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HEMATOLOGIC DISORDERS 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20.

Allergic Purpuras Aplastic Or Hypoplastic Anemias Disseminated Intravascular Coagulation Folic Acid Deficiency Anemia Granulocytopenia And Lymphocytopenia Hemolytic Disease of The Newborn Hemophilia Hereditary Hemorrhagic Telangiectasia Hyperbilirubinemia Idiopathic Thrombocytopenic Purpura Iron Deficiency Anemia Pernicious Anemia Polycythemia Vera Secondary Polycythemia Sickle Cell Anemia Sideroblastic Anemias Spurious Polycythemia Thalassemia Thrombocytopenia (reduced platelet count) Von Willebrands Disease

Blood, one of the body's major fluid tissues, continuously circulates through the heart and blood vessels, carrying vital elements to every part of the body. Reviewing blood basics Blood performs several physiologically vital functions through its special components: the liquid portion (plasma) and the formed constituents (erythrocytes, leukocytes, and platelets) that are suspended in it. Erythrocytes, or red blood cells (RBCs), carry oxygen to the tissues and remove carbon dioxide from them. Leukocytes, or white blood cells (WBCs), participate in inflammatory and immune responses. Plasma carries antibodies and nutrients to tissues and carries waste away; coagulation factors in plasma, with platelets (thrombocytes), control clotting. The average person has 5 to 6 L of circulating blood, Which constitutes 5% to 7% of body weight (as much as 10% in premature neonates). Blood is three to five times more viscous than water, with an alkaline pH of 7.35 to 7.45, and is either bright red (arterial blood) or dark red (venous blood), depending on the degree If oxygen saturation and the hemoglobin level. Formation and characteristics Hematopoiesis occurs primarily in the red bone marrow of the long bones and axial skeleton where primitive cells (stem cells) produce the precursors of erythrocytes (normoblasts), leukocytes, and thrombocytes (megakaryocytes). During embryonic development, blood cells are derived from mesenchyma and form in the yolk sac. As the fetus matures, blood cells are produced in the liver, spleen, and thymus; by the 5th month of gestation, blood cells also begin to form in the bone marrow. After birth, blood cells are usually Produced only in the marrow. Blood's functions The most important function of blood is to transport oxygen (bound to RBCs inside hemoglobin) from the lungs to the body tissues and to return carbon dioxide from

these tissues to the lungs. Blood also performs the following vital defensive and protective functions:

provides complement, a group of immunologically important protein substances in plasma transports granulocytes and monocytes to defend the body against pathogens by phagocytosis production and delivery of antibodies (by way of WBCs) formed by plasma cells and lymphocytes provides specific immunity against viruses and cancer cells through sensitized lymphocytes.

Other functions of blood include control of hemostasis by platelets, plasma, and coagulation factors that repair tissue injuries and prevent or halt bleeding; regulation of acid-base and fluid balance; regulation of body temperature by carrying off excess heat generated by the internal organs for dissipation through the skin; and transportation of nutrients and regulatory hormones to body tissues and transportation of metabolic wastes to the organs of excretion (kidneys, lungs, and skin). Blood dysfunction Because of the rapid reproduction of bone marrow cells and the short life span and minimal storage in the bone marrow of circulating cells, bone marrow cells and their precursors are particularly vulnerable to physiologic changes that can affect cell production. Resulting blood disorders may be primary or secondary, quantitative or qualitative, or both; they may involve some or all blood components. Quantitative blood disorders result from increased or decreased cell production or cell destruction; qualitative blood disorders stem from intrinsic cell abnormalities or plasma component dysfunction. Specific causes of blood disorders include trauma, chronic disease, surgery, malnutrition, drugs, exposure to toxins and radiation, and genetic and congenital defects that disrupt production and function. For example, depressed bone marrow production or mechanical destruction of mature blood cells can reduce the number of RBCs, platelets, and granulocytes, resulting in pancytopenia (anemia, thrombocytopenia, granulocytopenia). Increased production of multiple bone marrow components can follow myeloproliferative disorders.

Diagnosing hematologic disorders Laboratory studies that help determine blood composition, production, and function are vital in diagnosing hematologic disorders. Other common studies include tests to evaluate the coagulation and agglutination properties of the blood and biopsies to evaluate the blood's formed elements.

Allergic purpura is a nonthrombocytopenic purpura, an acute or a chronic vascular inflammation that affects the skin, joints, and GI and genitourinary (GU) tracts in association with allergy symptoms. When allergic purpura primarily affects the GI tract with accompanying joint pain, it is called Henoch-Schnlein syndrome or anaphylactoid purpura. However, the term allergic purpura applies to purpura associated with many other conditions such as erythema nodosum. An acute attack of allergic purpura can last for several weeks. Fully developed allergic purpura is persistent and debilitating. This disorder affects males more commonly than females and is most prevalent in children ages 3 to 7 years. The prognosis is more favorable for children than for adults. The course of Henoch-Schnlein syndrome is usually benign and self-limiting, lasting 1 to 6 weeks if renal involvement is not severe. Causes The most common identifiable cause of allergic purpura is probably an autoimmune reaction directed against vascular walls and triggered by a bacterial infection (particularly a streptococcal infection, such as scarlet fever). Typically,

upper respiratory tract infection occurs 1 to 3 weeks before the onset of signs and symptoms. Other possible causes include allergic reactions to some drugs and vaccines; allergic reactions to insect bites; and allergic reactions to some foods (such as wheat, eggs, milk, and chocolate). Diagnostic tests No laboratory test clearly identifies allergic purpura (although white blood cell count and erythrocyte sedimentation rate are elevated). Diagnosis necessitates careful clinical observation, often during the or third attack. These laboratory test results may aid diagnosis allergic purpura:

guaiac-positive stools hematuria identified on urinalysis elevated blood urea nitrogen and serum creatinine levels and proteinuria, indicating glomerular involvement normal coagulation and platelet function (with the exception of a positive tourniquet test).

Small-bowel X-rays may reveal areas of transient edema. Diagnosis must rule out other forms of nonthrombocytopenic purpura. Treatment In allergic purpura, treatment is usually based on symptoms; for example, severe allergic purpura may require corticosteroids to relieve edema and analgesics ro alleviate joint and abdominal pain. Some patients with chronic renal disease may benefit from immunosuppression with azathioprine or corticosteroids, along with identification of the provocative allergen.

Aplastic Or Hypoplastic Anemias

Aplastic and hypoplastic anemias are potentially fatal and result from injury to or destruction of stem cells in bone marrow or the bone marrow matrix, causing pancytopenia (anemia, leukopenia, thrombocytopenia) and bone marrow hypoplasia. Although often used interchangeably with other terms for bone marrow failure, aplastic anemias correctly refer to pancytopenia resulting from the decreased functional capacity of a hypoplastic, fatty bone marrow. These disorders usually produce fatal bleeding or infection, particularly when they're idiopathic or stem from chloramphenicol use or infectious hepatitis. Mortality for aplastic anemias with severe pancytopenia is 80% to 90%.

Causes Aplastic anemias usually develop when damaged or destroyed stem cells inhibit red blood cell (RBC) production. Less commonly, they develop when damaged bone marrow microvasculature creates an unfavorable environment for cell growth and maturation. About half of such anemias result from drugs (such as chloramphenicol), toxic agents (such as benzene), or radiation. The rest may result from , immunologic factors (suspected but unconfirmed), severe disease (especially hepatitis), viral infection ( especially in children), and preleukemic and neoplastic infiltration of bone marrow. Idiopathic anemias may be congenital. Two such forms of aplastic anemia have been identified: Congenital hypoplastic anemia (Blackfan-Diamond anemia) develops between ages 2 and 3 months, and Fanconi's syndrome, between birth and age 10. In the absence of a consistent familial or genetic history of aplastic anemia, researchers suspect that these congenital abnormalities result from an induced change in fetal development, such as in maternal rubella cytomegalovirus infection. Symptoms The following are the most common symptoms of aplastic anemia. However, each individual may experience symptoms differently. Symptoms may include:

headache dizziness nausea shortness of breath bruising lack of energy or tiring easily (fatigue) abnormal paleness or lack of color of the skin blood in stool nosebleeds bleeding gums fevers sinus tenderness enlarged liver or spleen oral thrush - white patches on a red, moist, swollen surface, occurring anywhere in the mouth.

