Antiphospholipid syndrome (APS) is characterised by venous or arterial thrombosis and/or pregnancy morbidity in the presence of persistent laboratory evidence of antiphospholipid antibodies. It may occur as a primary disorder or as a part of other autoimmune disorders mainly SLE. Rare causes include infections and drugs.
Clinical manifestations of APL include
- Thrombosis: APS increase the risk of arterial as well as venous thrombosis. Venous thrombosis are more common than arterial thrombosis. Lupus anticoagulant correlates strongly with thrombosis than positivity for other antibodies. According to the data collected by the Euro-Phospholipid project about 55% of the patients had venous thrombosis and arterial thrombosis related manifestations were seen in about 40% of the patients (J Autoimmun. 2014 Feb-Mar;48-49:20-5) . Thrombosis can recur. Recurrences are more common in patients with LA or when when patients have triple anti-phospholipid antibodies (LA, anti-cardiolipin, and anti–β2-GPI). An arterial thrombosis usually reccurs as an arterial thrombosis and a venous thrombosis as venous thrombosis,
- Venous Thrombosis: The commonest site of thrombosis is the deep veins is seen in about 38% of the patients with APL in the Euro-Phospholipid project. Other veins where thrombosis may occur include subclavian, jugular and superficial veins of the legs.
- Arterial Thrombosis: The commonest form of arterial thrombosis is that of the cerebral vasculature. This manifests and stroke or transient ischemic attack. Thrombosis may also involve retinal, coronary, renal, and mesenteric arteries.
- Pregnancy complications: APL is associated with pregnancy complications including
- Foetal loss: Both embryonic (early) loss and fetal death (late) after 10 weeks gestation may be seen. About half the pregnancies are complicated by foetal loss. Early loss is twice as common as late loss.
- Premature birth due to severe pre-eclampsia or placental insufficiency
- Haematological manifestations: Other than thrombosis the following haematological manifestations may be seen autoimmune haemolytic anaemia, cytopenia, platelet dysfunction and thrombotic microangiopathy (thrombotic thrombocytopenia purpura and haemolytic uraemia syndrome).
- Cutaneous manifestations: About 40% of the patients have cutaneous manifestations (Acta Reumatol Port. 2013 Jan-Mar;38(1):10-18). These include
- Livedo Reticularis: Livedo reticularis (LR) is a condition where there is mottled discolouration of the skin. LR is seen in about 25% of the patients with antiphospholipid syndrome and is a presenting manifestation ins about 15%. It is not specific to anti-phospholipid syndrome and may be seen in other conditions. It may be seen in association with strokes (Sneddon’s syndrome).
- Cutaneous Necrosis and Ulcers : Cutaneous necrosis and ulcers are seen in about 5% of the patients. They present as acute onset retiform non-inflammaroty necrolysing purpura. The purpura is followed by necrotic plaques with active purpura borders and bullies lesions.
- Digital gangrene: Digital gangrene is a major thrombotic event that is preceded by ischemic symptoms in the involved digit. It is seen in about 3% of the patients.
- Primary Aneloderma: Primary aneloderma is a rare conditions characterised by circumscribed depression or patches of slack skin with atrophy
- Other Manifestations: Other manifestations include subungual splinter haemorrhages, pseudovasculitic lesions, levedoid vasculopathy and atrophie blanche and Degos’-like skin lesions (see Acta Reumatol Port. 2013 Jan-Mar;38(1):10-18 for detailed discussion)
- Neurological manifestations: The nervous system may be involved secondary to thrombosis or due to direct involvement of nervous tissue.
- Manifestations from Vascular Involvement: Strokes from thrombosis or embolism of cardiac vegetations is the commonest neurological manifestation of APL. Sneddon’s syndrome is a combination of levidio reticularis and stroke. Half the patients with this syndrome have APL. About 30% of the patients have stroke or TIA.
- Other Manifestations: The other neurological features of APL include seizures, migraine, cognitive dysfunction, multi-infact dementia, chorea and other movement disorders, transverse myelitis, pseudotumour cerebri, mononeuritis multiplex and amaurosis fugax (Clin Exp Rheumatol 2004; 22: 771-775)
- Pulmonary Manifestations: Pulmonary manifestations include pulmonary embolism, thrombosis and pulmonary hypertension and alveolar haemorrhage.
- Cardiac Manifestations: APL is associated with valvular thickening and valve nodules (nonbacterial vegetations or Libman-Sacks endocarditis). Mitral valve is most commonly involved. The aortic valve lesions can embolism and cause stroke.
- Other Manifestations: APL may have ocular manifestations (Amaurosis fugax, retinal artery thrombosis), Involvement of bone and joint (arthritis, avascular necrosis), renal manifestations (glomerular thrombosis, renal infarction, renal artery thrombosis, renal vein thrombosis), ischaemia of the gastrointestinal tract splenic infarct and perforation of the nasal septum.
- Catastrophic APL Syndrome: Catastrophic APL syndrome is charterized by acute widespread thrombosis with multi organ failure. The thrombi involve small rather than large vessels. It needs to be differentiated from other cause of widespread thrombosis.
Primary vs Secondary APL Syndrome
Secondary APS (usually SLE associated) are more likely to have arthritis, livedo reticularis, heart valve disease, thrombocytopenia, leukopenia positive Coombs’ test, lymphocytopenia, antinuclear antibodies, antibodies to dsDNA and to ENA, and hypocomplementemia (J Rheumatol. 1999 Oct;26(10):2131-6) than patients with primary APS. Between 13-23% of the the patients of primary APS evolve to SLE over 9 years.