Management issues in other thrombophilia

Ng Heng JooDepartment of HaematologySingapore 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. 2010 Apr 29;362(17):1586-96.

• 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. 2010 May 27;115(21):4162-7.

• Small subgroups of patients with thrombophilia• ALIFE2 – recruiting• LMWH vs nothing

Screening for adverse pregnancy outcome?

Please don’t, not at the moment

ACOGBCSH GuidelinesACCP

If you do, DON’T refer to me!!!

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