This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bijsterveld, N. R. Articles by Peters, R. J. G. Search for Related Content PubMed PubMed Citation Articles by Bijsterveld, N. R. Articles by Peters, R. J. G.

CLINICAL STUDY: ACUTE CORONARY SYNDROMES

Rebound thrombin generation after heparin therapy in unstable angina

A randomized comparison between unfractionated and low-molecular-weight heparin

Nick R. Bijsterveld, MD^*, Arno H. Moons, MD^*, Joost C. M. Meijers, PhD, Jan G. P. Tijssen, PhD^*, Harry R. Büller, MD, PhD, Marcel Levi, MD, PhD and Ron J. G. Peters, MD, PhD^*,*

^* Department of Cardiology, Academic Medical Center, Amsterdam, Netherlands
Department of Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands

Manuscript received July 11, 2001; revised manuscript received November 14, 2001, accepted December 3, 2001.

^* Reprint requests and correspondence: Dr. Ron J. G. Peters, Department of Cardiology, Room F3-236, Academic Medical Center, P.O. Box 22660, 1100 DD Amsterdam, Netherlands.
R.J.Peters{at}amc.uva.nl

OBJECTIVES: This study compared rebound coagulation in patients with acute coronary syndrome patients after discontinuation of unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH).

BACKGROUND: Up to a quarter of patients hospitalized for unstable angina experience recurrent ischemia after discontinuation of UFH or LMWH therapy, which may be the result of rebound coagulation activation and subsequent thrombosis. It is unknown whether UFH and LMWH differ in this respect.

METHODS: We randomized 71 patients admitted with unstable angina to intravenous UFH or subcutaneous LMWH (dalteparin) and measured plasma markers of coagulation before, during, and after treatment.

RESULTS: A complete series of measurements was obtained in 59 patients. Plasma prothrombin fragment 1+2 (F₁₊₂) levels decreased in both groups during treatment. After loss of therapeutic plasma drug levels, F₁₊₂ increased (within 3 h) to a maximum level at 12 to 24 h that was higher than before or during treatment in both groups (p < 0.0001). In both groups, F₁₊₂ levels remained higher than pretreatment up to 24 h after discontinuation. Similarly, thrombin-antithrombin (TAT) levels exceeded treatment and pretreatment levels, at a slower rate after dalteparin than after UFH. However, after dalteparin a higher peak value of TAT was observed.

CONCLUSIONS: Rebound coagulation activation occurs within hours after discontinuation of both UFH and dalteparin. With both drugs, thrombin generation is significantly greater after treatment than before or during treatment. A longer duration or weaning of treatment, or continuation with another anticoagulant treatment, may reduce rebound coagulation activation and ischemic events.

Abbreviations and Acronyms   LMWH   ACS   acute coronary syndromes   APC   activated protein C   CK-MB   creatinine kinase-MB   ECG   electrocardiogram   F1+2   prothrombin fragment 1+2   IV   intravenous   LMWH   low-molecular-weight heparin   PAP   plasmin-antiplasmin complexes   TAT   thrombin-antithrombin complexes   TFPI   tissue factor pathway inhibitor   UFH   unfractionated heparin

This article has been cited by other articles:

				A. G.G. Turpie New oral anticoagulants in atrial fibrillation Eur. Heart J., January 2, 2008; 29(2): 155 - 165. [Abstract] [Full Text] [PDF]

				M. Levi, M. Levy, M. D. Williams, I. Douglas, A. Artigas, M. Antonelli, D. Wyncoll, J. Janes, F. V. Booth, D. Wang, et al. Prophylactic Heparin in Patients with Severe Sepsis Treated with Drotrecogin Alfa (Activated) Am. J. Respir. Crit. Care Med., September 1, 2007; 176(5): 483 - 490. [Abstract] [Full Text] [PDF]

				A. G.G. Turpie Oral, Direct Factor Xa Inhibitors in Development for the Prevention and Treatment of Thromboembolic Diseases Arterioscler. Thromb. Vasc. Biol., June 1, 2007; 27(6): 1238 - 1247. [Abstract] [Full Text] [PDF]

				G. Ferretti, E. Bria, D. Giannarelli, P. Carlini, A. Felici, M. Mandala, P. Papaldo, A. Fabi, M. Ciccarese, F. Cuppone, et al. Is Recurrent Venous Thromboembolism After Therapy Reduced by Low-Molecular-Weight Heparin Compared With Oral Anticoagulants? Chest, December 1, 2006; 130(6): 1808 - 1816. [Abstract] [Full Text] [PDF]

				M. Di Nisio, N. R. Bijsterveld, J. C.M. Meijers, M. Levi, H. R. Buller, and R. J.G. Peters Effects of Clopidogrel on the Rebound Hypercoagulable State After Heparin Discontinuation in Patients With Acute Coronary Syndromes J. Am. Coll. Cardiol., October 18, 2005; 46(8): 1582 - 1583. [Full Text] [PDF]

				N. R. Bijsterveld, R. J. G. Peters, S. A. Murphy, P. J. L. M. Bernink, J. G. P. Tijssen, M. Cohen, and TIMI 11B/ESSENCE Study Groups Recurrent cardiac ischemic events early after discontinuation of short-term heparin treatment in acute coronary syndromes: Results from the thrombolysis in myocardial infarction (TIMI) 11B and efficacy and safety of subcutaneous enoxaparin in Non-Q-Wave coronary events (ESSENCE) studies J. Am. Coll. Cardiol., December 17, 2003; 42(12): 2083 - 2089. [Abstract] [Full Text] [PDF]