Antiphospholipid Syndrome (APS)
BSH Guidelines on the investigation and management of antiphospholipid syndrome. Published: Jul 2024.
Guidelines
Investigation and Diagnosis
Indications for APS Testing
- All newly diagnosed SLE
- Unprovoked venous thrombosis
- <50 y/o with arterial thrombosis with no other vascular risk factors
- Obstetric APS clinical criteria (all the following assume a morphologically normal fetus, i.e. in the absence of anatomical and chromosomal anomalies)
- ≥3 consecutive unexplained miscarriages <10 weeks
- ≥1 unexplained fetal death ≥10 weeks
- ≥1 premature births <34 weeks due to severe pre-eclampsia / eclampsia / placental insufficiency
BSH guidelines advise against testing for APL in those with VTE associated with a transient reversible major risk factor (e.g. surgery, immobilisation), or active cancer
Diagnostic Criteria
- At least 1 clinical event (objectively confirmed thrombotic event and/or pregnancy complication), AND
- +ve antibodies (any of the following) on 2 occasions at least 12 weeks apart
- Lupus anticoagulant
- Anticardiolipin (IgM / IgG)
- Anti-β2 glycoprotein-1 (IgM/IgG)
Laboratory changes (not part of the diagnostic criteria):
- Thrombocytopaenia (mild to moderate)
- Prolonged aPTT
Management
Anticoagulation is generally NOT recommended for asymptomatic patients who have positive serology (suggesting APS) but no history of thrombosis or obstetric APS.
There are 2 main approaches
- Primary prophylaxis: asymptomatic APL carrier without any history of thrombotic or obstetric events
- Secondary prophylaxis: APL carriers with previous thrombotic or obstetric events
Primary Thrombosis Prophylaxis
Consider low-dose aspirin in those with high thrombotic risk (e.g. triple-positive, high titer +ve, persistent lupus anticoagulant), weighing against bleeding risk
- BSH endorse a personalised risk-stratified approach instead of an universal recommendation
Secondary Thrombosis Prophylaxis
In short: warfarin is the choice of anticoagulation in secondary prophylaxis.
Venous Thrombosis
1st line: indefinite anticoagulation with warfarin
- Target INR 2.0-3.0
DOACs are not the choice of anticoagulation in APS (esp. triple +ve APS). In patients with APS, DOACs are associated with an increased risk of recurrent arterial thrombosis (esp stroke & myocardial infarction)[ref]
Arterial Thrombosis (Stroke)
1st line: warfarin
- If warfarin contraindicated → dual antiplatelet therapy
If there are additional vascular risk factors (and no significant risk of bleeding): add an antiplatelet in addition to warfarin
Recurrent Thrombosis Despite Anticoagulation
Refer to specialist
If not on warfarin (e.g. DOAC or antiplatelet) → switch to warfarin
If already on warfarin:
- 1st line: increase target INR to 3.0-4.0 or add antiplatelet while maintaining target INR 2.0-3.0
- 2nd line: consider hydroxychloroquine
- 3rd line: consider rituximab for refractory cases
APS in Pregnancy
Once the woman is pregnant
- Stop warfarin
- Give aspirin + LMWH (prophylactic dose) during pregnancy
Catastrophic APS
Catastrophic APS should be suspected in a patient with APS presenting with multiple sites of thrombosis including microvascular thrombosis leading to organ failure
- 1st line: triple therapy with therapeutic dose IV heparin + high-dose corticosteroid + IVIG and/or plasma exchange
- 2nd line: retixumab and seek specialist input