A promising new alternative for the rapid reversal of warfarin coagulopathy in traumatic intracranial hemorrhage
Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. American journal of surgery
(Impact Factor: 2.29).
09/2008; 197(6):785-90. DOI: 10.1016/j.amjsurg.2008.04.003
Internationally, Factor IX complex (FIX complex) has been used to correct warfarin-induced coagulopathy. We present our experience with 28 patients using FIX complex.
A retrospective chart review was conducted between November 2002 and July 2006 on patients with warfarin-induced coagulopathy. We recorded the dose and timing of FIX complex, serial international normalized ratios (INRs), early adverse events, and patient outcome.
Twenty-eight patients met criteria. The mean INR on admission was 5.1, and after FIX complex infusion was reduced significantly to 1.9 (P = .008). Eleven patients had a repeat INR drawn within 30 minutes after FIX complex infusion. The mean time to correction was 13.5 minutes. There were no early thrombotic events or allergic reactions.
FIX complex results in an immediate reversal of coagulopathy within 15 minutes after administration. Its use should be considered as an alternative treatment to fresh-frozen plasma and recombinant Factor VIIa. Prospective randomized trials are needed to confirm these findings.
Available from: Scott A. Chapman
- "In our study groups, the incidence of thromboembolic events was equal in both groups. Safaoui et al. reported no thromboembolic events in 28 patients receiving 2000 units of PCC3 (Konyne™ or Profilnine™) . In a recent case report a dose of 50 units/kg of PCC for warfarin reversal was associated with fatal intracardiac thrombosis in a patient who had also received 24 micrograms of desmopressin for suspected uremic platelet dysfunction and fifty minutes later underwent pericardiocentesis . "
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ABSTRACT: Prothrombin complex concentrate (PCC) and recombinant Factor VIIa (rFVIIa) have been used for emergent reversal of warfarin anticoagulation. Few clinical studies have compared these agents in warfarin reversal. We compared warfarin reversal in patients who received either 3 factor PCC (PCC3) or low-dose rFVIIa (LDrFVIIa) for reversal of warfarin anticoagulation.
Data were collected from medical charts of patients who received at least one dose of PCC3 (20 units/kg) or LDrFVIIa (1000 or 1200 mcg) for emergent warfarin reversal from August 2007 to October 2011. The primary end-points were achievement of an INR 1.5 or less for efficacy and thromboembolic events for safety.
Seventy-four PCC3 and 32 LDrFVIIa patients were analyzed. Baseline demographics, reason for warfarin reversal, and initial INR were equivalent. There was no difference in the use of vitamin K or fresh frozen plasma. More LDrFVIIa patients achieved an INR of 1.5 or less (71.9% vs. 33.8%, p =0.001). The follow-up INR was lower after LDrFVIIa (1.25 vs. 1.75, p < 0.05) and the percent change in INR was larger after LDrFVIIa (54.1% vs. 38.8%, p = 0.002). There was no difference in the number of thromboembolic events (2 LDrFVIIa vs. 5 PCC3, p = 1.00), mortality, length of hospital stay, or cost.
Based on achieving a goal INR of 1.5 or less, LDrFVIIa was more likely than PCC3 to reverse warfarin anticoagulation. Thromboembolic events were equivalent in patients receiving PCC3 and LDrFVIIa.
Available from: Meena Zareh
- "However, the majority of the patients in these studies also received FFP and vitamin K; therefore, it is unclear if rFVIIa alone can be effective in acute warfarin reversal. Additionally, its high cost for an average patient ($5,542 for an average dose versus $2,205 for the same patient on PCC) and short half-life of 2.5 to 3 hours make it a less favorable candidate with which to treat warfarin-induced coagulopathy.44 The incidence of thrombotic adverse events associated with rFVIIa is rare, 24.5 per 105 infusions, with an elevated risk for cerebrovascular thrombosis.45 "
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ABSTRACT: Warfarin, an oral vitamin K antagonist, is used to prevent arterial and venous thromboembolism in patients suffering from a multitude of diseases. In 2004, 31 million warfarin prescriptions were dispensed in the United States. Warfarin inhibits the activation of the vitamin K-dependent clotting factors (Factors II, VII, IX, and X) and regulatory proteins (proteins C, S, and Z). It is one of the leading drugs implicated in emergency room visits for adverse drug reactions. Annually the frequency of bleeding complications associated with overanticoagulation is 15% to 20%, with fatal bleeds measuring as high as 1% to 3%. The most effective method of warfarin reversal involves the use of Four Factor Prothrombin Complex Concentrate (PCC), which is widely used throughout Europe but is unavailable in the United States. The current therapies available to emergency room physicians in the United States are fresh frozen plasma, recombinant Factor VIIa (rFVIIa), Factor Eight Inhibitory Bypassing Activity, or Three Factor PCC concomitantly administered with vitamin K. We review the advantages and disadvantages of these therapies and recommend Three Factor PCC with small doses of rFVIIa and with vitamin K in life-threatening situations if Four Factor PCC is unavailable.
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ABSTRACT: This chapter discusses the adverse effects of drugs that affect blood coagulation, fibrinolysis, and hemostasis. Calciphylaxis (vascular calcification, thrombosis, and skin necrosis) has been attributed to warfarin, a coumarin anticoagulants, in a patient with diabetes mellitus. However, in a study, patients with diabetes and hypertension, half of whom were taking warfarin, there was no effect on systolic blood pressure or pulse pressure. The teratogenic effects of warfarin (‘warfarin embryopathy’) include chondrodysplasia punctata, frontal bossing, a short neck, low birth weight, short limbs, polydactyly, and respiratory difficulty secondary to choanal atresia. The anticoagulants in modern rodenticides, so-called ‘superwarfarins', have very long durations of action. In cases of overdose with such agents, prolonged therapy may be required before coagulation returns to normal, as another case has demonstrated. Lepirudin, a direct thrombin inhibitor, has been associated with anaphylactic reaction in a patient, who had received five courses of lepirudin therapy uneventfully. Bleeding is uncommon with fondaparinux, indirect factor Xa inhibitors, but can be serious when it occurs, as has been illustrated by a case of spontaneous retroperitoneal bleeding from a ruptured lumbar artery in a 78-year-old man with only one kidney.
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