Published online Sep 18, 2020. doi: 10.5312/wjo.v11.i9.400
Peer-review started: June 18, 2020
First decision: July 2, 2020
Revised: July 16, 2020
Accepted: August 1, 2020
Article in press: August 1, 2020
Published online: September 18, 2020
Total joint arthroplasty is one of the most common options for end stage osteoarthritis of major joints. However, we must take into account that thrombosis after hip/knee arthroplasty may be related to mutations in genes encoding for blood coagulation factors and immune reactions to anticoagulants [heparin-induced thrombocytopenia (HIT)/thrombosis]. Identifying and characterizing genetic risk should help to develop diagnostic strategies or modify anticoagulant options in the search for etiological mechanisms that cause thrombophilia following major orthopedic surgery.
To evaluate the impact of patients’ coagulation profiles and to study specific pharmacologic factors in the development of post-arthroplasty thrombosis.
In 212 (51 male and 161 female) patients that underwent primary total hip arthroplasty (100) or total knee arthroplasty (112) due to osteoarthritis during a period of 1 year, platelet counts and anti-platelet factor 4 (PF4)/heparin antibodies were evaluated pre/postoperatively, and antithrombin III, methylenetetrahydrofolate reductase, factor V and prothrombin gene mutations were evaluated preoperatively. In a minimum follow-up of 3 years, 196 patients receiving either low-molecular-weight heparins (173) or fondaparinux (23) were monitored for the development of thrombocytopenia, anti-PF4/heparin antibodies, HIT, and thrombosis.
Of 196 patients, 32 developed thrombocytopenia (nonsignificant correlation between anticoagulant type and thrombocytopenia, P = 0134.) and 18 developed anti-PF4/heparin antibodies (12/173 for low-molecular-weight heparins and 6/23 for fondaparinux; significant correlation between anticoagulant type and appearance of antibodies, P = 0.005). Odds of antibody emergence: 8.2% greater in patients receiving fondaparinux than low-molecular-weight heparins. Gene mutations in factor II or V (two heterozygotes for both factor V and II) were identified in 15 of 196 patients. Abnormal low protein C and/or S levels were found in 3 of 196 (1.5%) patients, while all patients had normal levels of von Willebrand factor, lupus anticoagulant, and antithrombin III. 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 & V mutations). Thrombosis was not significantly correlated to platelet counts or HIT. The correlation of thrombosis to antibodies, factor II, factor V was P = 0.076, P = 0.043, P = 0.013, respectively.
Screening of coagulation profile, instead of platelet monitoring, is probably 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.
Core Tip: This prospective study evaluated the impact of genetic profiles of patients and pharmacologic factors on the development of thrombosis after lower limb arthroplasty. Thrombosis was related to the development of anti-platelet factor 4 (anti-PF4)/heparin antibodies and was correlated significantly to factor II and V mutations. Thus, screening of coagulation profile preoperatively could minimize the risk of post-arthroplasty thrombosis. Platelet monitoring does not uncover all cases of anti-PF4/heparin antibody formation, while antibody monitoring postanticoagulant administration is probably unnecessary. Fondaparinux can lead to the formation of anti-PF4/heparin antibodies and may cause heparin-induced thrombocytopenia.