The symptoms of aplastic anemia may resemble other blood disorders or medical problems. Always consult your physician for a diagnosis.

Diagnostic tests In addition to a complete medical history and physical examination, diagnostic procedures for anemia include additional blood tests and a bone marrow biopsy. Treatment Effective treatment must eliminate any identifiable cause and provide vigorous supportive measures, such as packed RBC, platelet, and experimental histocompatibility antigen-matched leukocyte transfusions. Even after elimination of the cause, recovery can take months or may never occur. Bone marrow transplantation is the treatment of choice for anemia due to severe aplasia and for patients who need constant RBC transfusions. The patient with low leukocyte counts is at risk for infection. Prevention of infection may range from frequent hand washing to filtered air flow. The infection itself may require specific antibiotics; however, they are not given prophylactically because they tend to encourage resistant strains of organisms. Patients with low hemoglobin levels may need respiratory support with oxygen in addition to blood transfusions. Other appropriate forms of treatment include corticosteroids to stimulate erythroid production (successful in children, unsuccessful in adults); marrowstimulating agents, such as androgens (which are controversial); antilymphocyte globulin (experimental); and immunosuppressant agents (if the patient doesn't respond to other therapy). A group of agents called colony-stimulating factors encourage the growth of specific cellular components and show some promise in trials of patients who have received chemotherapy or radiation therapy. These agents include granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and erythropoietic stimulating factor.

Disseminated Intravascular Coagulation

Disseminated intravascular coagulation (DIC) is also known as consumption coagulopathy and defibrination syndrome. DIC complicates diseases and conditions that accelerate clotting, causing occlusion of small blood vessels, organ necrosis, depletion of circulating clotting factors and platelets, and activation of the fibrinolytic system. This, in turn, can provoke severe hemorrhage. Clotting in the microcirculation usually affects the kidneys and extremities but can occur in the brain, lungs, pituitary and adrenal glands, and G1 mucosa. Other conditions, such as vitamin K deficiency, hepatic disease, and anticoagulant therapy, can cause similar hemorrhage.

DIC is usually acute but can be chronic in cancer patients. The prognosis depends on early detection and treatment, the severity of the hemorrhage, and treatment of the underlying disease or condition. Causes DIC may result from:

infection - gram-negative or gram-positive septicemia; viral, fungal, or rickettsial infection; protozoal infection obstetric complications - abruptio placentae, amniotic fluid embolism, retained dead fetus, eclampsia, septic abortion, postpartum hemorrhage neoplastic disease - acute leukemia, metastatic carcinoma, lymphomas disorders that produce necrosis - extensive burns and trauma, brain tissue destruction, transplant rejection, hepatic necrosis, anorexia other disorders and conditions - heatstroke, shock, poisonous snakebite, cirrhosis, fat embolism, incompatible blood transfusion, drug reactions, cardiac arrest, surgery necessitating cardiopulmonary bypass, giant hemangioma, severe venous thrombosis, purpura fulminans, adrenal disease, adult respiratory distress syndrome, diabetic ketoacidosis, pulmonary embolism, and sickle cell anemia.

Why such conditions and disorders lead to DIC is unclear, as is whether they lead to DlC through a common mechanism. In many patients, the triggering mechanisms may be the entrance of foreign protein into the circulation and vascular endothelial injury. Regardless of how DlC begins, the typical accelerated clotting results in generalized activation of prothrombin and a consequent excess of thrombin. Excess thrombin converts fibrinogen to fibrin, producing fibrin clots in the microcirculation. This process consumes exorbitant amounts of coagulation factors (especially platelets, factor V, prothrombin, fibrinogen, and factor VIII), causing thrombocytopenia, deficiencies in factors V and VIII, hypoprothrombinemia, and hypofibrinogenemia. Circulating thrombin activates the fibrinolytic system, which lyses fibrin clots into fibrinogen degradation products (FDPs). The hemorrhage that occurs may be due largely to the anticoagulant activity of FDPs as well as to depletion of plasma coagulation factors. Signs and Symptoms You may experience bleeding and haemorrhage from any or several body parts. The bleeding may be heavy. Common signs of bleeding include:

Bloody vomit or red or black stools; Vaginal bleeding; Red or cloudy urine; Unexplained bruising; Severe abdominal or back pain caused by bleeding into body organs; Rarely convulsions; Rarely a coma.

Diagnostic tests Although numerous blood tests are often performed on patients prone to DIC, the important measures are: full blood count (especially the platelet count), fibrin degradation products or D-dimer tests (markers of fibrinolysis ), bleeding time and fibrinogen levels. Decreased platelets, elevated FDPs or D-dimers, prolonged bleeding time and decreased fibrinogen are markers of DIC. Treatment Successful management of DlC requires prompt recognition and adequate treatment of the underlying disorder. Treatment may be supportive (when the underlying disorder is self-limiting. for example) or highly specific. If the patient isn't actively bleeding, supportive care alone may reverse DIC. Active bleeding may require administration of blood, fresh frozen plasma, platelets, or packed RBCs to support hemostasis. Heparin therapy is controversial. It may be used early in the disease to prevent microclotting but may be considered a last resort in the patient who is actively bleeding. If thrombosis does occur, heparin therapy is usually mandatory. In most cases, it's administered in combination with transfusion therapy. Drugs such as antithrombin III and gabexate are being considered for use as antithrombins to inhibit the clotting cascade. Prevention Get prompt treatment for conditions known to bring on this disorder.

Folic Acid Deficiency Anemia

Folic acid deficiency anemia is a common, slowly progressive megaloblastic anemia. It's most prevalent in infants, adolescents, pregnant and lactating women, alcoholics, and elderly people and in people with malignant or intestinal diseases.

Causes Alcohol abuse suppressing the metabolic effects of folate is probably the most common cause of folic acid deficiency anemia. Additional causes include:

poor diet (common in alcoholics, narcotic addicts, elderly people who live alone, and infants, especially those with infections or diarrhea). Some adolescents whose diet consists mainly of non nutritious food develop folate deficiency. impaired absorption (due to intestinal dysfunction from such disorders as celiac disease, tropical sprue, regional jejunitis, and bowel resection) bacteria competing for available folic acid excessive cooking of foods, which destroys the available nutrient limited storage capacity in infants prolonged drug therapy with such drugs as anticonvulsants, estrogens, and methotrexate increased folic acid requirements during pregnancy; during rapid growth periods in infancy (especially in surviving premature infants); during childhood and adolescence because of consumption of folate-poor calf's milk; and in patients with neoplastic diseases and some skin diseases, such as exfoliative dermatitis.

Signs and symptoms Signs and symptoms of folic acid deficiency anemia gradually produces clinical features similar to other megaloblastic anemias, but without neurologic manifistations of B12 deficiency. Symptoms include the following:

progressive fatigue shortness of breath heart palpitations Sore mouth and tongue nausea anorexia headache fainting irritability forgetfulness pallor weakness weight loss

Diagnostic tests Diagnostic procedures include blood tests to measure hemoglobin, an ironcontaining compound that carries oxygen to cells throughout the body. Symptoms may be reevaluated after the patient has taken prescription folic acid supplements. Treatment Medical treatment consists primarily of folic acid supplements and elimination of contributing causes. Supplements may be given orally (1 to 5 mg/day) or parenterally (to patients who are severely ill, have malabsorption, or are unable to take oral medication). Many patients respond favorably to a well-balanced diet. Dietary treatment consists of increasing the intake of green, leafy vegetables and citrus fruits. Prevention Adequate dietary intake in high-risk individuals and folic acid supplementation during pregnancy may help prevent the onset of this anemia.

