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Use of antithrombin III in cancer patients with sepsis complicated with disseminated intravascular coagulopathy


Mortality rate from sepsis is estimated to be 20% to 60% with disseminated intravascular coagulation (DIC) often accompanying sepsis. Replacement therapy with antithrombin III (ATIII) concentrate has been hypothesized to be a means for attenuating DIC, since ATIII is rapidly consumed during DIC. A reliable index of poor prognosis is an initial decrease of serum ATIII level. The purpose of this pilot study was to evaluate the effects of the administration of ATIII in patients sepsis complicated by DIC.


All adult patients admitted to the surgical intensive care unit at the University of Texas M.D. Anderson Cancer Center with clinical evidence of sepsis and DIC were eligible for inclusion. Exclusion criteria consisted of leukemia and treatment with heparin. Patients received 100 units/kg of ideal body weight of antithrombin III (Thrombate III®) at time zero, repeated 12 h later, and daily for three days. Serum ATIII levels were drawn prior to enrollment, prior to and after each dose, and for 2 days after the last dose. Levels were analyzed at the conclusion of the study. No other intervention was provided by the investigators. Patients were otherwise managed by their primary care providers and consultants as their clinical situation warranted.


The study population included 4 women and 1 man with an average age of 59.6 years (33–84). Severity of illness was measured by a mean APACHE II of 21.8 (19–24) and a mean TISS of 55.6 (45-70) at the time of study enrollment. The ICU and hospital mortality rate were 80%, with one patient not surviving to complete the study regimen. Serum ATIII levels at the time of enrollment ranged from 22 to 78 MUI/ml, averaging 45.4 (normal 80–120). The one surviving patient had the highest ATIII level (78 MUI/ml) prior to study enrollment. A rise in ATIII levels after treatment was found in each patient, with all but one patient having levels normal or supranormal after the first dose of treatment. One patient, with the lowest pretreatment level (22 MUI/ml), had levels that remained below normal during most of treatment and was decreased (51 MUI/ml) at day 2 post treatment.


We have found a variable response in ATIII levels in patients with sepsis after ATIII treatment. Future studies involving ATIII replacement should include the use of ATIII levels to guide dosing regimens.

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Polansky, M., Varon, J. & Hoots, W. Use of antithrombin III in cancer patients with sepsis complicated with disseminated intravascular coagulopathy. Crit Care 2 (Suppl 1), P024 (1998).

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