Platelet activation following intravenous injection of a conventional heparin: absence of effect with a low molecular weight heparinoid (Org 10172).
1. The effects of an intravenous injection of a conventional high molecular weight heparin (HMWH) were compared with those of a low molecular weight heparinoid (Org 10172). A bolus injection of HMWH (5000 iu) was associated with: (a) a small but significant prolongation of bleeding time (BT); (b) a significant fall in PRP platelet count; (c) significantly enhanced platelet aggregation; and (d) significantly increased platelet thromboxane A2 (TXA2) release. These changes were not observed following the intravenous injection of Org 10172 (3200 anti Xa U). 2. These experiments were repeated following the oral administration of acetylsalicylic acid (ASA). HMWH again caused some enhancement of platelet aggregation despite the ASA-mediated inhibition of platelet aggregation and TXA2 release. Administration of Org 10172 to subjects taking ASA did not alter any of the platelet function indices. 3. In additional control experiments the injection of 5000 iu of HMWH was associated with a significant fall in PRP but not whole blood platelet counts. This finding suggests that the fall in PRP platelet count is a methodological artefact. 4. The HMWH also induced a significantly greater increase in serum non-esterified fatty acid (NEFA) concentrations than Org 10172. 5. The present findings indicate that Org 10172 is a less potent stimulator of platelet aggregation and lipolysis than HMWH. 6. The minor prolongation of the BT after HMWH is not compatible with enhanced aggregation but may be a consequence of alterations in the activity of coagulation factors and vascular-platelet interactions or of ongoing platelet activation accompanied by granule depletion. 7. The different effects of the two anticoagulants assessed suggests a therapeutic advantage in favour of Org 10172, especially in patients with hyperactive platelets.
Department of Chemical Pathology and Human Metabolism, Royal Free Hospital, London.
D P
DP
Mikhailidis
V A
VA
Fonseca
M A
MA
Barradas
J Y
JY
Jeremy
P
P
Dandona
D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects*; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D006497:Heparan Sulfate; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008970:Molecular Weight; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D013928:Thromboxane A2 / Q000097:blood
D000925:Anticoagulants; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D005230:Fatty Acids, Nonesterified; D006025:Glycosaminoglycans; D006493:Heparin; D006497:Heparan Sulfate; D013928:Thromboxane A2; C035838:danaparoid