title: A prospective analysis of heparin-platelet factor 4 antibodies in pregnant women treated with the low-molecular-weight heparin, dalteparin.
abstract: 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.
authors.affiliation: DRK Kliniken Berlin Köpenick, Department of Internal Medicine, Vascular Center Berlin Köpenick, Germany. fgerdsen@hotmail.com
authors.forename: Frank
authors.initials: F
authors.lastname: Gerdsen
authors.forename: Beate
authors.initials: B
authors.lastname: Luxembourg
authors.forename: Florian
authors.initials: F
authors.lastname: Langer
authors.forename: Rupert
authors.initials: R
authors.lastname: Bauersachs
authors.forename: Edelgard
authors.initials: E
authors.lastname: Lindhoff-Last
mesh_terms: D000328:Adult; D000918:Antibody Specificity; D016824:Antigens, Human Platelet / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D017985:Dalteparin / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D010976:Platelet Count; D010978:Platelet Factor 4 / Q000276:immunology*; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control; D011446:Prospective Studies; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology*; D019851:Thrombophilia / Q000209:etiology; D013927:Thrombosis / Q000517:prevention & control
chemical_list: C057260:4a alloantigen, human; D016824:Antigens, Human Platelet; D001323:Autoantibodies; D001324:Autoantigens; D005343:Fibrinolytic Agents; D010978:Platelet Factor 4; D006493:Heparin; D017985:Dalteparin