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Manifestation of Antiphospholipid Syndrome among Saudi patients :examining the applicability of sapporo
Criteria
Farjah H AlGahtani Associate professor ,MD,MPH
Leukemia ,Lymphoma in adolescent ,Thromboembolic Disease
Oncology Center , King Saud University
OUTLINE :
• Historical Back ground of APS
• APS Morbidity
• Pathogenesis
• Sign and symptoms of APS
• Clinical criteria of APS
• APS in Saudia Arabia
1952-1963 Circulating anticoagulants in SLE are named lupus
anticoagulants ( LA) because they prolong the clotting
times in phospholipid dependent assays.LA believed to
cause clinical hemorrhagic disease
1963 LA are reported by Bowie et al to be associated with
thrombosis in SLE patients.
1983 LA are identified by Harris et al to be antibodies that
react with cardiolipin Lupus anticoagulants react with
purified cardiolipin and they are identified as anticardiolipin
antibodies by RIA
1963 Edward John Walter Bowie, MD Mayo Medical School identified APS as an acquired thrombophilia
1984 Graham Robert Vivian Hughes MD FRCP. St Thomas Hospital UK identified APS as a generalized autoimmune disorder
hassouna
Hughes syndrome
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Hassouna February 2, 2010 8
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Antiphospholipid antibodies the most significant target antigen is the Beta 2 glycoprotein-1
In 1990 Monica Galli and her group in Bergamo, Italy reported that the true antigenic targets of antiphospholipid antibodies are not the phospholipids but a plasma protein beta 2 glycoprotein-1 bound to an anionic surface. Galli M,Comfurius P, Massen C et al. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein co-factor. Lancet 1990;334: 1544-1547
APS morbidity
• APS is the most common cause of acquired thrombophilia.
• Prevalence in general population: 2-4%
• 15-20% of all DVT with or without PE.
• 1/3 of new strokes in patients < 50 years age.
• 10-15% women with recurrent pregnancy losses.
• APS: significant proportion of thromboembolic disease and pregnancy loss in SLE.
• APL Abs present in 30-40% SLE. One third of those patients have clinical manifestations of APS.
• aCL positivity may precede a more severe form of SLE.
PATHOGENESIS
Two mechanisms are identified in the induction of autoimmune Antiphospholipid antibodies (a PL).
• Apoptotic phospholipid beta 2 glycoprotein-1 complexes.
• Phospholipids released from injured cells bound to beta 2 glycoprotein 1
• Infection related
antiphospholipid antibodies.
• From experiments in mice, antiphospholipid antibodies are produced by binding of beta2-glycoprotein 1 to phospholipid viral or bacterial proteins by molecular mimicry
“Listen to your patients , he is telling you the diagnosis”
Multiple Strokes
in a Young Woman
(Brain MRI)
Occlusion of Right Middle Cerebral Artery
In a 3 Years Old Child with
Severe Headache and Hemiparesis
With aCL Antibodies +
Other recognized features of APS
Thrombocytopenia Haemolytic anaemia Livedo reticularis Cerebral involvement
Epilepsy, cerebral infarction, chorea and migraine, transverse myelopathy/myelitis mitral valve
Heart valve disease Hypertension Pulmonary hypertension Leg ulcers
1000 patients with APS
• Deep vein thrombosis / PE 48%
• Pregnancy loss 35%
• Thrombocytopenia 30%
• Livedo reticularis 24%
• Stroke / TIA 20%
• Superficial thrombophlebitis 9%
• Hemolytic anemia 7%
Cervera et al. Arthritis Rheum 2002
Thrombotic events n = 1000 over 10 years
Baseline 10 years DVT 39% 4% Stroke/TIAs 31% 9% Pulmonary emboli 14% 4% Myocardial infarction 6% 2%
Cervera R et al Ann Rheum Dis 2015;74:1011
Antiphospholipid syndrome
Cervera R et al Ann Rheum Dis 2015;74:1011
Antiphospholipid syndrome
Obstetric manifestations n = 1000 over 10 years Baseline 10 years Pre-eclampsia 5% 6% Early pregnancy loss < 10 wks 35% 17% Late pregnancy loss ≥ 10 wks 17% 5% Live birth with prematurity 11% 48% Live birth with IUGR 2% 26%
Clinical criteria for the diagnosis of APS
Thrombosis Venous
Arterial
Small vessel (e.g. thrombotic microangiopathy in
kidney)
Pregnancy
morbidity ≥3 consecutive miscarriages (
Diagnosis Of APS
• Anticardiolipin antibodies are measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Medium or high titres of IgG or IgM are required.
• Firm diagnosis of APS requires two or more positive readings for LA and/or aCL at least 6 -12weeks apart, plus at least one of the clinical criteria listed before.
Background
Objectives
Method
Results Conclusion
• Antiphospholipid syndrome (APS) is a systematic autoimmune disease featured with vascular thrombosis and pregnancy morbidity.
• The revised Sapporo criteria are widely used classification criteria for APS.
• This study aims to examine clinical and serological manifestations of a cohort of Saudi APS patients.
• To examine the applicability of revised Sapporo criteria in this cohort.
