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2238 Part XII: Hemostasis and Thrombosis Chapter 131: The Antiphospholipid Syndrome 2239

Registry, cerebral manifestations occurred in 62 percent of patients patients show histologic evidence of microangiopathy mainly affecting
and caused 13 percent of deaths. Recurrent strokes are more likely small vessels of the kidneys, lungs, brain, heart, and liver. Only a minor-
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in patients with APS and other risk factors for cerebrovascular disease, ity of patients experience large-vessel occlusions. Laboratory evidence
such as cigarette smoking, hypertension hyperlipidemia, oral contra- for disseminated intravascular coagulation is frequently present. An LA
ceptive use, and SLE. 159,160 is present in 81.7 percent of patients, and the aCL IgG is the most com-
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Most APS patients with stroke have arterial thromboembolic occlu- mon positive aPL antibody. Improved treatment has reduced mor-
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sive events that are clinically indistinguishable from the more common tality from approximately 50 percent to approximately 20 percent.
arteriosclerotic strokes. APS should be suspected in young patients with Relapse is rare in survivors. The only identified predictive factor for
TIAs or stroke, particularly when the more typical risk factors for cer- adverse outcome is underlying SLE. 179
ebrovascular disease are absent. Cerebral venous thrombosis is less
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common in APS patients and presents at a younger age, and is more
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extensive than in non-APS patients with the disorder. In one series of PREGNANCY LOSSES, OBSTETRIC
40 cases of cerebral venous thrombosis, three patients (8 percent) had COMPLICATIONS, AND INFERTILITY
163
elevated aPL antibody levels. Superior sagittal sinus thrombosis has At this time, aPL screening of otherwise asymptomatic with no history
been reported with primary APS. 164 of prior complications obstetrical patients is not warranted because of
There is controversy about whether migraines in patients with aPL the high frequency of false-positive tests; most studies have estimated
antibodies should be regarded as thromboocclusive events. Other the prevalence of aPL antibodies among general obstetric populations
165
neurologic abnormalities reported to be associated with aPL antibodies to be approximately 5 percent or less and most of these aPL-positive
166
include seizures/epilepsy, chorea, Guillain-Barré syndrome, transient patients are not clinically affected. 180
global amnesia, dementia, diabetic peripheral neuropathy, and ortho- Among obstetric patients with recurrent fetal losses, approximately
167
static hypotension. Recurrent acute transverse myelopathy has been 16 to 38 percent have aPL antibodies. In addition, pregnant women
described with APS. 168–172 However, in one study of 315 SLE patients, with elevated aPL antibodies had significantly more obstetric compli-
including 10 with a history of transverse myelopathy, that disorder was cations, including preeclampsia, abruption placentae, miscarriage, pre-
not associated with aPL antibodies. Multiple sclerosis patients have a maturity, intrauterine fetal demise, intrauterine growth restriction, and
173
high incidence of elevated aCL antibody levels (in one series, 9 percent oligohydraminos, than aPL antibody-negative pregnant women. 181–183 In
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had IgG antibodies and 44 percent had IgM antibodies), however, no approximately half of patients, the pregnancy losses occur in the first
clinical distinctions were found between aPL-positive and aPL-negative trimester. Other patients present with later losses, most in the second
patients and the antibodies do not appear to be associated with throm- trimester, but some even later, including stillbirth. Pregnancy complica-
bosis. Patients with psychotic disorders have an increased prevalence of tions attributable to APS include three or more recurrent spontaneous
LA and aCL antibodies, even in the absence of treatment with antipsy- first trimester miscarriages, one or more fetal losses during the second
chotic drugs. 175 trimester, stillbirth, episode of preeclampsia, preterm labor, placental
abruption, intrauterine growth restriction, and oligohydramnion. 184–186
CATASTROPHIC ANTIPHOSPHOLIPID Pregnant patients with APS are also more prone to developing deep
SYNDROME vein thrombosis during pregnancy or the puerperium. Rarely, pregnant
patients develop CAPS.
The best predictor for pregnancy loss in
187,188
CAPS is a relatively infrequent but devastating presentation of APS, a patient who tests positive for aPL antibodies has been demonstrated
is characterized by severe widespread vascular occlusions. Diag- to simply be a previous history of pregnancy loss, complications, or
176
nostic criteria for CAPS include evidence of involvement of at least thrombosis. 146,189 A recent study reported that any aPL antibody-positive
three organs, systems, and/or tissues; development of manifestations women with an unexplained early loss prior to 10 weeks have a higher
190
simultaneously or in less than 1 week; histopathologic confirmation of risk of complications in their second pregnancy but the degree of lab-
small-vessel occlusion; and laboratory confirmation of the presence of oratory abnormalities were not associated with increased risk. Positivity
177
aPL antibodies. According to the CAPS Registry, a web-based data- by more than one assay appears to correlate with increased pregnancy
base of 433 patients with CAPS (https://ontocrf.costaisa.com/en/web/ morbidities. 182,191 Histologic abnormalities were found in many, but
192
caps/), the majority of CAPS patients are female (69 percent), in their not all, placentas of aPL patients. Studies of placental pathology in
late thirties (mean age of 38.5 years), but the condition can present at patients with aPL antibodies, but without a prior history of fetal loss,
any age (range: 0 to 85 years). In half of the CAPS cases, the patients’ showed that approximately half had evidence of uteroplacental vascu-
catastrophic event was their first APS manifestation. Precipitating fac- lar pathology, approximately half had evidence of thrombotic occlu-
tors of CAPS include infections, drugs (sulfur-containing diuretics, cap- sion, and approximately one-third had chronic villitis and/or decidual
topril, and oral contraceptives), surgical procedures, and cessation of plasma cell infiltrates. 193,194
prior anticoagulant therapy. In 26.9 percent of cases, the patients also Overall, it appears that the presence of aPL antibodies does not
had SLE. The most frequently affected organ was the kidney (73 percent affect the success rate of implantation. Although one group has reported
of episodes), followed by lungs (58.9 percent), the brain (55.9 percent), data that indicated that women with recurrent implantation failure were
the heart (49.7 percent), and the skin (45.4 percent). Other organs were more likely to have positive assays for aPL antibodies compared to fer-
195
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also affected, including the peripheral vessels, intestines, spleen, adrenal tile negative controls, a review of 29 studies showed mixed results.
glands, pancreas, retina, and marrow. Patients present with evidence for Many of the studies were noted to have limitations, including problems
severe multiorgan ischemia/infarction, often with concurrent dissemi- with study design and statistical power. The current consensus is that
197
nated microvascular thrombosis. Patients with CAPS can present with aPL antibodies are not a cause of infertility. Recently, the14th Inter-
renal insufficiency, respiratory failure resulting from acute respiratory national Congress on Antiphospholipid Antibodies Task Force also
distress syndrome (ARDS) and pulmonary emboli, cerebral manifes- concluded that “there are no data to support the inclusion of infertility
tations such as encephalopathy, stroke and seizures, cardiac problems as criteria for APS and investigation of APS in patients with infertility
such as heart failure, myocardial infarction and valvular defects, and should not be done in routine clinical practice, being reserved only for
skin complications such as livedo reticularis and skin necrosis. Most research purposes.” 196
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