LABORATORY EVALUATION LABORATORY EVALUATION OF ANTIPHOSPHOLIPID OF ANTIPHOSPHOLIPID

SYNDROMESYNDROME

Antiphospholipid syndrome Antiphospholipid syndrome (APS)(APS)

Lupus anticoagulant syndromeLupus anticoagulant syndromeHughes syndromeHughes syndromeSneddon syndromeSneddon syndromeDEFINITION:DEFINITION: Disorder characterized by recurrent Disorder characterized by recurrent

venous or arterial thrombosis and/ or venous or arterial thrombosis and/ or fetal losses associated with fetal losses associated with characteristic laboratory characteristic laboratory abnormalities such as evidence of a abnormalities such as evidence of a circulating anticoagulant or circulating anticoagulant or persistently elevated levels of persistently elevated levels of anticardiolipin antibodies.anticardiolipin antibodies.

Primary APS : APS occur in patients Primary APS : APS occur in patients without evidence of any definable without evidence of any definable associated diseaseassociated disease

Secondary APS : APS occurs in Secondary APS : APS occurs in association with SLE or another association with SLE or another Rheumatic or autoimmune disorderRheumatic or autoimmune disorder

Catastrophic APS : Acute, severe, Catastrophic APS : Acute, severe, multiple organ APS illnessmultiple organ APS illness

Clinical manifestationsClinical manifestations

Arterial & Venous thromboembolic Arterial & Venous thromboembolic disease:disease:

Most commonMost common Extremity Deep vein thrombosisExtremity Deep vein thrombosis Axillary, retinal or hepatic veins & Axillary, retinal or hepatic veins &

cerebral venous sinus thrombosiscerebral venous sinus thrombosis Cerebral thrombosis or mesentric Cerebral thrombosis or mesentric

artery occlusion, GI ischemia or artery occlusion, GI ischemia or ulcerationulceration

Obstetric manifestations:Obstetric manifestations: Criteria :Criteria : 1 or more unexplained deaths of a 1 or more unexplained deaths of a

morphologically normal fetus at or morphologically normal fetus at or beyond the 10beyond the 10thth week of gestation week of gestation

oror 1 or more premature births of a 1 or more premature births of a

morphologically normal neonate morphologically normal neonate before the 34before the 34thth week of gestation week of gestation

oror 3 or more unexplained consecutive 3 or more unexplained consecutive

spontaneous abortions before the spontaneous abortions before the 1010thth week of pregnancy excluding week of pregnancy excluding anatomic , hormonal & anatomic , hormonal & chromosomal abnormalities chromosomal abnormalities

Hematologic :Hematologic :

Bleeding : coexistent Bleeding : coexistent thrombocytopenia, platelet thrombocytopenia, platelet dysfunction, prothrombin deficiency dysfunction, prothrombin deficiency or other underlying coagulopathiesor other underlying coagulopathies

Neurologic Syndromes:Neurologic Syndromes:

acute ischemia (CVA, TIA, acute ischemia (CVA, TIA, encephalopathy), severe migraine, encephalopathy), severe migraine, multiple infarct dementia, cognitive multiple infarct dementia, cognitive dysfunction, seizures dysfunction, seizures

Dermatologic disorders:Dermatologic disorders:

Ischemic dermatologic syndromes Ischemic dermatologic syndromes include livedo reticularis, include livedo reticularis, acrocyanosis, widespread cutaneous acrocyanosis, widespread cutaneous necrosis, pyoderma gangrenosum necrosis, pyoderma gangrenosum like skin lesionslike skin lesions

Cardio pulmonary disorders:Cardio pulmonary disorders:

MI, intracardiac thrombotic mass, MI, intracardiac thrombotic mass, peripheral arterial disease, peripheral arterial disease, thromboembolic & non thrombotic thromboembolic & non thrombotic pulmonary hypertensionpulmonary hypertension

Catastrophic Antiphopholipid Catastrophic Antiphopholipid Antibody Syndrome:Antibody Syndrome:

diffuse small vessel ischemia & diffuse small vessel ischemia & occlusion with extensive tissue occlusion with extensive tissue damage including MI, limb ischemia, damage including MI, limb ischemia, DIC & a high mortality rate.DIC & a high mortality rate.

SAPPORO CriteriaSAPPORO CriteriaCLINICAL EVENT:CLINICAL EVENT: Venous thrombosisVenous thrombosis Arterial thrombosisArterial thrombosis Small vessel thrombosisSmall vessel thrombosis Complications of pregnancyComplications of pregnancy

LABORATORY ABNORMALITY:LABORATORY ABNORMALITY: Positive Lupus anticoagulant testPositive Lupus anticoagulant test Positive Anticardiolipin antibodiesPositive Anticardiolipin antibodies Positive Positive ß2 glycoprotein1 antibodiesß2 glycoprotein1 antibodies

Laboratory abnormality should Laboratory abnormality should persist for 2 or more occasions at persist for 2 or more occasions at least 12 weeks apartleast 12 weeks apart

The diagnosis of APS requires the The diagnosis of APS requires the presence of at least one clinical presence of at least one clinical event & at least one laboratory event & at least one laboratory abnormality abnormality

ANTIPHOSPHOLIPID ANTIBODIESANTIPHOSPHOLIPID ANTIBODIES

Family of antibodies reactive with Family of antibodies reactive with proteins which are themselves proteins which are themselves complexed with negatively charged complexed with negatively charged phospholipids.phospholipids.

Lupus anticoagulant & Anticardiolipin Lupus anticoagulant & Anticardiolipin antibodies antibodies

Lupus AnticoagulantLupus Anticoagulant

Heterogenous class of Heterogenous class of immunoglobulins that may develop immunoglobulins that may develop spontaneously or as a consequence spontaneously or as a consequence of autoimmune diseasesof autoimmune diseases

Bind to proteins such as Bind to proteins such as ß2 ß2 glycoprotein1, prothrombin or others glycoprotein1, prothrombin or others in complex with negatively charged in complex with negatively charged phospholipids, thus prolong phospholipids, thus prolong phospholipid dependent coagulation phospholipid dependent coagulation tests tests

Lupus Anticoagulant are stronger Lupus Anticoagulant are stronger risk factor for thrombosis than risk factor for thrombosis than Anticardiolipin antibodiesAnticardiolipin antibodies

LA is a double misnomer for it is LA is a double misnomer for it is neither a test of lupus nor an in neither a test of lupus nor an in vivo anticoagulantvivo anticoagulant

Anticardiolipin antibodiesAnticardiolipin antibodies

APLA where APLA where ß2 glycoprotein1 ß2 glycoprotein1 serves as a mandatory protein serves as a mandatory protein cofactorcofactor

Detected by Solid- Phase Detected by Solid- Phase immunoassayimmunoassay