Preeclampsia: haemostatic status and the short-term effects of methyldopa and isradipine therapy.
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 effect 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, beta-thromboglobulin (beta-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 beta-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 subject 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.


CONCLUSIONS
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.
Department of Obstetrics and Gynaecology, National University Hospital, Singapore.
K H
KH
Yin
S C
SC
Koh
P
P
Malcus
S
S
SvenMontan
A
A
Biswas
S
S
Arulkumaran
S S
SS
Ratnam
D000959:Antihypertensive Agents / Q000627:therapeutic use*; D005260:Female; D006487:Hemostasis; D006801:Humans; D017275:Isradipine / Q000627:therapeutic use*; D008750:Methyldopa / Q000627:therapeutic use*; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000503:physiopathology*; D011247:Pregnancy; D013997:Time Factors; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D008750:Methyldopa; D017275:Isradipine