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Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently.

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Presentation on theme: "Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently."— Presentation transcript:

1 Antiphospholipid symdrome APS

2 Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently raised levels of anti-phospholipid antibodies. Primary: Occurs alone Secondary: Associated with other autoimmune or rheumatic diseases

3 Epidemiology of APLs Prevalance : Unknown Women : % Familial disease : Frequent HLA-DQB

4 Antiphospholipid Antibodies Common finding significant proportion of healthy (esp. elderly) population most never thrombosis may be transient

5 Antiphospholipid Antibodies Clinically significant antiphospholipid antibodies are not antiphospholipid antibodies Antibodies against phospholipid-bound proteins e.g. 2 glycoprotein 1, prothrombin

6 Anti-Phospholipid antibodies Lupus Anti-coagulant Anti-cardiolipin antibody Anti-ß2 glycoprotein I antibody Anti-prothrombin False + serologic test for Syphillis

7 Antiphospholipid syndrome Association of a thrombotic tendency venous or arterial thrombosis recurrent miscarriages with the persistence of one or more antiphospholipid antibodies confirmed by two different tests, or IgG or IgM by ELISA(LA,ACL) repeated after 6 week

8 Lupus Anti-coagulant Blocks In Vitro assembly of prothrombinase Prolongs aPTT dRVVT( Russell viper venum time ) KPC( Kaolin clotting )

9 Anti-cardiolipin antibody React with phospholipids such as cardiolipin Different immunoglobulin subclasses and isotypes are associated with anti-cardiolipin antibodies IgG, IgA, IgM (IgG 1-4) Increased levels of IgG acl incurs a greater risk of thrombosis 85% concordance LA and ACL

10 Anti-ß2 glycoprotein I antibody Inhibitor of coagulation (phospholipid binded) Occurs alone in 11% Also known Apolipoprotein H Phospholipid bound inhibitor of coagulation and platelet aggregation Inhibits contact activation of clotting Inhibits Prothrombin to Thrombin conversion Found in large percentage of primary and secondary APS

11 False + serologic test for Syphillis Phospholipid dependant tests Syphillis antigen-cardiolipin

12 Anti-prothrombin Associated with higher risk of recurrent thrombosis Risk independent of presence of ACL or LA

13 Pathogenesis

14 Mechanism of thrombosis Antiphospholipid Ab : Interference in cells of coagulation Selective inhibition of protein C anticoagulant pathway

15 Interference in cells of coagulation Antiphospholipid Ab activation Endothelial cell Inducing : Adhesion molecule, Tissue Factor Endothelin TX A2 Monocyte Expression : TF TXA2 Antiplatelet Ab Aggregation vasoconstriction Platelet activation Thrombosis

16 Mechanism of fetal loss Antiphospholipid Ab Direct effect on throphoblast Endothelial cell lesion of placental vessels Competes with Annexin Intraplacental thrombosis Tissue hypoxia Fetal loss

17 Clinical manifestation

18 Disease associations

19 Clinical manifestation Major : Vascular thrombosis Pregnancy morbidity Minor : Hematologic :Thrombocytopenia,… Dermatologic : ( Livedo reticularis….) Neurologic : ( CVA ….) Others

20 Vascular thrombosis Sporadic In < 50 years Unrelated to antibody level Recurrent Venous : Deep vein thrombosis of the leg Arterial : Stroke Small vessel : Kidneys & Skin

21 Pregnancy morbidity Unexplained fetal death Unexplained spontaneous abortion Premature birth before the 34 th weeks of gestation Others : Fetal distress, preclampsia, post partum thrombotic accident, HELLP syndrome, fetal growth disorder

22 Hematologic Thrombocytopenia : Mild to moderate(100,000 – 150,000 ) APL a/b in 70-82% of SLE and thrombocytopenia 30 – 40% with ITP ITP therefore may be associated with thrombosis Hemolytic anemia : Positive combs test

23 Dermatologic Raynoud phenomen Livedo reticularis Superficial thrombophelebitis Leg ulcer Cutaneous necrosis Splinter hemorrhage Acrocyanosis

