Antiphospholipid antibody syndrome (APS) is an autoimmune condition characterized by arterial or venous blood clots and/or pregnancy morbidity in the presence of antibodies that target phospholipid-binding plasma proteins. It can occur on its own (primary) or with other autoimmune diseases (secondary). APS is diagnosed based on clinical criteria of blood clots or pregnancy complications along with positive laboratory tests for antiphospholipid antibodies. Treatment involves blood thinners like warfarin to prevent clots. Prognosis can be poor as permanent organ damage or disability can occur in a third of patients within 10 years.
2. Introduction
Antiphospholipid
antibody syndrome (APS) is an
autoimmunity-mediated acquired thrombophilia
characterised by :
It
arterial or venous thrombosis
and/or pregnancy morbidity
in presence of autoantibodies against
phospholipid(PL)- binding plasma proteins
maybe
Primary : occuring alone
Secondary : in association with other autoimmune
disease
3. 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)
4. Epidemiology
In
normal blood donors
Low titer, transient aCL : 10%
Moderate-high titer aCL or positive LA : <1%
Prevalence
females
increases with age, more common in
5. 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
7. 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
9. Pathogenesis
Other 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
10. Clinical features
Venous thrombosis and related consequences
Deep vein thrombosis
Livedo reticularis
Pulmonary embolism
Superficial thrombophlebitis
Budd-Chiari syndrome
Thrombosis in various other site
11.
12. Clinical features
Arterial 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
14. Clinical features
Osteoarticular manifestations
Renal manifestations
Arthralgia
Severe hypertension
Arthritis
Renal failure
Hematologic manifestations
Neurologic of uncertain etiology
Thrombocytopenia
Migraine
Epilepsy
Chorea
Cerebellar ataxia
Transverse myelopathy
Autoimmune hemolytic anemia
15. 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
18. 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
22. 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
23. 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
24. Laboratory tests
False
does not fulfill laboratory criteria
Order aPL test
ANA
positive syphilis test
and Anti-dsDNA
Detected in aprrox. 45% primary APS
Does not mandate additional diagnosis of SLE
Other
tests:
Complete hemogram
Urine examination
25. 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
26. 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
27. 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
32. Treatment
Aspirin
LMW
: 81-325mg once daily
heparin :
Prophylactic dose : 30-40mg
subcutaneously/day
Therapeutic dose : 1 mg/kg, s/c BD or
1.5mg/kg OD
33. No controlled studies in APS for
Clopidogrel
Pentoxyfylline
Argatobran
Hirudin
And other new anticoagulants
34. 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
35. 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