title: Mechanical prophylaxis is a heparin-independent risk for anti-platelet factor 4/heparin antibody formation after orthopedic surgery.
abstract: Platelet-activating antibodies, which recognize platelet factor 4 (PF4)/heparin complexes, induce spontaneous heparin-induced thrombocytopenia (HIT) syndrome or fondaparinux-associated HIT without exposure to unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). This condition mostly occurs after major orthopedic surgery, implying that surgery itself could trigger this immune response, although the mechanism is unclear. To investigate how surgery may do so, we performed a multicenter, prospective study of 2069 patients who underwent total knee arthroplasty (TKA) or hip arthroplasty. Approximately half of the patients received postoperative thromboprophylaxis with UFH, LMWH, or fondaparinux. The other half received only mechanical thromboprophylaxis, including dynamic (intermittent plantar or pneumatic compression device), static (graduated compression stockings [GCSs]), or both. We measured anti-PF4/heparin immunoglobulins G, A, and M before and 10 days after surgery using an immunoassay. Multivariate analysis revealed that dynamic mechanical thromboprophylaxis (DMT) was an independent risk factor for seroconversion (odds ratio [OR], 2.01; 95% confidence interval [CI], 1.34-3.02; P = .001), which was confirmed with propensity-score matching (OR, 1.99; 95% CI, 1.17-3.37; P = .018). For TKA, the seroconversion rates in patients treated with DMT but no anticoagulation and in patients treated with UFH or LMWH without DMT were similar, but significantly higher than in patients treated with only GCSs. The proportion of patients with ≥1.4 optical density units appeared to be higher among those treated with any anticoagulant plus DMT than among those not treated with DMT. Our study suggests that DMT increases risk of an anti-PF4/heparin immune response, even without heparin exposure. This trial was registered to www.umin.ac.jp/ctr as #UMIN000001366.
authors.affiliation: Japanese National Hospital Organization (NHO)-Evidence-Based Medicine Study Group for the Clinical Study of Prevention and Actual Situation of Venous Thromboembolism After Total Arthroplasty, Tokyo, Japan; Division of Clinical Epidemiology, NHO Tokyo Medical Center, Tokyo, Japan;
authors.forename: Seiji
authors.initials: S
authors.lastname: Bito
authors.affiliation: Division of Transfusion Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan;
authors.forename: Shigeki
authors.initials: S
authors.lastname: Miyata
authors.affiliation: Japanese National Hospital Organization (NHO)-Evidence-Based Medicine Study Group for the Clinical Study of Prevention and Actual Situation of Venous Thromboembolism After Total Arthroplasty, Tokyo, Japan;
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Migita
authors.affiliation: Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Mie, Japan;
authors.forename: Mashio
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Japanese National Hospital Organization (NHO)-Evidence-Based Medicine Study Group for the Clinical Study of Prevention and Actual Situation of Venous Thromboembolism After Total Arthroplasty, Tokyo, Japan;
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Shinohara
authors.affiliation: Japanese National Hospital Organization (NHO)-Evidence-Based Medicine Study Group for the Clinical Study of Prevention and Actual Situation of Venous Thromboembolism After Total Arthroplasty, Tokyo, Japan;
authors.forename: Tomotaro
authors.initials: T
authors.lastname: Sato
authors.affiliation: Japanese National Hospital Organization (NHO)-Evidence-Based Medicine Study Group for the Clinical Study of Prevention and Actual Situation of Venous Thromboembolism After Total Arthroplasty, Tokyo, Japan;
authors.forename: Takeharu
authors.initials: T
authors.lastname: Tonai
authors.affiliation: Japanese National Hospital Organization (NHO)-Evidence-Based Medicine Study Group for the Clinical Study of Prevention and Actual Situation of Venous Thromboembolism After Total Arthroplasty, Tokyo, Japan;
