6.

ANTIPHOSPHOLIPID SYNDROME

DEFINITION

Antiphospholipid syndrome (APS) is a disorder characterized by a

hypercoagulability state recurrent arterial and venous thromboses and
pregnancy loss.

EPIDEMIOLOGY

It is a disease of young adult (20 -40 years old). The females are more affected.
The prevalence of primary APL is less than 0.5%.
1. Primary APS no autoimmune disorder association.
2. Secondary APS association with other autoimmune disorder (eg, SLE)
3. Catastrophic APS multiorgan failure due to acute thrombotic
microangiopathy associating a high mortality rate.

PATHOGENESIS

The pathogenesis of APS is not completely known. It is known the fact that the
antiphospholipid antibodies affect coagulation and thrombosis by:
upragulating tromboxane A2 and glycoprotein 2b-3a via binding to
platelets
binding to endothelial cells, monocytes will increase the levels of tissue
factors and the adhesion molecules
activating the complement and such initiating an inflammatory cascade
that would lead to thrombosis

CLINICAL MANIFESTATIONS

Clinical pattern differs according with the blood vessels involved. Usually the
most common findings are:
Venous thrombosis
 Arterial thrombosis
Pregnancy loss
Thrombocytopenia
Other manifestations:
Skin: livedo reticularis, Raynauds phenomenon
Obstetric: HELLP syndrome (hemolysis, elevated liver enzymes, low platelet
count), pre-eclampsia, eclampsia
Neurologic: stroke, myasthenia gravis, transverse myelopathy
Pulmonary: pulmonary embolus, pulmonary hypertension
Cardiovascular: myocardial infarction, intracardiac thrombosis
Renal: hypertension, renal insufficiency
Hematologic: haemolytic anemia
Musculoskeletal: deep venous thrombosis, avascular necrosis
Endocrine: adrenal insufficiency
LABORATORY FINDINGS

Three types of assays are available to detect APL:

1. the LAC (lupus anticoagulant)
2. the aCL antibodies (anticardiolipin antibodies)
3. the anti--2gpl antibodies (anti--2 antiglicoprotein antibodies)
Other tests:
complete blood count
blood chemistries liver and renal dysfunction

IMAGISTIC FINDINGS

CT/MRI assess damage and guide management.

CLASSIFICATION

Research criteria for defining the antiphospholipid syndrome (2006

International Society on Thrombosis and Haemostasis)
Clinical criteria

1. Vascular thrombosis
One or more clinical episodes of arterial, venous or small vessel thrombosis
2. Pregnancy morbidity
(a) One or more unexplained deaths of a morphologically normal fetus at or
beyond the 10th week of gestation
(b) One or more pre-term births of a morphologically normal neonate before the
34th week of gestation because of: (i) eclampsia or severe pre-eclampsia or (ii)
recognized features of placental insufficiency
(c) Three or more unexplained consecutive spontaneous miscarriages before the
10th week of gestation, with maternal anatomic orhormonal abnormalities and
paternal and maternal chromosomal causes excluded

Laboratory criteria

1. Lupus anticoagulant (LA) present in plasma, on two or more occasions at least

12 weeks apart
2. Anticardiolipin (aCL) antibody of immunoglobulin (Ig)G and/or IgM isotype in
serum or plasma, present in medium or high titre (i.e. >40GPL units or MPL
units, or > the 99th centile), on two or more occasions, at least 12 weeks apart
3. Anti-b2glycoprotein I antibody of IgG and/or IgM isotype in serum or plasma
(in titre >the 99th centile), present on two or more occasions at least 12 weeks
apart

Antiphospholipid antibody syndrome (APS) is present if at least one of the

clinical criteria and one of the laboratory criteria are met.

TREATMENT

Goal:
prevention of thrombosis.
Primary prophylaxis (aCL positive patients without previous thrombosis,
obstetric patients)
 Aspirin 325mg PO daily
Hydroxycloroquine 400mg PO daily protective against future
thrombosis
Secondary prophylaxis (APS patients with at least one thrombotic event)
long - term intensive anticoagulation is required based on the type of the
thrombotic event.
Venous event
Unfractioned heparin followed by warfarin with a goal of international
normalized ratio (INR) of 2.5 (range 2 to 3) first thrombotic event.
Do not stop medications in the first 6 months. The risk of recurrence is
high. The consensus is to treat indefinitely with anticoagulants.
In recurrent venous thrombosis the high anticoagulation is
recommended INR 3 to 4 or warfarin with INR 2 to 3 plus aspirin. If
unstable INR it is recommended to switch to low-molecular weight
heparin.
Arterial event the cerebral circulation is mostly involved (stroke, transient
ischemic attacks). The treatment used is:
Aspirin 325mg PO daily
Warfarin
Pregnancy morbidity prevention the treatment of pregnant women with
fetal loss and aCL antibodies is controversial.
Aspirin 81 mg daily should be started when attempting conception
Heparin (unfractionated or low molecular weight) should be started
when intrauterine pregnancy is confirmed. Both should be discontinued
in the third trimester.
Unfractionated heparin 5000-10.000 units q12h
Low molecular weight heparin enoxaparin 1mg/kg or 40-80 mg,
dalteparin 5000 units, nadroparin 3800 units once daily.
Catastrophic APS
It is a disorder characterized by multiorgan failure due to small-vessel occlusion
developing simultaneously or < 1 week. Histopathology confirms the occlusion in
at least one tissue or organ. The mortality is high.
treatment of precipitating factors (eg. SLE flares, infection etc.)
 7 to 10 days or longer anticoagulation with iv heparin
high-dose steroids for 3 or more days
IV immune globulin 0.4gm/kg body weight daily for 4 to 5 days or
plasma exchange for at least 3 to 5 days
Other therapeutical options:
cyclophosphomide in patients with secondary APL
rituximab in patients with thrombocytopenia or autoimmune
haemolytic anemia
smoking cessation
avoidance of supplemental estrogens
controlling hypertension
controlling diabetes

TAKE HOME MESSAGES

In APS, previous thrombosis is the strongest predictor of future events.

Anticoagulation in a patient with APS should be lifelong.

References:
1. Stone JH, A Clinicians Pearls and Myths in Rheumatology, Springer 2009,
493: 173-180
2. Kahl Leslie, Rheumatology Subspecialty Consult, Lippincott, Wiliams and
Wilkins 2012, 422: 329-355, ISBN: 978-1-4511-1412-5