Platelet production

White cell contamination of a platelet product can induce GvHD. It is beUeved that GvHD can be minimized by a contamination of less than 5 X 10 white cells per therapeutic dose of platelets, ie, 3-5 x 10. Blood cell separation technology is directed toward consistentiy achieving this goal. 

Filtration Filtration (qv) is appHed in blood cell separation to remove leukocytes from ted blood cell (RBC) and platelet concentrates. Centtifugational blood cell separators do not reduce white blood cells (WBC) in red cell and platelet products sufficiently to avoid clinical complications such as GvHD and alloimmunization. A post-apheresis filtration step is needed to further reduce the WBC load. Modem filters are capable of a 3-log reduction in white cell contamination of the blood product, eg, apheresis single-donor platelet units having a typical white cell contamination of 5 x 10 white cells in 4 x 10 platelets can be reduced to a 5 x 10 white cell contamination, a sufficiently low number to avoid severe transfusion reactions. 

Thrombocytopenia may occur because of decreased platelet production and splenic platelet sequestration. 

IgG autoantibody-coated platelets induce Fey receptor-mediated phagocytosis by mononuclear macrophages, predominantly in the spleen and liver. Thrombocytopenia develops as a consequence of megakaryocyte inability to increase platelet production and maintain a normal number of circulating platelets. Currently used treatments are directed at different aspects of the antibody production, platelet sensitization, and the clearance and production cycle.30... 

Glucocorticoids may increase platelet production by impairing bone marrow macrophage ability to destroy platelets. Response rate to oral prednisone (1-1.5 mg/kg per day) in adults is 50% to 75% and usually occurs within the first 3 weeks. In children, severe life-threatening bleeding is treated with either high-dose oral (4—8 mg/kg per day prednisone) or parenteral (30 mg/kg per day methylprednisolone) glucocorticoids. 

TPO is the haemopoietic growth factor now shown to be the primary physiological regulator of platelet production. This molecule may, therefore, represent an important future therapeutic agent in combating thrombocytopenia, a condition characterized by reduced blood platelet levels. The most likely initial TPO therapeutic target is thrombocytopenia induced by cancer chemo- or... 

Kaushansky, K. 1997. Thrombopoietin - understanding and manipulating platelet production. Annual Review of Medicine 48, 1-11. 

Kaushansky, K. and Drachman, J. 2002. The molecular and cellular biology of thrombopoietin the primary regulator of platelet production. Oncogene 21(21), 3359-3367. 

Presnell, S.R., O Hara, P.J., Hagen, F.S., Roth, G.J., and Foster, D.C. 1994. Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo. Nature 369, 565-568. 

Consumption of fish oil in excess can generate immunotoxic effects in laboratory animals. Rats fed a 17% fish oil diet had reduced wound-healing responses when compared to com oil [59], In a mouse model of bacterial resistance to S. typhimurium, lower survival rates were reported for those animals that ingested a 20% fish oil diet over 15 days [59], Similar fish oil-induced effects in guinea pigs were noted in a study of experimental tuberculosis leading the authors to conclude that this treatment resulted in decreased resistance to infectious disease. The consumption of fish oil has also been reported to result in alterations of hemostatic parameters such as platelet production and function. However, there is no indication that at doses normally consumed by humans, immunotoxicity will occur. 

Virtually all of the above cited studies were uncontrolled and involved acute oral or intravenous ISDN/ISMN administration followed within hours by in vitro platelet activity assessment. In contrast, Sinzinger et al. showed in an uncontrolled trial that oral ISDN (100 mg daily) administered to coronary artery disease patients over four weeks inhibited ADP-induced aggregation in platelet-rich plasma in vitro and reduced the number of circulating platelet aggregates and platelet production of thromboxane... 

USP received a medication error report involving the products Neumega (oprel-vekin) and Proleukin (aldesleukin). Oprelvekin, a recombinant human interleukin-11 product used to stimulate platelet production in selected patients undergoing chemotherapy, is sometimes abbreviated as IL-11. Aldesleukin, a recombinant human interleukin-2 derivative indicated in designated patient populations for the treatment of metastatic renal-cell carcinoma, is sometimes abbreviated as IL-2. 

TPO should alleviate thrombocytopenia in most instances by encouraging platelet production. Currently, the standard therapy for the condition entails administration of 5 units of platelets to the sulferer (1 unit equals the quantity of platelets derived in one sitting from a single blood donor). TPO therapy is a particularly attractive potential alternative because ... 

