The efficacy of recombinant human soluble thrombomodulin for obstetric disseminated intravascular coagulation: a retrospective study.
BACKGROUND
Recombinant human soluble thrombomodulin (rhTM) is a novel anti-coagulant agent that regulates the imbalanced coagulation system by reducing the excessive activation of thrombin. rhTM potentially reduces the morbidity and mortality in patients with sepsis-induced disseminated intravascular coagulation (DIC). However, the efficacy of rhTM in obstetric DIC has not yet been established. We performed this study to examine whether the administration of rhTM was a potentially effective treatment for DIC induced by one or more underlying obstetric disorders.


METHODS
This is a single-center, retrospective cohort study conducted between January 2007 and February 2015 using the records of the Department of Obstetrics at the Perinatal Medical Center of TOYOTA Memorial Hospital, Aichi, Japan. The eligibility criteria were known or suspected obstetric DIC documented on the basis of clinical and laboratory data and association with one or more major underlying obstetric disorders. Baseline imbalance between patients with and without treatment of rhTM was adjusted using an inverse probability of treatment weighting using propensity scores composed of the following independent variables: severe postpartum hemorrhage, placental abruption, and preeclampsia/eclampsia, including hemolysis, elevated liver enzymes, and low platelet syndrome, initial platelet counts, D-dimer levels, fibrinogen levels, and prothrombin time-international normalized ratio (PT-INR). We evaluated laboratory changes and clinical outcomes in the early phase of obstetric DIC.


RESULTS
In total, 66 of 4627 patients admitted to our department during the study period fulfilled the required criteria; of these, 37 and 29 patients were included in the rhTM and control group, respectively. After adjustment, treatment with rhTM was associated with significant improvements in platelet counts, D-dimer levels, fibrinogen levels, and PT-INR compared with the control group. The platelet concentrate transfusion volume was significantly lower in the rhTM treatment group (3.02 vs 6.03 units, P = 0.016). None of the adjusted group differences were statistically significant for all types of organ damage and failure.


CONCLUSIONS
rhTM administration was associated with clinical and laboratory improvement in patients with DIC caused by underlying obstetric conditions. Further clinical research is needed to clarify the optimal application of rhTM in each of the causative obstetric disorders.
Department of Obstetrics, Perinatal Medical Center, TOYOTA Memorial Hospital, 1-1, Heiwa-cho, Toyota, Aichi, Japan. masato.yoshihara.1209@gmail.com.
Masato
M
Yoshihara
Department of Obstetrics, Perinatal Medical Center, TOYOTA Memorial Hospital, 1-1, Heiwa-cho, Toyota, Aichi, Japan. kanjinkyaname@yahoo.co.jp.
Kaname
K
Uno
Department of Obstetrics, Perinatal Medical Center, TOYOTA Memorial Hospital, 1-1, Heiwa-cho, Toyota, Aichi, Japan. s.tano.141288@gmail.com.
Sho
S
Tano
Department of Obstetrics, Perinatal Medical Center, TOYOTA Memorial Hospital, 1-1, Heiwa-cho, Toyota, Aichi, Japan. marimo.mayama@gmail.com.
Michinori
M
Mayama
Department of Obstetrics, Perinatal Medical Center, TOYOTA Memorial Hospital, 1-1, Heiwa-cho, Toyota, Aichi, Japan. mayu_u_pro_1202@yahoo.co.jp.
Mayu
M
Ukai
Department of Obstetrics, Perinatal Medical Center, TOYOTA Memorial Hospital, 1-1, Heiwa-cho, Toyota, Aichi, Japan. kurokonoha@gmail.com.
Shinya
S
Kondo
Department of Obstetrics, Perinatal Medical Center, TOYOTA Memorial Hospital, 1-1, Heiwa-cho, Toyota, Aichi, Japan. tetsu_leo16_whp11@hotmail.co.jp.
Tetsuya
T
Kokabu
Department of Obstetrics, Perinatal Medical Center, TOYOTA Memorial Hospital, 1-1, Heiwa-cho, Toyota, Aichi, Japan. yasuyuki_kishigami@mail.toyota.co.jp.
Yasuyuki
Y
Kishigami
Department of Obstetrics, Perinatal Medical Center, TOYOTA Memorial Hospital, 1-1, Heiwa-cho, Toyota, Aichi, Japan. h_oguchi@mail.toyota.co.jp.
Hidenori
H
Oguchi
D015331:Cohort Studies; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology / Q000401:mortality; D005260:Female; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology / Q000209:etiology / Q000401:mortality*; D057216:Propensity Score; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012189:Retrospective Studies; D018805:Sepsis / Q000401:mortality; D016019:Survival Analysis; D018180:Thrombomodulin / Q000627:therapeutic use*; D016896:Treatment Outcome
D011994:Recombinant Proteins; C546931:THBD protein, human; D018180:Thrombomodulin