APLA Syndrome.pptx

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1. APLA Syndrome ( A ntiphospholipid antibody syndrome) Moderator : Dr Saroj Purohit Ma’am Presenter : Dr Monesh Dhakar

2. Synonyms: APS ( Aantiphospholipid syndrome) Hughes syndrome Familial lupus anticoagulant syndrome Definition: APLS is an autoimmune multisystem disorder characterized clinically by recurrent thrombosis & pregnancy morbidity & serologically by the presence of antiphospholipid antibodies ( lupus anticoagulant, anticardiolipin & anti-beta 2- glycoprotein Ⅰ antibodies ).

3. Primary APL syndrome : when the condition occurs in the absence of any other related disease 53% cases Secondary APL syndrome : when the condition occurs In the context of other autoimmune diseases, such as SLE

4. Occurs in young to middle aged adults with female preponderance Associated diseases SLE RA Sjogren syndrome Systemic sclerosis

5. Pathophysiology mechanism of thrombosis in APLS are: Increased expression of tissue factor on monocytes & endothelial cells Interference in the protein C anticoagulant pathway Inhibition of fibrinolysis Inhibition of annexin V binding to phospholipids

6. Genetic : T here is association between the HLA-DRB1*14 on chromosome 6p21.3 & familial primary APLS. B2GP1 Val/ Leu polymorphism was associated with susceptibility to APLS & thrombosis. Smoking: Can lead to endothelial injury & increase the pro-thrombotic susceptibility in patients with lupus anticoagulant.

7. Infections : Have role in APLS by causing molecular mimicry & by inducing antibody response E g : B orrelia burgdorferi T reponema L eptospira HIV Hep C Leprosy Drugs : A lter the processing & presentation of self antigen, thus causes the autoimmunity Eg : C hlorpromazine Procainamide Q uinidine P henytoin

8. Two hit phenomenon 1 st hit : Procoagulant state induced by the antiphospholipid antibodies by destroying the integrity of the endothelium 2 nd hit : Thrombosis takes place only in the presence of initiating factor such as trauma, infection or inflammation

9. Presentation of APLA syndrome Cutaneous findings Livedo reticularis with or without retiform purpura or retiform necrosis Superficial thrombophlebitis migrans P urpura Echymosis Livedoid vasculopathy / atrophie blanche Raynaud phenomenon Nailfold ulcers Wide spread cutaneous necrosis (catastrophic APLA) Leg ulcers Vasculitis like lesions Pyoderma gangrenosum like ulcers Splinter haemorrhages

10. Venous thrombosis Mainly present as deep vein thrombosis Pulmonary embolism O ther venous systems which may be involved are : Renal veins Portal veins Mesenteric veins Intracranial veins Arterial thrombosis: Less common than venous thrombosis M ost frequent site : cerebral vasculature resulting in transient ischaemia or stroke MI can also occur

11. Valvular involvement Cardiac valve involvement is very common in APLS Mitral & aortic valve are most commonly involved Thickening , nodules & Libman -Sacks endocarditis seen Hematological involvement Thrombocytopenia Hemolytic anemia

12. Neurological involvement MC presentations are in the form of TIAs or ischemic stroke Cognitive dysfunction, seizures , chorea & multi-infarct dementia also seen Blindness due to CRAO & CRVO SNHL Renal involvement HTN, proteinuria, & renal failure secondary to thrombotic microangiopathy

13. Catastrophic APLS : Rare but disastrous variant Develop over a short period of time Generalized microvascular thrombosis lead to widespread cutaneous necrosis & multiorgan failure, especially renal & pulmonary system Associated with high risk of mortality

14. Preliminary classification criteria for catastrophic APLS Evidence of involvement of three or more organs, systems &/or tissues Development of manifestations simultaneously or less than a week Confirmation by histopathology of small vessel occlusion Laboratory confirmation of the presence of antiphospholipid antibodies

15. Definite catastrophic APLS : all 4 criteria present Probable catastrophic APLS: All 4 criteria, except only two organs, systems &/or tissues involved All 4 criteria, except for the absence of laboratory confirmation of antiphospholipid antibodies Criteria 1,2 & 4 Criteria 1,3 & 4 with the development of a third event >1 week but within 1 month of presentation , despite anticoagulation

16. Histological findings : N oninflammatory thrombosis of small dermal blood vessels

17. Differential diagnosis HIT (heparin induced thrombocytopenia) TTP (thrombotic thrombocytopenic purpura ) DIC (disseminated intravascular coagulation)

18. Investigations Lupus anticoagulation test: This test is the strongest predictor of pregnancy related events It is more specific but less sensitive It is a 4 step test Prolonged phospholipid dependent coagulation screening test (APTT or DRVVT) Inability to correct the prolonged screening test despite mixing the pt’s plasma with normal platelet poor plasma. This indicates the presence of an inhibitor Improvement in the prolonged screening test after the addition of excess phospholipid Exclusion of other inhibitors

19. Anticardiolipin & anti-beta-2-glycoprotein Ⅰ antibodies These antibodies ( IgG & IgM isotypes ) are assessed by ELISA Medium or high titres (especially at or above the 99 th percentile) are deemed significant positives Initial positive test should be repeated to check for the persistence at least 12 weeks later. Other laboratory findings Thrombocytopenia Anemia Proteinuria Positive serologies specific for SLE (ANA, anti-Ds-DNA)

20. Criteria for antiphospholipid antibody syndrome require atleast one clinical & one laboratory criterion Clinical criteria Vascular thrombosis : one or more clinical episodes of arterial, venous or small vessel thrombosis Complications of pregnancy : One or more unexplained deaths of morphologically normal fetuses at or after 10 weeks of pregnancy or One or more premature births of morphologically normal neonates at or before 34 weeks of gestation or Three or more unexplained consecutive spontaneous abortions before 10 weeks of gestation

21. Laboratory criteria Anticardiolipin antibodies, IgG or IgM , present at moderate or high levels on two or more occasions at least 12 weeks apart Lupus anticoagulant antibodies on two or more occasions at least 12 weeks apart Beta 2 glycoprotein 1 antibodies on two or more occasions at least 12 weeks apart

22. Treatment Thrombosis management: Pts with positive blood test for APLA but no prior H/O thrombotic events : no treatment Pts with SLE with positive APLA: HCQ is recommended Low dose aspirin may also be considered Pts with a venous thrombotic event, warfarin with an INR goal of 2.0 to 3.0 is recommended

23. During pregnancy For pregnant female with positive APLA but no history of arterial or venous thrombosis 1 st pregnancy or single pregnancy loss <10weeks: no treatment is indicated H/O multiple pregnancy losses < 10 weeks: low dose aspirin with LMWH H/O one or more pregnancy losses >10 weeks: low dose aspirin with LMWH throughout pregnancy & can be continued 6 to 12 weeks postpartum For pregnant female with positive APLA & past history of arterial or venous thrombosis Low dose aspirin in combination with unfractionated heparin or LMWH throughout pregnancy. after delivery, these patients should be transitioned to warfarin, which should be continued life long with the INR goal of 2.0 to 3.0