Apas

apas

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 β 2 -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 β 2 -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 10 th week of gestation, with normal fetal morphology documented by ultrasound or B. one or more premature births of a morphologically normal neonate before the 34 th 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 10 th week of pregnancy, with maternal and paternal chromosomal causes Clinical Criteria for Diagnosis of APAS

11. Diagnosis : Lupus anticoagulant present in plasma, on two or more occasions atleast 12 weeks apart eg LA, DRVVT or aPTT Anticardiolipin antibody of IgG and or IgM isotype in serum or plasma present as > 40GPL or MPL or 99 th percentile on 2 or more occasions atleast 12 weeks apart 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 Primary – refers to patients with APS but no other autoimmune disorders Secondary - refers to patients with APS but with autoimmune disorders

14. Complications Maternal 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) Pre- eclampsia – 18-48% Auto-immune thrombocytopenia – 40-50% - less with LMWH

15. Complications Fetal Pregnancy loss and fetal death Fetal growth restriction (in particular with ACA) 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 2 nd trimester, 10, 000U 3 rd 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 2 nd trimester, 10, 000U 3 rd trimester SQ q12h LMWH (enoxaparin 30-40 mg SQ q12h or Dalteparin 5000U SQ q12

17. Treatment APAS with early recurrent pregnancy loss: low dose ASA and prophylactic heparin either UFH or LMWH 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