Terms in this set (37)

Antiphospholipid syndrome: arterial/venous thrombosis, miscarriage, livedo reticularis

Thrombocytopenia is associated with antiphospholipid syndrome

Antiphospholipid syndrome is an acquired disorder characterised by a predisposition to both venous and arterial thromboses, recurrent fetal loss and thrombocytopenia.
It may occur as a primary disorder or secondary to other conditions, most commonly systemic lupus erythematosus (SLE)
A key point for the exam is to appreciate that antiphospholipid syndrome causes a paradoxical rise in the APTT. This is due to an ex-vivo reaction of the lupus anticoagulant autoantibodies with phospholipids involved in the coagulation cascade

Risk factor for thrombosis Lupus anticoagulant is the greatest predictor of future thrombosis in patients with antiphospholipid syndrome

Diagnosis
antiphospholipid antibody syndrome (APAS) can be diagnosed if:
the patient has anticardiolipin antibodies, or lupus anticoagulant on two occasions, over a period of 12 weeks, and either:
has had a thrombus, or
a history of recurrent < 10 week pregnancy loss, or one pregnancy loss > 10 weeks in gestation when other causes of pregnancy loss have been excluded.

Antibodies
the most clinically important autoantibodies directed against phospholipid binding plasma proteins are:
1. The lupus anticoagulant
2. Anti-beta-2 glycoproetin I antibodies, and
3. The anticardiolipin antibodies.

Management - based on BCSH guidelines
initial venous thromboembolic events: warfarin with a target INR of 2-3 for 6 months
Other opinion: The occurrence of even a single thrombotic event in a patient with antiphospholipid syndrome warrants lifelong anticoagulation, as the risk of recurrence is 20-70%.
recurrent venous thromboembolic events: lifelong warfarin; if occurred whilst taking warfarin then increase target INR to 3-4
arterial thrombosis should be treated with lifelong warfarin with target INR 2-3
Colchicine is useful in patients with renal impairment who develop gout as NSAIDs are relatively contraindicated. The BNF advises to reduce the dose by up to 50% if creatinine clearance is less than 50 ml/min and to avoid if creatinine clearance is less than 10 ml/min.

Acute management
NSAIDs or colchicine are first-line
the maximum dose of NSAID should be prescribed until 1-2 days after the symptoms have settled. Gastroprotection (e.g. a proton pump inhibitor) may also be indicated
colchicine* has a slower onset of action. The main side-effect is diarrhoea
oral steroids may be considered if NSAIDs and colchicine are contraindicated. A dose of prednisolone 15mg/day is usually used
another option is intra-articular steroid injection
if the patient is already taking allopurinol it should be continued

Indications for urate-lowering therapy (ULT)
the British Society of Rheumatology Guidelines now advocate offering urate-lowering therapy to all patients after their first attack of gout
ULT is particularly recommended if:
→ >= 2 attacks in 12 months
→ tophi
→ renal disease
→ uric acid renal stones
→ prophylaxis if on cytotoxics or diuretics

Urate-lowering therapy
allopurinol is first-line
it has traditionally been taught that urate lowering therapy should not be started until 2 weeks after an acute attack, as starting too early may precipitate a further attack. The evidence base to support this however looks weak
in 2017 the BSR updated their guidelines. They still support a delay in starting urate lowering therapy because it is better for a patient to make long-term drug decisions whilst in pain
initial dose of 100 mg od, with the dose titrated every few weeks to aim for a serum uric acid of < 300 µmol/l. Lower initial doses should be given if the patient has a reduced eGFR
colchicine cover should be considered when starting allopurinol. NSAIDs can be used if colchicine cannot be tolerated. The BSR guidelines suggest this may need to be continued for 6 months
the second-line agent when allopurinol is not tolerated or ineffective is febuxostat (also a xanthine oxidase inhibitor)

Lifestyle modifications
reduce alcohol intake and avoid during an acute attack
lose weight if obese
avoid food high in purines e.g. Liver, kidneys, seafood, oily fish (mackerel, sardines) and yeast products

Other points
losartan has a specific uricosuric action and may be particularly suitable for the many patients who have coexistant hypertension
increased vitamin C intake (either supplements or through normal diet) may also decrease serum uric acid levels

*inhibits microtubule polymerization by binding to tubulin, interfering with mitosis. Also inhibits neutrophil motility and activity
;