Guideline sources The following summarized guidelines for the evaluation and management of prothrombin G20210A are prepared by our editorial team based on guidelines from the American Society of Hematology (ASH 2023), the British Society for Haematology (BSH 2022), the American Heart Association (AHA/ASA 2021; 2011), the European Society for Vascular Surgery (ESVS 2021; 2017), the American Association for the Study of Liver Diseases (AASLD 2021), the American College of Gastroenterology (ACG 2020), the European Stroke Organisation (ESO 2017), the European Society for Trauma and Emergency Surgery (ESTES 2016), the European Association for the Study of the Liver (EASL 2016), the Anticoagulation Forum (AF 2016), the Society for Vascular Surgery (SVS 2014), the Society of Obstetricians and Gynaecologists of Canada (SOGC 2014), the Central European Vascular Forum (CEVF/IUA/IUP 2012), and the British Committee for Standards In Haematology (BCSH 2012). 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Calculator Calculator Calculat Caprini Score for venous thromb Geneva Risk Score for venous th IMPROV Guidelines 1. Screening and diagnosis https://web.pathway.md/diseases/recMjDXmYpFg7NRNJ 1/5 6/29/23, 11:33 PM Prothrombin G20210A Pathway Indications for screening, general principles: As per BSH 2022 guidelines, do not obtain routine thrombophilia testing in first-degree relatives of patients with a history of VTE. D As per AF 2016 guidelines, do not obtain testing for thrombophilia in asymptomatic family members of patients with VTE or hereditary thrombophilia, including when contemplating pregnancy or estrogen therapy. D Indications for screening (minor provoking risk factors): avoid obtaining testing for prothrombin G20210A to guide thromboprophylaxis in patients with a family history of prothrombin G20210A (with or without VTE) and having a minor provoking risk factor for VTE, such as immobility or minor injury, illness, or infection. D Indications for screening (before combined oral contraceptives): do not obtain thrombophilia testing to guide the use of combined oral contraceptives in females in the general population. D Show 2 more Indications for screening (before hormonal therapy): avoid obtaining thrombophilia testing to guide the use of hormone-replacement therapy in patients from the general population. D Show 2 more Indications for screening (pregnancy): consider obtaining testing for the known familial thrombophilia in females with a family history of VTE and a known combination of factor V Leiden and prothrombin G20210A in the family. Consider administering antepartum thromboprophylaxis in patients with the same familial thrombophilia. C Show 2 more Indications for testing, first episode of thrombosis: As per BSH 2022 guidelines: Do not obtain genetic testing for prothrombin G20210A mutation to predict a first episode of venous thrombosis. D Do not obtain routine testing for heritable thrombophilic traits after a venous thrombotic event to guide management decisions. D As per AF 2016 guidelines, do not obtain thrombophilia testing following an episode of provoked or unprovoked VTE. D Show 2 more Indications for testing (deep vein thrombosis): do not obtain thrombophilia testing in patients with provoked deep vein thrombosis. D Show 2 more Indications for testing, cerebral vein thrombosis: As per ESO 2017 guidelines: Avoid obtaining thrombophilia testing in patients with cerebral venous thrombosis to reduce death, improve functional outcomes, or prevent recurrent venous thrombosis. D Consider obtaining thrombophilia testing in patients with a high pre-test probability of carrying severe thrombophilia (a personal and/or family history of venous thrombosis, young age at cerebral venous thrombosis, cerebral venous thrombosis without a transient or permanent risk factor) to prevent recurrent venous thrombotic events. E https://web.pathway.md/diseases/recMjDXmYpFg7NRNJ 2/5 6/29/23, 11:33 PM Prothrombin G20210A Pathway As per AHA/ASA 2011 guidelines: Consider obtaining testing for prothrombotic conditions, including prothrombin G20210A mutation, in patients with cerebral venous thrombosis. C Consider obtaining thrombophilia