Indications for heparin during pregnancy are expanding. Heparin-induced thrombocytopenia caused by heparin-platelet factor 4 antibodies (HPF4-As), however, remains a serious concern. While up to 50% of cardiovascular surgical patients develop HPF4-As while receiving heparin, the rate of seroconversion is lower in medical patients, suggesting an impact of the patient population on the underlying immune response. We therefore prospectively analyzed HPF4-As development in 31 pregnant women (32 +/- 5 years) receiving thromboprophylaxis with dalteparin for more than 4 weeks. According to their individual risk, study individuals were stratified to receive subcutaneous dosages of 2500-10 000 IU/day. The median treatment duration was 33 weeks (6-45 weeks). HPF4-As isotypes (IgG, IgM, IgA) were measured at baseline, on days 6-9, days 19-21 and subsequently every month until the end of therapy. Platelet counts and clinical examinations were carried out routinely or earlier if indicated. Throughout the study no thromboembolic event occurred, and in none of the patients was HPF4-As seroconversion noted. A prolonged drop in platelets to less than 50% from baseline was observed in one case (3%) after 35 weeks of treatment, which spontaneously resolved after child delivery. These findings suggest that long-term thromboprophylaxis with low-molecular-weight heparin is associated with a low rate of HPF4-As seroconversion in pregnancy.
[Show abstract][Hide abstract] ABSTRACT: Heparin has been used as an anticoagulant for decades. Recently, attention has been drawn to the non-anticoagulant activities of heparin. Experimentally and clinically those non-anticoagulant properties of heparin inhibit inflammation and metastatic spread of tumor cells. On the molecular level, heparin inhibits the function, expression and/or synthesis of adhesion molecules, cytokines, angiogenic factors and complement. However, despite a similar anticoagulant activity, those non-anticoagulant effects of heparin differ greatly among the different heparin preparations. The same holds true for the most common adverse events of heparin treatment. The incidence of immune mediated heparin-induced thrombocytopenia and cutaneous hypersensitivity responses is greatly, but not exclusively, influenced by the heparin preparation used. As the structure-function relationship of the anti-inflammatory and anti-metastatic effects of heparins are understood in more detail, and as the risk profile of different heparin preparations regarding the induction of adverse events have been identified, we propose to use the different heparin preparations according to the individual needs of each patient.
Current Drug Discovery Technologies 12/2009; 6(4):281-9. DOI:10.2174/157016309789869001
[Show abstract][Hide abstract] ABSTRACT: Pregnancy and the postpartum period are associated with an increased risk of venous thromboembolism (VTE), which complicates 1 to 2 of 1,000 pregnancies and represents a leading cause of mortality during pregnancy in developed countries. Strong evidence for the management of pregnancy-related VTE is missing, mostly because pregnant women have been excluded from all major trials investigating different diagnostic tools and treatment regimens. Nevertheless, proper evaluation of the involved risk factors is mandatory to reduce the incidence of pregnancy-related VTE and improve outcomes. Low-molecular-weight heparins are considered as a first-line option in the management of pregnancy-related VTE. With regard to future research, there is a need for methodologically strong studies in pregnant women, especially with respect to risk stratification, optimal heparin doses, usefulness of anti-FXa levels and their correlation with clinical outcomes, and correct management of anticoagulation during delivery.
Seminars in Thrombosis and Hemostasis 04/2013; 39(5). DOI:10.1055/s-0033-1343893 · 3.88 Impact Factor
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