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 also against PL binding

proteins, mainly β-2GPI and

prothrombin.

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

EPIDEMIOLOGY

PATHOGENESIS-• Preceding infections as initiating event

• Anti phospholipid antibodies

1)inactivate natural anticoagulants such as protein C(Activated protein C (APC) binds the pro-coagulant 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 39Livedo reticularis 24Pulmonary embolism 14Superficial thrombophlebitis 12

Arterial Thrombosis %

Stroke 20Cardiac involvement 14 Transient ischemic attack 11 Leg ulcers and/or digital gangrene 9Arterial thrombosis in the extremities 7Retinal artery thrombosis 7Ischemia of visceral organs 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 39%2)Arthritis 27%

OBSTETRIC MANIFESTATIONS1)Preeclampsia 10%2)Eclampsia 4%

FETAL MANIFESTATIONS1)Early fetal losses(<10 weeks) 35%2)Late fetal losses(>10 weeks) 17%3)Premature birth 11%

HEMATOLOGICAL MANIFESTATIONS1)Thrombocytopenia 30%2)Autoimmune hemolytic anemia 10%

DIAGNOSISPresence of at least one clinical and one laboratory criteriaCLINICAL CRITERIA1)Vascular thrombosis defined as one or more episodes of arterial, venous or small vessel thrombosis in any tissue or organ2)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 CRITERIA1)Lupus anticoagulant2)Anticardiolipin antibody3)Anti –β 2GPI antibodyat 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 excepta)Thrombocytosisb)Increased abortionsc)Rashesd)Arterial thrombosis

Ans .a

2)Isolated prolongation of APTT with bleeding caused by all except

a)Factor VIII Deficiencyb)Factor IX Deficiencyc)Factor XI Deficiencyd) 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 timeb)Prothrombin timec)Dilute russel viper venom timed)Thrombin time

Ans .c

4)Treatment of choice in a pregnant women with positive test for antiphospholipid antibodies

a)Aspirin onlyb)Aspirin +low molecular weight heparinc)Aspirin +warfarind)Rituximab/IVIG

Ans .b

5)True about lupus anticoagulant include all except

a)Life threatening bleeding episodesb)Increased aPTTc)May occur without clinical signsd)Recurrent mid trimester abortions

Ans .a

6)Most common hematological manifestation of Antiphospholipid antibody syndrome isa)Anemia b)Leucopenia c)Thrombocytopeniad)a+b

Ans .c