APLA syndrome is an autoimmune disorder characterized by recurrent blood clots and pregnancy complications caused by antiphospholipid antibodies. It can occur on its own or in the context of other autoimmune diseases like lupus. Common clinical manifestations include venous thromboses, arterial thromboses, heart valve problems, neurological issues, and pregnancy losses. Diagnosis requires both clinical criteria of blood clots or pregnancy morbidity and positive laboratory tests for antiphospholipid antibodies on two occasions at least 12 weeks apart. Treatment involves long-term anticoagulation with warfarin or low molecular weight heparin.
2. • Synonyms:
APS ( Aantiphospholipid syndrome)
Hughes syndrome
Familial lupus anticoagulant syndrome
• Definition:
APLS is an autoimmune multisystem disorder
characterized clinically by recurrent thrombosis &
pregnancy morbidity & serologically by the
presence of antiphospholipid antibodies ( lupus
anticoagulant, anticardiolipin & anti-beta 2-
glycoproteinⅠantibodies).
3. • Primary APL syndrome: when the condition
occurs in the absence of any other related
disease
53% cases
• Secondary APL syndrome: when the condition
occurs In the context of other autoimmune
diseases, such as SLE
4. • Occurs in young to middle aged adults with
female preponderance
• Associated diseases
SLE
RA
Sjogren syndrome
Systemic sclerosis
5. • Pathophysiology
mechanism of thrombosis in APLS are:
a. Increased expression of tissue factor on
monocytes & endothelial cells
b. Interference in the protein C anticoagulant
pathway
c. Inhibition of fibrinolysis
d. Inhibition of annexin V binding to
phospholipids
6. • Genetic :
There is association between the HLA-DRB1*14 on
chromosome 6p21.3 & familial primary APLS.
B2GP1 Val/Leu polymorphism was associated
with susceptibility to APLS & thrombosis.
• Smoking:
Can lead to endothelial injury & increase the pro-
thrombotic susceptibility in patients with lupus
anticoagulant.
7. • Infections :
Have role in APLS by causing molecular mimicry & by inducing antibody
response
Eg: Borrelia burgdorferi
Treponema
Leptospira
HIV
Hep C
Leprosy
• Drugs :
Alter the processing & presentation of self antigen, thus causes the
autoimmunity
Eg: Chlorpromazine
Procainamide
Quinidine
Phenytoin
8. Two hit phenomenon
1st hit : Procoagulant state
induced by the antiphospholipid
antibodies by destroying the
integrity of the endothelium
2nd hit: Thrombosis takes place
only in the presence of initiating
factor such as trauma, infection
or inflammation
9. Presentation of APLA syndrome
• Cutaneous findings
Livedo reticularis with or without retiform purpura or retiform necrosis
Superficial thrombophlebitis migrans
Purpura
Echymosis
Livedoid vasculopathy/atrophie blanche
Raynaud phenomenon
Nailfold ulcers
Wide spread cutaneous necrosis (catastrophic APLA)
Leg ulcers
Vasculitis like lesions
Pyoderma gangrenosum like ulcers
Splinter haemorrhages
10. • Venous thrombosis
Mainly present as deep vein thrombosis
Pulmonary embolism
Other venous systems which may be involved are :
Renal veins
Portal veins
Mesenteric veins
Intracranial veins
• Arterial thrombosis:
Less common than venous thrombosis
Most frequent site : cerebral vasculature resulting in
transient ischaemia or stroke
MI can also occur
11. • Valvular involvement
Cardiac valve involvement is very common in APLS
Mitral & aortic valve are most commonly involved
Thickening, nodules & Libman-Sacks endocarditis seen
• Hematological involvement
Thrombocytopenia
Hemolytic anemia
12. • Neurological involvement
MC presentations are in the form of TIAs or
ischemic stroke
Cognitive dysfunction, seizures , chorea & multi-
infarct dementia also seen
Blindness due to CRAO & CRVO
SNHL
• Renal involvement
HTN, proteinuria, & renal failure secondary to
thrombotic microangiopathy
13. • Catastrophic APLS:
