. These occur due to trauma or injuries to the superficial blood vessels under the skin. Individuals who take anti-coagulant medication are more prone to subcutaneous hematomas.
Intra-abdominal hematomas and hemorrhage may be due to a variety of injuries or illnesses. Regardless of how the blood gets into the abdomen, the clinical finding is peritonitis (irritation of the lining of the abdomen). Hematomas may occur in solid organs such as the liver, spleen, or kidney. They may occur within the walls of the bowel, including the small intestine (duodenum, jejunum, ileum) or the large intestine (colon). Hematomas may also form within the lining of the abdomen called the peritoneum or behind the peritoneum in the retroperitoneal space (retro=behind).
Passing clots or hematomas is a common complaint when women menstruate. Blood can accumulate in the vagina as part of the normal menses and instead of flowing out immediately, it may form small blood clots. Passing blood clots after delivering a baby is also relatively common. However, vaginal bleeding and passing blood clots or hematomas while pregnant is not normal and should be a sign to seek medical attention.
Hematomas may occur anywhere in the body. Regardless of how a hematoma is described or where it is located, it remains a collection of clotted blood outside of a blood vessel.

What are the symptoms of a hematoma?

Hematomas cause irritation and inflammation. Symptoms depend upon their location and whether the size of the hematoma or the associated swelling and inflammation causes structures nearby to be affected. The common symptoms of inflammation include redness, pain, and swelling.
In general, superficial hematomas of skin, soft tissue, and muscle tend to resolve over time. The initial firm texture of the blood clot gradually becomes more spongy and soft as the clot is broken down by the body and the shape changes as the fluid drains away and the hematoma flattens. The color changes from that of a purplish-blue bruise to yellows and browns as the blood chemicals gradually are removed and the hematoma resolves. Depending upon its location, the discolorations may travel through different tissue planes by gravity. For example, a forehead hematoma may cause bruising beneath the eyes and seem to travel to the neck as it resolves over time.
Intracranial, epidural, subdural, and intracerebral hematomas often need neurosurgical intervention to stabilize the injury.

When should I call my doctor about a hematoma?

Most hematomas have little consequence. They are due to minor trauma where the patient was aware of the injury, knows what part of the body was injured and can expect to recover with few problems. Bumps and bruises are part of every child's growth.
Some hematomas may be more important because of their location and it is usually the nearby affected structures that cause symptoms. For example, medical care would be sought for a head injury victim for significant headache, vomiting , or difficulty being aroused. Intracranial (intra= within + cranium=skull) hematomas need to cause pressure on the brain before symptoms manifest themselves, thus any significant head injury should be evaluated by a health care practitioner.
Patients taking blood thinners are at higher risk for bleeding from minor injuries. It is often wise for these people to seek medical attention if they are involved in even minor accidents or sustain minor injuries.

How is a hematoma diagnosed?

Hematomas of the skin and soft tissues, such as muscle and joints, are often diagnosed by physical examination alone.
For patients exhibiting signs of internal bleeding, the health care practitioner will decide what imaging modality is best to evaluate the situation. Plain X-rays may be needed to assess for bone fracture. Patients with significant head injury often require CT scanning. Ultrasound is the testing modality of choice for pregnant patients.

What is the treatment for a hematoma?

Hematomas of the skin and soft tissues are often treated with RICE (rest, ice, compression, elevation). Some health care practitioners may advocate heat as another treatment alternative. The pain of a hematoma is usually due to the inflammation surrounding the blood and may be treated with over the counter pain medications. The choice of medication depends upon the underlying health of the patient. For those patients who are taking anti-coagulation medications, ibuprofen is relatively contra-indicated because of the risk of gastrointestinal bleeding. Patients with liver disease should not take over the counter acetaminophen. When in doubt, it is wise to ask the health care practitioner or pharmacist for a recommendation.
Treatment for hematomas involving other organs in the body depends upon what organ system is involved. In these cases, treatment will be tailored to the specific situation.

What are the complications of a hematoma?

