Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by blood clots in arteries and veins, pregnancy complications, and the presence of antiphospholipid antibodies. The syndrome can occur alone or in association with other autoimmune diseases like lupus. Treatment involves long-term anticoagulation with blood thinners and aspirin to prevent new clots from forming. Management of pregnancy in APS patients depends on their history and involves low-dose aspirin with or without low or high dose blood thinners.

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.