Platelet activation following intravenous injection of a conventional heparin: absence of effect with a low molecular weight heparinoid (Org 10172).

Abstract

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.Keywords heparin low molecular weight heparinoid platelet count platelet aggregation thromboxane A2 non-esterified fatty acids

Studies of interaction of a low-molecular-weight heparinoid (Org 10172) with cloxacillin and ticarcillin in healthy male volunteers

“…This could be evaluated only by determination of the (12). As expected, Org 10172 had no effects on platelet aggregation and bleeding time (22). The lack of an effect by ticarcillin on bleeding time is in agreement with the findings of Brown et al (7).…”

Increased platelet responsiveness following coronary stenting Heparin as a possible aetiological factor in stent thrombosis

“…Furthermore, heparin has been known to activate platelets since Eika reported enhanced platelet aggregation with the drug in 1972 [8] . Subsequently, heparin has been shown to induce platelet aggregation in vitro in platelet-rich plasma [9,29] and using the same techniques, similar effects have been observed in vivo [10] . Heparin increases platelet interaction with fibrin-rich clots [30] and augments P-selectin expression in response to agonist stimulation in patients undergoing cardiopulmonary bypass [31] .…”

“…The beneficial clinical effects of ticlopidine suggest an important role for adenosine diphosphate-dependent, shear stress-induced platelet activation since ticlopidine, but not aspirin [6] inhibits the effect of adenosine diphosphate on platelets However, differences in outcome between patients treated with anticoagulant and antiplatelet therapy might be explained not only on the basis of the favourable pharmacological actions of ticlopidine, but also by adverse platelet effects of anticoagulant drugs. In particular, heparin has been reported to activate platelets [8][9][10] both in vitro and in vivo. Direct assessment of expression of activation antigens on individual platelets can be measured by fluorescence-activated flow cytometry [11] .…”

A Comparative Review of the Adverse Effect Profiles of Heparins and Heparinoids

“…Because of its pharmacological features it has a very high specific ratio of anti-factor Xa : anti-factor IIa activity of 28, which theoretically should provide a lower tendency to enhance bleeding than unfractionated and LMW heparins that have specific ratios of 1 and <4, respectively. In addition, the heparinoid had no effect on normal platelet function, as assessed by bleeding time measurements, in healthy volunteers [6) and it caused minimal induction of platelet aggregation in vitro compared with unfractionated heparinJ6, 7) In this paper we review and compare the tolerability profiles of heparin, LMW heparins, and danaparoid sodium on the basis of results of previously published clinical prophylaxis studies.…”