Hematomas cause swelling and inflammation. It is often these two consequences that cause irritation of adjacent organs and tissues and cause the symptoms and complications of a hematoma.
One common complication of all hematomas is the risk of infection. While the hematoma is made of old blood, it has no blood supply itself and therefore is at risk for colonization with bacteria.

Can hematomas be prevented?

Accidents happen and most hematomas are inevitable once the trauma has occurred.
For patients taking anti-coagulation medications, it is wise to avoid participating in events with high risk of injury. For patients taking warfarin (Coumadin), it is important to make certain that the dosing is appropriate and the blood is not thinned excessively.

Hematoma At A Glance

• A hematoma is a collection of blood outside of a blood vessel.
  
• Symptoms of hematomas depend upon their location and whether adjacent structures are affected by the inflammation and swelling associated with the bleeding.
  
• Treatment of a hematoma depends upon which organ or body tissue is affected.
  
• Superficial hematomas of the skin and soft tissue, such as muscle, may be treated with rest, ice compression, and elevation. Heat may also be considered.

References:

Rosen's Emergency Medicine: Concepts and Clinical Practice, 6th Edition, 2006.

Emergency Medicine: a Comprehensive Study Guide 6th Edition, 2003.

REFERENCES:

Andreoli, Thomas E., et al. Andreoli's and Carpenter's Cecil Essentials of Medicine. Saunders; 7 edition, 2007.

Kelainan Hemodinamika

Kelainan Hemodinamika : Trombosis, Embolisme, dan Infark

Trombosis
Trombosis adalah peristiwa aktivasi pembuluh dara yang tidak tepat dalam pembuluh darah yang tidak mengalami jejas atau merupakan oklusi trombotik pembuluh darah setelah terjadi jejas yang rlatif ringan. Trombosis adalah pembentukan massa bekuan darah dalam sistem kardiovaskuler yang tak terkendali. Massa bekuan darah itu disebut trombus, dan jika masa bekuan darah tersebut terlepas dan mengikuti ikut aliran darah maka disebut embolus. Ada 3 faktor primer yang mempengaruhi pembentukan trombus, yang disebut dengan trias Virchow:
1. Jejas endotel bersifat dominan dan jejas ini dapat menyebabkan trombosis (misalnya endokarditis atau plak aterosklerosis yang mangalami ulserasi). Jejas juga dapat terjadi karena stress hemodinamik, misalnya hipertensiatau aliran turbulen pada katup jantung dengan sikatriks.
2. Perubahan dalam aliran darah yang normal dalam menyebabkan trombosis.
3. Hiperkoagulabilitas didefinisikan sebagai perubahan pada lintasan koagulasi yang merupakn predisposisi trombosis. Hypercoagulability (Pembekuan darah lebih cepat daripada biasanya)
Darah dimaksudkan untuk mengalir; jika ia menjadi terhambat, ada penyebab yang membuat darah menjadi membeku/menggumpal. Darah dalam vena-vena secara terus menerus membentuk bekuan-bekuan yang mikroskopik yang secara rutin diuraikan oleh tubuh. Jika keseimbangan dari pembentukan bekuan dan pemecahan dirubah, pembekuan/penggumpalan yang signifikan dapat terjadi. Berikut adalah keadaan yang dapat menyebabkan terbentuknya trombus :
Imobilitas (Keadaan Tak Bergerak)
• Perjalanan dan duduk yang berkepanjangan, seperti penerbangan-penerbangan pesawat yang panjang ("economy class syndrome"), mobil, atau perjalanan kereta api
• Opname rumah sakit
• Operasi
• Trauma pada kaki bagian bawah dengan atau tanpa operasi atau gips
• Kehamilan, termasuk 6-8 minggu setelah partum
• Kegemukan
Hypercoagulability (Pembekuan darah lebih cepat daripada biasanya)
• Obat-obat (contohnya, pil-pil pengontrol kelahiran, estrogen)
• Merokok
• Kecenderungan genetik
• Polycythemia (jumlah yang meningkat dari sel-sel darah merah)
• Kanker
Trauma pada vena
• Patah tulang kaki
• Kaki yang memar
• Komplikasi dari prosedur yang invasif dari vena
Thrombosis dapat terjadi pada arteri, disebut sebagai thrombosis arteri (arterial thrombosis), dapat juga terjadi pada vena disebut sebagai thrombosis vena (venous thrombsis). Thrombus arteri berbeda sifatnya dengan thrombus vena. Komponen thrombus arteri sebagian besar terdiri dari platelet (thrombosit) diselingi oleh anyaman fibrin, komponen eritrositnya sangat rendah sehingga thrombus berwarna putih disebut sebagai hhite trombus. Sedangkan thrombus vena sebagian besar terdiri dari sel darah merah disela- sela anyaman fibrin, komponen thrombosit sangat sedikit, thrombus berwarna merah disebut sebagai red trombus. Trombus dapat terbentuk dimana saja di dalam sistem kardiovaskular.
1. Trombosis vena dalam
Trombosis Vena Dalam (Deep Vein Thrombosis (DVT)) adalah suatu keadaan yang ditandai dengan ditemukannya bekuan darah di dalam vena dalam. Bekuan yang terbentuk di dalam suatu pembuluh darah disebut trombus. Trombus bisa terjadi baik di vena superfisial (vena permukaan) maupun di vena dalam, tetapi yang berbahaya adalah yang terbentuk di vena dalam. Trombosis vena dalam sangat berbahaya karena seluruh atau sebagian dari trombus bisa pecah, mengikuti aliran darah dan tersangkut di dalam arteri yang sempit di paru-paru sehingga menyumbat aliran darah. Trombus yang berpindah-pindah disebut emboli.

