Warfarin–Linezolid Interaction: A Case of Severe Coagulopathy

The management of coumarin-induced over-anticoagulation Annotation.

The British Journal of Haematology publishes original research papers in clinical, laboratory and experimental haematology. The Journal also features annotations, reviews, short reports, images in haematology and Letters to the Editor.

Author(s): Bower, Matthew M; Sweidan, Alexander J; Shafie, Mohammad; Atallah, Steven; Groysman, Leonid I; Yu, Wengui

Atrial Fibrillation and Thromboembolism

Thromboembolism and bleeding during therapeutic anticoagulation are the major chronic risks for patients after mechanical prosthetic heart valve replacement. Prophylaxis for thromboembolism based on pathogenesis and risk and the involvement of both fibrin and platelets has led to permanent long-term oral anticoagulant therapy for consistent protection.1 2 3 The incidence of thromboembolic events is related to the type of valve and its location; the incidence after aortic valve replacement is lower than after mitral valve replacement.2 3 The peak incidence of thromboembolism is during the first 3 months after surgery, probably reflecting the lack of endothelialization of the newly implanted prosthetic materials and delay in achieving therapeutic anticoagulation in the early days after operation.4 5 The Dacron sewing ring is common to all prosthetic heart valves and forms a substrate for platelet deposition as soon as blood flows across the valve.2 Current recommendations are levels of oral anticoagulation that prolong the prothrombin time ratio to an international normalized ratio (INR) of 2.5 to 3.5 for tilting-disk and bileaflet valves and probably for caged-ball valves.3 The study reported in this issue of Circulation by Acar et al and the AREVA Group6 is well designed, well conducted, and focused on lower-risk patients. It addresses the optimal target level for anticoagulation. They compared a target INR of 2.0 to 3.0 with 3.0 to 4.5 in a randomized trial after a single mechanical prosthetic valve replacement with either of two bileaflet mechanical prostheses (St Jude valve in 81% and Omnicarbon valve in 19% of the 433 patients) placed in …

The aims of the study were (i) to examine which antithrombotic therapy patients with known atrial fibrillation use at the point of time when they suffer an ischaemic stroke, (ii) to evaluate the effects of optimal antithrombotic treatment on outcome and severity of the stroke. Patients with known atrial fibrillation before onset of acute ischaemic stroke, and age >60 years were included. Antithrombotic therapy on admission was classified into four groups: no antithrombotic therapy, aspirin, sub-optimal anticoagulation (warfarin and international normalized ratio, INR<2.0) and optimal anticoagulation (warfarin and INR>or=2.0). modified Rankin Scale (mRS) 5 or 6 at day 7 poststroke. (i) death or discharge to a nursing home, (ii) death, (iii) stroke severity on admission assessed by Scandinavian Stroke Scale. A total of 394 patients were included. On admission 109 (28%) patients used no antithrombotic therapy, 169 (43%) aspirin, 52 (13%) warfarin and had an INR<2.0, and 64 (16%) used warfarin and had an INR>or=2.0. The proportion of patients with an mRS 5 or 6 and the corresponding odds ratios were: in the warfarin group with INR<2.0, 16 (31%), OR 3.1 (CI: 1.2-8.0), (P=0.019), in the group with no antithrombotic therapy 29 (27%), 2.5 (1.1-5.9), (P=0.034), and in the aspirin group 41(24%), 2.2 (1.0-5.1) (P=0.054), compared with the warfarin group with INR>or=2.0, where eight (13%) patients had a poor outcome. A significantly higher proportion of patients died or were discharged to a nursing home in the warfarin group with an INR<2.0 (P=0.014), in the aspirin group (P=0.018) and in the no-treatment group (P=0.035), compared with the warfarin group with an INR>or=2.0. No significant differences were found regarding death alone and stroke severity on admission. Few patients with known atrial fibrillation who suffer an ischaemic stroke receive optimal antithrombotic therapy prior to the onset of stroke. Optimal anticoagulation does not only reduce the risk of ischaemic stroke, but also appears to reduce death and severe dependency as well as the need for nursing home care, if an ischaemic stroke occurs.

Mechanical heart valves require anticoagulation to prevent valve-associated thrombosis and thromboembolic stroke. Oral vitamin K antagonists such as warfarin are prescribed universally; however, oral agents do not act immediately and usually require at least 5 days to achieve a therapeutic effect. Article p 564 Measurement of the prothrombin time, which is standardized by reporting the result as the international normalized ratio (INR), assesses the anticoagulant effect of warfarin. For most mechanical heart valves, the target INR ranges between 2.0 and 3.5. In the postoperative cardiac surgical setting, patients are usually started on low doses of warfarin because they tend to have impaired hepatic metabolism and suboptimal nutritional status. Even with low initial doses of warfarin, mechanical heart valve replacement patients are susceptible to excessively high INRs.1 This known exaggerated initial response to warfarin after heart valve replacement can lead to the habitual prescription of such low warfarin doses that warfarin as monotherapy may not achieve a stable and therapeutic INR for weeks after its initiation. To minimize the delay in achieving therapeutic anticoagulation, a “bridging” anticoagulant is prescribed. The “bridge” is administered parenterally, thereby providing an immediate anticoagulant effect. Traditionally, the “bridging” agent has been unfractionated heparin (UFH). More recently, physicians tend to select low-molecular-weight heparin (LMWH), even though few studies exist to validate the efficacy and safety of either LMWH or UFH in this setting. The rationale for shunning UFH has been to avoid the known perils and inconveniences of its use as a continuous peripheral intravenous infusion. UFH is rarely administered in an immediately therapeutic dose because of fear of precipitating bleeding complications. Especially in postoperative mechanical valve replacement patients, there is reluctance to follow the high dosing requirements for initial bolus and infusion regimens published in standardized nomograms. Instead, UFH is usually started in cautious small …

