Antiphospholipid Syndrome

4. Definition:
Antiphospholipid syndrome (APS) is an autoimmune
disorder characterised by arterial and venous
thrombosis, adverse pregnancy outcomes (for mother
and fetus), and raised levels of antiphospholipid
(aPL) antibodies.

5. Synonyms:
• Anti-phospholipid syndrome. The immune system produces
abnormal blood proteins called antiphospholipid antibodies.
• lupus anti-coagulant syndrome: synonym can be
confusing bec. patients with APS may not necessarily have
SLE, LA is associated with thrombotic rather than
hemorrhagic complications.
• Anti-cardiolipin antibody syndrome

6. • Sticky blood syndrome. people with this condition are
more likely to form clots in blood vessels
• Hughes syndrome: named after Dr. Graham Hughes
along with his team in London who described the disease
between 1983 & 1985.

7. :History of APS
 Anti-phospholipid antibodies were first noted in a
group of people who had positive tests for syphilis
without signs of infection (false-positive tests).
 It was then noticed that some of these individuals
developed systemic lupus erythematosus (SLE) and
other rheumatic conditions.

8.  Later studies found a protein called the lupus
anticoagulant in a number of individuals with SLE,
provided further understanding of APS, including the
testing for anticardiolipin antibodies.

9. Epidemiology :
 1- 5% of healthy individuals have aPL antibodies.
 Incidence of APS: about 5 cases per 100,000 persons
per year.
 50 % of APS cases : not associated with another
rheumatic disease ( PAPS).
 APL antibodies : found in about 30-40% of patients
with SLE, but only about 10% have APS.

10.  APS is the cause of : - 14% of all strokes.
- 11% of MI.
- 10% of DVT.
- 6% of pregnancy morbidity.
- 9% of pregnancy losses.

11.  Catastrophic APS has mortality rate about 50% due to
multi-organ infarctions over a period of days.
 Sex : A female predominance specially for secondary
APS.
 Age : APS is common in young to middle-aged adults.

12. . •
Diagnostic criteria ( Sapporo
criteria):
At least:
 One of the clinical criteria
 One of the laboratory criteria .

13. I- Clinical criteria
 Vascular thrombosis: one or more episodes of arterial,
venous or small vessel thrombosis.
 Pregnancy morbidity:
 Three or more unexplained spontaneous abortion before 10
weeks of gestation where anatomical, hormonal and
chromosomal causes have been excluded.
 At least one unexplained death of a morphologically
normal fetus at or after the 10th week of gestation.
 At least one pre-term birth of a morphologically normal
neonate (before 34 weeks of gestation) due to eclampsia,
severe pre-eclampsia or placental insufficiency.

14. II - Laboratory criteria
 Lupus anticoagulant (LA) is positive.
 Anticardiolipin (aCL) antibody is present in serum, in
medium or high titre (ie ≥40 GPL units or MPL units or
≥99th percentile).
 Anti-B2-glycoprotein-1 antibody in serum (in titre ≥99th
percentile).
All should be present on two or more occasions, at
least 12 weeks apart.

16. • Diagnostic clues (but not as classification
criteria):
 Cardiac valve disease
 Livedeo reticularis
 Thrombocytopenia
 Renal thrombotic microangiopathy
 Neurological manifestations sp. chorea

17. :Pathophysiology
 The homeostatic regulation of blood coagulation is altered.
 Phospholipids are an integral part of platelet And endothelial
cell surface membranes , it is expected that these antibodies
have a effect on them.

18. PPaatthhoopphhyyssiioollooggyy
APL
Antibodies
platelets Coagulation
cascade Endothelial
cells
increase TF
, adhesion
molecules
and
proinflammatory
cytokines
Placental
tissue
decrease
Trophoblastic cell
growth,
increase apoptosis
Inhibit
Protein C,
Protein S
, thrombomodulin,
antithrombin III
fibrinolysis
Activate
platelet
aggregation

20. IInn pprreeggnnaannccyy

21. 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.

22. • Catastrophic form :
 A rapidely progressive lethal form of PAPS with
widespread vascular occlusion ( in medium or small
sized arteries) in multiple organs ( > 3 organs) in few
days.
 Mortality rate 50%

23.  Seronegative APS:
 Clinical picture is highly suggestive for APS, while the
laboratory tests fail to detect LAC or aCL.
 These cases could be APS with other aPL which are not
included in the criteria : e.g anti-cardiolipin IgA or other
aPL( e.g: false positive test for syphilis, AMA).
 It is also possible that during the acute event of thrombosis,
aPL cannot be detected bec. they are consumed in the blood
clot.
 Repeated measurement of these autoantibodies several
weeks later

24. Associated disorders ( secondary APS )
• SLE.
• Rheumatoid arthritis.
• Systemic sclerosis.
• Behçet's disease.
• Temporal arteritis.
• Sjögren's syndrome.
• Psoriatic arthropathy.

