This document discusses antiphospholipid syndrome (APS), a condition characterized by antibodies against cardiolipin and β2 glycoprotein that can cause blood clots, recurrent fetal loss, and other complications. The document provides details on: - Criteria for diagnosing APS based on clinical symptoms like blood clots or pregnancy loss combined with laboratory tests. - Associations between APS and other autoimmune diseases. - Mechanisms by which antiphospholipid antibodies are believed to cause clotting. - Varied clinical manifestations of APS affecting different organs. - Evaluations, treatments, and long-term outlook for patients with APS.

2. Dr Kamrun Nahar Safia Nishi

3. COMMON
ADMISSIONS IN
HOSPITAL WITH
NO CAUSE FOUND

4. DEPARTMENT OF NEUROLOGY
21 Years, Female, Student
Sudden Facial Palsy, Rt Sided Weakness

6. DEPARTMENT OF NEUROLOGY
26 Years, Female, Writer
Sudden and Repeated Painless Loss
of Vision of Both Eye.

8. DEPARTMENT OF
GASTROENTEROLOGY
35 Years, Male, Teacher
Sudden Abdominal Pain with Ascites.

11. DEPARTMENT OF MEDICINE
40 years, Female, Worker
Sudden Left Leg Oedema

13. DEPARTMENT OF SURGERY
22 years, Male, Non-smoker, Student
Gangrene in Toe of Left Leg, Skin
Colour Change

15. DEPARTMENT OF GYNAECOLOGY
24 Years, Female
3 Still births, 2 IUGR

18. DEPARTMENT OF HEAMATOLOGY
36 yrs Female, Housewife
Purpura, 1 time Haematemesis

23. Cerebrovascular Accidents
Myocardial Infarction
Pulmonary Thromboembolism
DVT
Recurrent Foetal Loss
Non-healing Ulcer
Livedo Reticularis
WITHOUT ANY KNOWN RISK FACTOR

24. Venous thrombosis
Arterial thrombosis
Recurrent abortion
Anti cardiolipin antibody (IgG)> 40
GPL or >99th percentile
Anti cardiolipin antibody (IgM)> 40
MPL or >99th percentile
Anti β2 glycoprotein 1 antibody (IgG)
20 SGU
Anti β2 glycoprotein 1 antibody (IgM)
> 20 SMU
Lupus anticoagulant
>

26. An Autoimmune, Hypercoagulable state caused by
Antibodies against proteins that bind to cell membrane
phospholipid.
- In particular, the disease is characterized by antibodies
against cardiolipin (anti-cardiolipin antibodies) and β2
glycoprotein .
-Also known as
Antiphospholipid Syndrome (APS)
Lupus anticoagulant syndrome (misnomer)
"Hughes syndrome", after the Rheumatologist Dr. Graham
R.V. Hughes who played a central role in the description of
the condition.

27. No defined racial predominance for primary APS has been
documented, although SLE is more common in African American and
Hispanic populations.
- In young, apparently healthy people for LA and aCL is 1-5%
- Prevalence ↑ with age ,in elderly with chronic disease.
- Mean age of onset - 31 yrs, lowest age - 8 months
- Without rheumatic disease at younger age and with at
older
- Women :men is 5:1 (particularly secondary APS)
- Females: arthritis, livedo, migraine
- Males: MI, epilepsy, lower extremity arterial thrombosis

28. In patients presenting with a deep venous thrombosis, up to
30% will have the APS.
In a person under age 50 with stroke, up to 46% will have
APS.
About 8% of primary APS patients later develop SLE
In SLE patients, about 30% have anticardiolipin and about
25% have the lupus anticoagulant.
The risk of venous thrombosis in a SLE patient with the lupus
anticoagulant is 50% by 20 years after diagnosis.
Idiopathic: aCL Ab- 24%,LA - 4%

30. International Consensus Statement on Classification
Criteria for APS (2006)
APS is present if at least one of the clinical criteria
and one of the laboratory criteria that follow are
met….
1. Clinical criteria:
Vascular thrombosis
Pregnancy morbidity
2. Laboratory criteria:
Lupus anticoagulant
Anticardiolipin IgG or IgM antibody
Anti-β2 glycoprotein I IgG or IgM antibody
-- Miyakis, et al., J.Thromb.Haemost., 2006; 4: 295-306.

