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Chapter 141 The Antiphospholipid Syndrome 2097

increased risk of cerebrovascular disease, and echocardiography should involvement of arteries and veins, neovascularization at presentation,
be considered for patients with APS and stroke because a high propor- and symptoms of systemic rheumatologic disease. Elevated aPL
tion of APS patients have cardiac valvular abnormalities (see later). antibody levels were present in 5% to 33% of patients with retinal
The diagnosis of APS is should be considered when young patients vein occlusion. Cilioretinal artery occlusion, optic neuropathy, and
present with a TIA or a stroke, particularly those without other risk severe vasoocclusive retinopathy have been described with APS.
factors. Rates of stroke were higher in younger patients with APS,
with a rate of up to 32% in a multinational childhood registry versus
16%–21% in adult APS patients. Case-control and prospective Other Organ Manifestations
studies have shown strong associations between aPL antibody or LA
positivity and ischemic stroke in young adults with an OR of 43.1 aPL antibodies have been described in patients with pulmonary
for positive LA tests and ischemic strokes. Younger patients present- hypertension. A multi-institutional study of 687 patients with
ing with stroke tended to have venous, rather than arterial, occlusion chronic thromboembolic pulmonary hypertension reported that aPL
with 7% of children presenting with cerebral vein thrombosis in the antibodies were a significant risk factor. In one prospective trial of 38
multinational childhood registry. In addition to the immediate consecutive patients with precapillary pulmonary hypertension,
impact, recurrent strokes may lead to multi-infarct dementia that can approximately 30% had aPL antibodies with various phospholipid
mimic other causes of dementia. specificities.
Acute adrenal failure secondary to bilateral infarction of the
adrenal glands has been reported as the first manifestation of primary
Cardiovascular Manifestations APS. Adrenal hemorrhage has also been reported. aPL antibodies
have also been associated with osteonecrosis. Skin manifestations may
APS should be considered in patients without the more typical risk be a first sign of APS. Skin ulcerations associated with skin necrosis
factors for coronary artery disease and in patients with evidence of are a presenting feature in 3.5% of cases.
thrombotic or embolic coronary occlusion who lack angiographic
evidence of atherosclerotic disease. In the RATIO population-based
case-control study, the presence of a LA was a significant risk factor Catastrophic Antiphospholipid Syndrome
for arterial occlusion. LA correlated with an increased risk of myo-
cardial infarction with an OR of 5.3, which increased to 21.6 in Rare patients present with a catastrophic form of APS, which is
women who used oral contraceptives and to 33.7 in women who characterized by severe widespread vascular occlusion and a high
smoked. Elevated anti-β 2GPI correlated with a mild increase in stroke mortality. The formal diagnostic criteria include evidence of involve-
but not with myocardial infarction. Antiprothrombin and anticardio- ment of at least three organs, systems and/or tissues, development of
lipin antibodies did not correlate with an increased risk of arterial manifestations simultaneously or within 1 week, histopathological
thrombosis. However, antiprothrombin antibodies were reported to confirmation of small vessel occlusion, and laboratory confirmation
be a predictor of myocardial infarction in middle-aged men, and one of the presence of aPL antibodies (Table 141.2).
study found that the interaction in risk between antiprothrombin In contrast to the diagnostic criteria for APS, the diagnostic criteria
antibodies and other risk factors was multiplicative. for CAPS permit the presence of histologic evidence of vasculitis
together with thrombosis. These patients present with evidence of
severe multiorgan ischemia/infarction, usually with concurrent
Hepatic and Gastrointestinal Manifestations microvascular thrombosis. Patients with CAPS can present with
massive venous thromboembolism, along with respiratory failure,
The liver is the most commonly affected abdominal organ in APS. stroke, abnormal liver enzymes, renal impairment, adrenal insuffi-
Occlusion of hepatic vessels supplying the biliary tree may present as ciency, and areas of cutaneous infarction. The respiratory failure is
acute acalculous cholecystitis with gallbladder necrosis. Gastro- usually caused by acute respiratory distress syndrome (ARDS) and
intestinal manifestations of APS also include esophageal necrosis with diffuse alveolar hemorrhage. Laboratory evidence for disseminated
perforation, intestinal ischemia and infarction, pancreatitis, colonic intravascular coagulation is frequently present.
ulceration, and giant gastric ulcerations. APS has been reported in According to the CAPS Registry, a web based database of 433
patients with mesenteric inflammatory venoocclusive disease and patients with CAPS (https://ontocrf.costaisa.com/en/web/caps/), the
with mesenteric and portal vein obstruction. majority of CAPS patients are female (69%), in their late thirties
(mean age of 38.5 years), but patients can present at any age (range
0 to 85 years). In half of the CAPS cases, the catastrophic event was
Renal Abnormalities their first manifestation of APS. Precipitating factors for CAPS
include infection, drugs (sulfur-containing diuretics, captopril, and
Patients with APS may present with vasoocclusive manifestations oral contraceptives), surgical procedures, and cessation of anticoagu-
such as renal artery stenosis and/or thrombosis, renal infarction and lant therapy. In 26.9% of cases, the patients also had SLE. The most
renal vein thrombosis, and with nonthrombotic manifestations, frequently affected organ was the kidney (73% of episodes), followed
described in the section on noncriteria manifestations. An entity by the lungs (58.9%), brain (55.9%), heart (49.7%), and skin
named APS nephropathy consists of vasoocclusive disease of small (45.4%). Other organs were also affected including the peripheral
intrarenal vessels characterized by fibrous intimal hyperplasia, focal vessels, intestines, spleen, adrenal glands, pancreas, retina, and bone
cortical atrophy, and thrombotic microangiopathy. The acute form marrow. An LA is present in 81.7% of patients, and aCL IgG is the
of this vascular nephropathy resembles other thrombotic microangi- most common positive aPL antibody. Improved treatment has
opathies, such as hemolytic uremic syndrome or thrombotic throm- reduced mortality from approximately 50% to 20%. Fortunately,
bocytopenic purpura. A chronic form that is frequently clinically relapse is rare in survivors. The only identified predictive factor for
silent until late stages manifests as a vasoocclusive process that adverse outcome is underlying SLE.
develops at all levels of the renal vasculature, from the main renal
artery to glomerular capillaries and renal veins.
Pediatric Antiphospholipid Syndrome

Retinal Abnormalities APS is a significant cause of thrombosis in the pediatric population.
In a European registry, children with primary APS tended to be
The diagnosis of APS retinopathy should be suspected in patients younger and had a higher frequency of arterial thrombotic events,
with diffuse retinal vasoocclusion, particularly when characterized by whereas those with secondary APS were older and were more likely