RHEUMATOLOGY 2013

ANTIPHOSPHOLIPID SYNDROME (APS OR APLA SYNDROME)

BY DR. OM LAKHANI , MD
IMPORTANT POINTS These notes are made from Standard Textbook of Medicine The current notes corresponds to Chapter 320 of Harrisons Internal medicine The Yellow shades refer to things you have to revise frequently (atleast once a week) The Blue shades refers to concepts The Pink shades refers to concepts that are not required for undergraduate level but useful for Postgraduate level.

INTRODUCTION Q. What is other name of APS ? Hughes syndrome

Q. What is the typical triad of APS ?

Recurrent fetal loss Thrombocytopenia Thrombosis Arterial and Venous Classification Primary APS without other conditions Secondary APS secondary to other conditions Catastrophic APS

Q. Define catastrophic APS Catastrophic APS (CAPS) is defined as a rapidly progressive thromboembolic disease involving simultaneously three or more organs, organ systems, or tissues leading to corresponding functional defects Q. Which are the Antiphospholipid antibodies ?

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Other Phosphatidyl serine Phosphatidyl inositol Anticardiolipin Lupus anticoagulant Anti beta2 glycoprotein 1

Q. What is primary APLA ? Primary APLA is without presence of associated connective tissue disease

Q. What % of patients with SLE have APLA syndrome positive ? 12-34% with SLE develop APS 50% of the patient of SLE have APLA positive. It is a hypercoaguable state

Q. What are the clinical criteria for classfication of APLA syndrome ?

Sapparos criteria 1. Vascular thrombosis Arterial Venous Small vessal

2. Pregnancy morbidity One or more unexplained fetal death >10 wk of gestation in other wise normal fetus Three of more embryonic death (<10 wk of gestation) not explained by maternal or paternal chromosomal abnormality or endocrinal condition One or more premature death of fetus due to preeclampsia, ecclampsia or placental insufficiency.

3. Laboratory criteria Anticardiolipin IgG or IgM (high to medium titre) Lupus anticoagulant positive Anti beta glycoprotein 1 Test positive 2 or more times 12 wks apart Page 2

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CRITERIA FOR DIAGNOSIS Atleast one of the clinical criteria and one of lab test is positive

CLINICAL FEATURES Q. What is the pattern of fetal loss in APLA ? Early fetal loss Q. Do all patients with APLA clot ? No, risk of clotting is 50% over 20 years Those with higher titre of anticardiolipin and antibeta2glycoprotein antibody are at higher risk Patients with OC pills, pregnency, homocystenemia are at greater risk

Q. What are the skin manifestation of APLA ? Livideo reticularis Splinter hemorrhages Superficial thrombophlebitis Leg ulcers

Q. What are the causes of Livideo reticularis ? SLE APLA Cryoglobinemia Vasculitis Cholestrol emboli

Q. What are the pulmonary manifestations of APS ? Pulmonary emboili Pulmonary infarct Pulmonary capillitis

Q. What are the Cardiac manifestations of APS ? Libman Sack endocarditis Involves mitral and aortic value mainly Mitral incompetence can occur Page 3

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Q. What are CNS manifestations of APS? Stroke Dementia Cognitive impairment Chorea- non thrombotic Transverse myelitis- non thrombotic Optic neuropathy

Q. In which trimester of pregnancy does APLA cause abortion ? APLA cause abortion in 1st , 2nd and third trimester of pregnency

Q. What % of patient with APLA have valve involvement ? Cardiac manifestation around found n 40% patient with APS 35% have valvular involvement It is in form of thickening and fibrosis Mitral valve is commonest involved MR is commonest lesion Libman Sacks endocarditis is presence of vegetations on the valves

LAB TESTS Q. Why should you go for RPR in patient with APS ? RPR (rapid plasma reagin) from Syphilis is false positive in APS

Q. Why is lupus anticoagulant a misnomer ? It is present in only 50% of patient with lupus It is a procoagulant not an anticoagulant

Q. How is test for Lupus anticoagulant time done ? Patients plasma and Normal plasma are taken and are made platelet free by platelet filtration First step is testing the plasma for Intrinsic pathway- dilute activated plasma trhomboloplastin time or kaolin clotting time Extrinsic pathway dilute PT Common pathway Dilute Russel viper venom time These are typically elevated if Lupus anticoagulant are present Second step is patients plasma is now mixed with normal plasma and the raised times fail to be corrected Third step is adding excess of phospholipid, the prolonged time is now corrected. Page 4

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Q. How is anticardiolipin tested ? It is tested by ELISA IgG, IgM and IgA forms exist

Q. What are the other genetic hypercoagble states ? Factor V Leiden mutation- venous Prothrombin mutation- venous and arterial Protein C and protein S- venous Anti thrombin III mutation- venous thrombosis Homocystenemia- arterial thrombosis and atherosclerosis

Q. What are the acquired forms of hypercoaguable states ? Pregnency OC pills Estrogen replacement Surgery Vasculitis malignancy

TREATMENT Q. What is the management of Thrombosis of APS ? Start with Unfractioned heparin or warfarin and overlap with Warfarin Warfarin is mainstay of therapy Target INR is debatable some studies say 2.5-3.5 with or without Asprin

Q. What is management of pregnancy fetal loss ? Heparin 10,000 sc BD + Asprin LMWH twice a day + Asprin equally efficacious but need to be replaced by UFH during delivery as LMWH has prolonged duration of action Those not responding to above require IVIG during delivery

Q. Can we continue with anticoagulants if platelet is low ? Patient should continue with warfarin even if platelet is <50,000 Addition prednisolone and IVIG may be required if platelet is very low. Page 5

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Q. How long should warfarin be given in patient with APS ? Lifelong Q. How will you manage anticoagulation in pregnency ? Heparin during first trimester Second and third trimester warfarin may be given 2-3 wks before delivery switch to heparin Post partum warfarin can be used

Q. What is the effect of Warfarin during pregnency ? Effect mainly in 6-9th wk 1. Spontaneous abortion and still birth 2. Effects bones and cartilage Post translation modification of the calcium binding proteins Chondromalacia puncta- stippled cartilage and epiphysis Nasal and limb hypoplasia 3. CNS manifestations Optic atrophy Mental retardation Spasticity 4. Fetal hemorrhage- Esp. used in 2nd and 3rd trimester OTHER POINTS Q. What is Evans syndrome Often associated with APS Autoimmune hemolytic anemia associated with ITP Q. What is Sneddon syndrome It is triad of livideo reticularis Hypertension Cerebrovacular disease

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