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Effects of antithrombin III (ATIII) treatment (high dose) in severe pre-eclampsia and HELLP syndrome with alterations of coagulation inhibitors and inflammatory markers: a preliminary report

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Objective

Several investigations and our recent experience indicate that the intravascular inflammatory response and the clotting alterations registered during severe pre-eclampsia and HELLP syndrome are not an epiphenomenon but the cause of the clinical syndrome. The aims of this study were to investigate the effects of the ATIII substitutive treatment on cytokine plasma concentrations, assumed as a marker of endothelial damage and of the associated systemic inflammatory response. A secondary objective was to correlate the ATIII treatment with the evolution of both single or multi-organ dysfunction syndrome (MODS).

Materials and methods

The study involved four patients with severe pre-eclampsia and three HELLP syndrome patients. Diagnostic criteria for severe pre-eclampsia were those published by the American College of Obstetricians and Gynecologists (diastolic blood pressure >110 mmHg and proteinuria ≥ 0.5 g/l). Diagnostic criteria for HELLP syndrome required, in association with hypertension and proteinuria, thrombocytopenia (<150000 cells/μl), evidence of hepatic dysfunction (aspartate aminotransferase [AST] and alanine aminotranserase [ALT] levels >40 IU/L with lactate dehydrogenase [LDH] level of >600 IU/l) and evidence of hemolysis (increased LDH and anemia). Plasma levels of tumor necrosis factor (TNFα and interleukins [IL1β and IL6]) were measured by enzyme-linked immunoadsorbent assay (ELISA). Plasma concentrations of Antithrombin III (ATIII) and Protein C (P-C) were measured by a chromogenic assay. ATIII was administered after the first sampling (admission) by a loading dose of 3.000 IU in bolus infusion and a maintenance dose of 1500 U/12 h over 4 days. Results were compared using the Mann-Whitney test. Maternal parameters and clinical data were compared using unpaired Student t-test.

Results and discussion

Clinical data are listed in Table 1 and results are shown in Table 2. These results demonstrate significant changes in fibronectin and ATIII concentrations between levels at admission compared with levels after ATIII treatment. It is very interesting to register a decrease in blood levels of cytokines and a reduced pro-inflammatory activity. The pro-inflammatory activity was increased in women with severe pre-eclampsia and HELLP syndrome patients and this result could also be explained by specific effects which are independent from the coagulation cascade (anti-inflammatory actions).

Conclusions

The preliminary results of this study confirm our hypothesis as well as the utility of marker monitoring and substitutive treatment. We believe that it is necessary to develop a large study (as a phase III trial) to confirm our hypothesis and to achieve other significant results.

Table 1 Clinical data
Table 2 Markers and cytokines levels

References

  1. 1.

    Redman CWG, et al.: . Am J Obstet Gynecol 1999, 180: 499.

  2. 2.

    Okajima K, et al.: . Thromb Res 1998, 24: 27-32.

  3. 3.

    Souter , et al.: . Int Care Med 1999., 19:

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Keywords

  • Proteinuria
  • HELLP Syndrome
  • Cytokine Plasma
  • Bolus Infusion
  • Substitutive Treatment