Promotion of proinflammatory interactions between platelets and monocytes by unfractionated heparin

Harding, S. A.; Din, J. N.; Sarma, J.; Josephs, D. H.; Fox, K. A. A.; Newby, D. E.
November 2006
Heart;Nov2006, Vol. 92 Issue 11, p1635
Academic Journal
Objectives: To determine the in vitro effects of unfractionated heparin, fractionated heparin and direct thrombin inhibition on platelet-monocyte aggregation, and to establish the in vivo effects of unfractionated heparin and direct thrombin inhibition on platelet-monocyte aggregates in patients scheduled for percutaneous coronary intervention (PCI). Design: Platelet-monocyte aggregates were assessed in whole blood from 18 healthy volunteers after the addition of unfractionated heparin (1 U/mI), enoxaparin (0.8 U/mI) or lepirudin (5.6 g/ml), and in 28 patients scheduled for elective PCI before and after administration of 100 U/kg of unfractionated heparin or 0.75 mg/kg bivalirudin. The influence of P-selectin-mediated platelet-monocyte aggregation was assessed with specific blocking antibodies. Results: Addition of unfractionated heparin in vitro was associated with a higher level of platelet-monocyte aggregates than in controls (20.1 (1.9)% v 16.2 (1.6)%, respectively, p < 0.001). However, platelet-monocyte aggregation was not affected by enoxaparin or lepirudin (16.9 (2.0)% and 17.0 (2.2)%, respectively, NS). Intravenous unfractionated heparin in vivo also resulted in an increase in platelet-monocyte aggregates (absolute Δ 7.1 (2.7)%, p < 0.01), whereas intravenous bivalirudin had no effect (absolute Δ -1.5 (2.4)%, NS). The addition of P-selectin blockade abolished any increase in platelet-monocyte aggregates associated with heparin. Conclusions: In vitro and in vivo unfractionated heparin is associated with increased platelet-monocyte aggregation through a P-selectin-dependent mechanism. These findings provide a potential explanation for the superior cardiovascular outcomes associated with fractionated heparins and direct thrombin inhibitors.


Related Articles

  • Heparin induced thrombocytopenia: diagnosis and management update. Ahmed, I.; Majeed, A.; Powell, R. // Postgraduate Medical Journal;Sep2007, Vol. 83 Issue 983, p575 

    Heparin-induced thrombocytopenia (HIT) is a potentially devastating immune mediated adverse drug reaction caused by the emergence of antibodies that activate platelets in the presence of heparin. Despite thrombocytopenia, bleeding is rare; rather, HIT is strongly associated with thromboembolic...

  • Effects of Glycosaminoglycans and Protamine Chloridrate on Platelet Aggregation Induced by Collagen and Thrombin. Luzzatto, Guido; Paolini, Rossella; Stevanato, Francesco; Simioni, Paolo; Cella, Giuseppe // Angiology;Mar1989, Vol. 40 Issue 3, p170 

    The effects of heparin (HE), dermatan sulfate (DS), heparan sulfate (HS) and protamine chloridrate (PC) on platelet aggregation were studied. Both PC and the three glycosaminoglycans (GAGs) did not influence collagen-induced platelet aggregation. In contrast, all the tested GAGs blocked...

  • Enoxaparin but not unfractionated heparin causes a dose-dependent increase in plasma TGF-{beta}1 during haemodialysis: a cross-over study. Beata Naumnik; Jacek Borawski; Krystyna Pawlak; Michal Mysliwiec // Nephrology Dialysis Transplantation;May2007, Vol. 22 Issue 6, p1690 

    Background. Transforming growth factor-β1 (TGF-β1) is a multi-functional cytokine that presents as a mediator of the heparins pleiotropic action. In this cross-over study, we compared the effects of enoxaparin and unfractionated heparin (UFH) used as anticoagulants during...

  • Lack of In Vitro Cross-Reactivity Predicts Safety of Low-Molecular Weight Heparins in Heparin-Induced Thrombocytopenia. Farag, Sherif S.; Savoia, Helen; O'Malley, Cindy J.; McGrath, Katherine M. // Clinical & Applied Thrombosis/Hemostasis;Jan1997, Vol. 3 Issue 1, p58 

    Alternative anticoagulation in patients with heparin-induced thrombocytopenia (HIT) is often problematic. The relatively high cross-reactivity rate reported for the low-molecular-weight heparins (LMWH) has discouraged their use in this setting. This study has investigated the safety of using the...

  • RECOMBINANT APROTININ VARIANTS BLOCK PLATELET ACTIVATION VIA PAR 1. Day, I. R. S.; Haskard, D.; Taylor, K. M.; Landis, R. C. // Heart;May2004 Supplement 2, Vol. 90, pA38 

    This article focuses on a study related to recombinant aprotinin variants block platelet activation via protease activated receptors (PAR1). Cardiopulmonary bypass causes platelet dysfunction and aprotinin helps prevent this. Thrombin signalling on platelets is mediated by PAR1 and 4 and...

  • Effect of Ticlopidine on Monocyte-derived Microparticles and Activated Platelet Markers in Diabetes Mellitus. Shouzu, Akira; Nomura, Shosaku; Omoto, Seitaro; Hayakawa, Takashi; Nishikawa, Mitsushige; Iwasaka, Toshiji // Clinical & Applied Thrombosis/Hemostasis;Apr2004, Vol. 10 Issue 2, p167 

    Platelet-derived microparticles, activated platelets, and monocyte-derived microparticles were measured in 73 patients with diabetes mellitus. A comparative study of these parameters was performed before and after administration of ticlopidine. The number of platelet-derived microparticles and...

  • Phlegmasia Cerulea Dolens and Its Association with Hypercoagulable States: Case Reports. Cohen, David J.; Briggs, Richard; Head, Harold D.; Acher, Charles W. // Angiology;May1989, Vol. 40 Issue 5, p498 

    Six patients who developed phlegmasia cerulea dollens are described. All patients had associated hypercoagulable states: heparin-induced thrombocytopenia (2 patients), congenital deficiency of protein C (1 patient), and antithrombin Ill deficiency (3 patients). Their clinical course and...

  • Molecular basis of heparin-induced thrombocytopenia; new therapeutical perspectives. Woszczyk, Dariusz // Polish Surgery / Chirurgia Polska;2006, Vol. 8 Issue 1, p89 

    Heparin-induced immune thrombocytopenia is a relatively common and severe complication of heparin treatment, especially of its unfractionated form. It results in a high mortality rate, especially when not diagnosed. This paper covers the molecular basis, clinical picture and treatment methods of...

  • Heparin Monitoring and Patient Safety. Valenstein, Paul N.; Walsh, Molly K.; Meier, Frederick // Archives of Pathology & Laboratory Medicine;Apr2004, Vol. 128 Issue 4, p397 

    Context.—Appropriate laboratory monitoring of unfractionated heparin therapy promotes effective anticoagulation while minimizing hemorrhagic complications. Objectives.—To measure heparin therapy monitoring in a "real-world" setting and to assess the degree of anticoagulation...


Read the Article


Sign out of this library

Other Topics