Antiphospholipid antibody syndrome (APAS) is caused by antibodies that target phospholipids or phospholipid-binding proteins, activating coagulation and inhibiting natural anticoagulants. This can cause blood clots, recurrent pregnancy loss, or complications like preeclampsia. Two criteria are needed for diagnosis: clinical evidence of blood clots or pregnancy morbidity, and laboratory tests positive for lupus anticoagulant, anticardiolipin antibodies or anti-β2 glycoprotein I. Treatment involves low-dose aspirin and prophylactic heparin during pregnancy. Women with a history of clots may require therapeutic anticoagulation to prevent complications like further clotting events or late fetal loss.

1. ANTIPHOSPHOLIPID ANTIBODY
SYNDROME (APAS)

2. Phospholipids are the main lipid constituents of
cell and organelle membranes.
 Thee are proteins in plasma that associate noncovalently with these
phospholipids

3. Antiphospholipid antibodies
 are directed against these phospholipids or phospholipid-
binding
proteins
 This antibody group may be of IgG, IgM, and IgA classes,
alone or in combination.

4. Pathophysiology
 Mediated by one of the following:
 (1) activation of various procoagulants,
 (2) inactivation of natural anticoagulants,
 (3) complement activation,
 (4) inhibition of syncytiotrophoblast differentiation

5. Specific phospholipid or phospholipid-binding
protein
1. β2-glycoprotein I—also known as apolipoprotein H
 is a phospholipid-binding plasma protein that inhibits prothrombinase activity within
platelets and inhibits ADP-induced platelet aggregation
 its normal action: to inhibit procoagulant binding and prevent coagulation cascade
activation.
 antibodies directed against β2-glycoprotein I would inhibit its anticoagulant activity
and promote thrombosis.
 Complement activation
 β2-glycoprotein I may be involved in implantation, and it may result in pregnancy
loss via an inflammatory mechanism

6. Specific phospholipid or phospholipid-
binding protein
2. lupus anticoagulant (LAC)
 is a heterogeneous group of antibodies directed also against phospholipid-binding
proteins
 induces prolongation in vitro of the prothrombin, partial thromboplastin, and
Russell viper venom times
 thrombotic in vivo

7. Specific phospholipid or phospholipid-
binding protein
3. Anticardiolipin antibodies (ACAs)
 Are directed against one of the many phospholipid cardiolipins found in
mitochondrial membranes and platelets

8. Some Clinical Features of Antiphospholipid
Antibody Syndrome
 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
 Other—neurological manifestations, migraine headaches, epilepsy; renal artery, vein,
or glomerula17
 r thrombosis; arthritis and arthralgia
 Pregnancy—preeclampsia syndrome, recurrent miscarriage, fetal death

9. Screening
Risk factors
• 3 or more spontaneous unexplained first trimester losses >10 weeks
• One or more unexplained fetal loss/death >10 weeks
• Early onset (34 weeks) preeclampsia or FGR leading to indicated PTB
• SLE
• History of vascular thrombosis (VTE< PE, stroke)

10. Diagnosis :
1. Vascular thrombosis
One or more clinical episodes of arterial venous, or small vessel thrombosis, in any tissue or organ.
Thrombosis must be confirmed by objective criteria (e.g. Imaging or Doppler studies or histopathology)
2. Pregnancy morbidity
A. one or more unexplained deaths of a morphologically normal fetus at or beyond the 10th
week of gestation, with normal fetal morphology documented by ultrasound or
B. one or more premature births of a morphologically normal neonate before the 34th week
of gestation because of: eclampsia or severe preeclampsia or features consistent with
placental insufficiency (e.g. abnormal Doppler flow, abnormal fetal testing, AFI < 5, SGA)
C. three or more unexplained consecutive spontaneous abortion before the 10th week of
pregnancy, with maternal and paternal chromosomal causes
Clinical Criteria for Diagnosis of APAS

11. Diagnosis :
1. Lupus anticoagulant present in plasma, on two or more occasions atleast 12
weeks apart eg LA, DRVVT or aPTT
2. Anticardiolipin antibody of IgG and or IgM isotype in serum or plasma present as >
40GPL or MPL or 99th percentile on 2 or more occasions atleast 12 weeks apart
3. Anti B2 glycoprotein I of IgG or IgM isotype in serum of plasma present in 2 or
more occasions atleast 12 weeks apart
Laboratory Criteria for Diagnosis of APAS

12. Epidemiology/Incidence
APAS
 found in 5% of healthy individuals
 25 – 35% of SLE patients
ACAs – present in 15% with recurrent miscarriage
LA – found in 8% with recurrent miscarriage
- found in 30% in women with mid-trimester loss
 70% of APAS have both ACAs and LA

13. Classification
1. Primary – refers to patients with APS but no other
autoimmune disorders
2. Secondary - refers to patients with APS but with autoimmune
disorders

14. Complications
 Maternal
1. Venous, arterial thromboembolism – risk is 5-12% in pregnancy
Most are venous (65-70%)
Arterial – occurs in atypical sites such as retina, subclavian or MCA (MC vessel involved
when stroke occurs in patients)
2. Pre-eclampsia – 18-48%
3. Auto-immune thrombocytopenia – 40-50%
- less with LMWH

15. Complications
 Fetal
1. Pregnancy loss and fetal death
2. Fetal growth restriction (in particular with ACA)
3. Preterm birth (

16. Suggested prophylaxis for APAS
Condition Regimen
APAS without previous thrombosis and
recurrent early (<10 weeks) miscarriage
Low dose aspirin with either
• UFH 5000-7500u 1st rimester, 7500-
1000U 2nd trimester, 10, 000U 3rd
trimester SQ q12h
• LMWH (enoxaparin 30-40 mg SQ q12h
or Dalteparin 5000U SQ q12
APAS with previous VTE Low dose aspirin with either
• UFH 5000-7500u 1st rimester, 7500-
1000U 2nd trimester, 10, 000U 3rd
trimester SQ q12h
• LMWH (enoxaparin 30-40 mg SQ q12h
or Dalteparin 5000U SQ q12

17. Treatment
1. APAS with early recurrent pregnancy loss: low dose ASA and prophylactic heparin
either UFH or LMWH
2. APS with VTE during the current pregnancy: therapeutic anticoagulation
Enoxaparin 1mg q12 SQ or dalteparin 200u/kg q12SQ
3. APAS with VTE in a prior pregnancy: prophylactic heparin (either UFH of LMWH)
both in antepartum and postpartum period (6 weeks)
4. APAS with late fetal death
APAS with a medically indicated preterm birth secondary to early onset IUGR or
severe preeclampsia

18. Antepartum Testing
 Early ultrasound for accurate dating
 Detailed Ultrasound at about 18-20 weeks and followup US about 4-6 weeks for
growth, fluid volume and Doppler evaluation of the fetus if needed
 Fetal surveillance test (NST or BPP) starting age 32 weeks
 Daily fetal kick counts

19. Anesthesia
 If on UFH – after 6 to eight hours after the dose of if with normal aPTT
 If on LMWH – delayed until 24 hours

20. Delivery
 Sent placenta to pathology to check for decreased placental weight, ischemic-
hypoxic change, infarctions, decidual and fetal thrombi, chonic villitis