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Japanese National Hospital Organization (NHO)-Evidence-Based Medicine Study Group for the Clinical Study of Prevention and Actual Situation of Venous Thromboembolism After Total Arthroplasty, Tokyo, Japan;
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: Japanese National Hospital Organization (NHO)-Evidence-Based Medicine Study Group for the Clinical Study of Prevention and Actual Situation of Venous Thromboembolism After Total Arthroplasty, Tokyo, Japan;
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kishi
authors.affiliation: Japanese National Hospital Organization (NHO)-Evidence-Based Medicine Study Group for the Clinical Study of Prevention and Actual Situation of Venous Thromboembolism After Total Arthroplasty, Tokyo, Japan;
authors.forename: Chikara
authors.initials: C
authors.lastname: Kubota
authors.affiliation: Japanese National Hospital Organization (NHO)-Evidence-Based Medicine Study Group for the Clinical Study of Prevention and Actual Situation of Venous Thromboembolism After Total Arthroplasty, Tokyo, Japan;
authors.forename: Shinnosuke
authors.initials: S
authors.lastname: Nakahara
authors.affiliation: Japanese National Hospital Organization (NHO)-Evidence-Based Medicine Study Group for the Clinical Study of Prevention and Actual Situation of Venous Thromboembolism After Total Arthroplasty, Tokyo, Japan;
authors.forename: Toshihito
authors.initials: T
authors.lastname: Mori
authors.affiliation: Japanese National Hospital Organization (NHO)-Evidence-Based Medicine Study Group for the Clinical Study of Prevention and Actual Situation of Venous Thromboembolism After Total Arthroplasty, Tokyo, Japan;
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Japanese National Hospital Organization (NHO)-Evidence-Based Medicine Study Group for the Clinical Study of Prevention and Actual Situation of Venous Thromboembolism After Total Arthroplasty, Tokyo, Japan;
authors.forename: Shusuke
authors.initials: S
authors.lastname: Ota
authors.affiliation: Japanese National Hospital Organization (NHO)-Evidence-Based Medicine Study Group for the Clinical Study of Prevention and Actual Situation of Venous Thromboembolism After Total Arthroplasty, Tokyo, Japan;
authors.forename: Takeshi
authors.initials: T
authors.lastname: Minamizaki
authors.affiliation: Japanese National Hospital Organization (NHO)-Evidence-Based Medicine Study Group for the Clinical Study of Prevention and Actual Situation of Venous Thromboembolism After Total Arthroplasty, Tokyo, Japan;
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Japanese National Hospital Organization (NHO)-Evidence-Based Medicine Study Group for the Clinical Study of Prevention and Actual Situation of Venous Thromboembolism After Total Arthroplasty, Tokyo, Japan;
authors.forename: Naofumi
authors.initials: N
authors.lastname: Shiota
authors.affiliation: Department of Anesthesiology, National Cerebral and Cardiovascular Center, Osaka, Japan; and.
authors.forename: Masataka
authors.initials: M
authors.lastname: Kamei
authors.affiliation: Japanese National Hospital Organization (NHO)-Evidence-Based Medicine Study Group for the Clinical Study of Prevention and Actual Situation of Venous Thromboembolism After Total Arthroplasty, Tokyo, Japan; Department of Orthopedic Surgery, NHO Nagasaki Medical Center, Nagasaki, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Motokawa
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000077425:Fondaparinux; D006493:Heparin / Q000276:immunology / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D048228:Intermittent Pneumatic Compression Devices; D008297:Male; D008875:Middle Aged; D010978:Platelet Factor 4 / Q000276:immunology; D011134:Polysaccharides / Q000627:therapeutic use; D053828:Stockings, Compression; D013923:Thromboembolism / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D001323:Autoantibodies; D001324:Autoantigens; D006495:Heparin, Low-Molecular-Weight; D011134:Polysaccharides; D010978:Platelet Factor 4; D006493:Heparin; D000077425:Fondaparinux