This document summarizes a case discussion on antiphospholipid syndrome (APS). It presents the case of a 32-year-old woman with involuntary movements for 9 years and 4 pregnancy losses. Tests found positive antinuclear antibody, lupus anticoagulant, and anticardiolipin antibody. She was diagnosed with APS based on clinical and laboratory criteria. The document then reviews the classification, pathogenesis, clinical manifestations, diagnosis, and management of APS, including primary and secondary thromboprophylaxis, obstetric APS, catastrophic APS, and alternative therapies.

1. CASE DISCUSSION ON APS
Presenter:- Shiferaw Debele (R2)
Moderator: Dr Becky A (Consultant Internist and Rheumatologist)
May 21,2021
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2. Outline
•Case presentation
•Introduction to APS
•Diagnosis APS
•Management APS
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3. HISTORY
A 32-year- old married women was presented at the neurologic follow up clinic
TASH exhibiting irregular, involuntary movement involving her head, arm and
legs since 9 years.
This symptom started all over the body (hands, legs and head) and was milder in
severity.
In additional to this she had pregnancy loss four times with no known reasons
'given or interventions done, despite having multiple physician visits over 8 years.
The pregnancy loses in the first to fourth pregnancy occurred at 9,3,4 and 6
months of gestation respectively.
She had no family history of abnormal body movement and no history of
recurrent sore throat or chest discomfort,no rash,oral ulcer and dryness of eye
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4. Generally she was healthy looking,
 Having records of systolic and diastolic hypertension, T=36.7.
Mini Mental Status examination was normal (30/30).
HEENT Pink conjunctiva
CHEST is clear and good air entry
CVS had holosystolic murmur at apex
Abdomen No sign of fluid collection and organomegaly
Integumentary. No oral or skin discoloration
Physical Examination
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5. Laboratory tests
CBC, lipid profile, VDRL all were normal.
UAA proteinuria (+1) and hematuria (+3)
 RFT creatinine of 1.1 and urea 31
Anti Nuclear Antibody (ANA) was positive
Double stranded DNA (Ds DNA) was negative
Serum Lupus Anticoagulant (LA) and Anticardiolipin Antibody (aCL)
were positive with high titers in two serial tests done 12 weeks apart
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6. Imaging
TTE showed moderate mitral regurgitation
Brain MRI showed left basal ganglia and periventricular infarction
and mild cerebral atrophy.
Index=ischemic stroke
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7. INTRODUCTION
Antiphospholipid syndrome (APS) is an autoimmune
multisystemic disorder
Recurrent thrombosis (arterial and venous), pregnancy
morbidity, or both
Associated with the presence of persistent antiphospholipid
antibodies (aPLs).
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8. Classification
Primary APS : when occurs
in patients without evidence
of any associated disease.
Secondry APS: occurs in
association with SLE or
another rheumatic &
autoimmune disorders.
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Associated disorders
SLE.
Rheumatoid arthritis.
Systemic sclerosis.
Behçet's disease.
Temporal arteritis.
Sjögren's syndrome.
Psoriatic arthropathy

9. In healthy people frequency of aPL antibodies is 1-5%
Prevalence ↑ with age ,in elderly with chronic disease.
SEX-Women :men is 5:1
AGE- Young and middle age adults
Females---arthritis,livedo,migraine
Males—MI,epilepsy,lower extremity arterial thrombosis
APLab 30-40% in SLE (only of 5-10% have APLS)
EPIDEMIOLOGY
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10. Classification criteria for the diagnosis of APS
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At least:
One of the clinical
criteria
One of the laboratory
criteria

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12. Pathogenesis
Despite the persistent presence of aPLs in circulation
 Thrombotic events occur only occasionally in patients with aPLs,
Presence of aPLs is necessary but not sufficient for clot formation in
vivo.
The “two-hit hypothesis” has been proposed, which holds that aPLs (first
hit) can exert their prothrombotic action only in the presence of another
thrombophilic condition (second hit).
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13. 6/12/2021 13
Pathogenesis…

14. Clinical Features of Antiphospholipid Syndrome
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15. 6/12/2021 15

16. Catastrophic Antiphospholipid Syndrome(CAPS)
A syndrome of multisystem involvement .
(3 or more different organ systems involved)
 <1% of patients
Multiple small vessel occlusions---multi organ failure.
Acute onset
Acute microangiopathy is characteristic
ARF, ARDS, Cerebral Injury, myocardial ischemia.
Trigger factors involved
Infections,trauma,neoplasia,pregnancy,lupus flares.
SLE-higher mortality
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 Involvement of three or more
organs/systems/tissues
 Manifestations developing
simultaneously or within less
than one week
 Histopathological
confirmation of small vessel
occlusion in at least one
organ/tissue
 Laboratory confirmation of the
presence of APLA

