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The role of natural coagulation inhibitors in correlation with clinic scores in critical patients with obstetric diseases


To validate the correlation among the most significant inflammatory cytokines and the coagulation inhibitors system (AT III, Protein C and TFPI), used as markers, and the levels of organ dysfunction in patients with severe pre-eclampsia and HELLP syndrome.

Materials and methods

Patients involved in the study were those admitted (more than 48 hours) in ICU from 1 January 2000 to 30 September 2001). Two groups of patients were studied according with diagnostic and clinic criteria: (NP) normal pregnancy as control group; (SPH) Severe Pre-eclampsia and HELLP syndrome as study group. We have registered inflammatory cytokines plasma levels (IL 6, TNF-a, IL 10) by an ELISA assay; Antithrombin III (ATIII), Protein C (PC) and Tissue Factor Pathway Inhibitor (TFPI) as coagulation inhibitor markers are assessed via functional (activity) and immunological (antigen). We have also monitored the organ dysfunction score with a SOFA modified score (ODS: 0 = no organ dysfunction; 16 = max organ dysfunction).


We have included 18 patients aged from 17 to 41 years in the SPH group and we have compared these patients with 18 normal pregnancies, aged from 17 to 41 years, before and after the cesarean section. Table 1 shows synthetically our data.

Table 1


These data confirm our hypothesis about the role of well known markers as IL6 and TNF-a in the inflammatory response associated with severe pre-eclampsia and HELLP syndrome [1]. This is also true for some natural coagulation inhibitors and specially for AT III [2]. Protein C and TFPI show, in these data, a new significant role and contribute to confirm a multiple genesis for the coagulation disorders and the organ dysfunction associated to this obstetric disease. In addition to the well known endothelial dysfunction there is a systemic activation of maternal inflammatory cell responses in association with clotting alterations and this is supported by the correlation between the high levels of the pro-inflammatory cytokines and the low levels of coagulation inhibitors. The inhibitory substitutive treatment with AT III, that we have experienced, and with these natural inhibitors (specially Protein C) could modulate the excessive and altered inflammatory response and might restore a normal coagulation and a good organ function reducing the admission and/or the permanence of these patients in ICU.


  1. Redman CWG, Sacks GP, Sargent IL: Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol 1999, 180: 499-506.

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  2. Giarratano A, Capogna G, Celleno D, Mangione S: A new appproach in the treatment of severe preeclampsia and HELLP sindrome using high doses of antithrombin III. Int Care Med 2000,26(suppl 3):s321(417).

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Giarratano, A., Raineri, M., Di Giacinto, C. et al. The role of natural coagulation inhibitors in correlation with clinic scores in critical patients with obstetric diseases. Crit Care 6 (Suppl 1), P125 (2002).

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