Semakin sedikit peradangan di sekitar suatu trombus, semakin longgar trombus melekat ke dinding vena dan semakin mudah membentuk emboli. Darah di dalam vena tungkai akan mengalir ke jantung lalu ke paru-paru, karena itu emboli yang berasal dari vena tungkai bisa menyumbat satu atau lebih arteri di paru-paru. Keadaan ini disebut emboli paru. Emboli paru yang besar bisa menghalangi seluruh atau hampir seluruh darah yang berasal dari jantung sebelah kanan dan dengan cepat menyebabkan kematian.



PENYEBAB
Ditemukan 3 faktor yang berperan dalam terjadinya trombosis vena dalam:
• Cedera pada lapisan vena
• Meningkatnya kecenderungan pembekuan darah : terjadi pada beberapa kanker dan pemakaian pil KB (lebih jarang).
Cedera atau pembedahan mayor juga bisa meningkatkan kecenderungan terbentuknya bekuan darah.
• Melambatnya aliran darah di dalam vena : terjadi pada pasien yang menjalani tirah baring dalam waktu yang lama karena otot betis tidak berkontraksi dan memompa darah menuju jantung.
Misalnya trombosis vena dalam bisa terjadi pada penderita serangan jantung yang berbaring selama beberapa hari dimana tungkai sangat sedikit digerakkan; atau pada penderita lumpuh yang duduk terus menerus dan ototnya tidak berfungsi.
2. Trombosis Aterial
Disamping konsekuensi obstruksi yang ditimbulkan oleh trombus arterial, trombus mural kardiak dan aorta dapat pula mengadakan embolisasi ke perifer, oetk, ginjal, dan lien merupakan target primer. Infark miokardium dengan diskinesia dan kerusakan endokardium dapat menyebabkan trombus mural. Penyakit katup reumatik stenosis dapat menyebabkan katup mural yang diikuti oleh dilatasi atrium kiri dan pembentukan trombus dalam atrium atau apendiks aurikular. Fibrilasi atrium yang terjadi secara bersamaan akan menambahsatatis darah atrium. Ateroskelerosis merupakan penyebab utama trombus arterial. Aliran vaskuler abnormal terkait dan kehilangan integritas endotel.
Embolisme
Embolisme merupakan oklusi / sumbatan beberapa bagian sistem kardiovaskuler oleh suatu massa (embolus) yang tersangkut dalam perjalanannya ke suatu tempat melalui aliran darah. Embolei mengacu pada setiap masa intravakuler yang padat, cair atau berbentuk gas dan terbawa oleh aliran darah ketempat yang jauh dari asal terbentuknya emboli tersebut. Sebagian besar keadaan yang terjadinya dari trombus istilah yang digunakan adalah tromboemboli. Emboli berasal dari trombus. Bentuk-bentuk emboli yang lain meliputi butir-butir lemak, gelembung-gelembung gas, debris ateroskelerotik, fragmen tumor, sumsum tulang atau benda asing seperti peluru. Emboli yang terjepit didalam pembuluh darah berukurn terlalu kecil untuk bisa berjalan lebih lanjut sehingga terjadi okulasi vaskuler persial atau total dan nekrosis iskemik pada jaringan disebelah distal (infark).
dapat mengakibatkan :
• Obstruksi mekanis / regangan masif jantung
• Gangguan nafas / paru
• Infark paru, jantung, ginjal, dll
• Kematian
asal emboli :
1. Trombus (> 95 %) = tromboemboli
2. Tetesan lemak (co: pada patah tulang panjang)
3. Gelembung udara / gas (penyakit Caison)
4. Debris aterosklerotik (kolesterol)
5. Pecahan tumor
6. Sum-sum tulang
7. Bahan lain (peluru dll)
8. Cairan amnion
Macam-macam Emboli
1. Tromboemboli paru

