Page 869 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPTEr 61 Antiphospholipid Syndrome 839

results among different commercial laboratories ranges from TREATMENT
64% to 88%, with moderate agreement for IgG and IgM, but
marginal agreement for aCL IgA. 14 Treatment recommendations for persistently aPL-positive patients
Antiphospholipid antibody tests developed based on phos- are determined by the specific clinical indication (Table 61.6).
phatidylserine, phosphatidylinositol, phosphatidylethanolamine,
or prothrombin are not well standardized or widely accepted; Asymptomatic Individuals
their clinical significance is unknown. IgA aCL can occur rarely The ideal strategy for primary thrombosis prevention in asymp-
as the only aPL in patients with APS. When positive, an IgA aCL tomatic, persistently aPL-positive individuals requires a risk-
may justify a diagnosis of APS in LA- and aCL-IgG/IgM test- stratified approach based on aPL profile, age, systemic autoimmune
negative patients with clinically typical disease. A false-positive diseases, traditional cardiovascular disease, or risk factors for
test for syphilis is not diagnostic for APS. venous thrombosis. Elimination of reversible risk factors for
Antinuclear and anti-DNA antibodies occur in approximately thrombosis (smoking, oral contraceptives) and prophylaxis during
45% of patients with APS who are not diagnosed as having SLE. high-risk periods (surgical interventions or prolonged immobiliza-
Thrombocytopenia occurs in APS and is usually modest (>50,000/ tion) is crucial for primary thrombosis prophylaxis in persistently
3
mm ); proteinuria and renal insufficiency occur in patients with aPL-positive individuals. The effectiveness of aspirin is not
thrombotic microangiopathy. Erythrocyte sedimentation rate supported by the literature; in a randomized, double-blind,
and hemoglobin and leukocyte count are usually normal in placebo-controlled trial, low-dose aspirin (81 mg) appeared to
patients with uncomplicated APS, except during acute thrombosis. be no better than placebo in preventing first thrombotic episodes
15
Complement levels are usually normal or only modestly low. in persistently asymptomatic aPL-positive patients. The general-
population cardiovascular disease (CVD) risk prediction tools
Imaging Studies and prevention guidelines formulated based on risk–benefit
MRI studies show vascular occlusion and infarction consistent calculations should play the primary role in decision making for
with clinical symptoms, without special characteristics, except aspirin therapy. Estrogen and estrogen-containing oral contracep-
that multiple otherwise unexplained cerebral infarctions in a tives are considered unsafe for asymptomatic women serendipi-
young person suggest the syndrome. Multiple small hyperintense tously known to bear high-titer antibody. There is no reliable
white matter lesions are common and do not unequivocally information regarding the safety of progestin-only contraception,
imply brain infarction (Fig. 61.2). Occlusions usually occur in “morning after” contraception, or raloxifene, bromocriptine, or
vessels below the resolution limits of angiography; hence angi- leuprolide in APS patients. However, progestin-only contraception
ography or magnetic resonance angiography is not indicated
unless clinical findings suggest medium- or large-vessel disease.
Echocardiography or cardiac MRI may show severe Libman-Sacks
endocarditis and intracardiac thrombi. TABLE 61.6 Treatment recommendations
in Persistently antiphospholipid
Pathological Studies antibody–Positive Patients

Clinical Circumstance recommendation
Asymptomatic No treatment a
CLiNiCaL PEarLS Venous or arterial Warfarin international normalized ratio
thrombosis (INR) 2–3.0 indefinitely
• The clinical manifestations of antiphospholipid antibodies (aPL) represent Recurrent thrombosis Warfarin INR 3–3.5 indefinitely ±
a spectrum (from asymptomatic to catastrophic antiphospholipid low-dose aspirin
syndrome [APS]); thus patients should not be evaluated and managed First pregnancy No treatment a
as having a single disease manifestation. Single pregnancy loss, No treatment a
• Stroke and transient ischemic attack are the most common presentation <10 weeks
of arterial thrombosis; deep vein thrombosis, often accompanied by Recurrent fetal loss or Prophylactic-dose heparin with
b
pulmonary embolism, is the most common venous manifestation of loss after 10 weeks; low-dose aspirin throughout the
APS. history of no pregnancy, discontinue heparin 6–12
• Pregnancy losses in patients with aPL typically occur after 10 weeks’ thrombosis weeks postpartum
gestation (fetal loss), but early losses also occur (preembryonic or Recurrent fetal loss or Therapeutic-dose heparin with low-dose
c
embryonic losses). loss after 10 weeks; aspirin throughout pregnancy, warfarin
• Catastrophic APS is a rare, abrupt, life-threatening complication of history of thrombosis postpartum
APS, which consists of multiple thromboses of medium and small Catastrophic Anticoagulation + corticosteroids +
arteries occurring over a period of days. antiphospholipid intravenous immunoglobulin or plasma
• APS diagnosis should be made in the presence of characteristic clinical syndrome (APS) exchange
manifestations and persistently (at least 12 weeks apart) positive aPL. Livedo reticularis No treatment
Valve nodules or No known effective treatment; full
deformity anticoagulation if emboli or intracardiac
thrombi are demonstrated
Skin, renal, and other tissues show noninflammatory occlusion Thrombocytopenia, No treatment
>50 000/mm
3
of all caliber arteries and veins, acute and chronic endothelial Thrombocytopenia, Prednisone and/or intravenous
injury and its sequelae, and recanalization in late lesions. The ≤50 000/mm 3 immunoglobulin
finding of inflammatory necrotizing vasculitis suggests con-
comitant SLE or other connective tissue disease. There are no a b Aspirin 81 mg/day may be given.
other diagnostic immunofluorescence or electron microscopical c Prophylactic dose such as enoxaparin 30–40 mg subcutaneously (SQ) once daily.
Therapeutic dose such as enoxaparin 1 mg/kg SQ twice daily or 1.5 mg/kg SQ once
findings. daily.