[Complications and risks associated with an anticoagulation therapy combining low molecular weight heparin and Warfarin after total replacement of large joints—our experience]

P Míka, J Behounek, M Skoták, L Nevsímal
Acta Chirurgiae Orthopaedicae et Traumatologiae Cechoslovaca 2004, 71 (4): 237-44

PURPOSE OF THE STUDY: This study deals with the efficacy and safety of anticoagulation therapy, using a combination of low molecular weight heparin (LMWH) and Warfarin, administered after total arthroplasty (TA) of large joints. Patients with a high rate of complications due to bleeding comprised the first evaluated group. After the causes had been analyzed and eliminated (or reduced), the second group of patients was evaluated. The aim of the study was to ascertain whether risks and complications did not overweight the benefits of Warfarin administration in the prophylaxis of deep venous thrombosis (DVT) and whether this combined anticoagulation therapy, which is cheaper than LMWH alone, was generally applicable.

MATERIAL: Group 1 comprised 100 consecutive patients undergoing surgery in 2001. Group 2 consisted of 122 consecutive patients operated on in 2002. Only patients with elective either total knee or hip arthroplasties were included. In all of them, Warfarin therapy was initiated at 2 days after surgery and preoperative LMWH administration was carried on until 6 to 7 days postoperatively.

METHODS: Both groups were examined for the frequency and extent of postoperative hematomas, INR (international normalized ratio) fluctuation at the time of Warfarin initiation and during its long-term administration, and thrombotic and bleeding complications associated with anticoagulation therapy. The results were statistically evaluated and compared between the groups, and conclusions were drawn for further treatment policy.

RESULTS: In group 1, 20% of hospitalized patients and 21% within 10 weeks of discharge from hospital experienced bleeding or thrombotic complications. A markedly high INR at Warfarin initiation was found in 8% of the patients. After discharge, 11% were not followed up, 5% were found underdosed and 12% overdosed. In group 2, 3.2% of the patients had bleeding complications during hospitalization, but no thrombotic events occurred; at 10 weeks of follow-up, bleeding or thrombotic complications were recorded in 10.6% of the patients. Extreme values of INR at Warfarin initiation were found in 5.7% of the patients. After discharge, 5% were not followed up, 30% were found underdosed and 8.1% overdosed. The distinctly better results in group 2 were attributed to the measures taken to eliminate most of the factors increasing hazards of Warfarin anticoagulation therapy, i. e., pre-operative administration of non-steroid antirheumatic drugs (NSA), high initial Warfarin doses, strict requirement for INR values in the range of 2-2.5, failure to keep the recommended diet after discharge, poor compliance with taking the prescribed Warfarin dose and insufficient INR monitoring by general practitioners.

DISCUSSION: In patients undergoing total arthroplasty of large joints, the authors compare the anticoagulation therapy based on LMWH and Warfarin with other treatments for DVT prevention in terms of efficacy, safety and economy. They prefer LMWH administration as early as 12 h before surgery. Although Warfarin administration has proved a safe therapy with regard to bleeding complications in a number of conditions, this is not the case in patients undergoing total knee or hip replacements. These procedures result in great stress for the organism, particularly after long-term preoperative NSA treatment, and this is associated with a risk of gastric ulcer development or manifestation of existing mucosal lesions. The risk of bleeding may be increased by unexplained fluctuation of INR values at Warfarin initiation.

CONCLUSIONS: The results of this study suggests that correctly administered, preventive drug treatment of thromboembolic events is an important adjunct to other measures, such as early rehabilitation including standing and walking, compression of the lower extremities or sufficient liquid intake, taken to prevent the development of deep venous thrombosis. The combination of LMWH with Warfarin was used as an anticoagulation therapy in this study. The effective and safe Warfarin treatment should be based on the experience of an attending physician, who starts and monitors the therapy. Warfarin administration requires careful and relatively complex follow-up, with frequent INR check-ups. However, the use of appropriate dosage and thorough follow-up do not make Warfarin administration completely safe in all cases. For instance, a high INR value at Warfarin initiation, which is difficult to influence, carries a high risk of bleeding for patients with occult gastrointestinal lesions. The authors do not routinely use preventive treatment with LMWH alone, primarily for its high cost.

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