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Effect of ethanol on thrombopoiesis. Br J Haematol 1986 Feb;62(2):345-54

Date

02/01/1986

Pubmed ID

3947552

DOI

10.1111/j.1365-2141.1986.tb02938.x

Scopus ID

2-s2.0-0022635826 (requires institutional sign-in at Scopus site)   66 Citations

Abstract

Chronic ethanol abuse causes thrombocytopenia but the underlying mechanism is unknown. To determine the target cells involved, we examined the effects of the drug in vitro on both megakaryocyte progenitor cells (CFU-Meg) and isolated, maturing megakaryocytes. In the presence of ethanol concentrations of 0.05-2.0 g/dl, megakaryocyte colony formation by mouse CFU-Meg in soft agar was normal. At 5 g/dl ethanol, colony formation was reduced by 50%; with 7 g/dl ethanol, no megakaryocyte colonies were formed. Acetaldehyde did not inhibit colony formation unless very high concentrations (100 mg/dl) were employed. Isolated guinea-pig megakaryocytes can maintain their viability and incorporate 3H-leucine into TCA-precipitable protein for at least 24 h. Incubation of these maturing megakaryocytes with ethanol did not affect their viability, but at concentrations greater than 120 mg/dl ethanol progressively inhibited protein synthesis. At 0.5 g/dl ethanol, protein synthesis was decreased by 23% while viability was still 93% of control. Like CFU-Meg, maturing megakaryocytes were resistant to the toxic effects of acetaldehyde. To determine the in vivo correlates of these results, guinea-pigs were fed 5 g/dl ethanol in a liquid diet. By 11 d, when blood ethanol levels were 20-150 mg/dl, platelet counts in the animals were reduced by 17-29%, while the number of marrow megakaryocytes was unaltered. These data indicate that the site of action of ethanol in suppressing thrombopoiesis is at the level of the maturing megakaryocyte.

Author List

Levine RF, Spivak JL, Meagher RC, Sieber F

Author

Fritz Sieber PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetaldehyde
Animals
Blood Platelets
Cells, Cultured
Ethanol
Guinea Pigs
Hematopoiesis
Hematopoietic Stem Cells
Megakaryocytes
Mice
Platelet Count
Protein Biosynthesis