2. INTRODUCTION: - APS is an Autoimmune mediated
acquired thrombophilia c / b – recurrent arterial or venous thrombosis
&/ or Pregnant morbidity in the presence of variety of circulating
antibodies directed against the phospholipids and or Phospholipids –
binding plasma protein like Prothrombin & Beta2 Gycoprotein I.
• It affects primarily Females.
*APS occurs :- 1. Alone i.e Primary a/w – HLA DR 7 & HLA DRW53.
2. Secondary :- associated with :-
a. Autoimmune diseases like SLE ( MC ) , RA , Systemic sclerosis ,
Primary Sjogren’s syndrome , Vasculitis , IBD , Idiopathic
inflammatory myositis.
b. Drugs:- Procainamide , Phenothiazine , OC Pills, Quinine ,
Ethosuximide , Chlorothiazide.
c. Infection :- Bacterial , Viral , Parasitic , Spirochaeatal.
d. Malignancy :- Lymphoid & myeloid Leukemias , Multiple myeloma.
e. Others :- Sickle cell disease , pernicious anaemia , ITP , DM ,
Autoimmune thyroid disease.
3. Epidemiology :- Incidence is 5 cases per 1 Lac persons per year
Anti Phospholipid antibodies occur in 1-5 % of the general population
and their prevalence increase with age.
•1/3 of patients with SLE & Other autoimmune disease possess these
antibodies with only 5 – 10 % of them developing APS.
•PATHOGENESIS :- initiating factors for induction of antibodies
to PL – binding protein is – infection , oxidative stress ,& major physical
stresses such as Surgery, trauma.
• All these factors induce ↑ apoptosis of vessels endothelial cells &
subsequent exposure to PLs. Later it bound to serum proteins like Beta2
Glycoprotein or Prothrombin lead to neoantigen formation which in turn
triggers induction of anti PLs. The binding of anti PLs to the disrupted
endothelial cells lead to initiation of Intravascular coagulation &
thrombus formation.
4. And also effects the Coagulation pathway including pro-coagulant
action of the antibodies upon protein c , annexin V , Platelets , serum
protease , Tall like receptors , tissue factors, & impaired fibrinolysis.
•Acute thrombotic microangiopathy with minimal or no inflammation is
the pathological hallmark. Chronic changes ranges from hypoperfusion
to atrophy & fibrosis.
•Most commonly accepted explanation for development of aPL is that
they occur in susceptible individual following incidental exposure to
infection agents like infection or milieu of rheumatic disease like SLE.
•Second hit Hypothesis is required for development of Full -blown
syndrome. The potention condidates are smokers , pregnancy ,
Prolonged immbolization , post partum period , HRT , OC PILL ,
Malignancy , NS , HTN , Dyslipidemia.
5.
6. 1.These antibodies acting on Protein C and Inhibiting it- that lead to
uncontrolled activation of Factor 5 & 8 & it predisposition to thrombosis.
2. Antibodies acting on platelets – cause thrombocytopenia (PC- >
1LAC/Micro L) not low Enough to produce bleeding.
* Thrombocytopenia without bleed with Thrombosis suggestive APLA.
7.
8. CLINICAL MANIFESTATION :-
1. Venous Thrombosis:-
• Typically DVT in L/L.
• Unusual sites – U/L, intracranial veins, IVC, SVC, hepatic veins ( Budd-
Chiari syndrome ) , Portal vein, renal vein & retinal vein . Rarely superior
Sagital sinus.
• Thrombosis of the cerebral veins -acute cerebral infarction.
2. Arterial thrombosis :- Less common than venous thromboses.
• Most commonly – TIA or stroke (50%) or MI (23%).
• aCL - risk factor for 1st stroke.
• May involve large and small vessels.
• Sites- Brachial and Subclavian, Axillary artery ( aortic arch
syndrome) , aorta, iliac, femoral, renal, mesenteric, retinal, and
other peripheral arteries.
9. 3. Cardiac Disorders:-
* CAD- Thrombotic or Embolic.
* Premature ATH accelerated by aPL.
• Routine aPL tests in CAD not recommended unless young age and
lack of identifiable risk factors suggest a rare etiology.
•Manifestations like Valvular thickening , vegetations , regurgitation,
premature CAD, MI, DCMP, CCF, PE, and pulmonary HTN.
10. 4.Cutaneous Manifestation :- Livedo reticuaris:-is mottled
reticular vascular like lacy network pattern purplish in colour d/t venous
obstruction causing venular dilatation & others manifestation are Leg
ulcer , Gangrene , Nail fold infarct , Necrotising Purpura , Cutaneous
infarct.
11. 5. Neurological Manifestation :-
* Transient Ischemic attack & Stroke mc presentation.
• Recurrent small strokes - multiple-infarct dementia.
• Typical APLS with stroke - young and lack other classical risk factors
of stroke!
• Chorea, migraine headache, Sneddon’s syndrome, seizures,
Transverse Myelitis, GBS, cognitive dysfunction, psychosis, and
optic neuritis , multiple sclerosis like lesions.
