Post-marketing surveillance of thrombomodulin alfa, a novel treatment of disseminated intravascular coagulation - safety and efficacy in 1,032 patients with hematologic malignancy.
BACKGROUND
Post-marketing surveillance of thrombomodulin alfa (TM-α) was performed to evaluate safety and efficacy in patients with disseminated intravascular coagulation (DIC) with hematologic malignancy.


METHODS
All patients treated with TM-α from May 2008 to April 2010 in Japan were included. Information about baseline characteristics, safety, and efficacy were collected. The DIC resolution rate, survival rate on Day 28 after the last TM-α administration, and changes in DIC score and coagulation tests were evaluated.


RESULTS
The underlying diseases associated with DIC were acute myeloid leukemia (except for acute promyelocytic leukemia, n=350), lymphoma (n=199), acute promyelocytic leukemia (n=172), acute lymphoblastic leukemia (n=156), myelodysplastic syndromes (n=61), and other (n=94). The incidence rates of bleeding-related adverse events and adverse drug reactions were 17.8% and 4.6%, respectively. In subjects with bleeding symptoms at baseline, 55.0% were assessed as disappeared or improved based on symptoms after TM-α treatment. The DIC resolution and survival rates were 55.9% and 70.7%, respectively. The DIC score and coagulation tests including thrombin-antithrombin complex (TAT) were significantly improved. Coagulation tests were significantly improved after TM-α treatment even in subjects whose clinical course of underlying disease was assessed as unchanged or exacerbated.


CONCLUSIONS
This surveillance confirmed the safety and efficacy of TM-α in clinical practice, thus TM-α may be an ideal treatment for patients with DIC based upon hematologic malignancy.
Department of Internal Medicine (III), Kanazawa University School of Medicine, Kanazawa, Japan. Electronic address: hasakura@staff.kanazawa-u.ac.jp.
Hidesaku
H
Asakura
Department of Internal Medicine, Niigata Prefectural Kamo Hospital, Niigata, Japan; The Japanese Society on Thrombosis and Hemostasis Post-Marketing Surveillance Committee for Recomodulin(®) Injection.
Hoyu
H
Takahashi
Department of Blood Transfusion, Kyoto Prefectural University of Medicine, Kyoto, Japan; The Japanese Society on Thrombosis and Hemostasis Post-Marketing Surveillance Committee for Recomodulin(®) Injection.
Hajime
H
Tsuji
Department of Transfusion Medicine, Nagoya University Hospital, Aichi, Japan; The Japanese Society on Thrombosis and Hemostasis Post-Marketing Surveillance Committee for Recomodulin(®) Injection.
Tadashi
T
Matsushita
ART project, Pharmaceutical Sales Division Asahi Kasei Pharma Corporation, Tokyo, Japan.
Hideyuki
H
Ninomiya
ART project, Pharmaceutical Sales Division Asahi Kasei Pharma Corporation, Tokyo, Japan.
Goichi
G
Honda
Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, School of Medicine, Tochigi, Japan; The Japanese Society on Thrombosis and Hemostasis Post-Marketing Surveillance Committee for Recomodulin(®) Injection.
Jun
J
Mimuro
Critical and Intensive Care Medicine, Shiga University of Medical Science, Shiga, Japan; The Japanese Society on Thrombosis and Hemostasis Post-Marketing Surveillance Committee for Recomodulin(®) Injection.
Yutaka
Y
Eguchi
Department of Clinical Laboratory and Molecular Pathology, Graduate School of Medical and Pharmaceutical Science, University of Toyama, Toyama, Japan; The Japanese Society on Thrombosis and Hemostasis Post-Marketing Surveillance Committee for Recomodulin(®) Injection.
Isao
I
Kitajima
Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, School of Medicine, Tochigi, Japan; The Japanese Society on Thrombosis and Hemostasis Post-Marketing Surveillance Committee for Recomodulin(®) Injection.
Yoichi
Y
Sakata
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000188:drug therapy*; D005260:Female; D019337:Hematologic Neoplasms / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use*; D018180:Thrombomodulin / Q000097:blood / Q000627:therapeutic use*; D055815:Young Adult
D011994:Recombinant Proteins; C546931:THBD protein, human; D018180:Thrombomodulin
Disseminated intravascular coagulation; Hematologic malignancy; Post-marketing surveillance; Thrombomodulin