The platelet proaggregating and potentiating effects of unfractionated heparin, low molecular weight heparin and heparinoid in intensive care patients and healthy controls.
Heparin binds to platelets and can cause platelet proaggregating and potentiating effects, possibly causing thrombocytopenia, particularly in patients in intensive care with hyperaggregable platelets. In this study we compared the platelet proaggregating and potentiating effects of unfractionated heparin (UH), 2 low molecular weight (LMW) heparins, enoxaparin and dalteparin, and a heparinoid, danaparoid sodium (orgaran), to platelets of an ICU patient population and a normal control group. In both populations UH caused platelet aggregation in a dose-dependent manner. This occurred in the therapeutic range of the drug, with as little as 0.5 U/ml UH. The LMW heparins caused less and the heparinoid least platelet aggregation. Generally, the aggregation observed in ICU patients was greater than in the normal population. The potentiating effects of the 4 drugs in association with physiological agonists was examined. Similar patterns of potentiation were observed in both populations, with UH causing significant enhancement of platelet aggregation, the LMW heparins intermediate and heparinoid least enhancement. There was substantial variability in the individuals' platelets' reactions to the drugs, in particular to UH. Our findings suggest that UH has the greatest effect, the low molecular weight heparins an intermediate effect and the heparinoid the least propensity to cause platelet activation.
Burgess
J K
JK
Centre for Thrombosis and Vascular Research, University of New South Wales, Australia.
Chong
B H
BH
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology; D002809:Chondroitin Sulfates / Q000494:pharmacology; D016638:Critical Illness; D017985:Dalteparin / Q000494:pharmacology; D003871:Dermatan Sulfate / Q000494:pharmacology; D004357:Drug Synergism; D017984:Enoxaparin / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006496:Heparinoids / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000494:pharmacology; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D012016:Reference Values
D000244:Adenosine Diphosphate; D000925:Anticoagulants; D002809:Chondroitin Sulfates; D017985:Dalteparin; D003871:Dermatan Sulfate; D017984:Enoxaparin; D004837:Epinephrine; D006493:Heparin; D006495:Heparin, Low-Molecular-Weight; D006496:Heparinoids; D006497:Heparan Sulfate; C035838:danaparoid