APC-resistance Is a Risk Factor for Postoperative Thromboembolism in Elective Replacement of the Hip or Knee – A Prospective Study

Abstract

SummaryPostoperative venous thromboembolic complications are commonly seen after total replacement of the hip or knee. Recently, an inherited defect with resistance to the anticoagulant activity of activated protein C (APC-resistance) has been detected. APC-resistance seems to be a common risk factor, especially in Sweden, and it increases the propensity for venous thrombosis. This study assesses the prevalence of APC-resistance in a general population and its clinical significance for patients undergoing surgery associated with a high risk of thromboembolic complications. In a prospective cohort study, we analysed for APC-resistance in 645 consecutive patients before elective replacement of the hip or knee at 3 hospitals in southern Sweden. Thromboprophylaxis with LMWH-heparin was given to all patients throughout the hospitalisation period. We recorded events of clinical thromboembolism for 3 months postoperatively. Venography, ultrasonography or pulmonary scintigraphy was requested by the clinicians according to the existing routines, i.e. only patients with symptoms of thromboembolism were examined. A thromboembolic complication was registered in 20 (3.1%) patients. Fifty per cent of the venous thrombi had a proximal location. Only 0.3% of the patients had verified pulmonary embolism. APC-resistance was found in 14.1% of the patients, of whom 9.9% had experienced postoperative thromboembolism compared with 2.0% of the patients without APC-resistance (p <0.0007). We conclude that APC-resistance is a frequent risk factor for symptomatic postoperative deep venous thrombosis with an estimated relative risk of 5.0 (95% confidence interval: from 1.9 to 12.9) in elective replacement of the hip or knee.

Increased thrombin generation in splanchnic vein thrombosis is related to the presence of liver cirrhosis and not to the thrombotic event

“…Our findings confirm the findings by Tripodi et al [24], that hypercoagulability is linked to the presence of CLD. PVT and factor V Leiden corresponds to the actual prevalence of this mutation in Scandinavia [25]. As this mutation is very common and raises the risk for thrombosis about 3-fold [26], we did not adjust the thrombin generation results for this factor.…”

Potent Anticoagulants are Associated with a Higher All-Cause Mortality Rate After Hip and Knee Arthroplasty

“…Patients in Groups A (potent anticoagulants) and C (warfarin) did not receive pneumatic compression or aspirin after surgery. In five of the publications [8,14,34,37,49], the type of anesthetic was not specified for Group A (potent anticoagulants) or C (warfarin). In publications in which anesthesia was identified, 36% (3785 of 10,437) of patients in Group A (potent anticoagulants) and 29% (397 of 1342) of patients in Group C (warfarin) received spinal or epidural anesthesia.…”

Genetic Polymorphisms in Venous Thrombosis and Pulmonary Embolism After Total Hip Arthroplasty: A Pilot Study

“…Three groups did not find an association between the presence of factor V Leiden mutation and symptomatic DVT with and without PE or isolated PE after THA or TKA [8,31,41]. In contrast to these authors, Lindahl et al [20] investigated 645 patients after THA or TKA and estimated an OR of 5.0 (95% CI, 1.9-12.9) for the association between activated protein C and symptomatic postoperative DVT. Recently, Baba-Ahmed et al [5] reported an association (OR, 10.5; 95% CI, 1.3-86) between factor V Leiden mutation and symptomatic DVT and/or PE in patients who underwent major orthopaedic surgery, including THA.…”

“…For other genetic markers, such an association is suspected and discussed controversially, eg, methylenetetrahydrofolate reductase (MTHFR) C677T and/or A1298C and plasminogen activator inhibitor 1 (PAI-1) 4G/5G polymorphisms [1-3, 10, 11, 16, 22, 30, 32, 34, 37, 44]. Results of former studies are conflicting regarding whether the single or combined presence of such genetic mutations may further increase the already very high risk for DVT after major orthopaedic surgery, justifying costly preoperative screening and additional antithrombotic prophylactic measures in these patients [5,6,8,18,20,21,23,29,31,36,[40][41][42][43]. One reason for the conflicting results may be found in the different clinical end points set in the studies varying among venographically diagnosed DVT, clinically symptomatic DVT with or without PE, or symptomatic PE only.…”

“…Most of these authors found no association between one of the previously named genetic polymorphisms and the incidence of symptomatic or asymptomatic DVT after major orthopaedic surgery [18,21,23,29,31,36,40,42]. When concentrating their analysis on symptomatic DVT, however, results are conflicting [5,6,8,20,31,40,41]. Asymptomatic DVT diagnosed by venogram may be associated with an increased risk for asymptomatic and symptomatic PE or have an increased mortality rate compared with those without thrombosis [15,38].…”