Induction Of Thrombocytopenia Research Articles

Induction of Thrombocytopenia by Thrombopheresis in Man: Patterns of Recovery in Normal Subjects During Ethanol Ingestion and Abstinence

Using the technique of thrombophoresis (TP), platelet and megakaryocyte dynamics following acute thrombocytopenia were studied in two normal subjects during periods of ethanol ingestion and abstinence. Thrombocytopenia was induced over a period of 12 hr. A logarithmic decline in platelet count during TP and the serial morphologic changes in megakaryocytes during recovery from thrombocytopenia are described. Although these parameters were not affected by ethanol ingestion, platelet counts after TP did not return to normal until ethanol was discontinued. 51Cr-labeled platelet survival was normal in one subject studied, and no evidence of increased platelet sequestration was found. It is concluded that heavy ethanol ingestion induces, augments, or sustains thrombocytopenia by impairing megakaryocytopoiesis in man. The mechanism by which ethanol induces thrombocytopenia may be due, in part, to "ineffective thrombopoiesis," impairment of the differentiation of precursor cells into the megakaryocytic compartment, or a combination of these factors.

Induction of thrombocytopenia by thrombopheresis in man: patterns of recovery in normal subjects during ethanol ingestion and abstinence

Using the technique of thrombophoresis (TP), platelet and megakaryocyte dynamics following acute thrombocytopenia were studied in two normal subjects during periods of ethanol ingestion and abstinence. Thrombocytopenia was induced over a period of 12 hr. A logarithmic decline in platelet count during TP and the serial morphologic changes in megakaryocytes during recovery from thrombocytopenia are described. Although these parameters were not affected by ethanol ingestion, platelet counts after TP did not return to normal until ethanol was discontinued. 51Cr-labeled platelet survival was normal in one subject studied, and no evidence of increased platelet sequestration was found. It is concluded that heavy ethanol ingestion induces, augments, or sustains thrombocytopenia by impairing megakaryocytopoiesis in man. The mechanism by which ethanol induces thrombocytopenia may be due, in part, to “ineffective thrombopoiesis,” impairment of the differentiation of precursor cells into the megakaryocytic compartment, or a combination of these factors.

Stimulation of megakaryocytopoiesis by acute thrombocytopenia in rats

Rats were made acutely thrombocytopenic by injection of antiplatelet serum. Marrow sections and squash preparations were made at intervals during 120 hr. Determinations were made of mitotic index, stage of maturation, ploidy level, and cell size of megakaryocytes; number and size of platelets were measured. Increased endomitosis among megakaryocytes was followed by an increase in the proportion of immature megakaryocytes, a greater average ploidy level of recognized megakaryocytes, and larger megakaryocytes. Maximum changes in these several parameters occurred between 32 and 72 hr after induction of thrombocytopenia. By 120 hr all megakarocyte parameters were near normal. For about 3 days, beginning at about 36 hr, platelet numbers increased rapidly. Average platelet size rose and returned to normal within about 60 hr. Changes in ploidy and size of megakaryocytes were measured in the immature and mature maturation stages. The results suggest that the initial stimulus in response to acute thrombocytopenia acts primarily on diploid precursors, programming them to mature into a population of megakaryocytes with an average ploidy approximately one level greater than in normal rats and a proportionate increase in cell size. The larger megakaryocytes presumably produce more platelets, accounting for a major part of the increased rate of platelet production. Since the changes in megakaryocytes begin to reverse before circulating platelet numbers have reached the normal level, reversal of the stimulus appears to be initiated by some change other than platelet mass.

Effect of Platelet Age on Adhesiveness to Collagen and Platelet Surface Charge

Adhesion to collagen was investigated as a function of platelet age in rat platelets. Platelet adherence was measured using EDTA-containing platelet- rich plasma which was added to preparations of collagen fibers clamped between magnetic stirrers by recording changes in light transmission. The plot of light transmission versus logarithm of time was linear and allowed calculation of a slope factor which related to the rate of adherence. Neither the amount of collagen nor the platelet count were limiting in the test. Young platelet populations (less than or equal to 1 day old) were obtained during the recovery phase from immune induced thrombocytopenia. Old platelet populations were prepared by blocking thrombopoiesis with cyclophosphamide. Young platelets showed a moderate but statistically significant increase in adhesivity to collagen but old platelets did not differ significantly from randomly aged platelets in this function. The electrophoretic mobility of platelets was not affected by their age.

Thrombocytopenia in experimental trypanosomiasis.

The effect of experimental trypanosomiasis on coagulation was studied because a patient in this hospital with Rhodesian trypanosomiasis developed thrombocytopenia with disseminated intravascular coagulation. Rats injected intraperitoneally with this strain of Trypanosoma rhodesiense consistently developed trypanosomiasis and severe thrombocytopenia without changes in hematocrit or concentration of fibrinogen or fibrin split products. At the time of 50% mortality (4-5 days) mean platelet counts per cubic millimeter of infected rats were 18,000+/-9,000 (+/-2 SEM) compared to 1,091,000+/-128,000 in uninfected controls. In vitro, concentrated trypanosomes and trypanosomefree supernates of disrupted organisms added to normal rat, rabbit, or human blood produced platelet aggregation within 30 min. This platelet aggregation was not blocked by inhibitors of ADP, kinins, or early or late components of complement. In vivo thrombocytopenia also occurred in infected rabbits congenitally deficient in C6 and in infected, splenectomized rats. Although the aggregating substance obtained from disrupted trypanosomes is heat-labile, it is active in the presence of complement inhibitors, suggesting that this trypanosomal product may be a protein enzyme or toxin. Since the phenomenon is independent of immune complexes, complement, ADP, and kinins, it appears to represent a new mechanism of microbial injury of platelets and the induction of thrombocytopenia.

Immunological Studies in a Case of Gold Salt Induced Thrombocytopenia

A woman developed severe thrombocytopenia a few days after the 8th injection of sodium aurothiomalate. She was treated with BAL, prednisone and a fresh blood transfusion, and the platelet count came back to normal after about 2 weeks. At that time the bone marrow contained many megakaryocytes, and the platelet life span was nearly normal. These observations suggest that the thrombocytopenia was due to an immune mechanism, but in vitro techniques failed to detect lytic, agglutinating, complement binding, or radioactive aurothiomalate‐binding antibodies.