Antiphospholipid Antibody Syndrome

Antiphospholipid Antibody Syndrome (APS)

What is it?

Primary APS- occurs as an isolated problem unassociated with other disease

Secondary APS- occurs in association with SLE, other rheum dz, infection, drugs, or Sneddon’s syndrome (livedo and ischemic strokes)

*Clinical features are generally similar in 1° or 2° except SLE pts. are more likely to have AIHA, neutropenia and low C4. Rare transformation of primary APS into SLE

Pathophysiology

Autoantibodies directed toward 1) phospholipids or 2) plasma proteins bound to phospholipids
Thrombotic microangiopathy with minimal vascular or perivascular inflammation (can also be seen in HUS and scleroderma)

Clinical Manifestations
Venous & Arterial Thromboses Recurrent Miscarriages Thromocytopenia

Thrombosis:	DVT’s: calf, liver, renal and retinal veins Arterial : cerebral, coronary, renal, mesenteric, bypass grafts Arterial thrombi or emboli from Libman Sacks endocarditis Single or multiple TIA’s/CVA’sà dementia & other neuro deficits
Pulmonary:	PE, Pulm HTN, PA thrombosis & pulmonary microthrombosis, ARDS, Intralveolar pulmonary hemorrhage, Fibrosing alveloitis, Postpartum syndrome (Fever, CP, SOB, pleural effusion)
Cardiac:	Valvular thickening & vegetations, Other: pericardial effusion, CM, intracardiac thrombi, ?incresed risk of MI
Heme:	Trombocytopenia, TTP, Prothrombin antibodies (bleeding)
Renal:	Microthrombotic lesions of the glomerulus & small arteries (like HUS); May present with proteinuria, renal failure, flank pain; Arterial or venous thrombi in small or medium vessels, Postpartum HUS
GI	Ischemia of any portion of bowel
Cutaneous	Livedo, livedoid vasculitis, cutaneous necrosis/infarction, thrombophlebitis, gangrene of digits, skin ulcerations, vasculitc nodules/macules, splinter hemorrhages
Other Rheum:	PMR/TA
Fetal Loss

Diagnosis:	Requires 1 Clinical & 1 Laboratory Feature
Clinical:	One or more episodes of venous/arterial thrombi and/or morbidity with pregnancy
Lab:	4 types of Antiphospholipid antibodies have been characterized Either IgG or IgM anticardiolipin antibody Lupus anticoagulant activity AntiB2glycoprotein-I antibodies False positive serologic test for syphilis Should be found on 2 or more occasions @ least 6 weeks apart

Prognosis

Uncertain…In one retrospective study of 70 pts, 53% had recurrent thrombotic event in the next 5 years. In another, 69% had recurrent emboli with median time of 12 months after primary event. Another study in SLE pts found increased risk of death with arterial occlusion, thrombocytopenia, renal involvement, pleuritis and disease activity.

Therapy

Aspirin alone of no benefit
Low intensity coumadin (INR < 3) +/- ASA, offers some protection
High intensity coumadin (INR > 3) +/- ASA offers best protection (only 1.3% of pts per yr with recurrent thromboses)
In general, immunosuppressants such as steroids or cyclophosphamide are of no benefit (except perhaps with thrombocytopenia)

Minor initial event--Since lab tests for APL can be falsely positive (or these APL Ab’s can exist in "normal" people), some do not advocate lifelong anticoagulation if the initial event is minor (calf vein DVT).

Major initial event--Most recommend lifelong coumadin with INR >3 if major thrombotic event (arterial, DVT/PE)

Prophylaxis for asymptomatic individuals found to have APL Ab’s--controversial

AEbright 8/2000