Granulocytopenia And Lymphocytopenia

Granulocytopenia is characterized by a marked reduction in the number of circulating granulocytes. Although this implies that all granulocytes (neutrophils, basophils, and eosinophils) are reduced, granulocytopenia usually refers to decreased neutrophils, a condition known as neutropenia. This disorder, which can occur at any age, is associated with infections and ulcerative lesions of the throat, GI tract, other mucous membranes, and skin. Its severest form is known as agranulocytosis. A rare disorder, lymphocytopenia (lymphopenia) is a deficiency of circulating lymphocytes (leukocytes produced mainly in lymph nodes). In granulocytopenia and lymphocytopenia, the white blood cell (WBC) count may reach dangerously low levels, leaving the body unprotected against infection. The prognosis in both disorders depends on the underlying cause and whether it can be treated. Untreated, severe granulocytopenia can be fatal in 3 to 6 days. Causes Granulocytopenia may result from diminished production of granulocytes in bone marrow, increased peripheral destruction of granulocytes, or greater use of granulocytes. Diminished production of granulocytes in bone marrow generally stems from radiation therapy or drug therapy, is a common adverse effect of antimetabolites and alkylating agents, and can occur in the patient who is

hypersensitive to phenothiazines, sulfonamides (and some sulfonamide derivatives, such as chlorothiazide), antibiotics, or antiarrhythmics. Drug-induced granulocytopenia usually develops slowly and typically correlates with the dosage and duration of therapy. Granulocyte production also decreases in such conditions as aplastic anemia and malignant bone marrow diseases and in some hereditary disorders (infantile genetic agranulocytosis). The growing loss of peripheral granulocytes results from increased splenic sequestration, diseases that destroy peripheral blood cells (viral and bacterial infections), and drugs that act as haptens (carriers of antigens that attack blood cells, causing acute idiosyncratic or non-dose-related drug reactions). Infections such as mononucleosis may cause granulocytopenia because of the increased use of granulocytes. Similarly, lymphocytopenia may result from decreased production, increased destruction, or loss of lymphocytes. Decreased lymphocyte production may result from a genetic or thymic abnormality or from an immunodeficiency disorder, such as thymic dysplasia or ataxia-telangiectasia. Increased lymphocyte destruction may be caused by radiation therapy, chemotherapy, or human immunodeficiency virus infection. Loss of lymphocytes may follow postoperative thoracic duct drainage, intestinal lymphangiectasia, and impaired intestinal lymphatic drainage (as in Whipple's disease). Lymphocyte depletion can also result from elevated plasma corticoid levels (due to stress, corticotropin or steroid therapy, or heart failure). Other disorders associated with lymphocyte depletion include Hodgkin's disease, leukemia, aplastic anemia, sarcoidosis, myasthenia gravis, lupus erythematosus, protein-calorie malnutrition, renal failure, terminal cancer, tuberculosis and, in infants, severe combined immunodeiciency disease (SCID). Diagnostic tests Diagnosis of granulocytopenia necessitates a thorough patient history to check for precipitating factors. Physical examination for clinical effects of underlying disorders is also essential. Treatment Effective management of granulocytopenia must include identifying and eliminating the cause and controlling infection until the bone marrow can generate more leukocytes. This often means that drug or radiation therapy must be stopped and antibiotic treatment begun immediately, even before test results are known. Treatment may also include antifungal preparations. Administration of granulocyteor granulocytemacrophage colony-stimulating factor (G-CSF or GM-CSF) is another treatment used to stimulate bone marrow production of neutrophils. Spontaneous restoration of leukocyte production in bone marrow generally occurs within 1 to 3 weeks.

Treatment of lymphocytopenia includes eliminating the cause and managing the underlying disorder. For an infant with SCID, therapy may include bone marrow transplantation.

Hemolytic Disease of The Newborn

Hemolytic disease of the newborn, formerly known as erythroblastosis fetalis, affects the fetus and neonate. It stems from an incompatibility of fetal and maternal blood, resulting in maternal antibody activity against fetal red blood cells (RBCs). Intrauterine transfusions can save 40% of fetuses with this problem. In severe, untreated hemolytic disease of the newborn, the prognosis is poor, especially if kernicterus develops. About 70% of these infants die, usually within the first week of life; survivors inevitably develop pronounced neurologic damage. ABO incompatibility, another form of fetomaternal incompatibility, can also occur and can lead to hemolytic disease of the newborn. Causes Although more than 60 RBC antigens can stimulate antibody formation, hemolytic disease of the newborn usually results from Rh isoimmunization, a condition that develops in about 7% of all pregnancies in the United States. During her first pregnancy (whether it ends in delivery or abortion), an Rhnegative female becomes sensitized by exposure to Rh-positive fetal blood antigens inherited from the father. A female may also become sensitized by receiving blood transfusions with alien Rh antigens, causing agglutinins to develop. This sensitization is the result of inadequate doses of Rho(D) immune globulin (human) or from failure to receive Rho(D) immune globulin after significant fetal-maternal leakage from abruptio placentae. Subsequent pregnancy with an Rh-positive fetus causes increasing amounts of maternal agglutinating antibodies to cross the placental barrier, attach to Rh-positive cells in the fetus, and cause hemolysis and anemia in the fetus. To compensate for this, the fetus produces more RBCs and erythroblasts (immature RBCs) appear in the fetal circulation. Extensive hemolysis results in the release of large amounts of unconjugated bilirubin, which the liver is unable to conjugate and excrete, causing hyperbilirubinemia and hemolytic anemia in the fetus. Before the development of Rho(D) immune globulin, this condition was a major cause of kernicterus and neonatal death.

Symptoms The following are the most common symptoms of hemolytic disease of the newborn. However, each baby may experience symptoms differently. Some of the symptoms of Hemolytic disease of the newborn include:

Anemia Jaundice Neonatal jaundice Edema Hydrops fetalis

Diagnostic tests Diagnostic tests are performed on the mother and the neonate. The father may also be tested for blood group, Rh factor , and Rh zygosity. Treatment The choice of treatment depends on the degree of maternal sensitization and hemolytic effects on the fetus or neonate. Intrauterine transfusion is performed on a fetus When amniotic fluid analysis suggests that the fetus is severely affected and delivery is inappropriate because of fetal immaturity. The mother is admitted to the labor and delivery area and monitored closely. She is given a tocolytic agent I.V. to inhibit contractions, and ultrasonography is performed to locate the umbilical vein of the fetus. Then, using a procedure called percutaneous umbilical blood sampling, a needle is inserted into the umbilical vein and a blood sample is taken to identify fetal blood type, measure hemoglobin levels and hematocrit, and obtain other pertinent information. If the fetal blood sample verifies anemia, a blood transfusion of O-negative blood in utero can take place through the sampling needle. This procedure may be repeated periodically (about every 2 weeks) until the fetus is mature enough for delivery. Planned delivery usually is done 2 to 4 weeks before term date, depending on maternal history, serologic tests, and amniocentesis; labor may be induced from the 34th to 38th week of gestation. During labor, the fetus should be monitored electronically; capillary blood sampling (from the scalp) determines acid-base balance. Any indication of fetal distress necessitates immediate cesarean delivery. Phenobarbital administered during the last 5 to 6 weeks of gestation may lower serum bilirubin levels in the neonate. An exchange transfusion removes antibody-coated RBCs and prevents hyperbilirubinemia through removal of the infant's blood and replacement with fresh group O Rh-negative blood. Albumin infusion binds bilirubin, reducing the risk of

hyperbilirubinemia. Phototherapy by exposure to ultraviolet light reduces bilirubin levels. Administration of gamma globulin that contains anti-Rh-positive antibody (Rho[D]) can provide passive immunization, which prevents maternal Rh isoimmunization in Rh-negative females. However, it's ineffective if sensitization has already resulted from a previous pregnancy, abortion, or transfusion. Neonatal therapy for hydrops fetalis consists of maintaining ventilation by intubation, oxygenation, and mechanical assistance, when necessary, and removing excess fluid to relieve ascites and respiratory distress. Other appropriate measures include an exchange transfusion and maintenance of the neonate's body temperature. Administration of Rho(D) immune globulin (human) to an unsensitized Rhnegative mother as soon as possible after the birth of an Rh-positive infant or after a spontaneous or elective abortion prevents complications in subsequent pregnancies. The following patients should be screened for Rh isoimmunization or irregular antibodies:

all Rh-negative mothers during their first prenatal visit and at 24, 28, 32, and 36 weeks' gestation all Rh-positive mothers with histories of transfusion, a jaundiced baby, stillbirth, cesarean birth, induced abortion, placenta previa, or abruptio placentae.

