Recombinant human soluble thrombomodulin (thrombomodulin alfa) to treat disseminated intravascular coagulation in solid tumors: results of a one-arm prospective trial.
BACKGROUND
Disseminated intravascular coagulation (DIC) associated with solid tumors (DIC-ST) is often encountered in clinical practice. Patients with DIC-ST are usually in poor condition and have bleeding diathesis due to advanced or metastatic diseases. Although some affected patients are treated with heparin, this strategy has not been prospectively studied. Recombinant human soluble thrombomodulin (thrombomodulin alfa, TM-α) is a new anticoagulant developed in Japan. We conducted a prospective study that evaluated the efficacy and safety of TM-α in patients with DIC-ST.


METHODS
A prospective one-arm study with TM-α was conducted for DIC-ST. TM-α (380 U/kg) was given for 30 min intravenously once daily for 6-14 days. The primary efficacy endpoint was the DIC resolution rate. Change in DIC scores and improvement in bleeding symptoms and outcomes were also evaluated. Safety endpoints included the incidence of bleeding-related adverse events.


RESULTS
A total of 101 patients were treated with TM-α. The three main underlying malignant diseases were lung, stomach, and breast cancer, which accounted for 60 % of all patients. The DIC resolution rate was 34.0 % at the end of TM-α treatment. Improvement in DIC scores was seen in 55.2 % of patients, while only 22.9 % of patients had worsening of DIC scores. The overall survival rate was 55.4 % on day 28. The incidence of hemorrhage related to TM-α was 12.9 % until day 28. Cases of severe hemorrhage related to TM-α did not occur.


CONCLUSIONS
TM-α is effective and safe for DIC-ST. This agent is the treatment of choice for the management of DIC-ST.
Division of Medical Oncology, Hematology and Infectious Diseases, Department of Medicine, Fukuoka University Hospital, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, Fukuoka, 814-0180, Japan, ktamura@fukuoka-u.ac.jp.
Kazuo
K
Tamura
Hidehiko
H
Saito
Hidesaku
H
Asakura
Kohji
K
Okamoto
Jun
J
Tagawa
Toru
T
Hayakawa
Nobuo
N
Aoki
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006401:Hematologic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D011446:Prospective Studies; D018180:Thrombomodulin / Q000627:therapeutic use*; D055815:Young Adult
D006401:Hematologic Agents; C546931:THBD protein, human; D018180:Thrombomodulin