Platelet regulatory prostanoids and platelet release products in sickle cell disease.
Changes in platelet function have been observed for sickle cell disease (SCD). Levels of the arachidonic acid metabolites, thromboxane A2 (released by stimulated platelets) and prostacyclin (released from vascular endothelium), which stimulate and inhibit platelets, respectively, have been implicated in overall regulation of platelet function. Circulating basal levels of thromboxane and prostacyclin were determined in 1) a group of SCD volunteers (n = 21; at half-yearly steady state intervals and also at 24 hr, 72 hr, and 7 days after start of pain crisis) and 2) an age-, sex-, and race-matched control group (n = 18; single determinations). Circulating levels of beta-thromboglobulin (beta-TG), as well as thrombin (clotting)-stimulated platelet release of thromboxane, were also determined. Statistically significant decreases were found for prostacyclin, basal thromboxane, and thrombin-induced (maximal) thromboxane (alone or per platelet), for steady state SCD vs. normal controls. In addition, significant increases in maximal thromboxane were identified in crises (24, 72 hr) compared with steady state. Crisis beta-TG (24 hr) was significantly elevated compared with controls or steady state SCD. The ratio of basal thromboxane to prostacyclin was increased in crisis, but not significantly. Crisis frequency may correlate in part with changes in platelet function: steady state maximal thromboxane and released thromboxane per platelet were significantly lower in SCD volunteers who had crises during the study vs. those who did not (equivalent study time). The data support altered platelet function in SCD, possibly refractoriness (desensitization), manifest as decreased thromboxane release, to thrombin and/or other stimuli: alternate explanations are discussed.
Longenecker
G L
GL
Department of Biomedical Sciences, University of South Alabama, Mobile 36688.
Beyers
B J
BJ
Mankad
V N
VN
D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000097:blood*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D011464:Epoprostenol / Q000097:blood*; D006801:Humans; D008137:Longitudinal Studies; D008614:Meperidine / Q000494:pharmacology; D011446:Prospective Studies; D013931:Thromboxanes / Q000097:blood*; D001620:beta-Thromboglobulin / Q000378:metabolism*
D013931:Thromboxanes; D001620:beta-Thromboglobulin; D008614:Meperidine; D011464:Epoprostenol; D001241:Aspirin