Prevention Fortunately, HDN is a very preventable disease. Because of the advances in prenatal care, nearly all women with Rh negative blood are identified in early pregnancy by blood testing. If a mother is Rh negative and has not been sensitized, she is usually given a drug called Rh immunoglobulin (RhIg), also known as RhoGAM. This is a specially developed blood product that can prevent an Rh negative mother's antibodies from being able to react to Rh positive cells. Many women are given RhoGAM around the 28th week of pregnancy. After the baby is born, a woman should receive a second dose of the drug within 72 hours.

A hereditary bleeding disorder, hemophilia results from deficiency of specific clotting factors. Hemophilia A (classic hemophilia). which affects more than 80% of all hemophiliacs, results from deficiency of factor VIII; hemophilia B (Christmas disease), which affects 15% of hemophiliacs, results from deficiency of factor IX. Other evidence suggests that hemophilia may result from nonfunctioning factors VIII and IX, rather than from deficiency of these factors.

Hemophilia is the most common X-linked genetic disease and occurs in about 1.25 in 10,000 live male births. The severity and prognosis of bleeding disorders vary with the degree of deficiency and the site of bleeding. The overall prognosis is best in mild hemophilia, which doesn't cause spontaneous bleeding and joint deformities. Advances in treatment have greatly improved the prognosis, and many hemophiliacs live normal life spans. Causes Hemophilia A and B are inherited as X-linked recessive traits. Therefore, female carriers have a 50% chance of transmitting the gene to each daughter, who would then be a carrier, and a 50% chance of transmitting the gene to each son, who would be born with hemophilia. Hemophilia produces abnormal bleeding, which may be mild, moderate, or severe, depending on the degree of factor deficiency. After a person with hemophilia forms a platelet plug at a bleeding site, the lack of clotting factors impairs formation of a stable fibrin clot. Immediate hemorrhage is not prevalent, but delayed bleeding is common. Signs and Symptoms If you've just found out you have hemophilia, you probably have a milder form of the disease. Symptoms of hemophilia include:

bruises that are unusual in location or number nosebleeds that won't stop excessive bleeding from biting a lip or having a tooth pulled painful or swollen joints blood in the urine

Diagnostic tests In addition to a complete medical history and physical examination, your physician may perform numerous blood tests including clotting factor levels, a complete blood count (CBC), assessment of bleeding times, and/or DNA (deoxyribonucleic acid) testing. Treatment Hemophilia is not curable, but treatment can prevent crippling deformities and prolong life. Correct treatment quickly stops bleeding by increasing plasma levels of

deficient clotting factors to help prevent disabling deformities that result from repeated bleeding into muscles , joints, and organs. In hemophilia A, cryoprecipitated antihemophilic factor(AHF), lyophilized AHF, or both given in doses large enough to raise clotting factor levels above 25% of normal can permit normal hemostasis. Before surgery, AHF is administered to raise clotting factors to hemostatic levels. Levels are then kept within a normal range until the wound has healed. Fresh frozen plasma can also be given but has some drawbacks. Inhibitors to factor VIII develop after multiple transfusions in 10% to 20% of patients with severe hemophilia renders the patient resistant to factor VIII infusions. Desmopressin may be given to stimulate the release of stored factor VIII, raising the level in the blood. In hemophilia B, administration of factor IX concentrate during bleeding episodes increases factor IX levels. A person with hemophilia who undergoes surgery needs careful management by a hematologist with expertise in hemophilia care. The patient requires deficient factor replacement before and after surgery. Such replacement may be necessary even for minor surgery, such as dental extraction. In addition, aminocaproic is commonly used for oral bleeding to inhibit the active fibrinolytic system in oral mucosa. Prevention These steps may help you avoid excessive bleeding and protect your joints:

Exercise regularly. Drugs that can aggravate bleeding include aspirin and nonsteroidal antiinflammatory drugs (Advil, Motrin, others). Instead, use acetaminophen (Tylenol, others), which is a safe alternative for mild pain relief. Also avoid certain blood-thinning medications, such as heparin and warfarin (Coumadin), which prevent blood from clotting. Practice good dental hygiene.

Hereditary Hemorrhagic Telangiectasia

Hereditary hemorrhagic telangiectasia - also called Osler-Weber-Rendu disease - is an inherited vascular disorder in which venules and capillaries dilate to form fragile masses of thin convoluted vessels (telangiectases), resulting in an abnormal tendency to hemorrhage. This disorder affects both sexes but may cause less severe bleeding in females. A similar inherited disorder, ataxia-telangiectasia, produces some of the same signs and symptoms.

Causes Hereditary hemorrhagic telangiectasia is transmitted by autosomal dominant inheritance. The disorder seldom skips generations. In its homozygous state, it may be fatal. Symptoms Recurrent nosebleeds are a nearly universal symptom in this condition. Usually the nosebleeds begin in childhood and become worse with age. The skin changes begin at puberty , and the condition becomes progressively worse until about 40 years of age, when it stabilizes. Diagnostic tests Bone marrow aspiration showing depleted iron stores confirms secondary iron deficiency anemia. Hypochromic, microcytic anemia is common; abnormal platelet function may also be found. Coagulation tests are essentially irrelevant because hemorrhage in telangiectasia results from vascular wall weakness. Treatment Supportive therapy includes blood transfusions and the administration of supplemental iron. Ancillary treatment may consist of applying pressure and topical hemostatic agents to bleeding sites, cauterizing bleeding sites not readily accessible, and protecting the patient from trauma and unnecessary bleeding. Parenteral administration of supplemental iron enhances absorption to maintain adequate iron stores and prevents gastric irritation. Administering antipyretics or antihistamines before blood transfusion and using saline-washed cells, frozen blood, or other types of leukocyte-poor blood instead of whole blood transfusion may prevent febrile transfusion reactions. Prevention Hereditary hemorrhagic telangiectasia is an inherited disorder and cannot be prevented.

Elevated serum bilirubin levels and mild jaundice are hallmarks of hyperbilirubinemia, also known as neonatal jaundice. The disorder can be physiologic (with jaundice the only symptom) or pathologic (resulting from an underlying disease). Physiologic jaundice is widespread and is more common and severe in certain ethnic groups (Chinese, Japanese, Koreans, Native Americans)

whose mean peak of unconjugated bilirubin is about twice that of the rest of the population. Physiologic jaundice is self-limiting; the prognosis for pathologic jaundice varies, depending on the cause. Untreated, severe hyperbilirubinemia may cause kernicterus, a neurologic syndrome resulting from deposition of unconjugated bilirubin in the brain cells and characterized by severe neural symptoms. Causes Hyperbilirubinemia may develop when:

factors that disrupt conjugation and usurp albuminbinding sites are present, including drugs such as aspirin, tranquilizers, and sulfonamides and conditions such as hypothermia, anoxia, hypoglycemia, and hypoalbuminemia decreased hepatic function results in reduced bilirubin conjugation increased erythrocyte production or breakdown results from hemolytic disorders or from Rh or ABO incompatibility biliary obstruction or hepatitis results in blockage of normal bile flow maternal enzymes present in breast milk inhibit the infant's glucuronyltransferase conjugating activity.

Hyperbilirubinemia stems from hemolytic processes in the neonate. As erythrocytes break down at the end of the neonatal life cycle, the hemoglobin separates into globin (protein) and heme (iron) fragments. Heme fragments form unconjugated (indirect) bilirubin, which binds with albumin for transport to liver cells to conjugate with glucuronide, forming direct bilirubin. Because unconjugated bilirubin is fatsoluble and can't be excreted in urine or bile, it may escape ro extravascular tissue, especially fatty tissue and the brain, resulting in hyperbilirubinemia. Symptoms The following are the most common symptoms of hyperbilirubinemia. However, each baby may experience symptoms differently. Symptoms may include:

yellow coloring of the baby's skin (usually beginning on the face and moving down the body) poor feeding or lethargy

The symptoms of hyperbilirubinemia may resemble other conditions or medical problems. Always consult your baby's physician for a diagnosis. Diagnostic tests Jaundice and elevated levels of serum bilirubin confirm hyperbilirubinemia.

