Answer by drawing a diagram and explaining in a short paragraph your five favorite red blood cell disorders. (<250 words)

There are quite a few RBC problems that could be discussed. Here are several:

Hypochromic microcytic anemia: Small RBC's lack central pallor. Iron deficiency with blood loss in men and excessive menstruation or pregnancy in women or dietary lack in children are common causes. Serum iron and ferritin are decreased but transferrin is increased.

Macrocytic anemia: The RBC's are larger. Causes can be vitamin B12 deficiency from a gastrointestinal disorder such as atrophic gastritis with loss of parietal cells. Folate deficiency is similar but lacks neurologic sequelae. Impaired DNA synthesis leads to delayed cell maturation. Other cell lines are affected, so that hypersegmented PMN's can also be seen.

Microangiopathic hemolytic anemia: Disseminated intravascular coagulopathy or thrombotic thrombocytopenic purpura can lead to deposition of intravascular fibrin that leads to the appearance of schistocytes (fragmented RBC's) such as "helmet cells" in the peripheral blood.

Sickle cell anemia: A genetic mutation in the beta-globin chain with substitution of valine for glutamic acid leads to an unstable hemoglobin S which precipitates under low oxygen tension, leading to sickling of the RBC's, particularly in persons homozygous for this defect. These abnormal RBC's produce vaso-occlusive crises and infarcts, particularly of spleen.

Thalassemias: A defect in production of either alpha or beta globin chains leads to a relative excess of the other and this produces hypochromia from decreased hemoglobin within RBC's as well as aggregates of the excess chains which precipitate as Heinz bodies and lead to increased destruction of RBC's in marrow (ineffective erythropoiesis) and increased hemolysis in spleen.

Anemia of chronic disease: The RBC's in the peripheral blood appear normochromic and normocytic. The problem stems from a lack of iron utilization, not a lack of iron. Serum iron is low, but storage iron is increased. Chronic diseases such as malignancies, autoimmune diseases, and infections may lead to this condition.

Autoimmune hemolytic anemias: A drug may act as a hapten with RBC membrane antigens, autoantibodies may be produced in conjunction with autoimmune disease, or autoantibodies may appear with malignancy such as lymphoma. The RBC membranes are lysed or partly removed in the spleen with appearance of spherocytes in peripheral blood. The overall MCV may actually be increased, however, because of increased reticulocytosis.

Hereditary spherocytosis: This autosomal dominant disorder of defective membrane spectrin proteins seen in northern Europeans renders the RBC's smaller, less deformable, more rounded, with loss of central pallor and increased osmotic fragility. Their spherical shape makes it more difficult to traverse the spleen, so they are trapped and hemolyzed. Thus, splenectomy is usually curative of the anemia. Parvovirus infection may precipitate an aplastic crisis in these patients.

G6PD deficiency: This x-linked recessive disorder of persons of Mediterranean or African ancestry leads to the inability of the RBC to maintain adequate glutathione levels to prevent oxidative damage. Older RBC's are more susceptible to splenic hemolysis, and greater hemolysis may be triggered by drugs such as quinacrine and sulfa. Denatured hemoglobin precipitates as Heinz bodies with predispose to splenic removal of portions of RBC membrane and appearance of spherocytes.

Leukoerythroblastosis: If a myelophthisic process such as a myeloproliferative disorder with myelofibrosis is present, the replacement of the marrow cavity leads to the appearance of nucleated RBC's and immature WBC's in the peripheral blood. Metastatic carcinoma to marrow can also produce this effect. Myelofibrosis also leads to the appearance of tear drop RBC's.

Other disorders to be discussed could have included basophilic stippling with toxic marrow damage, sideroblastic anemia, reticulocytosis, polycythemia vera, target cells with liver disease or hemoglobinopathies, etc.

Explain how you would work up a patient who is found to have thrombocytopenia. (<250 words)

Thrombocytopenia can occur acutely with marked hemorrhage and volume replacement, but it more often represents an ongoing problem related to either decreased platelet production by megakaryocytes in marrow or to increased peripheral consumption or destruction. A bone marrow biopsy is performed to determine if there has been an idiopathic or drug related marrow aplasia with decreased megakaryocytes. A drug history should be obtained. The biopsy may also reveal the presence of a myelophthisic process with marrow replacement by metastatic carcinoma, leukemia, granulomatous infection, or myelofibrosis. Increased peripheral platelet consumption can occur with disseminated intravascular coagulation (DIC), and a d-dimer test and the presence of RBC fragmentation on a peripheral blood smear are indicators of this process, along with a prolonged protime and partial thromboplastin time. Thrombotic thrombocytopenic purpura (TTP) can also lead to platelet consumption, and can be diagnosed from finding transient neurologic deficits, renal failure, and fever. Platelets can also be sequestered in a large spleen, detected by physical examination or radiographic scan, as can be seen with the congestive splenomegaly of cirrhosis, with certain hemoglobinopathies such as hereditary spherocytosis, and with infections such as malaria. The peripheral destruction of platelets can occur with autoantibodies directed against platelets, as with idiopathic thrombocytopenic purpura (ITP). A bone marrow biopsy with ITP and other causes for peripheral platelet consumption will demonstrate megakaryocytic hyperplasia.