ANTIPHOSPHOLIPID ANTIBODY SYNDROME
By
Dr. Arvind Mishra M.D.
Professor
Department of Internal Medicine
LECTURE
AND
MCQs
ANTIPH0SPHOLIPID ANTIBODY
SYNDROME
Antiphospholipid antibody syndrome is
an
autoantibody-mediated
acquired
thrombophilia characterized by recurrent
arterial or venous thrombosis and/or
pregnancy morbidity in the presence of
autoantibodies against phospholipid (PL)binding plasma proteins.
Classification and Nomenclature of
Antiphospholipid Antibodies
1)Antibodies against cardiolipin (aCL), a
negatively charged phospholipid, detected by
enzyme-linked immunosorbent assay (ELISA).
2)Antibodies against apolipoprotein
β- 2 Glycoprotein I (antiβ-2GPI)
detected by ELISA in the absence of PL.
3)Lupus Anticoagulant detected by
clotting
assays.
LA
constitutes
a
heterogeneous group of antibodies
directed
proteins,
also
against
mainly
prothrombin.
PL
β-2GPI
binding
and
LA antibodies induce elongation
in vitro of the following clotting
times:
1. Activated partial thromboplastin time (aPTT)
2. Kaolin clotting time (KCT)
3. Dilute Russel viper venom test (dRVVT)
• Antibodies against phospholipids/cholesterol
complexes detected as biologic false-positive
serologic test for syphilis (BFP-STS) and Venereal
Disease Research Laboratory Test (VDRL).
•occur in 1–5% of general population
• Systemic lupus erythematosus (SLE)(1/3rd cases)
• Systemic sclerosis (scleroderma)
• Sjögren's syndrome
• Dermatomyositis
• Rheumatoid arthritis
PATHOGENESIS• Preceding infections as initiating event
• Anti phospholipid antibodies
1)inactivate natural anticoagulants such as
protein C(Activated protein C (APC) binds the procoagulant factors Va and VIIIa and inactivates
them)
2)activate cells involved in the coagulation
cascade to a prothrombotic phenotype
3) activate complement
4)activate nuclear factor kappa B (NF-kB) in
monocytes and endothelial cells leading to
the secretion of pro-inflammatory cytokines, ;
the expression of adhesion molecules and ;
and the expressions of tissue factor, changing
the phenotype of these cells to a
prothrombotic form
MANIFESTATIONS
Venous Thrombosis and Related Consequences
Deep vein thrombosis
Livedo reticularis
Pulmonary embolism
Superficial thrombophlebitis
%
39
24
14
12
Arterial Thrombosis
Stroke
Cardiac involvement
Transient ischemic attack
Leg ulcers and/or digital gangrene
Arterial thrombosis in the extremities
Retinal artery thrombosis
Ischemia of visceral organs
%
20
14
11
9
7
7
6
NEUROLOGIC MANIFESTATIONS
1)Migraine
20%
2)Epilepsy
7%
3)Chorea
1%
4)Cerebellar Ataxia
1%
5)Transverse Myelopathy
0.5%
RENAL MANIFESTATIONS
1)Renal artery thrombosis
2)Renal vein thrombosis
3)Fibrous intimal hyperplasia
OSTEOARTICULAR MANIFESTATIONS
1)Arthralgia
2)Arthritis
39%
27%
OBSTETRIC MANIFESTATIONS
1)Preeclampsia
2)Eclampsia
10%
4%
FETAL MANIFESTATIONS
1)Early fetal losses(<10 weeks)
2)Late fetal losses(>10 weeks)
3)Premature birth
35%
17%
11%
HEMATOLOGICAL MANIFESTATIONS
1)Thrombocytopenia
2)Autoimmune hemolytic anemia
30%
10%
DIAGNOSIS
Presence of at least one clinical and one laboratory
criteria
CLINICAL CRITERIA
1)Vascular thrombosis defined as one or more
episodes of arterial, venous or small vessel
thrombosis in any tissue or organ
2)Pregnancy morbidity defined as;
a)One or more unexplained death of a
morphologically normal fetus at or beyond the 10th
week of gestation.
b)One or more premature births of a morphologically
normal neonate before 34th week of gestation because
of eclampsia ,preeclampsia,or placental insufficiency.
c)Three or more unexplained consecutive spontaneous
abortions before 10th week of gestation.
LABORATORY CRITERIA
1)Lupus anticoagulant
2)Anticardiolipin antibody
3)Anti –β 2GPI antibody
at intermediate or high titres on two occasions,12 weeks
apart.
DIFFERENTIAL DIAGNOSIS
1)Inherited or acquired causes of thrombophilia
2)Coombs positive hemolytic anemia
3)Livedo reticularis can be seen in
a)Polyarteritis nodosa
b)Cryoglobulinemia
c)Lymphomas
d)Myeloproliferative disorders
e) Atherosclerosis
TREATMENT
a)Anticoagulants i.e. warfarin and aspirin for life long
to maintain INR b/w 2.5 to 3.5 if patient developed
thrombotic event.
b)In Pregnancy combination of heparin and aspirin.
c)80 mg aspirin daily in antiphospholipid antibody
positive patients to prevent thrombotic events.
If recurrent thrombotic events despite adequate
anticoagulation;
1)IVIG 400 mg/kg qd for 5 days
2)Anti-CD 20 monoclonal antibody 375 mg/m2
per week for 4 weeks
MCQs
1)All are true regarding lupus anticoagulant except
a)Thrombocytosis
b)Increased abortions
c)Rashes
d)Arterial thrombosis
Ans .a
2)Isolated prolongation of APTT with bleeding
caused by all except
a)Factor VIII Deficiency
b)Factor IX Deficiency
c)Factor XI Deficiency
d) Presence of Lupus anticoagulant
Ans .d
3)A 25 year old lady presented with history of
recurrent abortions.The most relevant
investigation to identify the cause is
a)Bleeding time
b)Prothrombin time
c)Dilute russel viper venom time
d)Thrombin time
Ans .c
4)Treatment of choice in a pregnant women
with positive test for antiphospholipid
antibodies
a)Aspirin only
b)Aspirin +low molecular weight heparin
c)Aspirin +warfarin
d)Rituximab/IVIG
Ans .b
5)True about lupus anticoagulant include all
except
a)Life threatening bleeding episodes
b)Increased aPTT
c)May occur without clinical signs
d)Recurrent mid trimester abortions
Ans .a
6)Most common hematological manifestation of
Antiphospholipid antibody syndrome is
a)Anemia
b)Leucopenia
c)Thrombocytopenia
d)a+b
Ans .c