BLOOD DISORDERS Hemophilia

Hemophilia is a rare bleeding disorder in which your blood doesn't clot normally. If you have hemophilia, you may bleed for a longer time than others after an injury. You also may bleed internally, especially in your knees, ankles, and elbows. This bleeding can damage your organs or tissues and may be life threatening. Overview Hemophilia usually is inherited. This means that the disorder is passed from parents to children through the genes. People born with hemophilia have little or no clotting factor. Clotting factor is a protein need for normal blood clotting. There are several types of clotting factors. These proteins work with platelets to help the blood clot. Platelets are small blood cell fragments that form in the bone marrowa sponge-like tissue in the bones. Platelets play a major role in blood clotting. When blood vessels are injured, clotting factors help platelets stick together to plug cuts and breaks at the site of the injury and stop bleeding. Without clotting factors, normal blood clotting can't take place. Some people who have hemophilia need injections of a clotting factor or factors to stop bleeding. There are two main types of hemophilia. If you have hemophilia A, you're missing or have low levels of clotting factor VIII (8). About 9 out of 10 people who have hemophilia have type A. If you have hemophilia B, you're missing or have low levels of clotting factor IX (9). Rarely, hemophilia can be acquired. This means that you can develop it during your lifetime. This can happen if your body forms antibodies (proteins) to the clotting factors in your bloodstream. The antibodies can prevent the clotting factors from working. This article focuses on inherited hemophilia. Outlook Hemophilia can be mild, moderate, or severe, depending on how much clotting factor is in the blood. About 7 out of 10 people who have hemophilia A have the severe form of the disorder. People who don't have hemophilia have a factor VIII activity of 100 percent; people who have severe hemophilia A have a factor VIII activity of less than 1 percent. About 18,000 people in the United States have hemophilia. Each year, about 400 babies are born with the disorder. Hemophilia usually occurs only in males (with very rare exceptions). TREATMENT FOR HEMOPHILIA

Replacement Therapy The mainstay of successful hemophilia therapy for either treatment or prevention of acute hemorrhage is prompt and sufficient intravenous replacement of factor VIII or IX to hemostatic plasma levels. Early treatment, at the first onset of symptoms, limits both the amount of the bleeding and the extent of the ensuing tissue damage. State-of-the-art replacement products are made from either plasma-derived or recombinant proteins. All such plasma-derived products have similar hemostatic efficacy and undergo viral attenuation. Single-donor-cryoprecipitate, derived from plasmapheresis of a DDAVP-treated plasmapheresis donor with negative viral serology, is a potential source of factor VIII suitable. Recombinant factor VIII has never been linked to transmission of hepatitis C or HIV-1, though it contains human albumin. In the late 1990s, concern has turned to the potential risk of the albumin in plasma for transmission of Creutzfeldt-Jacob disease (CJD), or "new-variant" CJD, the human syndrome linked to mad-cow disease in Great Britain. The therapeutic menu for factor IX has improved substantially over the past few years with the advent of monoclonal, and more recently, recombinant factor. Again, selection of factor IXcontaining products generally is based on issues of cost and product purity. Ancillary Therapy DDAVP. DDAVP, 1-deamino 8-D arginine vasopressin, stimulates a transient fourfold increase in plasma factor VIII levels, although its mechanism of action still has not been completely elucidated. Therefore, it provides an effective alternative therapy for less severe hemorrhage in most patients with mild Antifibrinolytic Therapy. Antifibrinolytic therapy is used to stabilize a clot by inhibiting the normal process of clot lysis by the fibrinolytic system. It is, therefore, very useful ancillary treatment in patients with hemorrhagic disorders. These agents provide important adjunctive therapy for the prevention or treatment of oral hemorrhage because saliva is a rich source of fibrinolytic enzymes. Two drugs are available: (1) epsilon aminocaproic acid (EACA) (Amicar) and (2) tranexamic acid (Cyklokapron). Gene Therapy for Hemophilia Both hemophilias A and B have been "cured" by orthotopic liver transplantation performed in the 1980s for transfusion-related liver failure. Since the factor VIII and IX genes were cloned, the hemophilias have been considered to be genetic diseases that are among the most amenable to gene therapy because of: (1) the lack of requirement for tissue-specific expression.

