ANTIPHOSPHOLIPID

SYNDROME
Gomez, Abraham III A.
CSU Junior Intern
Introduction
• also known as Hughes Syndrome
• autoantibody-mediated acquired thrombophilia with recurrent
thrombosis or pregnancy morbidity
• persistently positive serum tests for APA and with arterial
and/or venous thrombosis or obstetrical morbidity
Introduction
Antibodies involved
• Lupus Anticoagulant
• Anticardiolipin Antibody
• Anti-β2 glycoprotein-I Antibody
Pathophysiology
Mediated by:
• activation of various procoagulants
• inactivation of natural anticoagulants
• complement activation
• inhibition of syncytiotrophoblast diferentiation

Leads to
• arterial or venous thromboses
• Pregnancy morbidity
Clinical Manifestations
• cerebrovascular arterial and venous thrombosis
• psychiatric features
• multiple sclerosis
• renal failure
• recurrent pregnancy loss and placental dysfunction
Clinical Manifestation
Catastrophic Antiphospholipid Antibody Syndrome (CAPS)
• rapidly progressive thromboembolic disorder simultaneously
affecting three or more organ systems or tissues
• activation of cytokine storm
Specific APAs
β2- Gycoprotein I
• Apolipoprotein H
• inhibits prothrombinase activity within platelets and inhibits
platelet aggregation
• limit procoagulant binding preventing coagulation cascade
activation
• expressed in high concentrations on the syncytiotrophoblast
surface
• may be involved in implantation
Specific APAs
Lupus Anticoagulant (LAC)
• antibodies directed against phospholipid-binding proteins
• induces prolongation in vitro of PT, PTT, and Russell viper
venom time
Specific APAs
Anticardiolipin Antibodies (ACA)
• directed against cardiolipins found in mitochondrial
membranes and platelets.
Clinical Features
Venous thrombosis
• thromboembolism, thrombophlebitis, livedo reticularis
Arterial thrombosis
• stroke, transient ischemic attack, Libman-Sacks cardiac
vegetations, myocardial ischemia, distal extremity and
visceral thrombosis and gangrene
Hematological
• thrombocytopenia, autoimmune hemolytic anemia
Clinical Features
Other
• neurological manifestations, migraine headaches,
epilepsy; renal artery, vein, or glomerular thrombosis;
arthritis and arthralgia
Pregnancy
• preeclampsia syndrome, recurrent miscarriage, preterm
delivery, fetal-growth restriction, fetal death
Diagnosis
• Laboratory and clinical criteria
• vascular thrombosis or certain pregnancy morbidity
• elevated levels of LAC, ACA, and anti-β2 glycoprotein I
should be confirmed on two occasions 12 weeks apart
Diagnosis
Diagnosis
LAC tests
• PTT, dilute Russell viper venom test, platelet neutralization
procedure
ACA
• ELISA
Pregnancy and APAs
High ACA levels and LAC identification
• Increased risk for decidual vasculopathy, placental infarction,
fetal-growth restriction, early-onset preeclampsia, and
recurrent fetal death
• high incidence of venous and arterial thromboses, cerebral
thrombosis, hemolytic anemia, thrombocytopenia, and
pulmonary hypertension
Pregnancy Pathophysiology
• Platelet damage caused by:
• Directly or indirectly by APA
• indirectly by binding to β2-glycoprotein I
• Platelets susceptible to aggregation
Pregnancy Pathophysiology
• APA decrease decidual production of the prostaglandin E2
• activation of the tissue factor pathway → thrombosis in APS
• uncontrolled placental complement activation by APAs → fetal
loss and growth restriction
Adverse Pregnancy Outcomes
• APAs associated with higher rates of fetal wastage
• antibody prevalence and miscarriage are common
• incidence of antiphospholipid antibodies in the general
• obstetrical population 5%
• early pregnancy loss approximately 20%
Thrombosis Prevention
With prior thromboembolic events
• with APAs, at risk for recurrence in subsequent pregnancies
• prophylactic anticoagulation
• heparin thoughout pregnancy and heparin or warfarin 6
weeks postpartum
Without prior thromboembolic events
• close antepartum maternal observation with/without
prophylactic or intermediate-dose heparin
• postpartum anticoagulation for 4 to 6 weeks
Thrombosis Prevention
CAPS treatment
• full anticoagulation, high-dose corticosteroids, plasma
exchange, and/or intravenous immunoglobulins
• rituximab
Specific Therapy
• Aspirin 60-80 mg PO daily
• Unfractionated heparin 5000 to 10, 000 units SC q12°
• LMWH (enoxaparin) 40 mg QD

For women with SLE or those being treated for APS who develop
SLE
• corticosteroid therapy
• Prednisone maintained at lowest effective level
Specific Therapy
• IVIG when first-line therapies have failed
• 0.4g/kg/d for 5 days (total dose of 2 g/kg) repeated monthly,
or given as a single dose of 1 g/kg each month

• Hydroxychloroqione
• Statins
Treatment Efficacy
• Fetal loss – common in women with APS if untreated
• Recurrent fetal loss rates 20-30% even with treatment
• 30% of newborns demonstrate passively acquired APA
THANK YOU!