17. SERONEGATIVE ANTIPHOSPHOLIPID SYNDROM
Clinical manifestations highly suggestive of APS in
absence of the laboratory criteria such as LA, aCL
and aβ2GPI antibodies.
Seronegative APS is usually a diagnosis of exclusion
Additional testing for non-criteria biomarkers.
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19. MANAGEMENT
Prevention of thrombosis is a major goal of therapy in patients with aPLs,
and treatment considers two different clinical groups:
Patients with APS who have already experienced a thrombotic event
aPL carriers without previous clotting, that is,
Purely asymptomatic individuals,
Patients with SLE, and
Women with obstetric APS.
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20. Secondary thromboprophylaxis
In patients with definite APS and first thrombosis should be placed on
VKA with a target INR 2–3 is recommended
Direct oral anticoagulants (DOACs) could be considered
Patients not able to achieve a target INR despite good adherence to VKA
Contraindications to VKA (eg, allergy or intolerance to VKA)
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21. 6/12/2021 21
Secondary thromboprophylaxis…

22. Primary thromboprophylaxis
Thromboprophylaxis in asymptomatic aPL carriers should be
individualized based on the antibody profile.
Individuals with a high-risk profile (LAC or aPL triple positivity), low-
dose aspirin therapy is suggested.
Thromboprophylaxis with LMWH in high-risk situations, such as surgery,
prolonged immobilization, and the puerperium, is recommended
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23. Primary thromboprophylaxis…
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24. Obstetric APS
With proper management, more than 70% of pregnant women with APS
deliver a viable, healthy infant.
Preconceptional counseling is essential to estimate the chance of both fetal
and maternal problems.
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25. Pregnancy, women with APS must be categorized into one of three
groups:
Recurrent early miscarriage and no other features of APS,
One or more prior fetal deaths (more than 10 weeks’ gestation) or
prior early delivery (less than 34 weeks’ gestation)
• Severe preeclampsia or placental insufficiency
Previous thrombosis irrespective of pregnancy history.
Obstetric APS…
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26. Recurrent early miscarriage and no other features of APS
Recent expert guidelines recommend the combination of LDA with either
UFH or LMWH.
Monotherapy with aspirin cannot be discarded in this subgroup of women.
79% to 100% pregnancy success rates
Refractory aPL-related pregnancy losses may have improved pregnancy
outcomes with low-dose prednisolone taken until 14 weeks’ gestation.
Obstetric APS…
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27. One or more prior fetal deaths (more than 10 weeks’
gestation) or prior early delivery (less than 34 weeks’
gestation)
Combination therapy with aspirin and heparin is generally
recommended.
When used for obstetric purposes, aspirin is best started
preconceptionally.
Either UFH or LMWH, in combination with aspirin, can be given and is
started after pregnancy has been confirmed.
Obstetric APS…
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28. Previous thrombosis irrespective of pregnancy history
Low-dose aspirin and therapeutic-dose heparin or LMWH anticoagulation
are recommended.
Heparin does not cross the placenta and is not known to cause any adverse
fetal effects.
long-term use of heparin in pregnancy has been associated with osteoporosis in the
mother.
LMWH seems safer in this setting.
VKA are teratogenic and should be avoided between 6 and 9 weeks’
gestation.
Obstetric APS…
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Obstetric APS…

30. Management CAPS
Early diagnosis is crucial in the management of CAPS due to the high
mortality.
There are no randomized controlled trials for the management of CAPS.
Anticoagulation and high dose corticosteroids are used in combination
with IVIG, plasmapheresis, rituximab, cyclophosphamide,
or eculizumab.
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31. ALTERNATIVE THERAPIES FOR REFRACTORY AND DIFFICULT CASES
In patients with recurrent thrombosis, fluctuating INR levels, major
bleeding, or a high risk of major bleeding, long-term therapy with LMWH,
hydroxychloroquine, or statins have been suggested
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32. References
Hochberg Rheumatology 7th Edition
 Harrison 20th edition
EULAR recommendations for the management of APS 2019
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33. THANKS!
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