antiphospholipid antibody syndrome
TRANSCRIPT
ANTIPHOSPHOLIPID ANTIBODY SYNDROME
Presenter : Demitrost Laloo
Introduction
Antiphospholipid antibody syndrome (APS) is an autoimmunity-mediated acquired thrombophilia characterised by : arterial or venous thrombosis and/or pregnancy morbidity in presence of autoantibodies against
phospholipid(PL)- binding plasma proteins
It maybe Primary : occuring alone Secondary : in association with other autoimmune disease
Classification and Nomenclature of Antiphospholipid Antibodies : Antibodies against cardiolipin (aCL)
Antibodies against β2 Glycoproptein I (anti-β2GPI) Lupus anticoagulant(LA): heterogeneous group of
antibodies directed also against PL binding proteins, mainly β2GPI and prothrombin
Antibodies against phospholipids/cholesterol complexes detected as biologic false-positive serologic test for syphilis (BFP-STS) and Venereal Disease Research Laboratory Test (VDRL)
Epidemiology
In normal blood donors Low titer, transient aCL : 10% Moderate-high titer aCL or positive LA : <1%
Prevalence increases with age, more common in females
Epidemiology Antiphospholipid antibodies (aPL) positivity in
10-40% SLE approx. 20% Rheumatoid arthritis 10% of 1st stroke patient, more in young(upto
29%) 20% in women with 3 or more consecutive fetal
losses 14% in recurrent venous thromboembolic
disease
Pathogenesis Trigger unknown
Preceding infection have been proposed
aPL binds to phospholipid-binding plasma protein ß₂ GP I
Pathogenesis aPL most likely related to thrombosis through
multiple mechanisms
Activation of the classical complement pathway
Expression of adhesion molecules and tissue factor
Activation of monocytes and PMN: release of proinflammatory mediators and initiation of prothrombotic stage
Activation of p38 MAPK and NFkB: intracellular signaling cascade
Pathogenesis
PathogenesisOther possible contributory mechanisms inhibition of coagulation cascade
reactions catalyzed by phospholipids induction of tissue factor expression on
monocytes reduction of fibrinolysis interaction with the annexin V
anticoagulant shield in the placenta
Clinical features
Venous thrombosis and related consequences
Deep vein thrombosis
Livedo reticularis
Pulmonary embolism
Superficial thrombophlebitis
Budd-Chiari syndrome
Thrombosis in various other site
Clinical featuresArterial thrombosis and related consequences
Stroke
Cardiac valve thickening/dysfunction and/or Libman-Sacks vegetation's
TIA
Myocardial ischemia and coronary bypass thrombosis
Leg ulcers and/or digital gangrene
Arterial thrombosis in the extremities
Retinal artery thrombosis/amaurosis fugax
Ischemia of visceral organs or avascular necrosis of bone
Multi-infarct dementia
Clinical featuresPregnancy morbidity
Late Fetal losses >10 weeks
Early fetal losses <10 weeks
Early preeclampsia
HELLP syndrome
Premature birth
Clinical featuresOsteoarticular manifestations
Renal manifestations
Arthralgia
Arthritis
Severe hypertension
Renal failure
Hematologic manifestations Neurologic of uncertain etiology
Thrombocytopenia
Autoimmune hemolytic anemia
MigraineEpilepsyChoreaCerebellar ataxiaTransverse myelopathy
Clinical features
CAPS: Catastrophic Antiphospholipid Syndrome
Rare, abrupt, life threatening, mortality as high as 48% despite effective treatment
Multiple thrombosis of medium and small arteries involving multiple organs over a period of days
Causing: Stroke Cardiac, hepatic, adrenal, renal and intestinal
infarction Peripheral gangrene
Diagnostic criteria: Revised Sapporo classification
Diagnostic criteria: Revised Sapporo classification
Diagnostic criteria: Revised Sapporo classification Definite APS : at least 1 clinical and 1
laboratory criteria
Classification avoided if <12 weeks and >5yrs separate +ve aPL test and clinical manifestation
Other findings not included in the criteria but helpful in diagnosis
CAPS criteria
CAPS criteria
Laboratory tests Lupus anticoagulant test
More specific but less sensitive Requires a 4-step process
Anticardiolipin Sensitive but not specific Standardized ELISA test for IgG and IgM Moderate to high titer required for
diagnosis
Laboratory tests Anti ß2GP I
Standardized ELISA for IgG and IgM
Positive aPL test requires a repeat test after 12 or more weeks to rule out transient, clinically unimportant antibody
Laboratory tests False positive syphilis test
does not fulfill laboratory criteria Order aPL test
ANA and Anti-dsDNA Detected in aprrox. 45% primary APS Does not mandate additional diagnosis of SLE
Other tests: Complete hemogram Urine examination
Imaging
CT and MRI of brain for stroke
CT angio or MR angiography if clinical findings suggest medium or large vessel disease
Doppler study for DVT
Echocardiography or cardiac MRI for vegetations or intracardiac thrombi
Pathology
Biopsy of renal, skin or other tissues Thrombotic occlusion of all caliber arteries
and veins Acute and chronic endothelial injury Recanalisation in late lesions
Differential Dx Hereditable deficiency of Protein C, Protein S,
antithrombin III Factor V Leiden and antithrombin mutations Hyperhomocysteinemia Thrombocytopenic purpura Septicemia Disseminated Intravascular Coagulation Hemolytic Uremic Syndrome Polyarteritis nodusa Myxoma Sneddon’s syndrome
Treatment Asymptomatic : no treatment
Venous/arterial thrombosis : warfarin (INR 2.5) indefinitely
Recurrent thrombosis : warfarin (INR 3-4) ± low dose aspirin
Treatment Pregnancy 1st pregnancy : no treatment Single pregnancy loss <10 weeks : no treatment
>1 fetal loss or ≥3 (pre) embryonic loss, no thrombosis : prophylactic heparin + low dose aspirin throughout pregnancy, discontinue 6-12 weeks postpartum
Thrombosis regardless of pregnancy history: therapeutic heparin or low dose aspirin throughout pregnancy, warfarin postpartum
Treatment Valve nodules or deformity
Full anticoagulation if emboli or intracardiac thrombi demonstrated
Valve replacement
Thrombocytopenia >50,000/cumm : no treatment <50,000/cumm : prednisone, IVIG
Treatment CAPS : Anticoagulation + corticosteroids + IVIG
or plasmapheresis
Cyclophosphamide and rituximab in desperate situations
Treatment Aspirin : 81-325mg once daily
LMW heparin : Prophylactic dose : 30-40mg
subcutaneously/day Therapeutic dose : 1 mg/kg, s/c BD or
1.5mg/kg OD
No controlled studies in APS for Clopidogrel Pentoxyfylline Argatobran Hirudin And other new anticoagulants
Outcome Long term functional outcome is poor
At 10yrs : 1/3rd developed permanent organ damage and 1/5th unable to perform everyday activities
Pulmonary hypertension, neurological involvement, myocardial ischemia, gangrene of extremities and catastrophic APS associated with worse prognosis
Outcome 35% of obstretic APS without thrombosis
developed aPL-related clinical events during a 8yr follow up
Long term outcome of children born to APS pregnancies unknown
Many need valve replacement due to severe valvular disease
Rarely may develop renal failure Serious perioperative complications may
occur despite prophylaxis
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