A comparative double-blind randomized trial of activated protein C and unfractionated heparin in the treatment of disseminated intravascular coagulation.
A randomized prospective double-blind trial was performed to compare the safety and efficacy of human activated protein C (APC) and unfractionated heparin for the treatment of disseminated intravascular coagulation (DIC). One hundred thirty-two patients with DIC were enrolled in this study: 63 patients received APC (12.5 U [2.5 microg]/kg body wt per hour) and 69 patients received heparin (8 U/kg body wt per hour) by intravenous infusion for 6 days. Forty-nine APC-treated patients and 55 heparin-treated patients were evaluated for efficacy, and 52 APC-treated patients and 55 heparin-treated patients were evaluated for safety. The 2 groups were similar with respect to sex, age, body weight, underlying diseases, and coagulation/fibrinolysis parameters before treatment. Aggravation of bleeding was seen after treatment in 8 patients receiving heparin, but in none of the patients receiving APC. The number of patients who showed alleviation of bleeding was significantly higher in the APC group than the heparin group (P = .009). The effects on DIC-related organ dysfunction were not significantly different between the 2 groups. Fibrinogen-fibrin degradation products, D-dimer, thrombin-antithrombin complex (TAT), and plasmin-plasmin inhibitor complex (PIC) were all significantly decreased by treatment in both groups. Fibrinogen, protein C, and antithrombin were significantly increased in the APC group, whereas only protein C was significantly increased in the heparin group. Platelet count in the nonleukemic group was significantly increased in those patients receiving APC but not increased in those patients receiving heparin. Improvement of coagulation/fibrinolysis was assessed by scoring 4 parameters (soluble fibrin monomers, D-dimer, TAT, and PIC), and the results indicated that the APC group showed significantly greater improvement than the heparin group (P = .046). There was, however, no significant difference in the rate of complete recovery from DIC between the 2 groups. The rate of death from any cause within 28 days after treatment was 20.4% in the APC group, significantly lower than the 40% death rate observed in the heparin group (P < .05). There were no severe adverse events in either group. These results suggest that APC in a relatively small dosage can improve DIC more efficiently than can heparin, without increasing bleeding, and may be a better alternative.
Aoki
Nobuo
N
Department of Medicine, Tokyo Medical and Dental University, Japan. aoki.hema@med.tmd.ac.jp
Matsuda
Tamotsu
T
Saito
Hidehiko
H
Takatsuki
Kiyoshi
K
Okajima
Kenji
K
Takahashi
Hoyu
H
Takamatsu
Junki
J
Asakura
Hidesaku
H
Ogawa
Nobuya
N
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D019774:Blood Coagulation Factor Inhibitors / Q000378:metabolism; D001779:Blood Coagulation Factors / Q000187:drug effects / Q000378:metabolism; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020011:Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D011486:Protein C / Q000008:administration & dosage* / Q000627:therapeutic use
D000925:Anticoagulants; D015415:Biomarkers; D019774:Blood Coagulation Factor Inhibitors; D001779:Blood Coagulation Factors; D020011:Protective Agents; D011486:Protein C; D006493:Heparin