Antiphospholipid syndrome Flashcards
Define antiphospholipid syndrome.
Persistently elevated antiphospholipid antibodies associated with thromboses and pregnancy-related morbidity.
How common is APS?
Affects 1-5% pf the population
May increase with age
Common in SLE (30-40% affected) and RhA (6%)
What is the pathophysiology of antiphospholipid syndrome?
APL antibodies are directed against plasma protein bound to anionic phospholipids (e.g. beta2 glycoprotein-I)
ALP may develop in susceptible individuals (e.g. with rheumatic disease) following exposure to infectious agents
Once ALP are present a “second hit” is needed to develop the syndrome
Procoagulant actions of ALP may be mediated by their effect on beta2-GP-I (clotting and platelet aggregation inhibitor), protein C, annexin V, platelets and fibrinolysis. Complement activation is critical for pregnancy complications.
What are the risk factors for APS?
- SLE
- Rheumatological disorders
- Other AI disease
- AI haematological disorders (e.g. ITP)
What is shown?
Livedo reticularis
What are the clinical features of APS?
- Recurrent pregnancy loss
- Arterial thromboses (sx of stroke)
- Venous thromboses (sx of DVT, PE)
- Headaches (migraine)
- Livedo reticularis - affects 20%, non-blanching due to fibrin deposition
- Arthralgia/arthritis - common
- Petechial rash/mucosal bleeding symptoms (thrombocytopenia)
- Nephropathy
- Seizures
- Chorea
What type of cardiac condition may cause a new murmur in SLE?
Libman-Sacks endocarditis
Name 3 antiphospholipid antibodies.
Antiphospholipid antibodies:
- lupus anticoagulant
- anticardiolipin antibody
- +/- anti-beta2-glycoprotein I
What investigations would you do for APS?
APS antibodies - on 2 occasions at least 12 weeks apart required for diagnosis
ANA, dsDNA, extractable nuclear antigen antibodies - present in SLE
FBC - thrombocytopenia
Creatinine and urea - elevated if nephropathy is present
Thrombophilia screen - negative (includes protein C level, free protein S level, activated protein C resistance, antithrombin level, and PCR for prothrombin gene mutation (G-20210-A))
Imaging:
- venous Doppler USS - ?DVT
- venography or MRI - variable and may show evidence of DVT if not already confirmed
- CT angio chest - ?PE
- V/Q scan
- Echocardiography - ?valve vegetations
What is pregnancy related morbidity defined as in APS?
- _>_3 spontaneous abortions at <10 weeks gestation
- _>_1 otherwise unexplained fetal deaths at >10 weeks gestation
- _>_1 premature birth at <34 weeks gestation because of eclapsia, severe pre-eclampsia, or placental insufficiency.
What is the criteria used for APS diagnosis?
1 laboratory + 1 clinical criteria
Clinical:
_>_1 episodes of confirmed thrombosis
OR Pregnancy morbidity
Laboratory: 2 positive results 12 weeks apart for
- +/- Lupus anticoagulant
- +/- Anticardiolipin IgG or IgM
- +/- Anti-beta2-glycoprotein I antibody
NB: 1 in 3 are triple positive
What is the management of APS?
Manage acutely and prevent thrombosis and pregnancy morbidity
Education - reduction of risk factors for VTE like smoking, obesity, diabetes, HTN, immobilisation
Long term anticoagulation with WARFARIN - DOACs not recommended for APS. INR target 3-4 is best.
What is the management of APS in pregnancy?
If no hx of thrombosis:
Prophylactic low-dose aspirin until 6-8 weeks post-partum
If hx of thrombosis:
LMWH anticoagulation throughout
Fetal monitoring
Warfarin post-partum + vitamin K for infant - safe to breastfeed
What is catastrophic APS?
Thrombosis in 3 or more organs simultaneously - associated with 50% mortality
What are the complications of APS?
- Pregnancy loss
- Pre-eclampsia
- IUGR
- Placental abruption
- Recurrent DVT
- Ischaemic stroke
- TIA
