Page 870 - Clinical Immunology_ Principles and Practice ( PDFDrive )

840 ParT Six Systemic Immune Diseases

is theoretically safer than estrogen-based contraception. A small immunoglobulin (IVIG), and plasmapheresis have theoretical
retrospective review of women undergoing artificial reproductive bases for efficacy and have all been used. There are no systematic
technology procedures demonstrated no thrombotic events. studies of treatment for CAPS. Detailed reviews conclude that
the most effective treatment combines full-dose anticoagulation,
Venous and Arterial Thromboembolism high-dose corticosteroids, plasma exchange, and IVIG.
Anticoagulation with unfractionated heparin or low-molecular-
weight heparin (LMWH) followed by warfarin is the treatment Pregnancy Morbidity
for APS patients with vascular events. Heparin inhibits comple- Pregnancy is a prothrombotic state; management strategies in
ment, a fact that makes it theoretically a preferred but impractical persistently aPL-positive patients should focus on prevention of
agent in most patients. For patients with a positive LA test that both pregnancy morbidity and maternal thrombotic complica-
9
prolongs the aPTT, monitoring heparin can be accomplished by tions. In pregnancy, heparin and low-dose aspirin combination
measuring antifactor Xa levels. increases fetal survival rate from 50% to 80% among women
Two prospective controlled studies concluded that recurrence who have had a fetal loss and tests positive for aPL. If patients
of thromboses in APS patients can be prevented with warfarin to fail this regimen, the next step is to add IVIG, an approach not
an international normalized ratio (INR) of 2.0–3.0. 16,17 Although supported by controlled studies. Most experts in the field use
these studies provide strong evidence for moderate-intensity LMWH (e.g., enoxaparin) due to lower risk of thrombocytopenia
anticoagulation after an aPL-related venous event, the intensity and osteoporosis—prophylactic doses for women who have had
of the anticoagulation is still debatable for APS patients with only pregnancy morbidity, or full anticoagulant doses for women
arterial events, since such patients constituted a minority in these who have had prior thromboses (Table 61.6). Treatment begins
studies. Although some APS patients may require high-intensity after confirmation of pregnancy, continues until 48 hours before
anticoagulation, in the absence of risk-stratified studies the anticipated delivery (to allow epidural anesthesia), and resumes
definition of high risk is based currently on clinical judgment. for 8–12 weeks postpartum (if no prior thromboembolism), or
Most aPL-positive patients receive warfarin after ischemic else the patient is transitioned to warfarin for continued therapy.
strokes; however, the Antiphospholipid Antibodies and Stroke No studies unequivocally justify treatment of women with aPL
Study (APASS) concluded that for selected aPL-positive patients during a first pregnancy, women with only very early losses, or
who have neither atrial fibrillation nor high-grade arterial stenosis, women whose aPL titers are low or transient. Nonetheless, it is
aspirin (325 mg/day) and warfarin (target INR 1.4–2.8) are common to offer such patients low-dose aspirin.
equivalent in efficacy and in association with major bleeding
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complications. The generalizability of these results is limited, Other Clinical Manifestations of APS
as the study group had an average age of 60 years (higher than There is no consensus for the treatment of patients with non-
the average for APS populations), the aPL determination was criteria and/or nonthrombotic manifestations of aPL. Corticoster-
performed only once at study entry, and the cutoff for assigning oids and/or IVIG are the first-line treatments for platelet counts
3
a patient to the positive aCL group was very low. However, based less than 50 000/mm . An open-label phase IIa pilot study of aPL
on APASS results, aspirin is an option for older patients with a found that rituximab may be effective in controlling some but
single low positive aCL test who present with stroke. not all noncriteria manifestations of APS, although aPL profiles
Recently, four direct oral anticoagulants (DOACs) that target did not change with treatment. 21
thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, and
edoxaban) have been approved for the treatment of patients Perioperative Management
with venous thromboembolism. Use in patients with APS is Serious perioperative complications may occur despite prophy-
limited, and cases of therapeutic failure have been reported. A laxis. Patients with APS are at additional risk for thrombosis
prospective study investigated the use of rivaroxaban compared when they undergo surgery. Thus perioperative strategies should
with standard-intensity warfarin in patients with APS, using the be clearly identified before any surgical procedure or before
change in endogenous thrombin potential (ETP), a laboratory pharmacological and physical antithrombosis interventions are
parameter, as the primary outcome. Although the ETP did not vigorously employed; in addition, periods without anticoagulation
reach the noninferiority threshold, there was no increase in must be kept to an absolute minimum, and any deviation from
19
thrombotic events in patients taking rivaroxaban. The study a normal course must be considered a potential disease-related
was not powered for clinical outcomes, however, and other studies event. 22
are in progress.
Venous thrombosis in aPL-positive patients typically has a Additional Therapeutic Considerations
high recurrence rate if anticoagulation is discontinued, and There is experimental and clinical evidence in lupus patients
lifelong anticoagulation is usually recommended. A recent that hydroxychloroquine (HCQ) might decrease the incidence
systematic review of the literature revealed that the available of thrombosis, and recent in vitro studies have demonstrated
evidence in support of an association between the presence of that HCQ might protect endothelial cells and syncytialized
aPL and risk of recurrence is of low quality, however, suggesting trophoblast cell lines from the disruptive effect of antiphospho-
20
23
that indefinite anticoagulation may not be needed by all patients. lipid antibodies. In patients with systemic autoimmune diseases
For example, it is unknown whether patients whose event was (particularly lupus), HCQ is commonly employed for disease
triggered by an acquired, reversible risk factor for thrombosis control and should be considered independent of patients’ aPL
can discontinue anticoagulation or switch to aspirin when the status. However, further controlled studies are needed to determine
trigger factor is eliminated. Normalization of the LA or aCL the effectiveness of HCQ for primary prophylaxis in aPL-positive
tests is not an indication to discontinue anticoagulation. For patients.
well-anticoagulated patients who continue to have thromboses, Although statins have been used in primary and secondary
antiplatelet drugs, hydroxychloroquine, statins, intravenous cardiovascular disease prevention, no data exist for their use in