Post-marketing surveillance data of thrombomodulin alfa: sub-analysis in patients with sepsis-induced disseminated intravascular coagulationReport as inadecuate




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Journal of Intensive Care

, 2:30

First Online: 30 April 2014Received: 11 November 2013Accepted: 07 April 2014

Abstract

BackgroundThrombomodulin alfa TM-α, recombinant thrombomodulin significantly improved disseminated intravascular coagulation DIC when compared with heparin therapy in a phase III study. Post-marketing surveillance of TM-α was performed to evaluate the effects and safety in patients with sepsis-induced DIC.

MethodsFrom May 2008 to April 2010, a total of 1,787 patients with sepsis-induced DIC treated with TM-α were registered. DIC was diagnosed based on the Japanese Association for Acute Medicine JAAM criteria. The DIC resolution and survival rates on day 28 after the last TM-α administration, and changes in DIC, systemic inflammatory response syndrome SIRS, and sequential organ failure assessment SOFA scores and coagulation and inflammation markers were evaluated.

ResultsThe most frequent underlying disease was infectious focus-unknown sepsis 29.8%. The mean ± SD values of age, dose, and the duration of TM-α administration were 64.7 ± 20.3 years, 297.3 ± 111.4 U-kg-day, and 5.6 ± 3.4 days, respectively. A total of 1,320 subjects 73.9% received combined administration with other anticoagulants. Both coagulation and inflammation markers, such as fibrin-fibrinogen degradation products, prothrombin time ratio, thrombin-antithrombin complex, and C-reactive protein, as well as JAAM DIC, SIRS, and SOFA scores, significantly and simultaneously decreased after TM-α administration p < 0.001. DIC resolution and 28-day survival rates were 44.4% and 66.0%, respectively. The 28-day survival rate decreased significantly according to the duration of DIC before TM-α administration p < 0.001. Total adverse drug reactions ADRs, bleeding ADRs, and serious bleeding adverse events occurred in 126 7.1%, 98 5.5%, and 121 6.8% subjects, respectively. On day 28, after the last TM-α administration available for an antibody test, only one patient was positive for anti-TM-α antibodies 0.11%.

ConclusionOur results suggest that TM-α is most effective for treating patients with sepsis-induced DIC when administered within the first 3 days after diagnosis.

KeywordsAnticoagulant JAAM criteria Sepsis SIRS SOFA score AbbreviationsAEadverse event

ADRadverse drug reaction

APCactivated protein C

ATantithrombin

CIconfidence interval

CRPC-reactive protein

DICdisseminated intravascular coagulation

ELISAenzyme-linked immunosorbent assay

FDPfibrin-fibrinogen degradation products

FFPfresh frozen plasma

HMGB-1high mobility group box-1

ICUintensive care unit

JAAMJapanese Association for Acute Medicine

MedDRA-JMedical Dictionary for Regulatory Activities

ORodds ratio

PLTplatelet

PMSpost-marketing surveillance

PTprothrombin time

RCTrandomized controlled trial

SDstandard deviation

SIRSsystemic inflammatory response syndrome

SOFASequential Organ Failure Assessment

TATthrombin-antithrombin

TMthrombomodulin

TM-αthrombomodulin alfa

WBCwhite blood cell.

Electronic supplementary materialThe online version of this article doi:10.1186-2052-0492-2-30 contains supplementary material, which is available to authorized users.

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Author: Yutaka Eguchi - Satoshi Gando - Hiroyasu Ishikura - Daizoh Saitoh - Jun Mimuro - Hoyu Takahashi - Isao Kitajima - Hajime T

Source: https://link.springer.com/







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