Transitory hypomegakaryocytic thrombocytopenia: aetiological association with ethanol abuse and implications regarding regulation of human megakaryocytopoiesis.
We studied a patient with a long history of ethanol abuse who presented to the hospital with profound weakness, anaemia and thrombocytopenia. Evaluation of these problems revealed the patient's bone marrow to be hypercellular but severely iron depleted and almost totally devoid of morphologically recognizable megakaryocytes. However, we were able to detect the presence of non-morphologically recognizable, immature megakaryocytes in the same sample using an immunochemical detection technique. This circumstance allowed us to study the relative importance of both megakaryocyte maturation and peripheral blood platelet count on the production of megakaryocyte colony stimulating activity (Meg-CSA), a putative regulator of the megakaryocyte colony forming unit (CFU-M). The results of our investigations disclosed a rapid decline in serum Meg-CSA levels which preceded recovery of the platelet count and appeared to coincide with the maturation of megakaryocytes into the morphologically recognizable pool. The effect of ETOH on the patient's CFU-M cloning efficiency was also studied. ETOH in amounts up to 454 mg/dl did not inhibit cloning of the patient's peripheral blood CFU-M in plasma clot cultures. Our results suggest that regulation of Meg-CSA production is a complex function which appears to be dependent on a number of factors including the level of megakaryocyte maturation in the marrow. We also speculate that ethanol associated thrombocytopenia may occasionally be brought about by a disruption in the process of megakaryocyte maturation at the level of a progenitor more mature than the CFU-M.
D000368:Aged; D000437:Alcoholism / Q000150:complications*; D001853:Bone Marrow / Q000473:pathology; D002999:Clone Cells / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000032:analysis; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D006801:Humans; D008533:Megakaryocytes / Q000473:pathology; D010976:Platelet Count; D013920:Thrombocythemia, Essential / Q000209:etiology*
D003115:Colony-Stimulating Factors; D000431:Ethanol