High dose of intravenous antithrombin III without heparin in the treatment of disseminated intravascular coagulation and organ failure in four children

Abstract

In several animal experiments, high doses of antithrombin 111 concentrates have shown beneficial effects on mortality and reversal of coagulation abnormalities which had resulted from disseminated intravascular coagulation. Other experiments have suggested that antithrombin 111 infusion without heparin is effective in the treatment of organ failure. We clinically treated children suffering disseminated intravascular coagulation only with antithrombin concentrate. Four patients suffering disseminated intravascular coagulation with organ failure were selected. We started antithrombin 111 concentrate infusion as soon as the diagnosis was established. The dosage of antithrombin 111 was 120-250 unitdkgl day for 2 or 3 days. Heparin was not used. All 4 patients recovered completely and quickly without any complications within 14 days. We suggest that the high-dose antithrombin 111 infusion without heparin is an effective and safe therapy for disseminated intravascular coagulation with organ failure.

Coagulopathy of sepsis

“…Other studies of antithrombin substitution (113), antithrombin therapy (114), or combination therapy of antithrombin with heparin (115)(116)(117) were purely observational, with no control groups or randomization.…”

Hematologic Abnormalities in Severe Neonatal Necrotizing Enterocolitis: 25 Years Later

“…49 ATIII is another therapeutic option that attenuates organ damage by decreasing microthrombus formation and endothelial injury. 50 In children, one uncontrolled study in four patients 20 days to 17 months showed that high-dose ATIII, without heparin, was safe and effective in treating DIC and organ failure, likely through improved organ blood flow. 50 A placebo-controlled randomized trial of ATIII immediately after birth in intubated neonates with respiratory distress syndrome conferred no improvement in lung function and was associated with a greater mortality in the ATIII group.…”

“…50 In children, one uncontrolled study in four patients 20 days to 17 months showed that high-dose ATIII, without heparin, was safe and effective in treating DIC and organ failure, likely through improved organ blood flow. 50 A placebo-controlled randomized trial of ATIII immediately after birth in intubated neonates with respiratory distress syndrome conferred no improvement in lung function and was associated with a greater mortality in the ATIII group. 51 Although this study was not performed on neonates with NEC, the safety issues should increase caution in proceeding with trials of ATIII in adults or neonates with sepsis or in NEC.…”

Disseminated intravascular coagulation: Clinical and laboratory aspects

“…These results suggest that pharmacologic concentrations of ATIII may exert a beneficial effect by mechanisms other than that currently under-stood [43]. High-dose ATIII was also reportedly useful in ameliorating organ failure in a small pediatric case series with DIC [44].…”

“…Additionally, the efficacy of most of the drugs listed in Table II has only been demonstrated when they have been given prior to induction of experimental DIC. Notable exceptions to this statement include ATIII [42][43][44], gabexate [45,46], TFPI [56][57][58], and dithiocarbamates [62], which have been shown to ameliorate DIC in humans or experimental models after initiation of DIC.…”