Both mother and infant should be tested for blood group incompatibilities, and their hemoglobin levels and hematocrit should be measured. The direct Coombs' test also should be performed on both mother and infant. Diagnostic procedures for hyperbilirubinemia may include:

direct and indirect bilirubin levels red blood cell counts blood type and testing for Rh incompatibility (Coomb's test)

Treatment Depending on the underlying cause, treatment may include phototherapy, exchange transfusions, albumin infusion and, possibly, drug therapy. Phototherapy is the treatment of choice for physiologic jaundice and pathologic jaundice due to hemolytic disease of the newborn (after the initial exchange transfusion). Phototherapy uses fluorescent light to decompose bilirubin in the skin by oxidation. It usually is discontinued after bilirubin levels fall below 10 mg/dl and continue to decrease for 24 hours. Phototherapy seldom is the only treatment for jaundice due to a pathologic cause. An exchange transfusion, replacing the infant's blood with fresh blood (less than 48 hours old), thus removing some of the unconjugated bilirubin in serum, may be performed for severe hyperbilirubinemia. Other therapy for excessive bilirubin levels includes albumin administration (1 g/kg of 25% salt-poor albumin), which provides additional albumin for binding unconjugated bilirubin. This can be done 1 to 2 hours before exchange or as a substitute for a portion of the plasma in the transfused blood. Drug therapy, which is rare, usually consists of phenobarbital administered to the mother before delivery and to the infant several days after delivery This, drug stimulates the hepatic glucuronide-conjugating system. Prevention While hyperbilirubinemia cannot be totally prevented, early recognition and treatment are important in preventing bilirubin levels from rising to dangerous levels.

Idiopathic Thrombocytopenic Purpura

Thrombocytopenia that results from immunologic platelet destruction is known as idiopathic thrombocytopenic purpura (lTP). This form of thrombocytopenia may be acute (postviral thrombocytopenia) or chronic (Werlhof's disease, purpura hemorrhagica, essential thrombocytopenia, or autoimmune thrombocytopenia). The acute form usually affects children between ages 2 and 6; the chronic form mainly affects adults under age 50, especially women between ages 20 and 40.

Purpura refers to a purplish or reddish-brown skin rash caused by the leakage of blood from broken capillaries into the skin. Other names for ITP include purpura hemorrhagica and essential thrombocytopenia. Causes ITP is an autoimmune disorder. Antibodies that reduce the life span of platelets have been found in nearly all patients. The spleen probably helps to remove platelets modified by the antibody. The acute form usually follows a viral infection, such as rubella and chickenpox, and can result from immunization with a live vaccine. The chronic form seldom follows infection and is commonly linked with other immunologic disorders, such as systemic lupus erythematosus. Human immunodeficiency virus (HIV) infection has become a common cause of ITP and should be considered in the differential diagnosis. ITP can be the initial symptom of HIV infection - a symptom indicating AIDS-related complex or a complication of fully developed AIDS. It's also often a precursor to lymphoma. Symptoms

Bruising Nosebleed or oral bleeding Bleeding into the skin - also called pinpoint red spots and petechial rash Blood in the vomit, urine, or stool Abnormally heavy menstruation

Diagnostic tests In addition to a complete medical history and physical examination, diagnostic procedures for idiopathic thrombocytopenic purpura may include the following:

complete blood count (CBC) additional blood and urine tests careful review of the patient's medications

Sometimes, a bone marrow aspiration is performed to look at the production of platelets and to rule out any abnormal cells the marrow may be producing that could lower platelet counts. Treatment Acute ITP may be allowed to run its course without intervention, or it may be treated with glucocorticoids or immune globulin. Treatment with plasmapheresis or plateletpheresis with transfusion has been attempted with limited success.

For chronic ITP, corticosteroids are the treatment of choice to suppress phagocytic activity, promote capillary integrity, and enhance platelet production. Patients who fail to respond spontaneously within 1 to 4 months or who require high doses of corticosteroids to maintain platelet counts require splenectomy, Splenectomy may be up to 85% successful in adults when splenomegaly accompanies the initial thrombocytopenia. Before splenectomy, the patient may require blood, blood components, and vitamin K to correct anemia and coagulation defects. After splenectomy, she may need blood and component replacement and platelet concentrate. Normally, platelets multiply spontaneously after splenectomy. Alternative treatments include immunosuppressants (cytoxan or vincristine sulfate, for example) and highdose I.V. immune globulin in adults (85% effective). The use of immunosuppressants requires weighing the risks against the benefits. Immune globulin treatment has a rapid effect, raising platelet counts within 1 to 5 days, but the beneficial effect lasts only 1 to 2 weeks. Immune globulin is usually administered to prepare severely thrombocytic patients for emergency surgery. Prevention The causes and risk factors are unknown (except in children when it may be related to a viral infection), and prevention is unknown.

Iron Deficiency Anemia

Iron deficiency anemia is a common disease worldwide; it affects 10% to 30% of the adult population of the United States. It's most prevalent among premenopausal women, infants (particularly premature or low-birth-weight infants), children, adolescents (especially girls), alcoholics, and elderly people (especially those who are unable to cook). The prognosis after replacement therapy is favorable. Causes The main causes of iron deficiency are: poor absorption of iron by the body ( Vitamin C aides in iron absorption), inadequate daily intake of iron, pregnancy, growth spurts or blood loss due to heavy period or internal bleeding. Anemia develops slowly after the normal stores of iron have been depleted in the body and in the bone marrow. Women, in general, have smaller stores of iron than men. Women also lose iron more frequently than men because of the blood loss during menstruation.

In men and postmenopausal women, anemia is usually due to gastrointestinal blood loss associated with ulcers , the use of aspirin or nonsteroidal anti-inflammatory medications (NSAIDS), or colon cancer. Gaucher Disease may also cause anemia. Symptoms The following are the most common symptoms of iron-deficiency anemia. However, each individual may experience symptoms differently. Symptoms may include:

abnormal paleness or lack of color of the skin irritability lack of energy or tiring easily (fatigue) increased heart rate (tachycardia) sore or swollen tongue enlarged spleen a desire to eat peculiar substances such as dirt or ice (a condition called pica)

The symptoms of iron-deficiency anemia may resemble other blood conditions or medical problems. Always consult your physician for a diagnosis. Diagnostic tests Blood studies and stores in bone marrow may confirm iron deficiency anemia. However, the results of these tests can be misleading because of complicating factors, such as infection, pneumonia, blood transfusion, and iron supplements. Characteristic blood study results include:

low hemoglobin levels (males, less than 12 g/dl; females, less than 10 g/dl) low hematocrit (males, less than 47 ml/dl; females, less than 42 ml/dl) low serum iron levels with high binding capacity low serum ferritin levels low RBC count with microcytic and hypochromic cells (in early stages, RBC count may be normal, except in infants and children) decreased mean corpuscular hemoglobin in severe anemia.

Bone marrow studies reveal depleted or absent iron stores (done by staining) as well as normoblastic hyperplasia. GI studies, such as guaiac stool tests, barium swallow and enema, endoscopy, and sigmoidoscopy, rule out or confirm the diagnosis of bleeding causing the iron deficiency.

Diagnosis must rule out other forms of anemia, such as those that result from thalassemia minor, cancer, and chronic inflammatory, hepatic, and renal disease. Treatment The underlying cause of anemia must first be determined; then iron replacement therapy can begin. The treatment of choice is an oral preparation of iron or a combination of iron and ascorbic acid (which enhances iron absorption). In rare cases, iron may have to be administered I.M., for instance, if the patient is noncompliant with the oral preparation, if he needs more iron than he can take orally, if malabsorption prevents adequate iron absorption, or if a maximum rate of hemoglobin regeneration is desired. Total-dose I.V. infusions of supplemental iron can be administered to pregnant and elderly patients with severe iron deficiency anemia. The patient should receive this painless infusion of iron dextran in normal saline solution over 8 hours. To minimize the risk of an allergic reaction to iron, an I.V. test dose of 0.5 ml should be given first. Prevention The child's diet is the most important way to prevent and to treat iron deficiency. Many foods are good sources of iron:

Good -- Tuna, oatmeal, apricots, raisins, spinach, kale, greens, prunes. Better -- Eggs, meat, fish, chicken, turkey, soybeans, dried beans, peanut butter, peas, lentils, molasses. Best -- Breast milk (the iron is very easily used by the child), formula with iron, infant cereals, other iron-fortified cereals, liver, prune juice.