25.  Other clinical associations :
 Infections : HIV, hepatitis C, syphilis, malaria.
 Malignant lymphoma.
 Drug exposure: phenothiazines, phenytoin, hydralazine.
 Autoimmune thrombocytopenia.
 Autoimmune haemolytic anaemia.
 Sickle cell anaemia.

26. :Clinical presentation
Skin disorders: - Livedo reticularis (most common).
- Splinter haemorrhages .
- Leg ulcers.
-Superficial thrombophlebitis .
- Vasculitis.
Neurological defects: - Migraine headaches.
- Seizures.
- Dementia.
Cardiac abnormalities: - MI.
- Cardiac valve vegetations.

27. • Blood abnormalities: - Thrombocytopenia.
- Haemolytic anaemia.
• Renal abnormalities: - hypertension.
-proteinuria due to thrombotic microangiopathy.
• Catastrophic antiphospholipid syndrome : The condition
is serious and often lethal.

28. Levideo reticularis

29. Levideo reticularis

30. Splinter haemorrhages

31. Vasculitis

32. Differential Diagnosis :
 Disseminated Intravascular Coagulopathy(DIC).
 Infective Endocarditis.
 Thrombotic Thrombocytopenic Purpura(TTP).

33.  SO, Younger patients with a history of DVT,
pulmonary embolism, MI , or CVA need to be
investigated for antiphospholipid syndrome, particularly if
no other risk factors for thrombosis are present.

34. MANAGEMENT
OF APS

35. General roules:
 Treatment regimens for APS must be according to the patient's
clinical condition and history of thrombotic events.
 Asymptomatic individuals (with positive blood tests) :
no specific treatment.
 Prophylactic therapy: Elimination of risk factors (e.g : oral
contraceptives, smoking, hypertension, or hyperlipidemia.

36.  Prophylaxis is needed during surgery or hospitalization, as
well as any associated autoimmune disease.
 Low-dose aspirin is used widely in prophylaxis; however,
the effectiveness of low-dose aspirin as primary
prevention for APS remains unproven .
 In patients with SLE, consider hydroxychloroquine, which
may have intrinsic antithrombotic properties.

37. Thrombosis
• Full anticoagulation with IV or SC heparin followed by
warfarin therapy.
• Our target for INR is 2 - 3 for venous thrombosis and 3
for arterial thrombosis.
• Patients with recurrent thrombotic events, may require an
INR of 3 - 4.
• Severe or refractory cases : a combination of warfarin
and aspirin may be used.
• Treatment for significant recurrent thrombotic events in
patients with APS is generally lifelong.

38.  Rituximab can be considered for recurrent thrombosis
despite adequate anticoagulation. A prospective study
showed rituximab to be effective for non-criteria aPL
manifestations (ie, thrombocytopenia and skin ulcers).

39. APS & pregnancy
Asymptomatic (positive aPL) No TTT or LDA
Single pregnancy loss < 10 weeks No TTT or LDA
Recurrent pregnancy losses < 10
weeks or foetal loss > 10 weeks +
no history of thrombosis
LDA + prophylactic dose of
heparin ( continued till 6 – 12
weeks postpartum ) & then
switched to LDA.
Recurrent pregnancy loss < 10
weeks or foetal loss > 10 weeks +
history of thrombosis
LDA + therapeutic doses of
heparin) then switched to warfarin
postpartum

40. • Treatment of catastrophic APS:
 Hospitalization
 Anticoagulation
 Plasmapharesis
 IVIG
 Corticosteroids
 Cyclophosphamide (especially in SLE-associated CAPS).

41. DDoosseess
• Warfarin: 5 – 15 mg / day for 2-5 days
• LMWH : Low dose : 20-40mg/day SC.
High dose 1 mg/kg bid SC.
• Unfractionated heparin: 5000-10,000u /12h SC.
• Hydroxychloroquine : 200 – 400 mg/d
• IV IG : 400 mg/kg/d IV. for 5 days
• Steroids : Prednisolone 1 mg/kg
•Aspirin : 81 mg/day
• Rituximab 1000mg IV (2 doses separated by 2 weeks).

42. • Surgical care: Recurrent DVT may need an inferior vena
cava filter.
• Diet : If warfarin therapy is instituted, instruct the patient to
avoid excessive consumption of foods that contain vitamin K.
• Activities: No specific limitations (according to the clinical
condition).
 Avoid sports with excessive contact if taking warfarin.
 Limit activity in patients with DVT.
 Instruct the patient to avoid prolonged immobilization.