testing to identify underlying coagulation defects in pediatric patients with cerebral venous thrombosis. C Indications for testing, mesenteric vein thrombosis: As per ESVS 2017 guidelines, consider obtaining genetic testing for thrombophilia in patients with mesenteric vein thrombosis. C As per ESTES 2016 guidelines, obtain testing for thrombophilia in patients with mesenteric vein thrombosis. B Indications for testing (portal vein thrombosis): obtain testing for inherited thrombophilias, including prothrombin G20210A mutation, in patients with portal vein thrombosis. A Indications for testing, Budd-Chiari syndrome: As per AASLD 2021 guidelines, obtain a full thrombophilia workup at the time of hepatic vein thrombosis/Budd-Chiari syndrome diagnosis. Evaluate additional factors even when one causal factor is identified, and consult with a hematologist. E As per EASL 2016 guidelines, obtain testing for inherited thrombophilias, including prothrombin G20210A mutation, in patients with Budd-Chari syndrome. A Indications for testing, superficial vein thrombosis: As per BCSH 2012 guidelines, do not obtain routine testing for underlying thrombophilia in patients with superficial venous thrombosis. D As per CEVF/IUP/IUA 2012 guidelines, obtain testing for thrombophilia in patients with spontaneous nonvaricose superficial venous thrombosis or recurrent varicose superficial venous thrombosis. E Indications for testing (unusual site venous thrombosis): do not obtain testing for inherited thrombophilias in patients with thrombosis at an unusual site. D Indications for testing (recurrent thrombosis): consider obtaining thrombophilia testing in patients with a history of recurrent venous thrombosis and chronic recurrent venous leg ulcers. C Indications for testing (arterial thrombosis): do not obtain testing for inherited thrombophilias in patients with arterial thrombosis D or acute ischemic stroke, D including neonatal stroke. D 2. Medical management Management of venous thromboembolism (portal vein thrombosis): consider initiating anticoagulation in patients with chronic portal vein thrombosis with evidence of inherited thrombophilia. Consider continuing anticoagulation indefinitely in patients with thrombophilia. C Management of venous thromboembolism, mesenteric vein thrombosis: https://web.pathway.md/diseases/recMjDXmYpFg7NRNJ 3/5 6/29/23, 11:33 PM Prothrombin G20210A Pathway As per ACG 2020 guidelines, initiate indefinite anticoagulation in patients with mesenteric vein thrombosis and thrombophilia. B As per ESVS 2017 guidelines, initiate lifelong anticoagulation in patients with mesenteric vein thrombosis with proven thrombophilia. B As per ESTES 2016 guidelines, initiate anticoagulation for a minimum of 6 months in patients with mesenteric vein thrombosis and thrombophilia. B Management of venous thromboembolism (cerebral vein thrombosis): consider initiating indefinite anticoagulation with a target INR of 2.0-3.0 in patients with cerebral venous thrombosis with severe thrombophilia, including homozygous prothrombin G20210A mutation. C Management of acute ischemic stroke: consider initiating antiplatelet therapy to reduce the risk of recurrent stroke or TIA in patients with ischemic stroke or TIA of unknown source despite thorough diagnostic evaluation, no other thrombotic history, and having prothrombin 20210A mutation. C 3. Specific circumstances Pregnant patients: Initiate prophylactic dose thromboprophylaxis during pregnancy in asymptomatic patients with homozygous prothrombin gene mutation 20210A. B Administer pharmacologic thromboprophylaxis postpartum in patients with prothrombin gene mutation 20210A. B Clinical findings Past medical history Past obstetric history Acute ischemic stroke IUGR Budd-chiari syndrome Miscarriage Cerebral venous thrombosis Placental abruption DVT Preeclampsia FVL mutation Stillbirth Mesenteric vein thrombosis Genetic testing Portal vein thrombosis Splanchnic vein thrombosis F2 gene mutation Superficial vein thrombosis Family history VTE References https://web.pathway.md/diseases/recMjDXmYpFg7NRNJ 4/5 6/29/23, 11:33 PM Prothrombin G20210A Pathway 1. 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