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

Abstract

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.

Mathematical model of radiation effects on thrombopoiesis in rhesus macaques and humans

“…In particular, TPO is known to affect MK maturation; however, TPO does not affect the formation of platelets from the MK cytoplasm (Kaushansky, 2005). Following thrombopheresis in humans, platelet counts return to normal levels at the expected rate for the first 3-4 days given known production rates (Sullivan et al, 1977). However, after the fourth day following thrombopheresis, there is a subsequent increase in the platelet production rate, suggesting a negative feedback effect of platelet concentration on the maturation rate of early MKs.…”

“…First, model outputs were compared to platelet dynamic data from rhesus and human radiation exposures not used in the optimizations (Rhesus: Haigh and Paterson (1956) Mettler (2001)). Second, model output was compared to platelet dynamic data from thrombopheresis patients (Lasky et al, 1981;Weisbach et al, 1999;Sullivan et al, 1977). Third, the relative compartment sizes calculated using experimental data were compared to the relative compartment sizes calculated using model parameters.…”

“…Weisbach et al (1999), data points from 22 subjects (mean ± SD). Bottom left: Individual data from Sullivan et al (1977). Bottom right: Individual data from Sullivan et al (1977), subject underwent two platelet removal procedures.…”