title: Heparin-induced thrombocytopenia antibody and the pathogenesis of thrombotic microangiopathy after stem cell transplantation.
abstract: Thrombotic microangiopathy (TMA) that occurs after stem cell transplantation (SCT) is generally regarded as being different from thrombotic thrombocytopenic purpura (TTP), because it is reportedly not associated with deficiency of von Willebrand factor-cleaving protease, whereas this enzyme is deficient in TTP. However, better understanding of the pathogenesis of this condition is still required. Accordingly, we investigated the relationship between TMA occurring after SCT and heparin-induced thrombocytopenia (HIT), a condition related to low-dosed heparin therapy that features thrombocytopenia and generalized thrombotic disorders. Thirty-nine consecutive patients who underwent bone marrow transplantation were divided into a TMA group and a non-microangiopathy group (10 and 29 patients, respectively). Before SCT, the serum platelet factor 4 (PF4) levels of the TMA and non-microangiopathy groups were 0.123 +/- 0.023 and 0.132 +/- 0.025, respectively (p = NS). One week after recovery of the white blood cell count following transplantation, the TMA group (0.2902 +/- 0.0678) had a significantly higher PF4 level than the non-microangiopathy group (0.1548 +/- 0.0312) (p < 0.001, t-test). Thus, PF4 increased after engraftment of the transplanted stem cells in the patients who developed TMA. In patients who developed TMA, there was a significant correlation between the PF4 level and the grade of angiopathy according to the Zeigler grading system (p < 0.01 by linear regression analysis). These results suggest that a HIT antibody produced by donor cells may be involved in the development of TMA after SCT.
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan. htakatsu@hyo-med.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takatsuka
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nakajima
authors.forename: Kaori
authors.initials: K
authors.lastname: Nomura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Wakae
authors.forename: Akinari
authors.initials: A
authors.lastname: Toda
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Itoi
authors.forename: Masaya
authors.initials: M
authors.lastname: Okada
authors.forename: Mahito
authors.initials: M
authors.lastname: Misawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hara
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology; D005260:Female; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology*; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000276:immunology; D008875:Middle Aged; D010978:Platelet Factor 4 / Q000032:analysis; D013921:Thrombocytopenia / Q000097:blood / Q000276:immunology*; D013927:Thrombosis / Q000097:blood / Q000276:immunology*
chemical_list: D000906:Antibodies; D010978:Platelet Factor 4; D006493:Heparin