31. Clinical criteria:
1. Vascular thrombosis*:
One or more clinical episodes of arterial, venous or small vessel
thrombosis, occuring in any tissue or organ.
Thrombosis must be confirmed by imaging or doppler study.
2. Pregnancy morbidity:
One or more unexplained deaths of a morphologically normal fetus
at or beyond10th week of gestation.
Three or more unexplained spontaneous abortions at or prior to
10th week of gestation.
One or more premature births at or before the 34th week of
gestation due to eclampsia, preeclampsia or placental insufficiency.
*“Coexisting inherited or acquired thrombotic risk
factors are not reasons for excluding patients from a
diagnosis of APS trials.”
-- Miyakis, et al., J.Thromb.Haemost., 2006; 4: 295-306.

32. Laboratory criteria:
1. lupus anticoagulant present in plasma.
2. aCL Ab of IgG and/or IgM isotype in serum or plasma, present in
medium (> 40GPL or MPL) or high titer (> 99TH percentile)
3. anti β2 GP1 antibody of IgG and/or IgM isotype in serum or
plasma (in titre > 99th percentile)
--Measured On two or more occasions at least 12 weeks apart.
“Non-criteria” APS findings:
(Diagnostic clues for individual patients but not as classification
criteria for the purpose of clinical trials)
Cardiac valve disease
Livedo reticularis
Thrombocytopenia and/or Haemolytic anaemia
Renal thrombotic microangiopathy,
Neurological manifestations - chorea
-- Miyakis, et al., J.Thromb.Haemost., 2006; 4: 295-306.

33. SLE - 25-50%
Sjogren’s – 42%
RA-33%
Autoimmune Thrombocytopenic Purpura -30%
Autoimmune Haemolytic Anaemia – unknown
Mixed Connective Tissue Diseases -22%
Behcet’s -20%
Systemic Sclerosis – 25%
Polymyalgia Rhemutica – 20%

34. Classification
1. Primary antiphospholipid syndrome
APS occurs in the absence of any other related
disease.
2. Secondary antiphospholipid syndrome
APS occuring in the context of other autoimmune
diseases, such as systemic lupus erythematosus
(SLE).
3. Catastrophic antiphospholipid syndrome
In rare cases, APS leads to rapid organ failure due to
generalized thrombosis; this is termed CAPS and is
associated with a high risk of death.

36. Antiphospholipid Antibodies in other diseases
(Secondary APS):
Infection:
- Syphilis
- HIV
- TB
- HCV
- Q-fever,
- Spotted Fever
- Klebsiella
- Leprosy
Malignancy:
- Lymphoma
- CML
- Paraproteinaemia
Drug induced:
- Phenothiazines
- Procainamide
- Quinidine
- Valproate
- Lung Adenocarcinoma
- Breast Carcinoma
- Melanoma
- Phenytoin
- Hydralazine
- Chlorpromazine,

37. Retinal/ CNS/ Major organs
Arterial
Venous
Arterial and Venous
Obstetrical
Asymptomatic Antibody Positivity

38. Antiphospholipid antibodies react against proteins that bind to anionic
phospholipids on plasma membranes.
aPL Ab is related to thrombosis through multiple mechanisms:
1.Activation of vascular endothelium- platelet and monocyte binding.
2.Activation of monocyte and PMN- release of proinflammatory mediators
and initiation of prothrombotic cascade
3.Activation of platelets to enhance endothelial adherence.
4.Expression of adhesion molecules and tissue factor
5.Alternation of coagulation cascade by production of antibodies against
prothrombin, protein C, protein S, annexin and by reduction of fibrinolysis
6.Activation of classical compliment pathway
7.Non-immune procoagulant factors- oestrogen, inflammation, infection etc.

42. Sinus thrombosis, Cardiac valvulopathy,
Myocardial infarction, CVA
Livedo reticularis, Purpura, Infarcts/Ulceration
Thrombocytopenia, Haemolytic anaemia, Arterial
or venous thromboembolic disease
Avascular necrosis of bone, Other infarcts or
haemorrhage
Stroke, Transient ischaemic attack, Cognitive
dysfunction
Spontaneous abortion, Preeclampsia, Eclampsia,
Placental insufficiency, Preterm delivery (before
34 weeks)
Ocular thrombosis
Pulmonary embolism. Pulmonary hypertension

43. Livedo Reticularis

45. Gangrene

47. Endocarditis

49. Increased risk of thromboembolism & recurrent
pregnancy loss
20-50% criteria for APS are met at 10-20 years.
The higher the aCL Ab titre the greater risk of
thrombosis
Aspirin if cardiovascular or genetic risk factor for
thromboembolic diseases
Avoid OCP, especially if high estrogen content
SLE pts should be regularly assessed for aPL Abs (ACL
Ab, Anti β2 GP1 Ab, LA Ab)
Aspirin or HCQ prophylaxis for those with persistent
LA or aCL Ab at medium or high titre

