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Factor VIIa and antithrombin III activity during severe sepsis and septic
shock in neutropenic patients
RM Mesters, PM Mannucci, R Coppola, T Keller, H Ostermann and J Kienast
Department of Internal Medicine, University of Munster, Germany.
Septic shock and multiple organ failure may be associated with coagulation
activation, disseminated fibrin formation, and consumption of coagulation
inhibitors such as antithrombin III. We have evaluated prospectively
coagulation measurements in patients with severe chemotherapy-induced
neutropenia. This group of patients was chosen because of their high risk
of developing severe septic complications, thus allowing serial prospective
coagulation testing before and during evolving sepsis or septic shock.
Sixty-two patients with febrile infectious events were accrued to the
study. Of these, 13 patients progressed to severe sepsis and 13 additional
patients to septic shock as defined according to standard diagnostic
criteria. At the onset of fever, factor (F) VIIa activity, FVII antigen and
antithrombin III (AT III) activity decreased from normal baseline levels
and were significantly lower in the group of patients who progressed to
septic shock compared with those that developed severe sepsis (medians: 0.3
v 1.4 ng/mL, 21 v 86 U/dL and 45% v 95%; P < .001). The decrease of
these measurements in septic shock was accompanied by an increase in
prothrombin fragment 1+2 (median: 3.6 v 1.4 nmol/L; P = .05), a marker of
thrombin generation. These differences were sustained throughout the septic
episode (P < .0001). FVIIa and AT III levels of < 0.8 ng/mL and <
70%, respectively, at onset of fever predicted a lethal outcome with a
sensitivity of 100% and 85%, and a specificity of 75% and 85%,
respectively. In contrast, FXIIa-alpha antigen levels were not different
between groups at onset of fever but increased modestly during the course
of septic shock (P = .001). Thus, septic shock in neutropenic patients is
associated with increased thrombin generation. Furthermore, both FVIIa and
AT III measurements are sensitive markers of an unfavorable prognosis.
Volume 88,
Issue 3,
pp. 881-886,
08/01/1996
Copyright © 1996 by The American Society of Hematology
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