Emboli vena dapat menyangkut di pembuluh darah paru dan menyebabkan emboli paru (pulmonary embolism/PE) dan menghalangi aliran darah. Bila embolus menyumbat, bisa saja menyangkut di pembuluh darah paru-paru. Jika emboli paru tidak segera ditangani, dapat menyebabkan kematian. Sehingga penyakit VTE sangat penting untuk dicegah. Sekitar 80% trombosis vena dalam tidak diketahui (silent) secara klinis. Selain itu, lebih dari 70% emboli paru yang fatal hanya terdeteksi setelah kematian. Dr. RWM Kaligis SpJP (K) menyatakan bahwa thrombosis vena dalam merupakan penyakit yang memiliki fenomena menyerupai gunung es.
2. Tromboemboli sistemik
Tromboemboli sistemik mengaccu pada emboli didalam sirkulasi arterial. Kasus – kasus emboli sistemik berasal dari aneurisma aorta. Thrombus pada plak ateroskelerosis yang mengalami ulserasi, atau vegetasi valvular dan hanya kadng-kadnag terjadi emboli paradoksal. Konsekuensi tromboemboli sistemik bergantung pada pasokan vascular kolateral kerentang jaringan terhadap keadaan iskemia dan caliber pembuluh darah, biasanya emboli arterial menyeabkan infark disebelah distalnya.
3. Emboli Lemak
Emboli lemak terjadi karean pelepasan butir-butir mikroskopis lemak sesdah raktur tulang panjang, atu kadang-kadang terjadi sesudah luka baker atu trauma jaringan lunak.
Patogenesis meliputi obstruksi mekanik oleh mikroemboli lemak netral yang diikuti oleh agregasi local trombosit dan eritrosit. Pelepasan asam lemak yang kemudian terjadi menyebabkan jejas toksik pada endothelium, aktivasi tromcosit dan rekurtmen granulosit .
Diagnosis bergantung pada butir-butir lemak mikrovaskuler yang ditemukan. Karena pelarut histiologis yang rutin dipakai akan melarytkan lipid keluar dari jaringan. Edema dan pendarahan dapat terlihat pada pemeriksaan mikroskopis.
4. Emboli Udara
Emboli udara mengacu pada gelambung-gelembung udara dalam sirkulasi yang menyumbat aliran darah vaskulerdan menyebabkan iskemia. Udara dapat masuk kedalam sirkulasi pada saat dilakukannya prosedur obsterik atau setelah terjadinya trauma dinding dada. Contoh penyakit yang disebabkan oleh emboli udara adalah penyakit dekompresi. Yakni penyakit yang disebabkan oleh perubahan mendadak pada tekanan atmosfer; para penyelam laut dalam an penumpang pesawat tanpa pengaturan tekanan yang naik merupakan orang-orang yang berisiko tinggi terkena penyakit ini. Udara yang dihirup pada tekanan yang tinggi menyebabkan peningkatan jumlaj gas (khususnya nitrogen) yang larut didalam darah dan jaringan. Kenaikan cepat yang terjadi kemudian (deperesirusasi) membuat gas yang larut itu mengembang dan menggelambung keluar dari lautan untuk membentuk emboli gas.
5. Emboli Cairan Amnion
Emboli cairan amnion merupakan komplikasi yang serius pada persalinan dan periode pascapartum; komplikas akibat masuknya cairan amnion ke dalam sirkulasi darah maternal.
Infark
Infark adalah daerah nekrosis iskemik dalam jaringan atau organ akibat oklusi pasokan arteri atau aliran vena. Hampir semua infark terjadi karena peristiwa trombosis atau emboli. Penyebab lainnya meliputi vasospasme, kompresi ekstrinsik pembuluh darah ooleh tumor, edema tau penjepaitan pada akantong hernia dan pemuntiran pembuluh, setrta ruptur pembuluh. Infark dapat berupa infark merah (hemoragik), atau putih (pucat, anemik), atau dapat bersifat septik (infark septik) dan baln (infark biasa).
Penyebab :
1. Tromboemboli (99%)
2. Penggelembungan ateroma sekunder
3. Torsio / perputaran pembuluh darah
4. Penekanan pasokan darah (co: hernia)
5. Jeratan organ (co: perlekatan peritonium)
akibat klinis :
• Infark miokard = Penyakit Jantung Koroner ( PJK )
• Infark paru
• Infark otak (ensefalomalasia)
• Abses (bila ada infeksi bakteri)


