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
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Protein C
Natural Anticoagulants
Protein S
Antithrombin
Factor V Leiden and prothrombin gene mutation
• Acquired
– Malignancy
– Antiphospholipid syndrome
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
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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)
• 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!
Is it truly low?
Investigation as part of adverse
pregnancy outcomes
• Controversial
• Modest association suggested with congenital
thrombophilia
Obstet Gynecol. 2008;
ASH Education Book 2014
Interventional studies
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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 lowmolecular-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
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