Regular ArticleThe association of antiphospholipid antibodies with pregnancy-related first time venous thrombosis – a population-based case-control study
Introduction
Pregnancy is associated with progressive activation of coagulation and inhibition of fibrinolysis [1], [2]. These physiologic changes reduce the risk of bleeding during delivery, but increase the risk of venous thrombosis (VT), which is one of the leading causes of maternal morbidity and death in developed countries [3], [4], [5], [6]. Both congenital and acquired thrombophilia increase the risk of VT [7], [8]. Antiphospholipid antibodies (APAs) comprise a heterogeneous group of autoantibodies, and are considered to be among the most commonly acquired thrombophilias [9], [10]. The antiphospholipid syndrome is defined by venous or arterial thrombosis and/or specific pregnancy complications in patients with persistently positive tests for APAs [11]. The laboratory criteria include repeated positive tests for lupus anticoagulants (LA), anticardiolipin (aCL) antibodies, and/or anti-ß2 glycoprotein-1 (anti-ß2GP1) antibodies [11].
The major autoantigen for APAs is ß2GP1, which mediates the binding of APAs to target cells, such as endothelial cells, platelets, monocytes, and trophoblasts. APAs are thought to interfere with the procoagulant, anticoagulant, and fibrinolytic systems, to produce a prothrombotic environment and trigger thrombosis [12].
In patients with systemic lupus erythematosus and other autoimmune diseases APAs are established risk factors for VT [13], [14]. However, the role of APAs in the etiology of VT among healthy individuals and especially among healthy pregnant women has not yet been settled. Comparison of results across studies on the relationship between APAs and risk of VT is difficult because of different enrollment criteria, inconsistency in which type of APAs that are examined, different cut-offs for test positivity, and lack of assay standardization. The association of aCL antibodies, and especially the IgM isotype, to VT is uncertain, and there is an ongoing debate whether these antibodies should be included in the definition of APS [15], [16], [17], [18].
The aim of the present case-control study was to investigate the association of different APAs, either alone or in combination, to pregnancy-related first time VT, when considering the contribution of the factor V Leiden and/or the prothrombin gene G20210A polymorphisms (prothrombin polymorphism). Based on circumstantial evidence so far, our main hypothesis was that cases with a history of pregnancy-related VT had higher prevalence of APAs as compared with controls.
Section snippets
Selection of cases and controls
Women, who had completed 23 weeks of pregnancy, with a diagnosis of VT in pregnancy or within three months postpartum were identified at 18 hospitals by searching selected ICD-9 or -10 codes in the Norwegian Patient Registry and the Medical Birth Registry of Norway over the study period 1990-2003 [19]. Altogether 1231 women were identified with a diagnosis of VT in 1396 pregnancies. Diagnosis of deep vein thrombosis (DVT) and/or pulmonary embolism (PE) was validated through review of medical
Results
In total, 531 cases and 1092 controls were invited for study participation (Fig. 1). 313 cases and 353 controls agreed to participate, whereas 218 cases (41%) and 739 controls (67%) did not meet for further investigation. Table 1 displays the distribution of possible risk factors at time of index pregnancy among cases and controls, who agreed or did not agree to participate in the study. The distribution of possible risk factors for pregnancy associated VT were equally distribuated for most
Discussion
The main finding of the present study was that the prevalence of APAs assayed 3-16 years after a pregnancy-related first time VT was not significantly different from the prevalence in women without a history of VT, but nine cases and none of the controls were positive for at least two APAs.
Searching the Internet by Ovid Medline, Ovid Embase and Medline-in process, using the key words “pregnancy”, “antiphospholipid antibodies”, and “venous thrombosis/venous thromboembolism”, we found two studies
Statement of conflict of interest
The authors have no conflicts-of-interest.
Acknowledgements
The study was financially supported by grants from the Norwegian South-Eastern Health Authority, the Research Council of Norway (grant no 160805-V50), and the Oslo University Hospital Ullevål.
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2012, Thrombosis ResearchCitation Excerpt :The blood was analysed for LA, aCL, and anti-β2-glycoprotein 1 (anti-β2GP1) antibodies. The assays were performed at the Hematologic Research Laboratory, Department of Hematology, Oslo University Hospital Ullevål (formerly Ullevål University Hospital) as described earlier [18]. In short, the presence of LA was identified using validated in-house lupus ratio (LR) tests, which are automated, quantitative, integrated tests for LA [20,21].
Pregnancy-related venous thromboembolism: Risk and the effect of thromboprophylaxis
2012, Thrombosis ResearchCitation Excerpt :Data on antiphospholipid antibody (APLA) syndrome (APS) as risk factor for VTE during pregnancy are inadequate to allow conclusions, both for women with previous venous thrombosis, as well as for women without (i.e. APS with either arterial thrombosis or obstetric complications). One case–control study showed that the presence of any APLA (lupus anticoagulant, anti-cardiolipin or anti-beta2-glycoprotein-I antibodies) increased the risk of pregnancy-related VTE by 1.4 fold (95% CI 0.8-2.5) [47], but the validity of the results is limited by the fact that the presence of APLA was determined in a single sample, taken several years after the pregnancy related event. When thromboprophylaxis is indicated for pregnant women, a heparin should be considered as first choice drug, because it does not cross the placenta.