Robbins & Cotran. 2009. Dasar Patologis Penyakit. Ed7. Jakrta : Buku Kedokteran EGC.

Hemofilia

Hemofilia berasal dari bahasa Yunani Kuno, yang terdiri dari dua kata yaitu haima yang berarti darah dan philia yang berarti cinta atau kasih sayang. Hemofilia adalah suatu penyakit yang diturunkan, yang artinya diturunkan dari ibu kepada anaknya pada saat anak tersebut dilahirkan. Darah pada seorang penderita hemofilia tidak dapat membeku dengan sendirinya secara normal. Proses pembekuan darah pada seorang penderita hemofilia tidak secepat dan sebanyak orang lain yang normal. Ia akan lebih banyak membutuhkan waktu untuk proses pembekuan darahnya. Penderita hemofilia kebanyakan mengalami gangguan perdarahan di bawah kulit; seperti luka memar jika sedikit mengalami benturan, atau luka memar timbul dengan sendirinya jika penderita telah melakukan aktifitas yang berat; pembengkakan pada persendian, seperti lulut, pergelangan kaki atau siku tangan. Penderitaan para penderita hemofilia dapat membahayakan jiwanya jika perdarahan terjadi pada bagian organ tubuh yang vital seperti perdarahan pada otak. Hemofilia A dan B Hemofilia terbagi atas dua jenis, yaitu : - Hemofilia A; yang dikenal juga dengan nama : - Hemofilia Klasik; karena jenis hemofilia ini adalah yang paling banyak kekurangan faktor pembekuan pada darah. - Hemofilia kekurangan Factor VIII; terjadi karena kekurangan faktor 8 (Factor VIII) protein pada darah yang menyebabkan masalah pada proses pembekuan darah. - Hemofilia B; yang dikenal juga dengan nama : - Christmas Disease; karena di temukan untuk pertama kalinya pada seorang bernama Steven Christmas asal Kanada - Hemofilia kekurangan Factor IX; terjadi karena kekurangan faktor 9 (Factor IX) protein pada darah yang menyebabkan masalah pada proses pembekuan darah. Bagaimana ganguan pembekuan darah itu dapat terjadi? Gangguan itu dapat terjadi karena jumlah pembeku darah jenis tertentu kurang dari jumlah normal, bahkan hampir tidak ada. Perbedaan proses pembekuan darah yang terjadi antara orang normal (Gambar 1) dengan penderita hemofilia (Gambar 2). Gambar 1 dan Gambar 2 menunjukkan pembuluh darah yang terluka di dalam darah tersebut terdapat faktor-faktor pembeku yaitu zat yang berperan dalam menghentukan perdarahan. a. Ketika mengalami perdarahan berarti terjadi luka pada pembuluh darah (yaitu saluran tempat darah mengalir keseluruh tubuh), lalu darah keluar dari pembuluh. b. Pembuluh darah mengerut/ mengecil. c. Keping darah (trombosit) akan menutup luka pada