A 26-year-old pregnant woman presents with a history of spontaneous first trimester abortions. Laboratory workup reveals positive ANA and anticardiolipin antibodies. This raises concern for antiphospholipid syndrome (APS), a condition characterized by elevated antiphospholipid antibodies that can cause blood clots and recurrent pregnancy loss. APS has a prevalence of 5.6% and is associated with conditions like systemic lupus erythematosus. Management may involve anticoagulation therapy and low-dose aspirin to reduce the risk of complications during pregnancy.

1. Antiphospholipid
Syndrome
Ob/Gyn Presentation
Joel E. Rodriguez Ramos
Sunday, February 10, 13

2. Case
• 26 year old woman attends the afternoon clinics
for a routine examination of her current
pregnancy. The patient is 11 weeks pregnant, G6
P1 A4, with some scant vaginal spotting on
occasions. Upon further evaluation the patient
states that her previous abortions were during
the first trimester and spontaneous in nature.
The patient also states no prior history of illness
and denies coagulopathies. Upon follow-up
patient presents laboratories with positive ANA
and Anticardiolipin antibodies.
Sunday, February 10, 13

3. Differential Diagnosis
• Inherited Thrombophilia
• Thrombotic Thrombocytopenic Purpura
• Disseminated Intravascular Coagulation (DIC)
• Systemic Lupus Erythematous
• Anti-Phospholipid Syndrome
Sunday, February 10, 13

4. Epidemiology
• Prevalence: 5.6%
• Mean onset: 34 y/o
• Affects Females 5:1 over Males
• Associated with:
• SLE = ~40%
• Recurrent pregnancy loss = ~20%
• Thrombosis = ~14%
• RA = ~6%
Sunday, February 10, 13

5. Etiology
• No specific source has been identified
• Elevated antiphospholipid antibodies bind to various
phospholipid-binding plasma proteins (PBPP) forming
venous, arterial, and microvascular thromboses and/or
pregnancy associated morbidity.
Sunday, February 10, 13

6. • Phospholipid-Binding Plasma Proteins
include:
• Apolipoprotein-H (aka: !2-GlycoProtein I)
• Annexin A5
• Phospholipids on Platelets and
Trophoblasts cells
• Lupus Anticoagulant
• The Complement system, with the
association of resistance to Annexin A5, has
been implicated in the pathogenesis of
thrombosis and fetal loss.
Sunday, February 10, 13

7. Pathophysiology
• Anti-Annexin A5 antibodies
exposes phospholipid-
dependent coagulants to
coagulation.
• Anti-Cardiolipin Antibodies
binds to Apolipoprotein-H
prevents Protein C from
deactivating Factor VIIIa.
• Lupus Anticoagulant antibodies
bind to pro-thrombin, increasing
its cleavage to thrombin, thus
accelerating the formation of
fibrin.
Sunday, February 10, 13

8. Risk Factors
• Primary
• HLA-DR7
• Secondary
• SLE or RA
• HLA-B8
• HLA-DR2
• HLA-DR3
• Ethnicity
• African American, Hispanics
and Native American
Sunday, February 10, 13

9. Diagnostic Criteria
• One Serological test
• Must be positive twice at least 12 weeks apart
• Lupus Anti-Coagulant
• Anti-Cadiolipin antibodies via ELISA
• ApoH (Anti-!2-Glycoprotein I) antibodies
• ANA
• ds-DNA
Sunday, February 10, 13

10. Diagnostic Criteria
• One Clinical test
• Arteriovenous Ultrasound
Doppler
• MRI Venography
• 3+ unexplained consecutive
spontaneous abortions before
the 10th week of gestation.
Sunday, February 10, 13

11. Next Step in Management?
• Verify prothrombin time (PT)
• Use of amidolytic Factor X assay if a
suitable PT assay is not found
• Anticoagulation therapy with an INR target
between 2 and 3
• Antenatal heparin and low dose aspirin
throughout pregnancy for women no
prior history of thrombosis.
• Low dose aspirin for women with a
history of pre-eclampsia or fetal growth
restriction
• Post-partum thromboprophylaxis
Sunday, February 10, 13

12. Management Flow Chart
LMW Heparin
Acute
Fetal Monitoring
Thrombosis
Post-partum Warfarin
Prophylactic Low-Dose Aspirin + LMW Heparin
Obstretic APS Fetal Monitoring
Post-partum Warfarin
Prophylactic Low-Dose Aspirin + LMW Heparin
APS + Hx
Fetal Monitoring
Thrombosis
Post-partum Warfarin
aPL Low-Dose Aspirin
Sunday, February 10, 13

13. ACOG Guidelines
• Women with APS and no thrombotic history should receive
prophylactic low-dose aspirin, alone or along with heparin,
during pregnancy and the postpartum period (6-8 weeks).
• Women with APS and a previous history of thrombosis should
receive full anticoagulation throughout pregnancy and the
postpartum period (6-8 weeks).
• Frequent prenatal exams, serial ultrasonography, and
antepartum testing after week 32 of gestation, or earlier in cases
of fetal growth restriction, should be performed.
Sunday, February 10, 13

14. Prognosis
• Good prognosis of both the mother and fetus if the condition is
diagnosed and managed properly.
• Complications
• Thrombus formation
• Pulmonary emboli
• Transient Ischemic Attack (TIA)
• Placenta Abruptio
• Fetal growth restriction
• Abortion or still birth
• Pre-eclampsia
• Patients should have multidisciplinary follow-up monitoring by an
gynecologist, hematologist and rheumatologist.
Sunday, February 10, 13

15. Current Research
• New oral anticoagulants
• Direct thrombin inhibitors
• Oral Anti-Xa inhibitors (dabigatran, rivaroxaban)
• Demonstrated to be safe and efficacious primary and
secondary thromboprophylactic agents in limited studies.
• Hydroxychloroquine
• Widely used in the treatment of patients with SLE and has
been associated with a decreased risk of thrombotic events.
• Shown to reverse the binding of antiphospholipid
antibody-apoH complexes to phospholipid bilayers.
Sunday, February 10, 13

16. Doubts?
Sunday, February 10, 13

17. References
• American Congress of Obstreticians and Gynecologists - http://www.acog.org
• US Department of Health Guidelines - http://guidelines.gov
• E-Medicine - http://www.emedicine.com
• Medline Plus - http://www.nlm.nih.gov/medlineplus
• Pub Med Health - http://www.ncbi.nlm.nih.gov
Sunday, February 10, 13