In addition, restrict milk to no more than 32 ounces daily. If the diet is deficient in iron, iron should be taken orally. During periods of increased requirements, such as teen pregnancy and lactation, increase dietary intake or take iron supplements. If an oral iron supplement is recommended; patients should consult with their physicians to determine what type of iron is appropriate. Most OTC iron supplements are non-heme (meaning the iron included does not come from animal sources); but within that there are few types of iron to choose from. Those sensitive to ferrous sulfate can choose a carbonyl iron formulation.

Pernicious Anemia
Pernicious anemia - also known as Addison's anemia - is a megaloblastic anemia characterized by decreased gastric production of hydrochloric acid and deficiency of intrinsic factor, a substance normally secreted by the parietal cells of the gastric mucosa that is essential for vitamin B12 absorption. The resulting deficiency of vitamin B12 causes serious neurologic, psychological, gastric, and

intestinal abnormalities. Increasingly fragile cell membranes induce widespread destruction of red blood cells (RBCs), resulting in low hemoglobin levels. In the United States, pernicious anemia is most common in New England and the Great Lakes region because of ethnic concentration. It's rare in children, Blacks, and Asians. Onset typically is between ages 50 and 60; incidence increases with advancing age. Causes Familial incidence of pernicious anemia suggests a genetic predisposition. This disorder is significantly more common in patients with immunologically related diseases, such as thyroiditis, myxedema, and Graves' disease. An inherited autoimmune response may cause gastric mucosal atrophy and, consequently, decreases hydrochloric acid and intrinsic factor production. Intrinsic factor deficiency impairs vitamin B12 absorption. The resultant vitamin B12deficiency inhibits the growth of all cells, particularly RBCs, leading to insufficient and deformed RBCs with poor oxygen-carrying capacity. Pernicious anemia also impairs myelin formation. Initially, it affects the peripheral nerves but gradually it extends to the spinal cord, causing neurologic dysfunction. Secondary pernicious anemia can result from partial removal of the stomach, which limits the amount of productive mucosa. Symptoms The following are the most common symptoms for pernicious anemia. However, each individual may experience symptoms differently. Symptoms may include:

weak muscles numbness or tingling in hands and feet difficulty walking nausea diarrhea weight loss sore mouth irritability lack of energy or tiring easily (fatigue) diarrhea smooth and tender tongue personality changes, "megaloblastic madness"

Diagnostic tests The results of blood studies, bone marrow examination, gastric analysis, and the Schilling test establish the diagnosis. Laboratory screening must rule out other anemias with similar symptoms, such as folic acid deficiency anemia, because treatment differs. Diagnosis must also rule out vitamin B12 deficiency resulting from malabsorption due to GI disorders, gastric surgery, radiation therapy, or drug therapy. Treatment Treatment of pernicious anemia requires the administration of lifelong injections of B12 . Vitamin B12 given by injection enters the bloodstream directly, and does not require intrinsic factor. At first, injections may need to be given several times a week, in order to build up adequate stores of the vitamin. After this, the injections can be given on a monthly basis. Other substances required for blood cell production may also need to be given, iron and vitamin C. Prevention Pernicious anemia is not preventable, but with early detection and treatment of vitamin B12 deficiency, complications are readily controlled.

Polycythemia Vera
Polycythemia (say: "polly-sigh-thee-me-ah") vera (PV) is a disease in which your body makes too many red blood cells. Polycythemia vera (also known as primary polycythemia, erythema, polycythemia rubra vera, splenomegalic polycythemia, and Vaquez-Osler disease) is a chronic, myeloproliferative disorder. It's characterized by increased red blood cell (RBC) mass, leukocytosis, thrombocytosis, and increased hemoglobin concentration, with normal or decreased plasma volume. It usually occurs between ages 40 and 60, most commonly among men of Jewish ancestry. It seldom affects children or blacks and doesn't appear to be familial. Causes In polycythemia vera, uncontrolled and rapid cellular reproduction and maturation cause proliferation or hyperplasia of all bone marrow cells (panmyelosis). The cause of such uncontrolled cellular activity is unknown, but it is probably the result of a multipotential stem cell defect. Symptoms The symptoms of polycythemia vera come on slowly. Because there are too many red blood cells, there is more blood in the body than normal, it is thicker than normal and has difficulty circulating in small blood vessels. Symptoms may include:

poor oxygen circulation - headache, dizziness, vertigo, ringing in the ears (tinnitus), vision changes, chest pain abnormal bleeding - nosebleeds, gums bleeding, bruising, digestive system bleeding enlarged spleen (splenomegaly) and/or liver (hepatomegaly) abnormal blood clots in veins in the body ( thrombosis ) may develop Budd-Chiari syndrome (obstruction of the main vein of the liver) itching (pruritis), especially after a hot bath ruddy (reddened) complexion - may be seen in the face, palms, nailbeds, mucous membranes in the mouth, and conjunctiva of the eye

Diagnostic tests In addition to a complete medical history and physical examination, diagnostic procedures for polycythemia may include additional blood tests to observe the increased number of red blood cells in the body, and distinguish it from other conditions which could cause the red blood cell count to increase (such as with certain cardiac and respiratory diseases, erythremia, and certain tumors). Treatment Phlebotomy, the primary treatment, can be performed repeatedly and can reduce RBC mass promptly. It's best used for patients with mild disease and for young patients. The frequency of phlebotomy and the amount of blood removed each time depend on the patient's condition. Typically, 350 to 500 ml of blood can be removed every other day until the patient's hematocrit is reduced to the low-normal range. After repeated phlebotomies, the patient develops iron deficiency, which stabilizes RBC production and reduces the need for phlebotomy. Phlebotomy doesn't reduce the WBC or platelet count and won't control the hyperuricemia associated with marrow cell proliferation. Myelosuppressive therapy may be used for patients with severe symptoms, such as extreme thrombocytosis, a rapidly enlarging spleen, and hypermetabolism. It's also used for elderly patients who have difficulty tolerating the phlebotomy procedure. Radioactive phosphorus (32P) or chemotherapeutic agents, such as melphalan, busulfan, and chlorambucil, can satisfactorily control the disease in most cases. However, these agents may cause leukemia and should be reserved for older patients and those with serious problems not controlled by phlebotomy. Patients of any age who have had previous thrombotic problems should be considered for myelosuppressive therapy. Pheresis technology allows removal of RBCs, WBCs, and platelets individually or collectively (and provides these cellular components for blood banks). Pheresis also permits the return of plasma to the patient, thereby diluting the blood and reducing hypovolemic symptoms.

As appropriate, additional treatments include administration of cyproheptadine (12 to 16 mg/day) and allopurinol (300 mg/day) to reduce serum uric acid levels. Treatment usually improves symptomatic splenomegaly; rarely, splenectomy may be performed.

Secondary Polycythemia
Secondary polycythemia - also called reactive polycythemia - is characterized by excessive production of circulating red blood cells (RBCs) due to hypoxia, tumor, or disease. It occurs in about 2 out of every 100,000 persons who live at or near sea level; incidence increases among people who live at high altitudes. Causes Secondary polycythemia may result from increased production of erythropoietin. This hormone, which is possibly produced and secreted by the kidneys, stimulates bone marrow production of RBCs. The increased production may be an appropriate (compensatory) physiologic response to hypoxemia, which may result from:

chronic obstructive pulmonary disease hemoglobin abnormalities (such as carboxyhemoglobinemia, which occurs in heavy smokers) heart failure (causing a decreased ventilationperfusion ratio) right-to-left shunting of blood in the heart (as in transposition of the great vessels) central or peripheral alveolar hypoventilation (as in barbiturate intoxication or pickwickian syndrome) low oxygen content of air at high altitudes.

Symptoms Weakness, headaches, and fatigue are usually the first symptoms of secondary polycythemia . Patients may feel lightheaded or experience shortness of breath . Visual disturbances associated with this disorder include distorted vision, blind spots, and flashes of light. The gums and small cuts are likely to bleed, and the hands and feet may burn. Extensive itching often occurs after taking a bath or shower. Pain in the chest or leg muscles is common. The face often becomes ruddy, then turns blue after exercise or other exertion. Confusion and ringing in the ears ( tinnitus ) may also occur. Diagnostic tests Laboratory results for secondary polycythemia include:

increased RBC mass, with increased hematocrit, hemoglobin levels, mean corpuscular volume, and mean corpuscular hemoglobin elevated urine erythropoietin levels increased histamine levels decreased or normal arterial oxygen saturation.