pembuluh. d. Faktor-faktor pembeku da-rah bekerja membuat anyaman (benang - benang fibrin) yang akan menutup luka sehingga darah berhenti mengalir keluar pembuluh. Gambar 1 a. Ketika mengalami perdarahan berarti terjadi luka pada pembuluh darah (yaitu saluran tempat darah mengalir keseluruh tubuh), lalu darah keluar dari pembuluh. b. Pembuluh darah mengerut/ mengecil. c. Keping darah (trombosit) akan menutup luka pada pembuluh. d. Kekurangan jumlah factor pembeku darah tertentu, mengakibatkan anyaman penutup luka tidak terbentuk sempurna, sehingga darah tidak berhenti mengalir keluar pembuluh. Gambar 2 Seberapa banyak penderita hemofilia ditemukan ? Hemofilia A atau B adalah suatu penyakit yang jarang ditemukan. Hemofilia A terjadi sekurang - kurangnya 1 di antara 10.000 orang. Hemofilia B lebih jarang ditemukan, yaitu 1 di antara 50.000 orang. Siapa saja yang dapat mengalami hemofilia ? Hemofilia tidak mengenal ras, perbedaan warna kulit atau suku bangsa. Hemofilia paling banyak di derita hanya pada pria. Wanita akan benar-benar mengalami hemofilia jika ayahnya adalah seorang hemofilia dan ibunya adalah pemabawa sifat (carrier). Dan ini sangat jarang terjadi. (Lihat penurunan Hemofilia) Sebagai penyakit yang di turunkan, orang akan terkena hemofilia sejak ia dilahirkan, akan tetapi pada kenyataannya hemofilia selalu terditeksi di tahun pertama kelahirannya. Tingkatan Hemofilia Hemofilia A dan B dapat di golongkan dalam 3 tingkatan, yaitu :  Klasifikasi  Kadar Faktor VII dan Faktor IX di dalam darah  Berat  Kurang dari 1% dari jumlah normalnya  Sedang  1% - 5% dari jumlah normalnya  Ringan  5% - 30% dari jumlah normalnya Penderita hemofilia parah/berat yang hanya memiliki kadar faktor VIII atau faktor IX kurang dari 1% dari jumlah normal di dalam darahnya, dapat mengalami beberapa kali perdarahan dalam sebulan. Kadang - kadang perdarahan terjadi begitu saja tanpa sebab yang jelas. Penderita hemofilia sedang lebih jarang mengalami perdarahan dibandingkan hemofilia berat. Perdarahan kadang terjadi akibat aktivitas tubuh yang terlalu berat, seperti olah raga yang berlebihan. Penderita hemofilia ringan lebih jarang mengalami perdarahan. Mereka mengalami masalah perdarahan hanya dalam situasi tertentu, seperti operasi, cabut gigi atau mangalami luka yang serius. Wanita hemofilia ringan mungkin akan pengalami perdarahan lebih pada saat mengalami menstruasi.

Referensi : Canadian Hemophilia Society, What is Hemophilia ? - 1999 World Federation of Hemophilia, Hemophilia in Pictures - 1998