Page 867 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPTEr 61 Antiphospholipid Syndrome 837

A proposed pathogenesis for aPL-mediated thrombosis and
placental injury begins with activation or apoptosis (by unknown
triggers, possibly infectious or traumatic) of platelets, endothelial
cells, or trophoblasts. Negatively charged phosphatidylserine
migrates from the inner to the outer cell membrane. Circulating
β 2 GPI binds to phosphatidylserine, which is followed by aPL
binding to a β 2 GPI dimer, activating a complement and, through
C5a, initiating a signaling cascade that induces cell surface tissue
factor (TF) expression and adhesion molecules (e.g., ICAM-1).
Other components of the innate immune system may also be
activated, leading to a milieu that promotes platelet activation
and thrombosis. In addition, aPL adversely affects formation of
a trophoblast syncytium, placental apoptosis, and trophoblast
invasion, all processes required for the normal establishment of
placental function. In vitro, pathogenic aPL induces adhesion
molecules and enhances adherence of leukocytes to cultured
endothelial cells.

DIAGNOSIS
Clinical Manifestations
The clinical manifestations associated with aPL represent a
spectrum from asymptomatic to catastrophic APS (Table 61.3).
The principal manifestations are venous or arterial thromboses
and pregnancy losses. Except for their severity, the youth of FiG 61.1 Livedo reticularis in a patient with primary antiphos-
affected patients, and unusual anatomical locations (Budd-Chiari pholipid syndrome.
syndrome, and sagittal sinus and upper extremity thromboses),
thromboses in APS do not clinically differ from thromboses
attributable to other causes. Stroke and transient ischemic attack TABLE 61.3 The Clinical Spectrum of
are the most common presentation of arterial thrombosis, whereas antiphospholipid antibodies
deep vein thrombosis and pulmonary embolism are the most a
common venous manifestations of APS. Glomerular capillary Asymptomatic antiphospholipid antibody (aPL)–positivity
Antiphospholipid syndrome with vascular events
endothelial cell injury or thrombosis of renal vessels (thrombotic Antiphospholipid syndrome with only pregnancy morbidity
microangiopathy) causes proteinuria without celluria or hypo- Asymptomatic aPL-positivity with noncriteria aPL manifestations
a
complementemia and may lead to severe hypertension and/or Catastrophic antiphospholipid syndrome
renal failure.
a No history of thrombosis or pregnancy morbidity as per the Sapporo Criteria. 1
Many patients have livedo reticularis (a lattice-like pattern of
superficial skin veins) (Fig. 61.1), cardiac valve disease (vegeta-
tions, valve thickening and dysfunction), or other nonthrombotic
manifestations described in several studies but not included in TABLE 61.4 Noncriteria Features of the
1
the revised Sapporo criteria due to nonspecificity or rarity (Table antiphospholipid Syndrome
61.4). These manifestations by themselves do not classify a patient
as having APS for clinical studies, but they add information to Type Features
the diagnosis of individual patients. The pathogenesis of cardiac Clinical Livedo reticularis
valve disease in APS is unknown; valve replacement may be Cardiac valve disease
necessary. A putative association of aPL and increased risk of Autoimmune hemolytic anemia 3
atherosclerosis may exist, but this is controversial; in studies Thrombocytopenia (usually 50 000–100 000/mm )
Multiple sclerosis–like syndrome and myelopathy
of atherosclerosis in patients with SLE, aPL protected against Nonfocal neurological symptoms
8
atherosclerosis. Some patients develop nonfocal neurological Chorea
symptoms such as lack of concentration, forgetfulness, and Laboratory IgA anticardiolipin and anti-β 2 -glycoprotein-I antibodies
dizzy spells. Small hyperintense lesions can be seen on magnetic Antiphosphatidylserine, phosphatidylinositol,
resonance imaging (MRI), primarily in the periventricular phosphatidylglycerol, phosphatidylethanolamine
antibodies
white matter, but do not correlate well with clinical symptoms Antiprothrombin antibodies
(Fig. 61.2). Antiphosphatidylserine-prothrombin antibodies
Pregnancy losses in patients with aPL typically occur after
10 weeks’ gestation (fetal loss), but early losses also occur
9
(preembryonic or embryonic losses). Patients with antiphos-
pholipid syndrome may develop severe early preeclampsia and Catastrophic APS (CAPS) is a rare, abrupt, life-threatening
HELLP (hemolysis, elevated liver enzymes, low platelets) syn- presentation. It consists of multiple thromboses of medium and
drome. Although placental infarction may be a cause of fetal small arteries occurring over a period of days, causing stroke;
growth restriction or death, nonthrombotic mechanisms of cardiac, hepatic, adrenal, renal, and intestinal infarction; and
placental dysfunction are likely more important. peripheral gangrene. Proposed diagnostic criteria for CAPS