British Society of Haematology Guidelines. Br J Haem 2012;157:47-58 Punnialingam, Khamashta. Curr Rheumatol Rep

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1 Kevin Pile

2 Key references British Society of Haematology Guidelines. Br J Haem 2012;157:47-58 Punnialingam, Khamashta. Curr Rheumatol Rep 2013;15:318 Alijotas-Reig. Lupus 2013;22:6-17 Cervera et al. Ann Rheum Dis 2009;68:1428-

3 Plan of presentation Introduction Management According to Clinical Pattern Incidental Venous thrombosis Ischaemic stroke Obstetric Catastrophic Refractory New anticoagulants

4 Antiphosholipid syndrome Acquired antibodies to phospholipid binding protein Persistent for 12 weeks or more acl typically detects anti-β2 glycoprotein I (aβ2gpi) LAC typically detects aβ2gpi and anti-prothrombin Clinical features Thrombosis Venous: any but often LL DVT or PE Arterial: usually stroke/tia then MI Microvasculature: (rare <1%) CAPS with multi-organ lung, brain, kidney Recurrent and late pregnancy loss (10-15% with recurrent foetal loss have apl)

5 Incidental apl Control rates: LAC 0.9% controls, aβ2gpi 3.4% controls point in time Persistent IgG acl 6.5% (36/552) no thrombosis during mean 12/12 fup 178 Asx apl carriers fup 36mths with no thrombosis detected 104 triple positive (LAC, apl, aβ2gpi) with mean fup 4.5yrs 5% per year thromboembolic events Overall do not treat incidentally found apl? If triple positive? aspirin ± PPI

6 SLE patients with no events Higher risk of thrombotic events, screen and start LDA HCQ reduces thrombotic events in SLE, especially if acl or apl positive (Hopkins cohort 2013 update) HCQ combines with LDA, and often has non-aps indications in SLE patients

7 GlobalAnti-phospholipid Syndrome Score (GAPSS): SLE derived Parameter Score acl IgG/IgM 5 LAC 4 aβ2gpi IgG/IgM 4 Hyperlipidaemia 3 Anti-phosphatidylserine/prothrombin IgG/IgM 3 Hypertension 1 Score 10 predictive of thrombosis and pregnancy loss AUC 0.74 Sciascia et al. Rheumatology 2013;52:1397-

8 Venous thrombosis Initial 3-6/12 anticoagulation as per normal, riskbenefit decision thereafter Unprovoked (APL- high recurrence risk 10%pa)?long term anticoagulation anyway, presence of persistent apl taken one week off anticoagulation may add additional support, test at normal ceasing point APS with non-recurrent venous thrombosis target INR 2.5 (2-3) Provoked with transient risk factor do not test apl as unlikely to influence long term Mx

9 Ischaemic stroke General pop. aspirin/dipyridamole or clopidogrel better than aspirin alone Stroke with apl had high stroke recurrence long term warfarin APASS study 720 single apl+ s from 1770 stroke patients (13% LAC, 20% acl, 7% both) Recurrence OR 0.99 for warfarin (INR ), OR 0.94 aspirin: equally protective pragmatically use antiplatelet as per general population (BJH guidelines) Cohort studies suggest stroke <50yrs and triple risk (LAC, acl, aβ2gpi) have high recurrence lifelong warfarin but evidence over aspirin is weak For ischaemic stroke only test apl in those <50yrs

10 13 th Congress on apl antibodies INR cf 2-3 = 22% bleeding vs 4% INR 2-3 cf INR 2-3 plus LDA has comparable pa bleeding Options become INR >3 OR INR 2-3 plus LDA High bleeding risk, low serological risk: use combination Low bleeding risk, high serological risk: use INR >3

11 Adjunct information Check baseline PT as prolongation w/o coagulopathy will need alternative PT reagent for monitoring Do not use point of care devices unless validated in APS Modify risk factors for thrombosis Smoking, obesity, exogenous oestrogens/progesterone Consider statins, hydroxychloroquine

12 Obstetric complications Test apl if 3 pregnancy losses before 10/40, test between pregnancy if possible UFH and aspirin incidence of loss in women with history of recurrent loss, LDA alone does not reduce risk cf placebo or routine care. LMWH pragmatically used due to ease of dosing and daily administration. LDA recommended in women with history of preeclampsia and FGR, similar if apl positive

13 Miscarriage only Preconception aspirin or at time of + pregnancy test Addition of heparin at pregnancy confirmation LDA/prophylactic heparin LMWH for miscarriage LDA intermediate dose heparin/lmwh for foetal death, early delivery APS with previous thrombosis and pregnancy planning Cease warfarin, commence LMWH when pregnancy confirmed (plus calcium, vit D)? Trimester anti-xa based adjustment Careful delivery planning wrt LDA, UFH

14 Post-partum thromboprophylaxis needed intensely prothrombotic time Postpartum LMWH for 6 weeks (possibly warfarin) If previous thrombosis, postpartum thromboprophylaxis is continued lifelong.

15 Catastrophic APS Find and treat trigger often infection Anticoagulation: heparin and warfarin Removal/inactivation of apl Plasmapharesis, IVIG, steroid, anti-bcell

16 Refractory APS ie events on anticoagulation Increase INR 3-4 thrombosis deaths > bleeding Add LDA Add clopidogrel (as per triple positives undergoing cardiac stenting) Add HCQ to non-sle with APS Statins recommended for stroke management Reduce VEGF, TNF, and soluble tissue factor which promote inflammatory thrombotic effects in APS

17 NOAC (new oral anticoagulants) in APS Direct thrombin inhibitors (dabigatran/pradaxa) Direct anti-xa inhibitors (rivaroxaban/xarelto, apixaban/eliquis, edoxaban/lixiana) TKR/THR prophylaxis Stroke reduction in non-valvular AF Treatment of DVT/PE and recurrence reduction No specific APS trials yet Rivaroxaban in AntiPhospholipid Syndrome (RAPS) IRSCTN Curr Rheumatol Rep 2013;15:331-

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