Rare but disastrous variant
Develop over a short period of time
Generalized microvascular thrombosis lead to
widespread cutaneous necrosis & multiorgan
failure, especially renal & pulmonary system
Associated with high risk of mortality
14. • Preliminary classification criteria for catastrophic APLS
1. Evidence of involvement of three or more organs,
systems &/or tissues
2. Development of manifestations simultaneously or less
than a week
3. Confirmation by histopathology of small vessel
occlusion
4. Laboratory confirmation of the presence of
antiphospholipid antibodies
15. • Definite catastrophic APLS :
all 4 criteria present
• Probable catastrophic APLS:
All 4 criteria, except only two organs, systems &/or
tissues involved
All 4 criteria, except for the absence of laboratory
confirmation of antiphospholipid antibodies
Criteria 1,2 & 4
Criteria 1,3 & 4 with the development of a third event
>1 week but within 1 month of presentation , despite
anticoagulation
18. Investigations
• Lupus anticoagulation test:
This test is the strongest predictor of pregnancy related events
It is more specific but less sensitive
It is a 4 step test
1. Prolonged phospholipid dependent coagulation screening test
(APTT or DRVVT)
2. Inability to correct the prolonged screening test despite mixing
the pt’s plasma with normal platelet poor plasma. This indicates
the presence of an inhibitor
3. Improvement in the prolonged screening test after the addition of
excess phospholipid
4. Exclusion of other inhibitors
19. • Anticardiolipin & anti-beta-2-
glycoproteinⅠantibodies
These antibodies (IgG & IgM isotypes) are assessed by ELISA
Medium or high titres (especially at or above the 99th percentile) are
deemed significant positives
Initial positive test should be repeated to check for the persistence at
least 12 weeks later.
• Other laboratory findings
Thrombocytopenia
Anemia
Proteinuria
Positive serologies specific for SLE (ANA, anti-Ds-DNA)
20. Criteria for antiphospholipid antibody
syndrome
require atleast one clinical & one laboratory criterion
Clinical criteria
• Vascular thrombosis: one or more clinical episodes of
arterial, venous or small vessel thrombosis
• Complications of pregnancy:
i. One or more unexplained deaths of morphologically
normal fetuses at or after 10 weeks of pregnancy or
ii. One or more premature births of morphologically
normal neonates at or before 34 weeks of gestation
or
iii. Three or more unexplained consecutive spontaneous
abortions before 10 weeks of gestation
21. Laboratory criteria
• Anticardiolipin antibodies, IgG or IgM, present
at moderate or high levels on two or more
occasions at least 12 weeks apart
• Lupus anticoagulant antibodies on two or
more occasions at least 12 weeks apart
• Beta 2 glycoprotein 1 antibodies on two or
more occasions at least 12 weeks apart
22. Treatment
• Thrombosis management:
Pts with positive blood test for APLA but no prior H/O
thrombotic events : no treatment
Pts with SLE with positive APLA:
HCQ is recommended
Low dose aspirin may also be considered
Pts with a venous thrombotic event, warfarin with an
INR goal of 2.0 to 3.0 is recommended
23. During pregnancy
For pregnant female with positive APLA but no history of
arterial or venous thrombosis
1st pregnancy or single pregnancy loss <10weeks: no treatment is indicated
H/O multiple pregnancy losses <10 weeks: low dose aspirin with LMWH
H/O one or more pregnancy losses >10 weeks: low dose aspirin with LMWH
throughout pregnancy & can be continued 6 to 12 weeks postpartum
For pregnant female with positive APLA & past history of
arterial or venous thrombosis
Low dose aspirin in combination with unfractionated heparin or LMWH
throughout pregnancy.
after delivery, these patients should be transitioned to warfarin, which
should be continued life long with the INR goal of 2.0 to 3.0