Treatment The goal of treatment is correction of the underlying disease or environmental condition. In severe secondary polycythemia when altitude is a contributing factor, relocation may be advisable. If secondary polycythemia has produced hazardous hyperviscosity, or if the patient doesn't respond to treatment for the primary disease, reduction of blood volume by phlebotomy or pheresis may be effective. Emergency phlebotomy is indicated for prevention of impending vascular occlusion and before emergency surgery. In the latter case, removal of excess RBCs and reinfusion of the patient's plasma is usually advisable.

Sickle Cell Anemia

Sickle cell anemia is a congenital hemolytic disease that results from a defective hemoglobin molecule (hemoglobin S) that causes red blood cells (RBCs) to become sickle shaped. Such cells impair circulation, resulting in chronic ill health (fatigue, dyspnea on exertion, swollen joints), periodic crises, long-term complications, and premature death. Sickle cell anemia is common among people whose ancestors come from subSaharan Africa, Spanish speaking regions of the world (South America, Cuba, and Central America), Saudi Arabia, India, and Mediterranean countries such as Turkey, Sicily, Greece, and Italy. Causes Sickle cell anemia is cause by a genetic change in hemoglobin, the oxygencarrying protein inside the red blood cells. This causes the cells to take on a sickleshape and have a shorter life span, which can cause anemia. Sickle cells are also less flexible and stickier than normal red blood cells, and can become trapped in small blood vessels preventing blood flow and starving tissues and organs. This compromises the delivery of oxygen, which may result in damage to associated tissues and organs. The disease is often inherited. Symptoms There are many symptoms for sickle cell. Individuals with sickle cell may not experience all of these symptoms. The symptoms include: family history of sickle cell anemia, fatigue, breathlessness, rapid heart rate, delayed growth and puberty,

susceptibility to infections ulcers on the lower legs (in adolescents and adults) jaundice, attacks of abdominal pain, weakness, joint pain, fever , vomiting, bloody (hematuria) urination, excessive thirst, excessive penis pain, priapism, chest pain and decreased fertility. Symptoms may not appear until 4 months after birth and are most severe during an acute episode. Diagnostic tests Most states in the U.S. perform a simple blood test on all babies born to detect sickle cell anemia. If the test shows the abnormal hemoglobin is present, a second blood test is done to confirm the diagnosis. Treatment Although sickle cell anemia can't be cured, treatments can alleviate symptoms and prevent painful crises. Certain vaccines, such as polyvalent pneumococcal and Haemophilus influenzae B vaccine; anti-infectives, such as lowdose oral penicillin; and chelating agents, such as deferoxamine, can minimize complications resulting from the disease and from transfusion therapy. Other medications, such as analgesics, may help to relieve the pain of vasoocclusive crisis. Iron supplements may be given if folic acid levels are low. A good antisickling agent isn't yet available; the most commonly used drug, sodium cyanate, has many adverse effects. Treatment begins before age 4 months with prophylactic penicillin. If the patient's hemoglobin level decreases suddenly or if his condition deteriorates rapidly, hospitalization is needed for transfusion of packed RBCs. In an acute sequestration crisis, treatment may include sedation and administration of analgesics, blood transfusion, oxygen therapy, and large amounts of oral or I.V. fluids. Despite the effectiveness of transfusions, some clinicians limit them because they increase blood viscosity and the risk of vascular occlusion. Prevention With the right precautions, teens with sickle cell disease can do most of the stuff other teens do. To stay as healthy as possible, people with sickle cell anemia should take these steps:

Eat a balanced, healthy diet. Take vitamins, including folic acid supplements, as prescribed. Avoid places low in oxygen. (For example, it's not a good idea to go hiking at high altitudes or spend lots of time swimming under water.)

Drink plenty of water to prevent dehydration. Get plenty of rest. Avoid alcohol , drugs , and smoking , which can aggravate sickle cell disease and its symptoms. Some people with sickle cell disease are prone to lung problems, so smoking is particularly risky.

Sideroblastic Anemias
Sideroblastic anemia is an umbrella term for a group of heterogenous disorders with a common defect: failure to use iron in hemoglobin synthesis despite the availability of adequate iron stores. As a result, iron is deposited in the mitochondria of normoblasts, and characteristic rings surround the nucleus of this cell. Sideroblastic anemias can be acquired or hereditary; the acquired form, in turn, can be primary or secondary. In many instances, hereditary sideroblastic anemia responds to treatment with pyridoxine (vitamin B6). Correction of the secondary acquired form depends on the causative disorder; the primary acquired (idiopathic) form resists treatment and usually proves fatal within 10 years after onset of complications or a concomitant disease. Causes Hereditary sideroblastic anemia is most prevalent in young males and appears to be transmitted by X-linked inheritance; females are carriers and usually show no signs of this disorder. The acquired form may be secondary to ingestion of or exposure to toxins, such as alcohol and lead, or to drugs, such as isoniazid and chloramphenicol. It can also occur as a complication of neoplastic and inflammatory diseases, such as lymphoma, rheumatoid arthritis, lupus erythematosus, multiple myeloma, tuberculosis, and severe infections. The primary acquired form, whose cause is unknown, is most common in elderly people but occasionally develops in young people. It's often associated with thrombocytopenia or leukopenia. Symptoms Symptoms of sideroblastic anemia vary depending on the severity of the condition. Sideroblastic anemia may occur without symptoms and be detected only during a medical examination that includes a blood test. When they occur, symptoms may include the following:

Rapid heartbeat. Lightheadedness or dizziness. Headache.

Irritability and other mood disturbances. Mental confusion. Loss of sexual drive. Shortness of breath on exertion.

Diagnostic tests Blood tests are used to examine the appearance and other characteristics of red cells and to measure the amount of iron in the blood. Bone marrow biopsy is also used. Treatment The underlying cause determines the course of treatment. Hereditary sideroblastic anemia usually responds to several weeks of treatment with high doses of pyridoxine. The acquired secondary form subsides after the causative drug or toxin is removed or the underlying condition is adequately treated. Folic acid supplements may be beneficial when concomitant megaloblastic nuclear changes in RBC precursors are present. Deferoxamine may be used to treat chronic iron overload in selected patients. Carefully crossmatched transfusions (providing needed hemoglobin) or high doses of androgens are effective palliative measures for some patients with the primary acquired form of sideroblastic anemia. This form is essentially refractory to treatment andusually leads to death from acute leukemia or from respiratory or cardiac complications. Some patients with sideroblastic anemias may benefit from phlebotomy to prevent hemochromatosis. Phlebotomy increases the rate of erythropoiesis and uses up excess iron stores; thus, it reduces serum and total-body iron levels.

Spurious Polycythemia
Spurious polycythemia is characterized by increased hematocrit and normal or decreased red blood cell (RBC) total mass. It results from decreasing plasma volume and subsequent hemoconcentration. This disease is also known as relative polycythemia, stress erythrocytosis, stress polycythemia, benign polycythemia. Gaisbck's syndrome, and pseudopolycythemia. Causes Possible causes of spurious polycythemia include the following:

dehydration. Conditions that promote severe fluid loss decrease plasma levels and lead to hemoconcentration. Such conditions include persistent vomiting or diarrhea, burns, adrenocortical insufficieny, aggressive diuretic therapy, decreased fluid intake, diabetic ketoacidosis, and renal disease. hemoconcentration due to stress. Nervous stress leads to hemoconcentration by some unknown mechanism, possibly by temporarily decreasing circulating plasma volume or by vascular redistribution of erythrocytes. high normal RBC mass and low normal plasma volume. In many patients, an increased hematocrit merely reflects a normally high RBC mass and low plasma volume.

Other factors that may be associated with spurious polycythemia include hypertension, thromboembolic disease, pregnancy, elevated serum cholesterol and uric acid levels, and familial tendency. Diagnostic tests Spurious polycythemia is distinguishable from true polycythemia vera by its characteristic normal or decreased RBC mass, elevated hematocrit, and the absence of leukocytosis. Treatment The principal goals of treatment are to correct dehydration and to prevent lifethreatening thromboembolism. Rehydration with appropriate fluids and electrolytes is the primary therapy for spurious polycythemia secondary to dehydration. Therapy must also include appropriate measures to prevent continuing fluid loss.