50. Preliminary criteria:
1. Involvement of three or more organs or tissues
2. Development of manifestations simultaneously or in <
1 week
3. Histopathologic evidence of small-vessel occlusion in
at least one type of tissu
4. Presence of LA or aCL Ab or both
Defitinitive Diagnosis:
- All four criteria are met

53. More specific but less sensitive
Requires a 4 step process
Sensitive but not specific
Standardized ELISA test for IgG or IgM
Moderate to high titre required for diagnosis
Standardized ELISA test for IgG or IgM
*(Positive aPL test requires a repeat test after or more weeks to
rule out transient, clinically unimportant antibody)

54. Does not fulfill lab criteria
Order aPL test
Detected in approximately 45% of primary APS
Does not mandate additional diagnosis of SLE
Complete haemogram
Urine test

55. APTT
Mixing test
Tissue thromboplastin inhibition test
Platelet neutralization procedure
Kaolin clotting test
Diluted Russell’s viper venom test

59. 1.
2.
3.
4.
5.
6.
1.
2.
3.
4.
5.
6.
Unexplained still birth
Recurrent pregnancy loss
Unexplained 2nd or 3rd foetal death
IUGR
Severe preeclampsia before 34 weeks
Placental abruption
False positive serology for syphilis
Autoimmune diseases: SLE, Thrombocytopenia
Unexplained thrombosis
Haemolytic anaemia
Stroke, specially between 25-50 years
Livedo reticularis

60. CT or MRI of brain for stroke
CT or MRI angiography if findings suggest medium
or large vessel disease
Doppler study for DVT
Echocardiography or cardiac MRI for vegetation or
intracardiac thrombi
USG for arterial or venous thrombosis
Biopsy of renal, skin or other tissue
Thrombotic occlusion of all caliber arties and veins
Acute and chronic endothelial injury
Recanalization in late lesion

61. Think of any other thrombophillic states before making
a diagnosis of APS
Hereditary deficiency of Protein C, S and Antithrombin
III
Factor V Leiden and antithrombin mutation
Homocysteinaemia
DIC
Haemolytic uraemic syndrome
Polyarteritis Nodosa
Myxoma
Septicaemia

63. Anti-thrombotic therapy usually not indicated
Some suggest low dose Aspirin prophylaxis
Elimination of other risk factors for thrombosis - OCP,
smoking, HTN, DM or hyperlipidaemia.
Prophylaxis with Heparin in high risk condition
HCQ – protective against thrombosis in SLE pt with aPL Ab
Warfarin (INR 2-3)
Warfarin (INR 3-4) and/or Low dose Aspirin
*
Recent trials suggests that INR of 2-3 is as good for
prevention of future thrombosis

64. 1st pregnancy/Single pregnancy loss <10 weeks:
no treatment
>1 foetal loss, or 3 or more embryonic loss, no thrombosis:
prophylactic Heparin + low dose Aspirin throughout pregnancy,
discontinue 6-12 weeks postpartum
Thrombosis regardless of pregnancy history:
therapeutic heparin or low dose Aspirin throughout pregnancy,
Warfarin postpartum
IVIG – in women with pregnancy loss despite treatment with
Heparin or Aspirin

65. Full anticoagulation if emboli or intracardiac thrombi demonstrated
Valve replacement
>50000/cmm: no treatment
<50000/cmm: Prednisolone, IVIG
Anticoagulation + Corticosteroids + IVIG or Plasmapheresis
Cyclophosphamide or Rituximab in desperate situation

67. Steroid is the choice
Others - Danazol, Dapsone, HCQ, Splenectomy
Aspirin, Warfarin
Valve replacement
Renal transplant - Prognosis is not good

68. Long term functional prognosis is poor
Worst prognostic factors are: pulmonary
hypertension, neurologic involvement, myocardial
ischemia, nephropathy, gangrene of extremities, and
CAPS
Rarely renal failure may develop due to renal
microangiopathy
Thrombosis may cause loss of a transplanted kidney
or other organ
Valvulopathy may need valve replacement
Perioperative complications may occur despite
prophylaxis
Mortality is 50% in CAPS

69. Young female with thrombosis and/or recurrent fetal
wastage – Think of APS
Livedo Reticularis –Think of APS
Chorea in young – Think of APS
Recurrent migraine headache in a young female – do aPL Ab
INR to be individualized and maintained at 2 – 3
Recurrent thrombosis – Target INR 3 – 4
Life long anticoagulation
CAPS - ICU care

70. Thank You