In thrombocytopenia

Increased intrahepatic resistance to portal flow increases pressure on the entire splanchnic bed an enlarged spleen (splenomegaly) is a common finding in cirrhotic patient and can result in thrombocytopenia due to splenic sequestration of the platelets. Portal hypertension mediates systemic and splanchnic arterial vasodilation through production of nitric oxide and other vasodilators in an attempt to counteract the increased pressure gradient. Nitric oxide causes a fall in systemic arterial pressure unfortunately, this activates both the renin-angiotensin-aldosterone and sympathetic nervous systems and... 

Since G-6-PDH has been shown to be present in platelets (L6, R7), its activity has been studied in thrombocytopenia and leukemia (W22). Activity was found normal in the former and decreased in the latter disorder. 

Reports on the alteration of serum and/or plasma acid phosphatase activity in thrombocytopenia have not always been consistent. Zucker and Woodard (Z2) described a series of 12 patients with thrombocyte-... 

Non-IgE-antibody-mediated immunological reactions Modification of erythrocyte surface components due to binding of beta-lactams or their metabolic products is thought to be the cause of the formation of antierythrocyte antibodies and the development of a positive Coombs test implicated in the development of immune hemolytic anemia (211). About 3% of patients receiving large doses of intravenous penicillin (10-20 million units/ day) will develop a positive direct Coombs test (212). However, only a small fraction of Coombs positive patients will develop frank hemolytic anemia (213). Antibody-coated erythrocytes are probably eliminated by the reticuloendothelial system (extravascular hemolysis) (214), or less often by complement-mediated intravascular erythrocyte destruction (215). Another mechanism implicates circulating immune complexes (anti-beta-lactam antibody/beta-lactam complexes), resulting in erythrocyte elimination by an innocent bystander mechanism (82). Similar mechanisms have been implicated in thrombocytopenia associated with beta-lactam antibiotics (216,217). 

Kajihara M, Kato S, Okazaki Y, Kawakami Y, Ishii H, Ikeda Y, et al. A role of auto antibody-mediated platelet destruction in thrombocytopenia in patients with cirrhosis. Hepatology 2003 37 1267-76. 

Certain stimuli may damage the marrow by reducing the number of megakaryocytes available. Drugs, chemicals, radiation, and infection are among the potential causes of marrow injury. Diseases that produce general bone marrow failure or those that invade the bone marrow may result in thrombocytopenia. Examples of the latter include cancers such as leukemia, lymphoma, myelofibrosis, myelodysplasia, and metastatic solid tumors (breast and prostate cancer), and infections such as those caused by mycobacteria. Suboptimal platelet production may also result from defects in maturation seen with vitamin Bi2 and/or folate deficiency or in congenital syndromes." ... 

Alteration in platelet distribution may also result in thrombocytopenia. Splenomegaly is the most frequent cause of increased platelet sequestration. 

The finite life span of most mature blood cells requires their continuous replacement, a process termed hematopoiesis. New cell production must respond to basal needs and states of increased demand. Red blood cell production can increase >20-fold in response to anemia or hypoxemia, white blood cell production increases dramatically in response to a systemic infection, and platelet production can increase 10-20-fold when platelet consumption results in thrombocytopenia. 

Recombinant DNA technology products aldesleukin (IL-2, used in renal cancer) erythropoietin (epoetin alfa, used in anemias) filgrastim (G-CSF, used in neutropenia) interferon alpha (used in hepatitis B and C and in cancer), interferon beta (used in multiple sclerosis) interferon gamma (used in chronic granulomatous disease) oprelvekin (IL-11, used in thrombocytopenia) thrombopoietin (used in thrombocytopenia) and sargramostim (GM-CSF, used in neutropenia). 

Table 8. Drugs frequently involved in thrombocytopenia. (Adapted from van Arsdel 1978 Parker 1980)...

The immune reaction to platelets is associated with three major alterations of platelet. There is an increased tendency to agglutination, the rate of platelets lysis is accelerated, and the susceptibility of platelets to phagocytosis is increased. Platelet precursors are also altered in thrombocytopenia. The megakaryocytes of the marrow are rare and immature. 

Witte CL, Ovitt TW, van Wyck DB, Witte MH, O Mara RE, Woolfenden JM (1976) Ischemic therapy in thrombocytopenia from hypersplenism. Arch Surg 111 1115-1121... 

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