Page 2332 - Hematology_ Basic Principles and Practice ( PDFDrive )

2074 Part XII Hemostasis and Thrombosis

specific inhibitor of the ternary complex of TF/factor VIIa and factor DIC. This is because these drugs block already suppress endogenous
Xa. Phase II trials of recombinant TFPI in patients with sepsis showed fibrinolysis, and may further compromise tissue perfusion. In support
promising results but phase III trials in patients with severe sepsis or of this concept there are reports of severe thrombosis in DIC patients
severe pneumonia and organ failure failed to show a survival advan- treated with these agents. However, in patients with DIC accompa-
tage with TFPI adminsitration. 26 nied by primary fibrino(geno)lysis, which occurs in some cases of
Recombinant human soluble thrombomodulin binds thrombin acute promyelocytic leukemia, giant cavernous hemangioma, heat
to form a complex that blocks the coagulant activity of thrombin and stroke, and metastatic carcinoma of the prostate, the use of fibrino-
promotes its capacity to activate protein C. In a phase III randomized lytic inhibitors can be considered if the patient has profuse bleeding
double-blind clinical trial in patients with DIC, soluble thrombo- that does not respond to replacement therapy and there is evidence
modulin was superior to heparin at reducing bleeding and improving of excessive fibrino(geno)lysis. In these situations, it is important to
the coagulation parameters. A systematic review and meta-analysis of replace depleted blood components before initiating treatment with
mostly retrospective studies on the effect of recombinant human fibrinolytic inhibitors.
soluble thrombomodulin in severe sepsis demonstrated a pooled rela-
tive risk of 0.81 (95% confidence interval (CI) 0.62–1.06) in three
randomized trials encompassing 838 patients, and a relative risk of REFERENCES
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