Antiphospholipid Syndrome
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Antiphospholipid Syndrome
Dror Mevorach, MDNovember , 2013
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Antiphospholipid Syndrome
• APLS is a disorder of recurrent arterial or venous thromboses, pregnant losses, and/or thrombocytopenia associated with persistently positive results of anticardiolipin or lupus anticoagulant tests
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Antiphospholipid Syndrome
History I• A hemorrhagic disorder caused by circulating
anticoagulant in a patient with SLE. Conley & Hartmann, JCI, 1952
• Thrombosis in SLE “despite” circulating anticoagulants. Bowie et al., JCI, 1963
• A peripheral vascular syndrome overlapping with SLE. Johansson et al., Dermatologia, 1977
• Intra-uterine death and circulating anticoagulant. Nilsson et al., Acta Med Sand, 1975
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Antiphospholipid Syndrome
History II• Lupus anticoagulants binds
negatively charged phopholipids. Thiagarajan et al., JCI, 1980
• Anticardiolipin antibodies: detection with RIA and association with thrombosis in SLE. Harris et al, Lancet, 1983
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Antiphospholipid Syndrome
LaboratoryFalse positive for syphilis:Common antigen: cardiolipin-cholesterol-
phophatidylcholine • Agglutination: RPR (rapid plasma reagin)• Flocculation: VDRL (Veneral disease research laboratories)• Complement fixation: WassermanNo false positive syphilis:• FTA-ABS (fluorescent treponemal antibody absorbed assay)
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Anticardiolipin
• IgG• IgM• IgA• 2GPI
• Low titer: 10 GPL/MPL/APL• Medium titer: 20/30-60• High titer: >60
• Correlation with thrombosis: High>Medium>>low
IgG>>IgM>IgA
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Date I
Failure of correction by normal plasma
Correction by phos-lipids
Date II
Failure of correction by normal plasma
Correction by phos-lipids
Activated PTT
KCT
dilute RVVT
Dilute prothrombin time
Textarin time
Lupus anticoagulant
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Anticardiolipin
False+ VDRL
Lupus anticoagulant
The different anti-phospholipids autoantibodies share antigen epitopes but are also targeted against different epitopes
Anti-b2GPI
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Antiphospholipid Syndrome
Clinical criteria:1. One or more clinical episodes of arterial,
venous or small vessel thrombosis, in any tissue or organ. Thrombosis must be confirmed by imaging or doppler studies or histopathology, with the exception of superficial venous thrombosis. For histologic confirmation, thrombosis should be present without significant evidence of inflammation in the vessel wall.
Arthritis @ Rheum 1999;42 (7):1309-1311
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•Clinical criteria:2. Pregnancy morbidity-One or more premature births of a morphologically normal neonate at or before the 34th week of gestation because of severe preeclampsia or eclampsia, or severe placental insufficiency OR-Three or more unexplained consecutive spontaneous abortions before the 10th week of gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal cause excludedArthritis @ Rheum 1999;42 (7):1309-1311
Antiphospholipid Syndrome
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Laboratory criteria (I):
1. Anticardiolipin antibody of IgG and/or IgM isotype in blood, present in medium or high titer, on 2 or more occasions, at least 6 weeks apart, measured by a standardized ELISA for beta-2-GPI-dependent anticardiolipin antibodies.
Antiphospholipid Syndrome
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Laboratory criteria (II):
2. Lupus anticoagulant present in plasma, on 2 or more occasions at least 6 weeks apart, detected according to the guidelines of the International Society on Thrombosis and Homeostasis in the following steps:•Prolonged phospholipid-dependent coagulation demonstrated on a screening test, e.g. activated PTT, KCT, dilute RVVT, dilute prothrombin time, Textarin time.
Antiphospholipid Syndrome
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Laboratory criteria (III):
3. Failure to correct the prolonged coagulation time on the screening test by mixing with normal platelet-poor plasma.•Shortening or correction of the prolonged coagulation time on the screening test by the addition of excess phospholipid.•Exclusion of other coagulopathies.
Antiphospholipid Syndrome
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Definite antiphospholipid syndrome is considered to be present if at least 1 of the clinical (thrombosis or pregnant morbidity) and 1 of the laboratory(anticardiolipin or lupus anticoagulant) criteria are met
Antiphospholipid Syndrome
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Antiphospholipid Syndrome:Clinical spectrum
• Arterial thrombosis: Aorta, eye, hepatic, splenic, brain, etc.
• Venous thrombosis: DVT, portal• Cardiac: Non-infectious
endocarditis, CAD• Cutaneous: Splinter
Hemorrhages, levido reticularis, skin infarcts
• Neurologic: TIA, CVA, seizures, dementia, TM
• Obstetrical: Pregnancy loss, IUGR, HELLP syndrome, pre-ecampsia
• Hematologic: Thrombocytopenia, hemolytic anemia, leukopenia
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Antiphospholipid Syndrome:Clinical spectrum
• Arterial thrombosis: Aorta, eye, hepatic, splenic, brain, etc.
• Venous thrombosis: DVT, portal• Cardiac: Non-
infectious endocarditis, CAD
• Cutaneous: Splinter Hemorrhages, levido reticularis, skin infarcts
• Neurologic: TIA, CVA, seizures, dementia, TM
• Obstetrical: Pregnancy loss, IUGR, HELLP syndrome, pre-ecampsia
• Hematologic: Thrombocytopenia, hemolytic anemia, leukopenia
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Antiphospholipid Syndrome:Clinical spectrum
• Arterial thrombosis: Aorta, eye, hepatic, splenic, brain, etc.
• Venous thrombosis: DVT, portal• Cardiac: Non-infectious
endocarditis, CAD• Cutaneous: Splinter
Hemorrhages, levido reticularis, skin infarcts
• Neurologic: TIA, CVA, seizures, dementia, TM
• Obstetrical: Pregnancy loss, IUGR, HELLP syndrome, pre-ecampsia
• Hematologic: Thrombocytopenia, hemolytic anemia, leukopenia
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Antiphospholipid Syndrome:Clinical spectrum
• Arterial thrombosis: Aorta, eye, hepatic, splenic, brain, etc.
• Venous thrombosis: DVT, portal• Cardiac: Non-infectious
endocarditis, CAD• Cutaneous: Splinter
Hemorrhages, levido reticularis, skin infarcts
• Neurologic: TIA, CVA, seizures, dementia, TM
• Obstetrical: Pregnancy loss, IUGR, HELLP syndrome, pre-ecampsia
• Hematologic: Thrombocytopenia, hemolytic anemia, leukopenia
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Antiphospholipid Syndrome:Clinical spectrum
• Arterial thrombosis: Aorta, eye, hepatic, splenic, brain, etc.
• Venous thrombosis: DVT, portal• Cardiac: Non-infectious
endocarditis, CAD• Cutaneous: Splinter
Hemorrhages, levido reticularis, skin infarcts
• Neurologic: TIA, CVA, seizures, dementia, TM
• Obstetrical: Pregnancy loss, IUGR, HELLP syndrome, pre-ecampsia
• Hematologic: Thrombocytopenia, hemolytic anemia, leukopenia
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Antiphospholipid Syndrome
Treatment:• Anticoagulation• Corticosteroids ???
Prevention? Aspirin or low dose LMW heparin for pregnancy lossFull anticoagulation for recurrent thrombotic eventHydroxychloriquine (in SLE) ?