title: Reduced induction of anti-PF4/heparin antibody in RA patients after total knee arthroplasty.
abstract: Heparin-induced thrombocytopenia is caused by antibodies (Abs) specific to platelet factor 4 (PF4)/heparin complexes. In this study, we evaluated the rates of seroconversion of anti-PF4/heparin Ab between patients with rheumatoid arthritis (RA) and with osteoarthritis (OA) who underwent total knee arthroplasty.
  
  
  
  The subjects of this randomized controlled trial were 124 patients who underwent total knee arthroplasty (TKA) and received edoxaban with or without a foot pump as thromboprophylaxis. We measured anti-PF4/heparin Abs before and 10 days after surgery, as well as preoperative PF4, using commercially available ELISAs. We also used the database of J-PSVT, a hospital-based, prospective cohort study designed to document the effectiveness of thromboprophylactic agents during arthroplasty.
  
  
  
  The rates of seroconversion to anti-PF4/heparin Ab were lower in RA patients (4.0 %) than in OA patients (25.5 %). The anti-PF4/heparin IgG optical density (OD) values did not differ before and after surgery in RA patients. In contrast, there was a significant increase in anti-PF4/heparin IgG OD values in OA patients after TKA. In the J-PSVT data, the postoperative seroconversion rates of anti-PF4/heparin Ab were lower in RA patients (10.4 %) than in OA patients (21.8 %) who received fondaparinux. The titers of anti-CCP Ab were significantly lower in RA patients with postoperative ant-PF4/heparin Ab compared with those without postoperative ant-PF4/heparin Ab There was no significant difference in preoperative PF4 levels between RA patients and OA patients. The heparin-binding affinity of the circulating PF4 was similar between RA patients and OA patients; however, the IgG fractions isolated from the sera of RA patients contained PF4 more frequently (69.2 %) than those from OA patients (10.2 %).
  
  
  
  Our results showed a reduced likelihood of postoperative anti-PF/heparin Ab production in RA patients compared with OA patients. This suggests that the mechanisms underlying the anti-PF4 immune response in RA patients differ from the mechanisms of the anti-PF4/heparin immune response seen in OA patients after joint replacement.
  
  
  
  ISRCTN 18090286. Registered 8 July 2016.
authors: Department of Molecular Immunology, Unit of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, Nagasaki, 852-8501, Japan.|Department of Orthopedic Surgery, NHO Nagasaki Medical Center, Kubara 2-1001-1, Omura, Nagasaki, 856-8562, Japan.
authors: Masahiro
authors: M
authors: Izumi
authors: Department of Molecular Immunology, Unit of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-7-1, Nagasaki, 852-8501, Japan.|Department of Orthopedic Surgery, NHO Nagasaki Medical Center, Kubara 2-1001-1, Omura, Nagasaki, 856-8562, Japan.
authors: Tatsuya
authors: T
authors: Sakai
authors: Department of Pharmacy, NHO Nagasaki Medical Center, Kubara 2-1001-1, Omura, Nagasaki, 856-8562, Japan.
authors: Atsunori
authors: A
authors: Shirakawa
authors: Department of Rheumatology, Clinical Research Center, NHO Nagasaki Medical Center, Kubara 2-1001-1, Omura, Nagasaki, 856-8562, Japan.
authors: Hideko
authors: H
authors: Kozuru
authors: Department of Rheumatology, Clinical Research Center, NHO Nagasaki Medical Center, Kubara 2-1001-1, Omura, Nagasaki, 856-8562, Japan.
authors: Yuka
authors: Y
authors: Jiuchi
authors: Department of Rheumatology, Clinical Research Center, NHO Nagasaki Medical Center, Kubara 2-1001-1, Omura, Nagasaki, 856-8562, Japan.
authors: Yasumori
authors: Y
authors: Izumi
authors: Department of Orthopedic Surgery, NHO Nagasaki Medical Center, Kubara 2-1001-1, Omura, Nagasaki, 856-8562, Japan.
authors: Tomohiko
authors: T
authors: Asahara
authors: Department of Orthopedic Surgery, NHO Nagasaki Medical Center, Kubara 2-1001-1, Omura, Nagasaki, 856-8562, Japan.
authors: Kenji
authors: K
authors: Kumagai
authors: Department of Orthopedic Surgery, Saga University Hospital, Nabeshima 5-1-1, Saga, 849-8501, Japan.
authors: Masaaki
authors: M
authors: Mawatari
authors: Department of Orthopedic Surgery, Nagasaki University Hospital, Sakamoto 1-7-1, Nagasaki, 852-8501, Japan.
authors: Makoto
authors: M
authors: Osaki
authors: Suga Orthopedic Hospital, Ono 332, Isahaya, 854-0034, Japan.
authors: Satoru
authors: S
authors: Motokawa
authors: Department of Rheumatology, Clinical Research Center, NHO Nagasaki Medical Center, Kubara 2-1001-1, Omura, Nagasaki, 856-8562, Japan. migita@fmu.ac.jp.|Department of Rheumatology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, Fukushima, 960-1295, Japan. migita@fmu.ac.jp.
authors: Kiyoshi
authors: K
authors: Migita
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000601:surgery; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D065427:Factor Xa Inhibitors / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000601:surgery; D010978:Platelet Factor 4 / Q000097:blood / Q000276:immunology*; D011725:Pyridines / Q000009:adverse effects*; D000069078:Seroconversion; D013844:Thiazoles / Q000009:adverse effects*; D013921:Thrombocytopenia / Q000139:chemically induced*; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D065427:Factor Xa Inhibitors; D007074:Immunoglobulin G; D011725:Pyridines; D013844:Thiazoles; D010978:Platelet Factor 4; C552171:edoxaban
keywords: Anti-PF4/heparin antibodies; Heparin-induced thrombocytopenia; Osteoarthritis; Platelet factor 4; Rheumatoid arthritis; Total knee arthroplasty