6. Renal manifestation :-
* aPL associated nephropathy (APLN).
• Thrombosis – RAS and/or malignant hypertension, renal infarction,
renal vein thrombosis, thrombotic microangiopathy, increased
allograft vascular thrombosis, and reduced survival of renal allografts.
.
12. 8. Retinal manifestation:-
* Venous and arterial thrombosis of the retinal
vasculature.
• Presentation strongly suggestive - diffuse occlusion of
retinal arteries, veins, or both, and neovascularization at
the time of presentation.
• optic neuropathy and cilioretinal artery occlusion.
9. Haematological Manifestation :-
• Thrombocytopenia (<100,000) -20% to 40%.(usually mild)
• Severe thrombocytopenia - CAPS and DIC or TTP.
• aPL-associated thrombocytopenia – aPL with thrombocytopenia
(<100,000) confirmed 12 weeks apart and exclusion of TTP, DIC,
Pseudo- thrombocytopenia or HITT.
10. PULMONARY Manifestation:-
• Antiphospholipid lung syndrome- Thromboembolism,
pulmonary HT , ARDS, Postpartum syndrome, and
others.
• Diffuse alveolar haemorrhages.
13. 11. OBSTETRIC MANIFESTATION :-
•Miscarriages and early fetal loss.
• Eclampsia , IUGR, oligohydramninos, HELLP syndrome,
and premature birth, systemic and pulmonary
hypertension.
• Of all hereditary and acquired thrombophilias, APLS is
the most common thrombotic defect leading to
fetal wastage.
7. Endocrine Manifestation:-
* Adrenal insufficiency - most common.
• Circulating aPL- autoimmune thyroid disease,
hypopituitarism (including a case of Sheehan’s syndrome),
DM and rarely ovarian and testicular disease
16. Revised Diagnostic criteria :- ( SAPPORO Criteria )
:-
* APS is present if at least one of the clinical criteria and one of the
laboratory criteria is compatible with diagnosis… they are :-
* Clinical criteria---
1.Vascular thrombosis:-
One or more clinical episodes of arterial , venous or small vessel
Thrombosis in any tissue or organ to be confirmed by
objective validated Criteria. Histopathologically thrombosis
should be present without significant evidence of inflammationin
the vessel wall.
2.Pregnancy morbidity:-
a. one or more unexplained deaths of morphologically normal
fetuses at or after the 10 week of gestation.
17. b. one or more premature births of morphologically normal
neonates before the 34th week of gestation b/c of eclampsia , severe
Preeclapsia or placental insufficiency.
c. three or more unexplained consecutive spontaneous abortions
before the 10th week of gestation with maternal anatomical ,
hormonal abnormalities and paternal and maternal chromosomal
cause excluded.
•Laboratory Criteria :-
1. Lupus anticoagulant present in plasma.
2. aCL of IgG and or IgM isotype in serum or plasma present in
medium or high titer (>40GPL, 40MPL, >99TH percentile)
3. anti β2GP1IgG or IgM isotype in serum or plasma
On two or more occasions at least 12 weeks apart measured according
to recommended procedures like ELISA .
18. Catastrophic Antiphospholipid Antibody Syndrome
(CAPS):-
is a life threatening rapidly progressive thromboembolic disease
involving ≥ 3 ORGANS simulataeneously or within I week.
And HisTOPATHOLOGICALLY SMALL VESSELS OCCLUSION WITH LAB
FINDINGS OF APLA.
* MC affected organ is kidney > lungs > cns > skin.
19.
20.
21. Treatment :- After the 1st thrombotic events ---Warfarin (5-15mg /
day ) for life long aiming to achieve an INR FROM 2.5 to 3.5 alone or
with Aspirin 80 mg .
• Pregnancy morbidity is prevented by Low molecular weight Heparin
with aspirin 80mg daily.
• IV immunoglobulin 400mg/kg every day for 5 days also prevent
abortion.
• Pregnancy :- if previous h/o Thrombosis due to APLA OR H/O
miscarriage OR Preterm Delivery due to APLA :- Rx- Heparin plus Low
dose Aspirin through out pregnancy plus warfarin post partum &
continued for life long.
• IN CAPS AND APS :-W/o recurrent thrombotic event despite
Anticoagulant, I.VIG 400mg /KG every day for 5 days may benefit.
22. * STEROID may be tried in CAPS.
•Inhibitors of phospholipid bound activated factor X (Fxa ) like
Fondaparinux 7.5 mg sc daily or Rivaroxaban 10 mg po daily in
thrombosis syndrome & Heparin Induced thrombocytopenia.
• In Setting of thrombosis despite thrombocytopenia , it is safe to start
anticoagulantion once Platelets count are > 50000/ micro l.
* Hydroxychroquine.- 200-400mg/day.
* RITUXIMAB :-1000mg iv for 2 doses seperated by 2 weeks.
. Rate at 50mg/h
