Evaluation of an optimal dose of low-molecular-weight heparin for thromboprophylaxis in pregnant women at risk of thrombosis using coagulation activation markers.
There is no consensus on the dose of low-molecular-weight (LMW) heparin for thromboprophylaxis in pregnant women at increased risk of thrombosis. Based upon monitoring with anti-factor Xa activity, the studies showed conflicting results suggesting either fixed dosages throughout the pregnancy or dosages adapted to the gestational age. We tested whether monitoring thromboprophylaxis with D-dimers and thrombin-antithrombin complexes (TAT) would provide additional information on the optimal dose of LMW heparin. Women (165 women and 202 pregnancies) with hereditary or acquired thrombophilia or a history of thrombosis were considered to receive prophylactic LMW heparin therapy. All women received initially 5,000 IU/day of dalteparin s.c. All further dosages were determined solely on the basis of TAT and/or D-dimer values which were determined every 2-3 weeks. As soon as one of these values increased above the normal range, the dose of LMW heparin was adjusted. In 84.6% of all pregnancies, TAT and/or D-dimer values increased above the normal range once or more during the pregnancy. Consequently, the dose of LMW heparin had to be adjusted at least once over the course of the pregnancy. The mean daily dose of LMW heparin increased from 5,000 to 11,200 U between the 6th and 40th week of gestation. Adverse effects included one major bleeding and six local complications, but no thromboembolic event. In conclusion, increasing doses of LMW heparin are needed to keep TAT and D-dimers within the normal range during pregnancy. Hence, to suppress thrombin generation, apparently, the dosage of LMW heparin should be adjusted to the gestational age rather than using fixed doses throughout the pregnancy. However, it remains to be further established whether elevated TAT and D-dimers truly reflect a prothrombotic state during pregnancy.
Bombeli
T
T
Coagulation Laboratory, Division of Hematology, Department of Internal Medicine, University Hospital of Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland. thomas.bombeli@dim.usz.ch
Raddatz Mueller
P
P
Fehr
J
J
D000293:Adolescent; D000328:Adult; D000933:Antifibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000990:Antithrombin III; D015415:Biomarkers / Q000097:blood; D017985:Dalteparin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005865:Gestational Age; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D010447:Peptide Hydrolases / Q000097:blood; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000188:drug therapy / Q000517:prevention & control; D012307:Risk Factors; D019851:Thrombophilia / Q000097:blood / Q000188:drug therapy; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control*
D000933:Antifibrinolytic Agents; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D006495:Heparin, Low-Molecular-Weight; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D000990:Antithrombin III; D010447:Peptide Hydrolases; D017985:Dalteparin