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Treatment with AT III Concentrate in Pre-Eclampsia

  • D. M. Paternoster
  • D. Snijders
  • M. Micaglio
  • J. De Toffoli
  • L. Becagli
  • A. Ambrosini
  • W. Moroder
Conference paper

Abstract

In pre-eclampsia, the administration of AT III concentrate may play an important role, because the available remedies for pre-eclampsia affect the symptoms permitting only temporary control of hypertension, vasoconstriction and reduced volemia. Therapeutic approaches to resolve the disease should be aimed at the endothelium, which plays a fundamental role in the pathogenesis of pre-eclampsia. AT III with its anticoagulant and, above all, anti-inflammatory activity, has a protective action on the endothelial cells, interacting and blocking the vicious circle of vasoconstriction which leads to multiple organ failure.

On the basis of the clinical approaches, we have carried out two trials on AT III therapy: the first was a prospective case trial, evaluating the modifications of clotting and clinical parameters before and immediately after delivery, in patients with pre-eclampsia treated or untreated with AT III concentrate. We analysed 41 patients with pre-eclampsia treated with AT III concentrate and 29 patients with pre-eclampsia untreated with AT III concentrate. Patients with AT III activity = 75% were treated with AT III concentrate = (100%-basal value) × kg (body weight).

The second trial, a pilot trial, was conducted to verify the therapeutic efficacy on clinical parameters of the administration of AT III concentrate in pregnancy complicated by intermediate pre-eclampsia. Seven patients with pre-eclampsia who were hospitalised between 24 and 34 weeks of gestation were included. Each patient received intravenous AT III concentrate (3000 U/l) once a day for 5 days. The main endpoints were the duration of pregnancy, gestational age at delivery, improvement of the proteinuria and hypertension, improvement of coagulation abnormalities, improvement of intra- and post-partum complications.

According to our results in the first trial, pre-partum administration of AT III concentrate avoids severe intra- and post-partum complications. Furthermore, the therapy with AT III shows:
  • a protective effect on endothelium,

  • a significant increase of AT III after delivery and

  • significant reduction of complications, intra-as well as post-partum.

In the second trial, with regard to biochemical parameters, we found that fibrinolysis (D-dimer) and plasma fibronectin levels (marker of endothelial damage) stabilized and that there was a reduction of uricemia. AT III treatment prolonged the pregnancy by approximately 6.5 days. Also, this treatment improved maternal clinical parameters (proteinuria and hypertension). According to our results, administration of AT III concentrate avoids severe intra- and postpartum complications, although this is not the only therapeutic advantage of AT III over traditional treatment, for example like fresh frozen plasma infusion. This therapy often yields a slight and unsatisfactory increase in AT III activity, with the risk of volume overload and pulmonary oedema.

The endothelium plays an important role in the pathogenesis of pre-eclampsia. It is target for the experimental therapy of this disease. The AT III is correlated not only to anticoagulative effects, but also to the anti-inflammatory action and to the development of integrate protective action of the endothelial cells. It blocks the vicious circle of the vasoconstriction, which can take to multiple organ failure (MOF). Time and doses are fundamental in order to achieve the prevention of MOF. Moreover, since at early gestational ages it allows better fetal development, this therapy may reduce the risks of pre-term delivery complication like RDS and intraventricular hemorrhagia. The treatment of preeclampsia with AT III concentrate improved clinical signs, corrected the hypercoagulability and improved fetal status and perinatal outcome.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • D. M. Paternoster
  • D. Snijders
  • M. Micaglio
  • J. De Toffoli
  • L. Becagli
  • A. Ambrosini
  • W. Moroder

There are no affiliations available

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