Recombinant hirudin for the treatment of disseminated intravascular coagulation in patients with haematological malignancy.
The purpose of this pilot study was to determine the effect of recombinant hirudin (r-hirudin) on coagulopathy and the relationship between concentrations of thrombin-antithrombin III (ATIII) complex (TAT) and thrombin-hirudin complex (THC) in patients with disseminated intravascular coagulation (DIC). Five patients with haematological malignancy associated with DIC were studied. r-Hirudin was administered by continuous intravenous infusion at a dose of 0.005 mg/kg/h for 4-9 days to each patient. Fibrin/fibrinogen degradation products (FDP), D-dimer, TAT and plasmin-alpha 2 antiplasmin complex (PAP) concentrations decreased after treatment with r-hirudin in four patients studied. However, in one patient, serum creatinine increased to 1.7 mg/dl and aPTT was prolonged to 74.4s. Statistical analysis disclosed significant positive correlations between plasma concentrations of hirudin and THC, and between concentrations of THC and TAT. The concentrations of THC were much higher than those of TAT. In conclusion, these findings indicate that r-hirudin more strongly inhibited thrombin than did ATIII without heparin, and that administration of r-hirudin to renal insufficiency required individual adjustment of dosage. The present findings also suggest that r-hirudin can be considered a new agent for the treatment of DIC.
Saito
M
M
Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
Asakura
H
H
Jokaji
H
H
Uotani
C
C
Kumabashiri
I
I
Morishita
E
E
Yamazaki
M
M
Aoshima
K
K
Matsuda
T
T
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000933:Antifibrinolytic Agents; D000990:Antithrombin III / Q000032:analysis; D001752:Blast Crisis / Q000097:blood / Q000150:complications; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005341:Fibrinolysin / Q000032:analysis; D024764:Hirudin Therapy; D006629:Hirudins / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007938:Leukemia / Q000097:blood / Q000150:complications*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000150:complications; D007951:Leukemia, Myeloid / Q000097:blood / Q000150:complications; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000150:complications; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000032:analysis; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D000979:alpha-2-Antiplasmin / Q000032:analysis
D000933:Antifibrinolytic Agents; D005338:Fibrin Fibrinogen Degradation Products; D006629:Hirudins; D011994:Recombinant Proteins; D000979:alpha-2-Antiplasmin; C046193:antithrombin III-protease complex; C037742:plasmin-plasmin inhibitor complex; D000990:Antithrombin III; D010447:Peptide Hydrolases; D005341:Fibrinolysin; C083544:lepirudin