24 Livedo reticularis

25 Livedo reticularis with necrotic finger tips in Antiphospholipid syndrome

26 Neurologic Migraine headache Stroke & TIA Chorea Memory loss Dementia Multiple sclerosis-like syndrome Transverse myelitis Seizure Non focal neurologic symptoms Guillene-barre

27 Others Libman-sacks endocarditis Valvular insufficiency Pulmonary hypertension Renal failure

28 Laboratory tests

29 Anti cardiolipin ( ACL ) & Lupus anti coagulant ( LA ) test : for people suspected of having APS Anti B2GP1 : for people with signs of APS but normal ACL & LA tests Platelet, ANA, ESR, Urinalysis : for patient with SLE

30 Drug induced APLa

31 Drug induced APS Phenytoin, Hydralazine, Chlorpromazine, Procainamide IgM isotype of antiphospholipid Ab Antiphospholipid no related to B2GP1 Thrombosis and Thrombocytopenia


33 Diagnosis Definite APS is considered to be persist if at least one of the clinical and one of the laboratory criteria are presented

34 Vascular thrombosis : One or more clinical episode of arterial, venous or small-vessel thrombosis in any tissue or organ and Thrombosis confirmed by imaging or Doppler studies or histopathology, with the exception of superficial venous thrombosis Histopathologic confirmation with thrombosis in the absence of inflammation in the vessel wall

35 Pregnancy morbidity Unexplained fetal death : After the 10 th weeks of gestation (one or more ) Unexplained spontaneous abortion : before the 10 th weeks of gestation (3 or more) Premature birth before the 34 th weeks of gestation (one or more)

36 Laboratory criteria ACL Ab IgG and/or IgM isotype in blood Medium or high titer on two or more occasions at least six weeks apart Measured by standard ELISA for B2GP1 dependent L.A Ab Present in plasma on two or more occasions at least six weeks apart,

37 Diseases association

38 Disease associations Long list of associated diseases SLE Main Groups Autoimmune Infections and drugs Neoplasms Genetic Other


40 Non-Autoimmune causes for positive Antiphosphospholipid Ab tests Assay Antibody type Causes ELISA B2GP1 independent Syphlis,lyme Leptospirosis, HIV B2GP1 dependent Advanced age Drug Lymphoproliferative Hyperimmunoglobulin M LA Either HIV, Drugs

41 Catastrophic APS

42 Catastrophic vascular occulsion syndrome Multiple vascular of medium and small arteries that occurring over a period of day Risk factors : Infection, Drugs, Small surgery, Anticoagulant withdrawal, Post partum period Often history of SLE or PAPS Stroke, Cardiac, Hepatic, Adrenal, Renal and Intestinal infarction, Peripheral gangrene, Thrombocytopenia, Hemolytic anemia, Hypertension Biopsy : Non-inflammatory vascular occlusion 50% mortality

43 Treatment

44 Treatment-General Thrombotic therapy Heparin Wafarin Pregnancy – controversial SC heparin and/or Aspirin Immunosuppresion – rarely used Treat associated condition eg.SLE Risk factor modification eg.smoking, OCP

45 APS treatment Asymptomatic Positive antiphospholipid Ab : no treatment Venous thrombosis : Peripheral venous thrombosis : INR = 2 Proximal thrombosis, Budd-chiari syndrome, Cavernous or sagittal sinus thrombosis, Pulmonary emboli : INR =3 Arterial Thrombosis : INR = 3

46 APS treatment First pregnancy, Single pregnancy loss < 10th week : Low dose Aspirin Recurrent fetal loss, loss after 10th week : Heparin 5000 U bid throughout pregnancy Discontinue 6-12 weeks postpartum Recurrent fetal loss, loss after 10th week +Thrombosis : Heparin 5000 U bid throughout pregnancy and Warfarin postpartum

47 Treatment-Other Plasmapharesis IVIG Experimental – fibrinolytics, prostacyclin anti- cytokines

48 Treatment - CAPS Uncontrolled data to suggest intensive treatment betters outcome(70% recovery) Anticoagulation Steroids Plasmapharesis or IVIG Treatment of any precipitant eg. Infection Cytotoxics (if indicated eg.Active SLE )


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