1. Antiphospholipid Syndrome
Dror Mevorach, MD
November , 2013

2. 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

3. 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

4. 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

5. Antiphospholipid Syndrome
Laboratory
False positive for syphilis:
Common antigen: cardiolipin-cholesterol-phophatidylcholine
Agglutination: RPR (rapid plasma reagin)
Flocculation: VDRL (Veneral disease research laboratories)
Complement fixation: Wasserman
No false positive syphilis:
FTA-ABS (fluorescent treponemal antibody absorbed assay)

6. Anticardiolipin IgG IgM IgA b2GPI Low titer: 10 GPL/MPL/APL
Medium titer: 20/30-60
High titer: >60
Correlation with thrombosis: High>Medium>>low
IgG>>IgM>IgA

7. Lupus anticoagulant Date I Failure of correction by normal plasma
phos-lipids
Date II
Activated PTT
KCT
dilute RVVT
Dilute prothrombin time
Textarin time

8. The different anti-phospholipids autoantibodies share antigen epitopes
Anticardiolipin
False+ VDRL
Lupus anticoagulant
Anti-b2GPI
The different anti-phospholipids autoantibodies share antigen epitopes
but are also targeted against different epitopes

9. Antiphospholipid Syndrome
Clinical criteria:
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.
Rheum 1999;42 (7):

10. Antiphospholipid Syndrome
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 excluded
Rheum 1999;42 (7):

11. Antiphospholipid Syndrome
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.

12. Antiphospholipid Syndrome
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.

13. Antiphospholipid Syndrome
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.

14. Antiphospholipid Syndrome
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

15. 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

18. 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

21. 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

23. 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

26. 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

29. Antiphospholipid Syndrome
Treatment:
Anticoagulation
Corticosteroids ???
Prevention?
Aspirin or low dose LMW heparin for pregnancy loss
Full anticoagulation for recurrent thrombotic event
Hydroxychloriquine (in SLE) ?