Management issues in other thrombophilia Ng Heng Joo Department of Haematology Singapore General Hospital

Thrombophilias A disorder of the hemopoietic system in which there is an increased tendency for thrombosis Inherited – Protein C – Protein S – Antithrombin – Factor V Leiden and prothrombin gene mutation Acquired – Malignancy – Antiphospholipid syndrome Natural Anticoagulants

Dear Haematologist, Kindly see this lady who has thrombophilia and advise the role and management of anticoagulation therapy…… Thank you, Your friendly obstetrician

Why was she tested?......whhyyy? Previous venous thromboembolism Screening prompted by family member with similar diagnosis Investigation of recurrent pregnancy losses or subfertility Not sure why

When was testing done? Physiological/pathological situations lowering natural anticoagulant levels – Active thrombosis (AT, PC, PS) – Liver disease (AT, PC, PS) – Heparin therapy (AT) – Nephrotic syndrome (AT, PS) – L-asaparaginase (AT) – DIC (AT, PC, PS) – Pregnancy (PS) – Vitamin K antagonist (PC, PS) – Non-vitamin K oral anticoagulant (variable) – Oral contraceptives (PS) – SLE(PS)

Is it truly low? Protein S levels lower in pre-menopausal women – Lab ranges needs to be determined for younger women Was test repeated and determined to be persistently low? Confirmed! Double confirmed!

Investigation as part of adverse pregnancy outcomes Controversial Modest association suggested with congenital thrombophilia Obstet Gynecol. 2008;

ASH Education Book 2014

Interventional studies Kaandorp SP, Goddijn M, van der Post JA, Hutten BA, Verhoeve HR, Hamulyák K, Mol BW, Folkeringa N, Nahuis M, Papatsonis DN, Büller HR, van der Veen F, Middeldorp S. Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. N Engl J Med Apr 29;362(17): Clark P, Walker ID, Langhorne P, Crichton L, Thomson A, Greaves M, Whyte S, Greer IA; Scottish Pregnancy Intervention Study (SPIN) collaborators. SPIN (Scottish Pregnancy Intervention) study: a multicenter, randomized controlled trial of low- molecular-weight heparin and low-dose aspirin in women with recurrent miscarriage. Blood May 27;115(21): Small subgroups of patients with thrombophilia ALIFE2 – recruiting LMWH vs nothing

Screening for adverse pregnancy outcome? Please don’t, not at the moment ACOG BCSH Guidelines ACCP

When, if ever, should we screen for thrombophilia in the pregnant or soon-to-be pregnant lady? Consider in patients with first degree relative with unprovoked VTE at young age (BCSH, RCOG) Counsel patients on issues related to testing of inherited disorders

Positive thrombophilia, no personal or family history of thrombosis Antepartum – Refer local expert, consider prophylaxis (RCOG) – No prophylaxis (ACCP) Postpartum – 6 weeks prophylaxis (RCOG) – No prophylaxis

Family history, no personal history of thrombosis, positive thrombophilia Antepartum – Refer local expert, consider prophylaxis (RCOG) – No prophylaxis (ACCP) Postpartum – 6 weeks of prophylactic or intermediate dose LMWH

Previous VTE, Anti-thrombin positive Antepartum and post-partum – Intermediate to full dose anticoagulation with LMWH – Post-partum for 6 weeks or until conversion to warfarin

Previous VTE, thrombophilia positive Antepartum and postpartum – Prophylactic or intermediate does LMWH – Continue for at least 6 weeks post-partum

Thank you