Increased thromboxane production in women with a history of venous thromboembolic event: effect of heparins.
We investigated the production of prostacyclin and thromboxane in pregnant women with a previous venous thromboembolic event before, during and after the use of unfractionated heparin and low molecular weight heparin (dalteparin). Twenty women were studied before starting heparin prophylaxis (before 20 weeks of gestation), during heparin prophylaxis (at 30 weeks of gestation) and after heparin prophylaxis (16 weeks after delivery). Ten pregnant women with no history of thromboembolism were studied as the control group. Urinary output of the stable metabolite of prostacyclin (2,3-dinor-6-keto-PGF1alpha) and that of thromboxane A2 (2,3-dinor-TxB2), as well as a number of markers of thrombophilia were measured and expressed as mean (+/-SEM). Women with a history of thromboembolism were characterized by normal prostacyclin production but elevated thromboxane production (44.0 +/- 4.1 versus 19.0 +/- 3.6 ng/mmol creatinine, P < 0.001) at 12 weeks of pregnancy. Heparin prophylaxis (regardless of the type) had abolished elevated thromboxane concentrations at 30 weeks of gestation. Four months after delivery, thromboxane dominance had returned (25.2 +/- 3.5 versus 13.6 +/- 2.1 ng/mmol creatinine, P < 0.01). The presence of hereditary thrombophilia (9/20) was not associated with any changes in prostanoid concentrations. Thus, women with a history of venous thromboembolic events have thromboxane dominance during and after pregnancy, but this dominance can be eliminated through the use of heparins.
Kaaja
R
R
Department of Obstetrics and Gynaecology, Helsinki University Hospital, Helsinki, Finland. rissto.kaaja@huch.fi
Pettilä
V
V
Leinonen
P
P
Ylikorkala
O
O
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives* / Q000652:urine; D000328:Adult; D000704:Analysis of Variance; D000925:Anticoagulants / Q000627:therapeutic use*; D015992:Body Mass Index; D016022:Case-Control Studies; D017985:Dalteparin / Q000627:therapeutic use; D005165:Factor V / Q000032:analysis; D005260:Female; D006493:Heparin / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D049590:Postpartum Period / Q000378:metabolism; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000378:metabolism* / Q000517:prevention & control; D011256:Pregnancy Outcome; D018709:Statistics, Nonparametric; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D013931:Thromboxanes / Q000096:biosynthesis* / Q000652:urine; D020246:Venous Thrombosis / Q000378:metabolism* / Q000517:prevention & control
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D013931:Thromboxanes; C095381:factor V Leiden; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C028965:2,3-dinor-thromboxane B2; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; D005165:Factor V; D006493:Heparin; D017985:Dalteparin