No abstract

SummaryStudies in experimental animals have demonstrated that there is a relationship between levels of low molecular weight (LMW) heparin and both bleeding and inhibition of thrombosis. The relationship between these outcomes and ex vivo anti-factor Xa levels has been examined in 163 patients undergoing total hip replacement who were given prophylaxis once daily with a LMW heparin (enoxaparine). Fifty patients received 60 mg of enoxaparine and 113 received 40 mg, both regimens being administered subcutaneously once daily. Blood samples for anti-factor Xa levels were collected 12 hours after the injection on the day of surgery and on days 1, 3 and 6, postoperatively. The incidence of wound hematoma was 5.3% when the maximum anti-factor Xa level was ≤0.2 units per ml, but increased to 24.5% when the anti-factor Xa level exceeded 0.2 units per ml, P = 0.0008. The incidence of postoperative thrombosis was low (6.3%) if the minimum anti-factor Xa level exceeded 0.1 units per ml, but increased to 14.6% when ≤0.1 units per ml, and to 18.8% if the anti-factor Xa level was ≤0.05 units per ml. Regression analysis revealed that there was a statistically significant relationship between anti-factor Xa level and wound hematoma, P = 0.002 and anti-factor Xa level and thrombosis, P = 0.03. These findings suggest that when enoxaparine is administered as a once daily subcutaneous injection, the 12 hour anti-factor Xa level should not exceed 0.2 units per ml to minimize bleeding and levels >0.05 units per ml should be obtained to optimize efficacy.

Summary.  Background: The incidence of postsurgical venous thromboembolism is thought to be low in Asian ethnic populations. Objective: We studied the incidence of deep‐vein thrombosis (DVT) in Asian patients undergoing major orthopedic surgery of the lower limbs. Patients/methods: We performed a prospective epidemiological study in 19 centers across Asia (China, Indonesia, South Korea, Malaysia, Philippines, Taiwan, and Thailand) in patients undergoing elective total hip replacement (THR), total knee replacement (TKR) or hip fracture surgery (HFS) without pharmacological thromboprophylaxis. The primary endpoint was the rate of DVT of the lower limbs documented objectively with bilateral ascending venography performed 6–10 days after surgery using a standardized technique and evaluated by a central adjudication committee unaware of local interpretation. Results: Overall, of 837 Asian patients screened for this survey, 407 (48.6%, aged 20–99 years) undergoing THR (n = 175), TKR (n = 136) or HFS (n = 96) were recruited in 19 centers. DVT was diagnosed in 121 of 295 evaluable patients [41.0%, (95% confidence interval (CI): 35.4–46.7)]. Proximal DVT was found in 30 patients [10.2% (7.0–14.2)]. Total DVT and proximal DVT rates were highest in TKR patients (58.1% and 17.1%, respectively), followed by HFS patients (42.0% and 7.2%, respectively), then THR patients (25.6% and 5.8%, respectively). DVT was more frequent in female patients aged at least 65 years. Pulmonary embolism was clinically suspected in 10 of 407 patients (2.5%) and objectively confirmed in two (0.5%). Conclusions: The rate of venographic thrombosis in the absence of thromboprophylaxis after major joint surgery in Asian patients is similar to that previously reported in patients in Western countries.

SummaryA double blind randomized trial comparing subcutaneous enoxaparin (40 mg once daily) with standard unfractionated calcium heparin administered at a dose of 5,000 units every 8 hours in patients undergoing elective hip replacement has been performed. Treatment regimens began 12 hours preoperatively with enoxaparin, 2 hours preoperatively with standard unfractionated calcium heparin, and were continued for 15 days or until discharge. Venography was performed in all patients. Two hundred thirty-seven patients were included in the study: 113 received unfractionated heparin and 124 received enoxaparin. The incidence of proximal deep vein thrombosis was reduced from 18.5% in the unfractionated heparin group to 7.5% in the enoxaparin group (p = 0.014), and the incidence of total deep vein thrombosis was similarly reduced from 25% to 12.5% (p = 0.03). There were two major bleeding episodes and one minor bleed in the enoxaparin group compared to two minor bleeds in the unfractionated heparin group. Patients who received enoxaparin required fewer red blood cell transfusions and had a significantly higher hemoglobin on postoperative days 3 and 4. Thus prophylaxis with enoxaparin, 40 mg once daily, is simple, safe and more effective than standard low dose unfractionated heparin in preventing deep vein thrombosis in patients undergoing elective hip replacement.

Summary. Studies in experimental animal models and in patients receiving low molecular weight heparin (LMWH) to prevent thromboembolic events after surgery have not demonstrated a clear relationship between anti-Xa and anti-IIa activities in plasma and either bleeding or prevention of thrombosis. The relationship between these clinical outcomes and ex vivo anti-Xa and anti-IIa activities, activated partial thromboplastin time (APTT) and D-dimers were evaluated in 440 patients undergoing total hip replacement and given prophylaxis once daily with a LMWH (tinzaparin or enoxaparin) in a multicentre doubleblind randomized study. 221 patients received 4500 anti-Xa IU of tinzaparin; 219 patients received 40 mg (4000 anti-Xa IU) of enoxaparin. Both regimens were administered subcutaneously once daily. Blood samples for anti-IIa, antiXa, D-dimers levels and APTT were taken at baseline, on day 1, day 5 and on the day of discharge (days 8-14) and clinical assessments were performed daily until day 14. All patients had bilateral venography between days 8 and 14.All coagulation tests were performed in central laboratories. A significant correlation was observed between anti-IIa activity and anti-Xa activity and the dose of each LMWH injected. The anti-Xa activity was significantly higher with enoxaparin and the anti-IIa activity was significantly higher with tinzaparin. No clear relationship between these two activities and the clinical outcomes was observed. This was also true with regards to APTT. Before and after surgery, Ddimers were significantly higher in patients with deep vein thrombosis (DVT) than in those without DVT but had no predictive value. Interestingly, a significant post-operative increase of D-dimers persisted in both groups of patients during the whole observation period, possibly suggesting that a longer duration of prophylactic treatment may be appropriate.