Erythropoiesis Information and Courses from MediaLab, Inc.

Conditions that affect the bone marrow can also lead to thrombocytopenia. It may be necessary to examine bone marrow smears and sections to diagnose the primary condition that is causing the decrease in circulating platelets. In leukemia, the platelet count is diminished as a result of displacement in the bone marrow of normal hematopoietic cells (including megakaryocytes and their precursor cells) by leukemic cells. If megakaryocytes are reduced in the bone marrow, the number of circulating platelets will be reduced. Chemotherapy can lead to transient thrombocytopenia since it interferes with the cell cycle of normal as well as tumor cells. In patients with aplastic anemia, where the stem cells are not functioning properly, thrombocytopenia occurs as the bone marrow becomes more and more hypoproliferative. Pancytopenia is often seen with megaloblastic anemias that are caused by folic acid or vitamin B12 deficiency. Thrombopoiesis (as well as erythropoiesis and granulopoiesis) is ineffective. The bone marrow contains a normal, or even increased number of megakaryocytes, but the number of platelets entering the peripheral circulation is decreased.

Children with beta thalassemia major, also called Cooley's anemia, usually develop clinical signs during their first year of life. They appear to be malnourished and may exhibit abdominal girth expansion. They show bone marrow expansion and skeletal deformations, which are a result of increased erythropoiesis due to low hemoglobin levels. A common finding is facial bone changes caused by this bone marrow expansion (sometimes referred to as Mongoloid facial features). Other clinical signs include frequent infections, hepatomegaly, splenomegaly, gall stones, leg ulcers, iron toxicity, and poor growth and sexual development. In addition, cardiac failure due to increased burden of the heart attempting to oxygenate the tissues, can lead to serious complications and death if the condition is not treated.In general, death usually occurs by the time these patients are in their early twenties unless treated with blood transfusions along with iron-chelating agents. If no chelating agent is used during treatment life will only be prolonged by about a decade.The different genotypes associated with beta thalassemia major are: B0/B0, B0/B+, or B+/B+.

Howell-Jolly bodies are round, smooth, almost pyknotic, dark-purple bodies ranging in size from 0.5 to 1.0 micron in diameter. These RBC inclusions contain DNA. Howell-Jolly bodies are thought to be nuclear remnants or aggregates of chromosomes that have separated from the mitotic spindle and remain behind after the remainder of the RBC nucleus is expelled. The spleen normally removes these bodies from the RBCs. However, Howell-Jolly bodies can be observed on a Wright-stained peripheral blood smear post-splenectomy or when the spleen is not functioning properly. Howell-Jolly bodies may also be seen in hemolytic anemias such as sickle cell anemia.When Howell-Jolly bodies are present, they usually occur singly, as shown in the image on the right. It is possible, though, that two or more may be seen in a single RBC, usually occurring in the presence of megaloblastic anemia or abnormal erythropoiesis.

Under normal conditions, Howell-Jolly bodies are thought to be remnants of nuclear fragments due to incomplete expulsion of the nucleus. In pathological conditions, they are aggregates of chromosomes which have separated from the mitotic spindle during abnormal mitosis. Single or multiple Howell-Jolly bodies may be found in a red cell. A single HJ body in a red cell may be seen in megaloblastic anemia, hemolytic anemia such as sickle cell anemia and after splenectomy. Megaloblastic anemia or abnormal erythropoiesis is usually present when multiple Howell-Jolly bodies are observed in a single cell.

Regulation of iron equilibrium occurs mainly through the process of absorption. Iron is absorbed through the mucosal cells lining the duodenum. A variety of proteins are involved in this process. Hepcidin, an antimicrobial protein primarily produced in the liver, has been recently found to be a major (negative) regulator of dietary iron absorption by disrupting cellular iron transport in the intestine. Decreased levels of hepcidin are related to increased iron absorption into the bloodstream. Hepcidin is increased in response to iron overload and inflammation. (4)Additional proteins involved in iron metabolism include transferrin (Tf), transferrin receptor (TfR), ferroportin, HFE protein, hemojuvelin, and others. Their roles in iron absorption are complex and in some instances incompletely understood.Factors affecting iron absorption include: Tissue stores, e.g., decreased stored iron is associated with a decrease in hepcidin and increase in iron absorption. Rate of hematopoietic activity, e.g., an increased rate of erythropoiesis is associated with a decrease in hepcidin and an increase in iron absorption. Oxygen concentration in tissues, e.g., hypoxia decreases hepcidin and increases iron absorption, thereby promoting increased erythopoiesis. Dietary intake, including form of iron ingested, e.g., heme iron is more readily absorbed than non-heme forms of iron. Condition of GI tract mucosal cells Intraluminal factors, e.g. intestinal motility