• This was a single center, retrospective study. • Data were collected from the records of APS patients in King
Saud University Medical City. • The Sapporo criteria were applied and divided patients into
definitive APS cases (fulfilled the criteria) and possible APS cases (failed the criteria).
• Independent sample T-test was used to examine the difference in clinical and laboratory manifestations and comorbidities between the two group.
• Logistic regression was used to examine the association between Sapporo criterial fulfillment and major clinical manifestations.
• A total of 72 (90%) females were included. The mean (±SD) age at diagnosis was 28.1 (± 8.7) years.
• 22 patients (27.5%) fulfilled the revised Sapporo criteria (definitive APS).
• There was no significant difference in the clinical manifestations or treatment between the two group (p>0.2).
• Most patients did not fulfill the revised Sapporo criteria. • Our study identified a gap in applying these criteria in Saudi
patients. • Future studies of examining the diagnostic validity of APS
laboratory manifestations are needed
Farjah Al-Qahtani1, Abdulrahman S. Arfaj2, Sayedah Asfar2 and Mohammed A. Omair2 1 Division of Hematology, Department of Medicine, King Saud University, Riyadh, Saudi Arabia 2 Division of Rheumatology, Department of Medicine, King Saud University, Riyadh, Saudi Arabia
Clinical and Laboratory Manifestations of Antiphospholipid Syndrome Among Saudi Patients: Examining the Applicability of Sapporo Criteria
Total (%, N=80)
Definitive APS (%, N=22)
Possible APS (%, N=58)
P value
Age at diagnosis, yr 28.5 (8.8) 29.7 (9.3) 28.1 (8.7) 0.46
Year at diagnosis 2002 (4) 2001 (4) 2002 (4) 0.6
Female 72 (90) 18 (81.8) 54 (93.1) 0.13
Nationality (Saudi) 71 (88.8) 18 (81.8) 53 (91.4) 0.23
Complications (Y/N) 10 (12.5) 6 (27.3) 4 (6.9) 0.014
Follow-up response
Remission without recurrent event 30 (37.5) 8 (36.4) 22 (37.9)
0.94 Recurrent event 14 (17.5) 4 (18.2) 10 (17.2)
Single visit 35 (43.8) 10 (45.5) 25 (43.1)
Died 1 (1.25) 0 (0) 1 (1.72)
Model 1 Model 2 Model 3
OR (95% CI) P value OR (95% CI) P value OR (95% CI) P value
Vascular thrombosis 1.87 (0.66, 5.25) 0.24 1.59 (0.55, 4.65) 0.39 1.61 (0.55, 4.71) 0.39
DVT or PE1 1.83 (0.68, 4.92) 0.23 1.54 (0.55, 4.32) 0.41 1.53 (0.55, 4.31) 0.42
Recurrent2 DVT or PE 0.65 (0.15, 2.79) 0.56 0.77 (0.14, 4.21) 0.77 0.67 (0.12, 3.81) 0.65
Pregnancy morbidity 0.53 (0.19, 1.46) 0.22 0.61 (0.21, 1.84) 0.39 0.63 (0.21, 1.92) 0.42
Serology Thrombosis2 Pregnancy morbidity3 Thrombocytopenia4 Asymptomatic Total
+ve5 aCL 7 (22.6) 12 (40) 3 (42.9) 6 (75) 28 (48.3)
+ve LA1 3 (9.7) 2 (6.7) 1 (14.3) 2 (25) 8 (13.8)
-ve 21 (67.7) 16 (53.3) 3 (42.9) - 40 (69.0)
Total 31 30 7 8
Table 1. Study population characteristics
Table 3. The association of Sapporo criteria fulfillment with major clinical manifestations
Model 1: crude associations Model 2: adjusted for age at diagnosis, gender, nationality Model 3: adjusted for covariates in model 2 and follow-up response 1 DVT: deep vein thrombosis; PE: pulmonary embolism 2 Analysis for recurrent DVT or PE was restricted to 35 patients with previous DVT or PE event
Table 2. The serology results of the possible APS patients in relation to their clinical manifestations (N=58)
Figure 1. The age distribution of definitive and possible APS cases
Lessons learned
• Diagnosis is absolutely necessary for the proper clinical management
• Lupus Anticoagulant is the “ identifier” or “ biomarker” unique to the
Antiphospholipid syndrome and consider the
• Auto-antibodies that prolong clotting times in phospholipid dependent
clotting assays are termed “lupus anticoagulant”
Special Coagulation Laboratory Recipe for APS diagnosis
• APTT clotting times must be prolonged at least twice control plasma clotting times (correlates with high antibody titer)
• APTT prolonged clotting times does not correct in mixing patient plasma with pooled normal plasma
• ELISA identifies beta2-glycoprotein 1 antigen and auto-antibodies.
• Testing is repeated as indicated. • APS induced by viral or bacterial proteins disappears after
infection is cured
SAUDI-APS RESEARCH GRUOP
AIMS of THE Saudi APS-Research Group :
• Describe outcomes of arterial venous and pregnancy complications .
• Describe CAPS presentation in Saudi Population and the outcome .
•Assess drug respond in APS . • assess quality of life / depression in APS patients
• Role of genetics Factors of APS including familial and sporadic cases
• Develop an APS registry and maybe guidelines under the hematology society
• We need to manage getting different national /international collaboration Centers onboard .
THANK YOU