Summary
The low dose heparin regimen (LDH) is not appropriate for prevention of intra- and postoperative thromboembolic complications in high risk patients, especially those undergoing elective hip replacement. Despite LDH prophylaxis, the incidence of deep-vein thrombosis (DVT) remains in a range of 20 to 35%. Adjusted-dose unfractionated heparin prophylaxis is thought to be one of the most effective regimens for thrombosis prophylaxis in this indication, but it requires two or three daily injections as well as precise monitoring of the activated partial thromboplastin time (aPTT). As an attractive alternative, we investigated the efficacy and safety of the low molecular weight heparin (LMWH) certoparin combined with dihydroergotamine (DHE) given once daily.
In a randomised, open clinical trial, a total number of 305 patients undergoing total elective hip replacement were enrolled and divided into two groups, either receiving a fixed-dose combination of LMWH (3,000 IU) and DHE (0.5 mg) subcutaneously once daily, or adjusted-dose unfractionated heparin (UFH) subcutaneously every 8 h. The UFH dosage was adjusted daily to keep an aPTT of about 50 s. The aPTT was determined 3 h after the morning injection. During the study, the starting dose (15,000 IU/day) was increased to a plateau value of 28,800 ± 7,150 IU/day (mean ± SD) to maintain the aPTT in the prescribed range. The plateau value was achieved after 8 postoperative days. For analysis of efficacy 289 patients were evaluable. The occurrence of deep vein thrombosis was determined by bilateral ascending venography, which was performed on the same day in patients with clinical signs suggesting DVT; and in all remaining patients at the end of the prophylaxis period. Deep vein thrombosis was diagnosed in 17 of 142 patients (12.0%) treated with LMWH/DHE and in 13 of 147 patients (8.8%) treated with adjusted-dose UFH. Combined distal-proximal thrombosis was more frequently in patients receiving UFH (n = 5; 3.4%) compared to the LMWH/DHE group (n = 2; 1.4%). These differences are statistically not significant. In the UFH group one case of non-fatal pulmonary embolism occurred. Both prophylaxis regimens were well tolerated; wound bleeding was observed in 8 (5.3%) patients in the LMWH group and in 6 (4.0%) patients in the UFH group. Intraoperative blood-loss volume (mean±SD) was 751 ± 339 ml (LMWH/DHE) and 736 ± 380 ml (UFH), whereas postoperative drain-loss volume (mean ± SD) was found to be 523 ± 333 ml (LMWH/DHE) and 581 ± 404 ml (UFH). Whole blood transfusion volumes (mean ± SD) were 570 ± 202 ml (LMWH/DHE) and 748 ± 455 ml (UFH). Additionally, red cell replacement volumes (mean ± SD) were 804 ± 435 ml (LMWH/DHE) and 720 ± 328 ml (UHF). Revision of wound or additional drainage were necessary in 3 LMWH/DHE and 7 UFH patients. One patient needed reoperation due to bleeding, 3 (2.0%) had petechia and 1 exhibited an allergic exanthema, all of them in the UFH group. A slight erythema at the injection site was observed in 6 (3.9%) patients receiving LMWH/DHE. During the course of prophylaxis, injection hematomas were documented in 57.9% (LMWH/DHE) and in 61.4% (UFH) of the patients. All differences were statistically not significant.
Single daily subcutaneous injections of LMWH/DHE appeared to be safe and efficacious compared to adjusted-dose UFH for prophylaxis of DVT in high-risk patients.