Anemia Anemia is a decrease in number of red blood cells (RBCs) or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin deficiency. Because hemoglobin (found inside RBCs) normally carries oxygen from the lungs to the tissues, anemia leads to hypoxia (lack of oxygen) in organs. Because all human cells depend on oxygen for survival, varying degrees of anemia can have a wide range of clinical consequences. Anemia is the most common disorder of the blood. There are several kinds of anemia, produced by a variety of underlying causes. Anemia can be classified in a variety of ways, based on the morphology of RBCs, underlying etiologic mechanisms, and discernible clinical spectra, to mention a few. The three main classes of anemia include excessive blood loss (acutely such as a hemorrhage or chronically through low-volume loss), excessive blood cell destruction (hemolysis) or deficient red blood cell production (ineffective hematopoiesis). There are two major approaches: the "kinetic" approach which involves evaluating production, destruction and loss, and the "morphologic" approach which groups anemia by red blood cell size. The morphologic approach uses a quickly available and low cost lab test as its starting point (the MCV). On the other hand, focusing early on the question of production may allow the clinician to more rapidly expose cases where multiple causes of anemia coexist. New Anemia Treatment A common treatment for anemia - a deficiency in red blood cells (rbcs) caused by their insufficient production, excessive destruction, or excessive loss - is administration of recombinant erythropoietin (Epo), a hormone that stimulates the production of rbc precursors by the bone marrow. Unfortunately, many patients with anemia do not respond to treatment with Epo. However, a new study in mice, by Anne Angelillo-Scherrer and her colleagues at the University Hospital Center and University of Lausanne, Switzerland, has indicated that the protein Gas6 might augment or replace Epo in the treatment of patients who are hyporesponsive or resistant to Epo, respectively. It was shown that following treatment with Epo, mouse rbc precursors released Gas6, which increased cell signaling in response to Epo treatment. In addition, mice deficient in Gas6 had decreased sensitivity to Epo and a reduced ability to recover from anemia. Administration of Gas6, either alone or in combination with Epo, was successful at treating both chronic and acute anemia in mice. The authors therefore concluded that Gas6 has a role in rbc formation and might have valuable therapeutic potential for the treatment of individuals with anemia who fail to respond to treatment with Epo.

CIRCULATORY DISORDERS Arteriosclerosis Arteriosclerosis is the medical term for hardening of the arteries. This is the process that leads to stenosis (blockage) of the arteries in any part of our body which results in insufficient blood (oxygen, nutrition) supply to the parts affected. Example is blockage of thigh artery that cuts off the flow of blood to the lower limb causing gangrene of the lower leg, or blockages in the coronary arteries leading a heart attack. Treatments and drugs Lifestyle changes, such as eating a healthy diet and exercising, are often the best treatment for atherosclerosis. But sometimes, medication or surgical procedures may be recommended as well. Various drugs can slow or sometimes even reverse the effects of atherosclerosis. Here are some common choices:

Cholesterol medications. Aggressively lowering your low-density lipoprotein (LDL) cholesterol, the "bad" cholesterol, can slow, stop or even reverse the buildup of fatty deposits in your arteries. Boosting your high-density lipoprotein (HDL) cholesterol, the "good" cholesterol, may help, too. Your doctor can choose from a range of cholesterol medications, including drugs known as statins and fibrates. Anti-platelet medications. Your doctor may prescribe anti-platelet medications, such as aspirin, to reduce the likelihood that platelets will clump in narrowed arteries, form a blood clot and cause further blockage. Beta blocker medications. These medications are commonly used for coronary artery disease. They lower your heart rate and blood pressure, reducing the demand on your heart and often relieve symptoms of chest pain. Beta blockers reduce the risk of heart attacks and heart rhythm problems. Angiotensin-converting enzyme (ACE) inhibitors. These medications can help slow the progression of atherosclerosis by lowering blood pressure and producing other beneficial effects on the heart arteries. ACE inhibitors can also reduce the risk of recurrent heart attacks. Calcium channel blockers. These medications lower blood pressure and are sometimes used to treat angina. Water pills (diuretics). High blood pressure is a major risk factor for atherosclerosis. Diuretics lower blood pressure. Other medications. Your doctor may suggest certain medications to control specific risk factors for atherosclerosis, such as diabetes. Sometimes specific medications to treat symptoms of atherosclerosis, such as leg pain during exercise, are prescribed.