Geddis, A. et al. (2002). Thrombopoietin a pan-hematopoietic cytokine. Cytokine Growth Factor Rev. 13(1), 61-73. Kaushansky, K. (1995). Thrombopoietin the primary regulator of platelet production. Blood 86(2), 419-431. Kaushansky, K. (1997). Thrombopoietin—understanding and manipulating platelet production. Armu. Rev. Med. 48, 1-11. 

Lok, S. et al. (1994). Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production... 

Mechanism of Action A hematologic agent that reduces platelet production and prevents platelet shape changes caused by platelet aggregating agents. Therapeutic Effect Inhibits platelet aggregation. 

Recombinant human IL-11 (oprelvekin) is a polypeptide of 177 amino acids. It differs from natural IL-11 due to lack of glycosylation and the amino-terminal proline residue. Oprelvekin is administered by subcutaneous injection, usually 6-24 h after chemotherapy, at a dose of 25-50 p,g/kg per day. The drug has a half-life of about 7h. It is used to stimulate bone marrow to induce platelet production in nonmyeloid malignancies in patients undergoing chemotherapy. The common side effects of oprelvekin include fluid retention, tachycardia, edema, nausea, vomiting, diarrhea, shortness of breath and mouth sores. Other side effects include rash at the injection site, blurred vision, paresthesias, headache, fever, cough and bone pain. Rarely, CLS may occur. 

E.N. Cheung, D. Terry, and W. Sheridan. 2000. Effects of megakaryocyte growth and development factor on platelet production, platelet life span, and platelet function in healthy human volunteers. Blood 95 2514-2522. 

Likewise, each unit of blood or blood component remains highly controlled through control of manufacturing, often more to control or prevent infectious disease transmission than to protect the red blood cells or platelet products from degradation. Just as plasma or vaccine products are controlled from the very start of manufacture or collection of source material, so is blood for transfusion or further manufacture. 

A serious complication of HIV infection is HIV-associated thrombocytopenia, This results from immune-mediated platelet destruction and decreased or defective platelet production due to infection of megakaryocytes with HIV-1 (211). HIV-related thrombocytopenia may be associated with an accelerated progression to AIDS and decreased survival rates. Hence management of thrombocytopenia in AIDS patient is crucial to prevent severe complications, Severe bleeding complications in HIV-infected hemophilia patients treated with protease inhibitors... 

The development of platelets or thrombocytes takes place chiefly in the bone marrow from primitive totipotential reticulum or stem cells. The normal concentration of thrombocytes in the peripheral circulation of the adult is approximately 250,000-355,000/mm . Thrombocyte activity is necessary in the process of coagulation. Quantitative platelet deficiency or thrombocytopenia is one of the most common causes of hemorrhagic diathesis, and it may be due either to decreased platelet production or to increased platelet destruction. 

The mechanisms of mild thrombocytopenia after multiple doses of interleukin-10 have been extensively explored in 12 healthy volunteers, of whom four received placebo and eight received subcutaneous interleukin-10 (8 micrograms/kg/day for 10 days) (2). Compared with placebo, there was a 40% fall in platelet count during interleukin-10 treatment and prompt normalization after interleukin-10 withdrawal. There were also moderate changes in hemoglobin concentration. Bone marrow function, platelet production, and serum thrombopoietin concentrations suggested that a reduction in bone marrow platelet production was the primary cause. 

Thrombin binds Thrombin stimuiates to platelet production of... 

Thrombopoiesis is the term used to describe the process of platelet production. The bone marrow manufactures 40,000 platelets/mL of blood each day. Proliferation and differentiation of platelet precursors are thought to be primarily influenced by cytokines such as IL-6, IL-11, leukemia inhibitory factor, and perhaps most specifically, by thrombopoietin (TPO or megakaryocyte growth and development factor see Fig. 98-6). Other hematopoietins that may act in concert, producing synergistic effects include IL-3, IL-1, GM-CSF, EPO, and Scf.34 The platelet survival time is a clinical test that can estimate the rate of platelet turnover. In healthy individuals, this time is 9.5 0.6 days.36... 

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." ... 

Thrombopoiesis—The process of platelet production from immature cells. 

Holmsen, H. "Platelets, Production, Function, Transfusion and Storage" Baldini, M. and Ebbe, S., Eds. Grune and Stratton New York, 1974 207-220. 

Aspirin irreversibly acetylates cyclooxygenase, preventing platelet production of thromboxane A2. 

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