Objective To evaluate the effectiveness of professional nurses in atrial fibrillation (AF) anticoagulation management system. Methods 217 consecutive patients with nonvalvular AF were enrolled. All patients received warfarin therapy for 3 -6 months after catheter ablation for AF, who were divided into experimental group (n=102) and control group (n=115) by random digits table. The patients of control group adjusted their warfarin doses by following doctor's advice when discharged and by visiting the outpatient clinic regularly after discharged. The patients of treatment group adjusted their warfarin doses under the guidance of one well-trained nurse. Days of the international normalized ratio (INR) value achieved therapeutic anticoagulation range (2.0-3.0) for the first time, the effective anticoagulation rate that defined as more than 70% of INR values between 2.0-3.0 after titration period, the ratio of times of INR value 2.0 -3.0 to total times after titrating and INR monitoring frequency were compared between the 2 groups. Results In treatment group, days of the INR value achieved therapeutic 2.0-3.0 for the first time were less than that in control group (8 d vs. 15 d,P<0.01), the effective anticoagulation rate [45.1%(46/102) ] and the ratio of times of INR value 2.0-3.0 to total times after titrating (67.6%±18.5%) was significantly higher than that in control group [31.3%(36/115) and 62.0%±23.1% respectively,P<0.05 ]. INR monitoring during the whole period and after titrating were more frequently in treatment group [(9.4±2.2)times vs. (8.4±2.7) times, P<0.05; (7.9±2.4) times vs. (6.3±2.8) times, P<0.01 ]. The number of patients in treatment group who monitor INR less than 3 times after titrating was larger than that in control group (18 vs. 1,P<0.01). Conclusions The participation of professional nurses in atrial fibrillation anticoagulation management system was helpful not only in achieving INR 2.0-3.0 more quickly but also in improving the effective anticoagulation rate. Key words: Nurses; Atrial fibrillation; Catheter ablation; International normalized ratio; Anticoagulation management system

ORAL ANTICOAGULANTS: CHALLENGES IN PAKISTAN. DO WE HAVE A SOLUTION?

A comparison of anticoagulation results of patients managed with narrow vs. standard international normalized ratio target ranges.

Warfarin Sensitivity Genotyping: A Review of the Literature and Summary of Patient Experience

Introduction: Warfarin is the drug that can monitor its effi cacy and safety of treatment by the usage of International normalized ratio (INR) value. The objective of this study is to determine the percentage of achieving therapeutic target INR in warfarin-administered patients at Prasat Neurological Institute. Methods: This study was retrospective-descriptive study design and data were collected from medical records of the patients receiving warfarin in outpatient department at Prasat neurological institute for 3 years (July 2009 - July 2012). Results: Three hundred eigthty nine patients were included into the study, average age was 63.04 years old. Most patients receiving warfarin for preventing embolism in patients with atrial fi brillation (36.76%). The average duration of INR monitoring was 1.05 years and the frequency of INR monitoring was 10.12 times per year. The percentage of achieving therapeutic target INR was only 37.28%. This study found that 47.08% was below and 15.64% was exceed the therapeutic target INR. Proportion of low variability of INR values was 8.74%. The most prescribed medications that had were potential drug interactions with warfarin was anti-dyslipidemia medications. Twenty-six events of warfarin adverse drug reactions were found including: 1.95 time/100 person-year of major bleeding and 4.39 time/100 person-year of minor bleeding. Conclusion: The results of this study can be used as a base line to organize the warfarin clinic at Prasat Neurological Institute.

Oral Anticoagulant Therapy Recommendations

Fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC) reverse oral anticoagulants such as Warfarin. We compared the standard dosage of FFP and PCC in terms of efficacy and safety for patients with mechanical heart valves undergoing interventional procedures while receiving Warfarin. Fifty patients were randomized (25 for each group) with mechanical heart valves [international normalized ratio (INR) >2.5]. FFP dosage was administered based on body weight (10-15 mL/Kg), while PCC dosage was administered based on both body weight and target INR. INR measurements were obtained at different time after PCC and FFP infusion. The mean ± SD of INR pre treatment was not significantly different between the PCC and FFP groups. However, over a 48-hour period following the administration of PCC and FFP, 76% of the patients in the PCC group and only 20% of the patients in the FFP group reached the INR target. Five (20%) patients in the PCC group received an additional dose of PCC, whereas 17 (68%) patients in the FFP group received a further dose of FFP (P=0.001). There was no significant difference between the two groups in Hb and Hct before and during a 48-hour period after PCC and FFP infusion. As regards safety monitoring and adverse drug reaction screening in the FFP group, the INR was high (INR > 2.5) in 86% of the patients. There was no report of hemorrhage in both groups. PCC reverses anticoagulation both effectively and safely while having the advantage of obviating the need to extra doses.

Reversal of the Anticoagulant Effects of Warfarin by Vitamin K1