Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study

Abstract

Thrombophilia is associated with increased risks of VTE in women taking oral oestrogen preparations and patients undergoing major elective orthopaedic surgery, and of VTE and adverse pregnancy outcomes in women with thrombophilia during pregnancy. There is considerable difference in the magnitude of the risks among different patient groups with different thrombophilic defects. In women who are on combined oral contraceptives, the OR of VTE among those who are carriers of the FVL mutation was 15.62 (95% confidence interval 8.66 to 28.15). However, in view of the prevalence of thrombophilia and the low prevalence of VTE in non-users of combined oral contraceptives, the absolute risk remains low. Significant risks for VTE and adverse pregnancy outcomes have been established with individual thrombophilic defects. Thrombophilic defects including FVL, high plasma factor VIIIc levels and prothrombin G20210A are associated with the occurrence of postoperative VTE in elective hip or knee replacement therapy. These associations are observed in patients who were given preoperative thromboprophylaxis and are, therefore, of clinical significance. Universal thrombophilia screening in women prior to prescribing oral oestrogen preparations, in women during pregnancy and in patients undergoing major orthopaedic surgery is not supported by current evidence. The findings from this study show that selective screening based on prior VTE history is more cost-effective than universal screening. Large prospective studies should be undertaken to refine the risks and establish the associations of thrombophilias with VTE among hormone users and in patients undergoing orthopaedic surgery. The relative value of a thrombophilia screening programme to other healthcare programmes needs to be established.

Screening for thrombophilia and antithrombotic prophylaxis in pregnancy: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET)

“…Indeed, the absolute risk of VTE in a woman carrier of FVL mutation is about 0.8% and the absolute risk of obstetric complications is even lower [14]. These conclusions are also supported by a systematic review [13] in which a cost-effectiveness analysis was made and by an economic study [34] both of which did not show a good costeffectiveness ratio of universal screening for thrombophilia. The former two studies refer to the British National Health Service system.…”

“…Several studies have demonstrated an association between thrombophilia and obstetric complications, such as RPL, unexplained IUFD, preeclampsia, HELLP syndrome, FGR and abruptio placentae [12,13,16,20]. A possible association between thrombophilia and a first pregnancy loss has also been shown [49].…”

“…Pregnant women carriers of thrombophilia have an increased risk of VTE by 3 to 52 fold depending on the type of thrombophilic defect [4,[8][9][10][11]. Thrombophilia is also associated with pregnancy complications and the strength of this association is controversial depending on the type of obstetric complication and of specific thrombophilia [12,13].…”

“…Tests to be included in the screening for thrombophilia, if testing is indicated Several studies, including systematic reviews and meta-analyses, evaluated the association between thrombophilia and VTE or obstetric complications [12][13][14][15][16][17][18][19][20][21][22]. The meta-analyses of heterogenous case-control studies suggest an increased prevalence in women with pregnancy complications of the following thrombophilic defects: antithrombin deficiency, protein C deficiency, protein S deficiency, factor V Leiden mutation (FVL), prothrombin 20210A mutation (PTM), mild hyperhomocysteinemia and antiphospholipid antibodies (APLA).…”

Genetic Polymorphisms in Venous Thrombosis and Pulmonary Embolism After Total Hip Arthroplasty: A Pilot Study

“…For other genetic markers, such an association is suspected and discussed controversially, eg, methylenetetrahydrofolate reductase (MTHFR) C677T and/or A1298C and plasminogen activator inhibitor 1 (PAI-1) 4G/5G polymorphisms [1-3, 10, 11, 16, 22, 30, 32, 34, 37, 44]. Results of former studies are conflicting regarding whether the single or combined presence of such genetic mutations may further increase the already very high risk for DVT after major orthopaedic surgery, justifying costly preoperative screening and additional antithrombotic prophylactic measures in these patients [5,6,8,18,20,21,23,29,31,36,[40][41][42][43]. One reason for the conflicting results may be found in the different clinical end points set in the studies varying among venographically diagnosed DVT, clinically symptomatic DVT with or without PE, or symptomatic PE only.…”