Sometimes more aggressive treatment is needed. If you have severe symptoms or a blockage that threatens muscle or skin tissue survival, you may be a candidate for one of the following surgical procedures:

Angioplasty. In this procedure, your doctor inserts a long, thin tube (catheter) into the blocked or narrowed part of your artery. A second catheter with a deflated balloon on its tip is then passed through the catheter to the narrowed area. The balloon is then

inflated, compressing the deposits against your artery walls. A mesh tube (stent) is usually left in the artery to help keep the artery open. Endarterectomy. In some cases, fatty deposits must be surgically removed from the walls of a narrowed artery. When the procedure is done on arteries in the neck (the carotid arteries), it's known as carotid endarterectomy. Thrombolytic therapy. If you have an artery that's blocked by a blood clot, your doctor may insert a clot-dissolving drug into your artery at the point of the clot to break it up. Bypass surgery. Your doctor may create a graft bypass using a vessel from another part of your body or a tube made of synthetic fabric. This allows blood to flow around the blocked or narrowed artery.

Deep Vein Thrombosis In medicine, deep vein thrombosis (also known as deep venous thrombosis and usually abbreviated as DVT) is the formation of a blood clot ("thrombus") in a deep vein. It is a form of thrombophlebitis (inflammation of a vein with clot formation). Deep vein thrombosis commonly affects the leg veins (such as the femoral vein or the popliteal vein) or the deep veins of the pelvis. Occasionally the veins of the arm are affected (if spontaneous, this is known as Paget-Schrtter disease). A DVT can occur without symptoms, but in many cases the affected extremity will be painful, swollen, red, warm and the superficial veins may be engorged. The most serious complication of a DVT is that the clot could dislodge and travel to the lungs, which is called a pulmonary embolism (PE). DVT is a medical emergency. All limb swellings however trivial, should be regarded as a DVT until proven otherwise. Untreated lower extremity DVT has a 3% PE-related mortality rate. Deaths associated with upper extremity DVT are extremely rare.[1] A late complication of DVT is the post-thrombotic syndrome, which can manifest itself as edema, pain or discomfort and skin problems. New Therapy Effectively Treats Deep Vein Thrombosis, Study Suggests ScienceDaily (Jan. 30, 2008) A novel treatment for blood clots in the legs appears to be safe and effective, according to a pilot study. The study found that injecting or "lacing" the clot with a fiber-binding thrombolytic agent effectively treats deep vein thrombosis (DVT) and reduces the risk of subsequent recurrence or bleeding.

"This treatment regimen is able to clear blood clots rapidly and safely, restoring blood flow in the veins of the lower leg, and the results are durable," said lead author Richard Chang, M.D., chief of the interventional radiology section of the Department of Radiology, Clinical Center, National Institutes of Health (NIH), Bethesda, Md. DVT is a common and serious health problem in which a blood clot, or thrombus, form in the deep veins, particularly in the lower leg or thigh. Complications occur when the clot breaks off and travels to the lungs, resulting in pulmonary embolism, a potentially fatal condition. Most patients with DVT are treated solely with anticoagulation therapy (blood thinners) and compression stockings. However, studies have shown that one-third of these patients will suffer from post-thrombotic syndrome, characterized by pain, swelling, or in severe cases by changes

in skin color or skin ulceration. Another third are likely to have another clot or pulmonary embolism within five years of their initial DVT. Treatments with thrombolytic (clot-dissolving) therapy could potentially protect against these occurrences, but can pose a bleeding risk. Therefore, Dr. Chang and colleagues sought to develop a safe, effective and affordable thrombolytic treatment regimen for DVT. Twenty patients with acute DVT were treated with direct intraclot lacing of the thrombus with a clot-dissolving agent called alteplase and full systemic anticoagulation. Alteplase binds to the clot, so the procedure does not require continuous infusion of the drug, as do some thrombolytic therapies. With this treatment, after lacing one vein segment with alteplase, the interventional radiologist can immediately direct catheters to treat other vein segments to ensure that the entire clot has been adequately treated. The results of the study showed that blood flow was restored throughout the deep venous system in 16 (80 percent) of the 20 patients during therapy with complete resolution of symptoms in 18 patients (90 percent) after six months of anticoagulation. Alteplase was cleared from the patients' circulatory system within two hours of treatment, reducing the risk of subsequent bleeding. There were no serious complications or bleeding during the treatment, and no cases of postthrombotic syndrome or recurrent clotting during follow-up of 3.4 years. "With this therapy, pain and swelling resolve rapidly, and, in most cases, the patient is able to resume all normal activity within a week," said the study's co-author, McDonald K. Horne III, M.D., from the hematology section of the Department of Lab Medicine, Clinical Center, NIH. The authors caution that larger clinical trials are required to further support the efficacy of this promising treatment.