Thalassemia is the name of a group of inherited blood disorders. Hemoglobin, the part of red blood cells that carries oxygen, is made up of two different proteins, called alpha and beta. If the body has an imbalance in the two proteins the red blood cells cannot carry enough oxygen. Two pairs of polypeptide chains - alpha and beta chains - make up hemoglobin. In thalassemia, diminished synthesis can affect either pair. Structurally, the chains are normal, but the genetic defect decreases their number. In alphathalassemia, alpha chain synthesis slows; in beta-thalassemia, beta chain synthesis slows. Some patients with beta-thalassemia have no normal hemoglobin - only hemoglobin S and the minor hemoglobins. In the most severe form of alpha-thalassemiahydrops fetalis - severe anemia and heart failure render the fetus hydropic. The fetus is stillborn or dies shortly after birth. Prenatal testing can be used to detect the condition.

Beta-thalassemia (the most common form of this disorder) occurs in three clinical forms: thalassemia major, intermedia, and minor. The severity of the resulting anemia depends on whether the patient is homozygous or heterozygous for the thalassemic trait. The prognosis for beta-thalassemia varies. Patients with thalassemia major seldom survive to adulthood; children with thalassemia intermedia develop normally into adulthood, although puberty is usua1ly delayed; patients with thalassemia minor can expect a normal life span. Causes Thalassemia major and thalassemia intermedia result from homozygous inheritance of the partially dominant autosomal gene responsible for this trait. Thalassemia minor is caused by heterozygous inheritance of the same gene. In all three types of thalassemia, total or partial deficiency of beta polypeptide chain production impairs hemoglobin synthesis and results in continual production of fetal hemoglobin, even after the neonatal period has passed. Symptoms

Fatigue Shortness of breath Jaundice Bone deformities in the face

Diagnostic tests The diagnosis of thalassemia trait and thalassemia major is made from microscopic examination of the blood, which shows many small, pale red blood cells, and from other blood tests that show reduced levels of adult hemoglobin in the blood. Treatment Treatment of thalassemia major is essentially supportive. For example, infections require prompt treatment with appropriate antibiotics. Folic acid supplements help maintain folic acid levels despite increase requirements. Transfusions of packed RBCs raise hemoglobin levels but must be used judiciously to minimize iron overload. Splenectomy and bone marrow uansplantation have been tried, but their effectiveness has not been confirmed. Thalassemia intermedia and thalassemia minor generally don't require treatment. Iron supplements are contraindicated in all forms of thalassemia. Treatment of children is more difficult. Regular blood transfusions may minimize physical and mental retardation, but transfusions increase the risk of deadly hemosiderosis and iron overload. Continuous subcutaneous infusion of iron-chelating

agents may help produce a negative overall iron balance. If rapid splenic sequestration of transfused RBCs necessitates more transfusions, a splenectomy may be performed. Prevention

Genetic counseling in families with known thalassemia Prenatal screening

Thrombocytopenia (reduced platelet count)

Thrombocytopenia is the term for a reduced platelet (thrombocyte) count. It occurs when platelets are lost from the circulation faster than they can be replaced from the bone marrow where they are made. Thrombocytopenia may either result from a failure of platelet production and/or an increased rate of removal from blood. Causes Thrombocytopenia may be congenital or acquired; the acquired form is more common. In either case, it usually results from decreased or defective production of platelets in the marrow (for example, in leukemia, aplastic anemia, and toxicity with certain drugs) or from increased destruction outside the marrow caused by an underlying disorder (such as cirrhosis of the liver, disseminated intravascular coagulation, and severe infection). Less commonly, thrombocytopenia results from sequestration (hypersplenism, hypothermia) or platelet loss. Acquired thrombocytopenia may result from the use of certain drugs, such as quinine, quinidine, rifampin, heparin, nonsteroidal antiinflammatory agents, histamine blockers, most chemotherapeutic agents. allopurinol, and alcohol. Thrombocytopenia may also occur transiently after a viral infection (such as Epstein-Barr) or infectious mononucleosis. An idiopathic form of thrombocytopenia also occurs. Symptoms The following are the most common symptoms of thrombocytopenia. However, each baby may experience symptoms differently. Symptoms may include:

bruising or petechiae (small red spots on the skin) signs of bleeding in other body systems jaundice

The symptoms of thrombocytopenia may resemble other conditions or medical problems. Always consult your baby's physician for a diagnosis. Diagnostic tests

CBC shows low platelets Bone marrow aspiration or biopsy may be normal or may show low megakaryocytes (platelet precursors) or an infiltrating disease. PTT clotting study is normal PT clotting study is normal Platelet associated antibodies may be present

Treatment Removal of the offending agents in drug-induced thrombocytopenia or proper treatment of the underlying cause, when possible, is essential. Corticosteroids may be used to increase platelet production or immune globulin. Platelet transfusions may be used to stop episodic abnormal bleeding caused by a low platelet count. If platelet destruction results from an immune disorder, platelet infusions may have only a minimal effect and may be reserved for lifethreatening bleeding. Splenectomy may be necessary to correct thrombocytopenia caused by platelet destruction. A splenectomy should significantly reduce platelet destruction because the spleen acts as the primary site of platelet removal and antibody production. Prevention Prevention depends on the specific cause.

Von Willebrands Disease

Also known as angiohemophilia, pseudohemophilia, or vascular hemophilia, von Willebrand's disease is a hereditary bleeding disorder characterized by prolonged bleeding time, moderate deficiency of clotting factor VIII (antihemophilic factor [AHF]), and impaired platelet function. Von Willebrand's disease commonly causes bleeding from the skin or mucosal surfaces and, in females, excessive uterine bleeding. Bleeding may range from mild and asymptomatic to severe hemorrhage. The prognosis is usually good because most cases are mild. Severe forms may cause hemorrhage after laceration or surgery as well as GI bleeding. Excessive postpartum bleeding is uncommon because factor VIII levels and bleeding time abnormalities become less pronounced during pregnancy. Massive soft-tissue hemorrhage and bleeding into joints seldom occur.

Bleeding episodes occur sporadically; a patient may bleed excessively after one dental extraction but not after another. The severity of bleeding may lessen with age. Causes Von Willebrand disease is almost always inherited. This means that parents pass a gene for the disease on to their children. The gene for the disease is usually dominant . That means that a parent with the disease has a 50 percent or 1 in 2 chance of passing the gene to each of his or her children. Type 1 and Type 2 von Willebrand disease are usually inherited this way. The gene for Type 3 von Willebrand disease is usually recessive . That means the child would have to inherit the gene from both parents. Even if both parents have mild or no symptoms, the child can have severe symptoms. In rare cases, von Willebrand disease can be acquired (developed later in life). Signs and Symptoms The symptoms of von Willebrand disease may include:

bruising that's unusual in location or frequency abnormal menstrual bleeding bleeding in the mucous membranes, such as the gums, nose, and lining of the gastrointestinal system excessive or prolonged bleeding after a tooth is pulled or tonsils are removed or prolonged oozing from cuts

Diagnostic tests

Normal platelet count Prolonged bleeding time Reduced von Willebrand factor level Reduced platelet aggregation ( platelet aggregation test ) Ristocetin co-factor is reduced

This disease may also alter the results of the following tests:

Factor VIII level Von Willebrand factor multimers

Treatment The objectives of treatment are to shorten bleeding time by local measures and to replace factor VIII (and, consequently, factor VIIIvwf) by infusion of cryoprecipitate or blood fractions that are rich in factor VIII.

In many cases, the disorder is so mild that unless surgical or dental procedures are needed, no treatment may be required other than having the patient avoid taking aspirin. However, preparation is necessary for these procedures even for patients with mild forms of the disease. During bleeding episodes and before even minor surgery, I.V. infusion of cryoprecipitate or fresh plasma (in quantities sufficient to raise factor VIII levels to 50% of normal) shortens bleeding time. Desmopressin may be effective in mild disease because it enhances cellular release of stored factor VIII.