Paradoxical platelet behaviour in diabetic ketoacidosis.
Thrombotic events may occur in patients who present with severe uncontrolled diabetes or with diabetic coma. As a possible explanation for this, platelet function was investigated at presentation with diabetic ketoacidosis and during treatment in 10 patients. Concentrations of the platelet-specific proteins, platelet factor 4 (PF4) and beta-thromboglobulin (beta TG) were elevated and fell towards normal with treatment. Despite evidence of increased aggregation in vivo, platelets from subjects with ketoacidosis were insensitive to adenosine 5'-diphosphate (ADP), sensitivity increasing with correction of ketoacidosis. Platelets from ketoacidotic diabetics were initially insensitive to the anti-aggregatory action of prostacyclin (PGI2) and became normal with treatment. Initial blood glucose concentrations correlated with log10 ADP concentrations (r = 0.72, p less than 0.01) and with log10 PGI2 ID50 (the PGI2 concentration required to half-inhibit ADP-induced aggregation) (r = 0.66, p less than 0.025). Glucose concentrations throughout the 2-week study period correlated with all log10 ADP concentrations (r = 0.32, p less than 0.005) and all log10 PGI2 ID50 concentrations (r = 0.51, p less than 0.001). The decrease in ADP sensitivity in ketoacidosis, paradoxical in view of the evidence of increased in vivo platelet aggregation, may result from an acquired platelet storage pool deficiency.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D001639:Bicarbonates / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D016883:Diabetic Ketoacidosis / Q000097:blood*; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D010978:Platelet Factor 4 / Q000032:analysis; D001620:beta-Thromboglobulin / Q000032:analysis
D001639:Bicarbonates; D001786:Blood Glucose; D001620:beta-Thromboglobulin; D010978:Platelet Factor 4; D000244:Adenosine Diphosphate; D011464:Epoprostenol