Preeclampsia: Haemostatic status and the short-term effects of methyldopa and isradipine therapy

Kyi Htay Yin, Stephen C.L. Koh, Peter Malcus, S. SvenMontan, Arjit Biswas, S. Arulkumaran, Shan S. Ratnam

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To determine the haemostatic status in preeclampsia and to investigate the effects of short-term use of anti-hypertensive drugs, methyldopa and isradipine. Methods: Thirty preeclamptic (PE) women admitted to the hospital for observation and treatment were randomized to receive either methyldopa or isradipine for 2 weeks. Their blood pressure were monitored for 24 h before treatment and again at 7 days and 14 days after treatment using the programmable automated ambulatory blood pressure (ABP) monitoring system. Blood sampling was performed before commencement of anti-hypertensive treatment, 7 days and 14 days after treatment and the haemostatic parameters studied was compared before treatment with normal pregnancy and the effects of anti-hypertensive treatment. Nineteen normal pregnant subjects with a total of 30 blood sampling at various gestation and good pregnancy outcome served as controls. The following haemostatic parameters were determined; thrombelastography, fibrinogen, antithrombin III (ATIII), thrombin-antithrombin (TAT)-complex, β-thromboglobulin (β-TG), plasminogen activators (t-PA, u-PA), plasminogen activator inhibitors (PAI-1, PAI-2), and plasminogen. Results: Significant lowering of blood pressure was evident at Days 7 and 14 of therapy with either methyldopa or isradipine. Increased mean plasma fibrinogen and decreased ATIII levels were seen in preeclampsia together with decreased u-PA and t-PA activity levels in contrast to increased t-PA antigen and β-TG. No significant differences were seen for TAT-complex, PAI-1, plasminogen and D-dimer levels although their mean levels were higher than observed in non-pregnant subjects except for PAI-2, the level was significantly reduced when compared with normal pregnancy. Two-way analysis of variance showed no significant alteration on all haemostatic parameters studied in preeclamptic women receiving either methyldopa or isradipine after 7 and 14 days of therapy. Conclusion: Enhance activation of coagulation was observed together with raised fibrinolysis in normal pregnancy and PE. However, in PE a further reduction in ATIII, u-PA and PAI-2 with increased fibrinogen and platelet activation could lead to an imbalance in the coagulation/fibrinolysis equilibrium which favours fibrin deposition. All these changes seen in PE including the coagulation kinetics were not altered by the short-term effects of methyldopa and isradipine even though significantly lowered blood pressure were observed during therapy.

Original languageEnglish
Pages (from-to)231-238
Number of pages8
JournalJournal of Obstetrics and Gynaecology Research
Volume24
Issue number3
Publication statusPublished - Jun 1998

Keywords

  • Coagulation and fibrinolysis
  • Isradipine
  • Methyldopa
  • Preeclampsia

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