Factors predisposing to thrombosis after major joint arthroplasty

ARTICLE HIGHLIGHTS

Research background

Numerous studies have emphasized the association of multiple risk factors, including varicose veins, congestive heart failure, female gender, age, hypertension, venous thromboembolism history, cancer, diabetes, dyslipidemia, obesity, black race, total joint arthroplasty (TJA) type (primary or revision), primary disease (osteoarthritis, rheumatoid arthritis), and procedure duration in the increased risk of deep vein thrombosis after TJA. Deep vein thrombosis can easily develop into pulmonary embolism leading to cardiopulmonary dysfunction and death.

Research motivation

Apart from the factors related to surgery, comorbidities, medical history, and decreased mobility after major TJA, there are many other well defined conditions that are associated with either a prothrombotic state or embolic phenomena, such as mutations or polymorphisms in genes that encode blood coagulation factors, metabolic syndrome, or immune reactions related to pharmacologic agents such as anticoagulants, which would possibly lead to increased risk of venous thromboembolism and its consequences. We aimed to assess the impact of different types of anticoagulants on the hematologic profile and the incidence of heparin-induced thrombocytopenia (HIT) and thromboembolism after TJA by selecting a strictly homogeneous patient sample uninfluenced by other predisposing factors for thrombotic events.

Research objectives

The aim of this prospective study was to evaluate the influence of individual genetic profiles and adverse pharmacologic (anticoagulant immunologic) reactions activating platelets and causing thrombocytopenia on the development of thrombotic episodes among patients undergoing lower limb TJA.

Research methods

In 212 patients that underwent primary total hip arthroplasty or total knee arthroplasty due to osteoarthritis during a period of 1 year, platelet counts and anti-platelet factor 4 (anti-PF4)/heparin antibodies were evaluated pre/postoperatively and antithrombin III, methylenetetrahydrofolate reductase, factor V, and prothrombin gene mutations were detected. In a minimum follow-up of 3 years patients receiving either low-molecular-weight heparins (LMWH) or fondaparinux were monitored for the development of thrombocytopenia, anti-PF4/heparin antibodies, HIT, and thrombosis.

Research results

Thirty-two patients developed thrombocytopenia (insignificant correlation between anticoagulant type and thrombocytopenia, P = 0.134), and eighteen developed anti-PF4/heparin antibodies (12/173 for LMWH and 6/23 for fondaparinux). There was a significant correlation between anticoagulant type and antibody appearance (P = 0.005). Odds of antibody emergence were 8.2% greater in patients receiving fondaparinux than LMWH. Four patients developed HIT (insignificant correlation between thrombocytopenia and antibodies), and five developed thrombosis. Two had positive antibodies and two were heterozygotes for both factor II and factor V mutations. Thrombosis was not significantly correlated to platelet counts or HIT. The correlation of thrombosis to antibodies, factor II, and factor V was P = 0.076, P = 0.043, and P = 0.013, respectively.

Research conclusions

Screening of coagulation profile, instead of platelet monitoring, is likely the safest way to minimize the risk of post-arthroplasty thrombosis. In addition, fondaparinux can lead to the formation of anti-PF4/heparin antibodies or HIT.

Research perspectives

Although the number of patients of our series was relatively small, the rigorous sample selection criteria optimized the process of drawing conclusions and limited the impact of bias. Statistical analysis indicated that symptomatic thrombotic events were not correlated to thrombocytopenia or HIT and platelet count monitoring does not necessarily uncover cases of formation of anti-PF4/heparin antibodies that may be correlated to venous thromboembolism. Moreover, both LMWH and fondaparinux were found to be responsible for the formation of anti-PF4/heparin antibodies. The correlation of thrombotic events to the formation of anti-PF4/heparin antibodies approached significance, whereas mutations of factors II and V were significantly correlated to symptomatic thrombosis. Thus, the evaluation of mutations of factor II and factor V preoperatively may reduce thrombotic complications in patients undergoing major joint replacement. Preoperative tests should be based on the clinical benefit and cost effectiveness ratio and should also lead to individual patient risk assessment or to the most optimal pharmacologic prophylaxis against venous thromboembolism and HIT after elective lower limb arthroplasties.