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Antithrombin Concentrate May Effectively Treat Severe Preeclampsia

Antithrombin (AT) concentrate as treatment for preeclampsia improved clinical signs, corrected hypercoagulability, and improved foetal status, according to a Japanese study.

Preeclampsia is a pregnancy-specific syndrome of unknown aetiology associated with vasospasms, pathological vascular lesions, and activation of the coagulation system. The main clinical findings are elevated blood pressure combined with proteinuria, which can lead to foetal and maternal complications.

The level of AT, the major inhibitor that forms irreversible complexes with various clotting factors, appears to be correlated with maternal and foetal morbidity in preeclampsia. Furthermore, evidence suggests that in preeclampsia, acquired AT deficiency is secondary to a hypercoagulable state and/or associated with impaired hepatic and/or renal function.

Takao Kobayashi, MD, PhD, of the Shinshu University of Health Sciences, Matsumoto City, Nagano Prefecture, Japan, and colleagues performed prospective feasibility study designed to determine whether AT therapy benefits clinical signs and foetal well being in cases of severe preeclampsia.

A total of 29 preeclamptic patients, at 24 to 36 weeks of gestation, were randomised to receive either intravenous AT concentrate 1500 U/day for 7 days with heparin 5000 U/day (AT group), or heparin 5000 U/day only (control group). No statistically significant differences existed in the clinical profiles between the two groups.

Study endpoints included gestosis index (GI) improvement, biophysical profile score (BPS) improvement, pregnancy duration, birth weight, gestational age at delivery, coagulation abnormality improvement, and neonatal death due to preeclampsia or stillbirth.

Response to treatment was assessed based on the difference between pre- and post-treatment values. Results showed that compared with the control group, the AT group showed a significantly better response in both GI (P = .046) and BPS (P = .022). Additionally, the AT antigen levels and AT activity both increased significantly (P < .001, each), but showed no significant changes in the control group.

While no significant changes occurred between groups for individual coagulation parameters, the coagulation index decreased significantly (P = .008) in the AT group, with no significant change in the control group.

Few drug-related adverse events occurred in either group, and no significant difference was found between the AT group and control group.

Additionally, significant differences were not observed between the 2 groups in pregnancy and neonatal outcome. One neonatal death, which was attributed to extreme prematurity resulting from severe preeclampsia, occurred in the control group.

"These results support the hypothesis that the pathogenesis of preeclampsia involves hypercoagulability, especially thrombin-induced endothelial cell dysfunction," the researchers concluded.

Semin Thromb Hemost 2003 Dec;29:6:645-52. "Treatment of severe preeclampsia with antithrombin concentrate: results of a prospective feasibility study"

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