Page 2356 - Hematology_ Basic Principles and Practice ( PDFDrive )

2098 Part XII Hemostasis and Thrombosis

to have venous thrombotic events associated with hematologic and antibody levels. The frequency was even higher in patients with more
skin manifestations. Children with rheumatic diseases with persis- severe cirrhosis. One review reported that about 20% of patients with
tently positive criteria aPL assays were reported to have resistance to chronic hepatitis B and hepatitis C had elevated aPL antibodies, most
annexin A5 anticoagulant activity compared with patients with of which were cofactor independent, i.e., similar to antibodies in
transiently positive antibodies. The catastrophic form of the syndrome infections that recognize phospholipid directly rather than antibodies
has been reported in children, but occurs less frequently than it does that recognize phospholipid-binding proteins such as β 2GPI. Hepa-
in adults. Thrombosis is rare in newborns delivered by mothers with titis C may be an exception because patients can present with “true”
APS, although aPL antibodies have been found in up to 30% of such autoimmune aPL antibodies; the most common features reported
offspring. were intraabdominal thrombosis and myocardial infarction. Primary
biliary cirrhosis has also been associated with aPL antibodies.
“Noncriteria” Clinical Manifestations Associated With
Antiphospholipid Antibodies and Renal Manifestations
Antiphospholipid Syndrome
Several nonthrombotic types of renal lesions have also been identified
Cardiovascular Manifestations in APS patients. Patients with aPL antibodies may present with
glomerulonephritis without vasoocclusive disease. A review of 29
consecutive renal biopsies from patients with primary APS, performed
In the absence of thrombotic occlusion, coronary artery disease is not at 2 institutions over 22 years, described 20 cases of APS nephropathy
a criterion for APS. However, aPL antibodies have been associated and identified 9 cases with distinct pathologic features including
with increased susceptibility to atherosclerosis. aPL antibodies also membranous nephropathy, minimal change disease/focal segmental
appear to be a risk factor for adverse outcomes after all coronary glomerulonephritis, mesangial C3 nephropathy, and pauci-immune
revascularization procedures, interventional and surgical. crescentic glomerulonephritis.
A remarkably large proportion of patients with the primary APS,
approximately 35%, have cardiac valvular abnormalities detectable
by echocardiography. When patients with cardiac valvular diseases Dermatologic Manifestations
that were not suspected to be associated with APS were evaluated for
aPL antibodies, about 20% had evidence of aPL antibodies compared Livedo reticularis is relatively common, occurring in 24% of a series
with about 10% of matched controls. Valvular abnormalities were of 1000 aPL patients (Fig. 141.4). Livedo reticularis is usually wide-
reported in about half of patients with the combination of SLE spread and can localize on nonadjacent areas on the limbs, trunk, and
and aPL antibodies; these abnormalities included leaflet thickening, buttocks. Its prevalence was found to be higher in APS that was
vegetations, regurgitation, and stenosis. The mitral valve is most associated with SLE compared with primary APS, in women com-
commonly affected, followed by the aortic valve. In a prospective pared with men, and in patients with high levels of aCL antibodies.
follow-up of 89 patients with severe, nonspecific valvular heart Livedo reticularis may be associated with other manifestations of APS
disease, thromboembolic events were significantly more frequent such as cerebral or ocular ischemic arterial events (OR, 10.8; 95%
in the aPL antibody–positive group than in the aPL antibody- CI, 5.2–22.5), seizures (OR, 6.5; 95% CI, 2.6–16), arterial events
negative group; however, the presence of aPL antibodies was not (OR, 6; 95% CI, 2.9–12.6), heart valve abnormalities detected
an independent risk factor for thromboembolic events. There was on echocardiography (OR, 7.3; 95% CI, 3.6–14.7), and arterial
one dissenting study that failed to find a relationship between systemic hypertension (BP >160/90 mmHg) (OR, 2.9; 95% CI,
increased aCL antibodies and valvular abnormalities in patients with 1.5–5.7). Necrotizing vasculitis, livedoid vasculitis, thrombophlebitis,
SLE, progressive systemic sclerosis, rheumatoid arthritis, and primary cutaneous ulceration and necrosis, erythematous macules, purpura,
APS. ecchymoses, painful skin nodules, subungual splinter hemorrhages,
anetoderma (macular atrophy), discoid lupus erythematosus, and
cutaneous T cell lymphoma have all been reported.
Neurologic Manifestations

aPL antibody-associated neurologic abnormalities, other than stroke,
include migraine headache, seizures, chorea, Guillain-Barré Syn-
drome, transient global amnesia, dementia, diabetic peripheral neu-
ropathy, and orthostatic hypotension. In the pediatric APS registry,
migraine headache (7%), chorea (4%), and epilepsy (3%) were the
most common nonthrombotic neurologic manifestations.
Elevated aCL antibodies are often seen in patients with multiple
sclerosis but these are not associated with an increased risk for
thrombosis or stroke. In one series of patients with multiple sclerosis,
9% had IgG antibodies and 44% had IgM antibodies, but there was
no clinical distinction between those with or without these antibod-
ies. Patients with psychotic disorders have also been reported to have
an increased prevalence of LA and aCL antibodies. In one study, 32%
(11/34) of the unmedicated psychotic patients had elevated aPL
antibodies, but these patients did not appear to have an increased risk
of thrombosis.

Hepatic Manifestations

aPL antibody levels are frequently elevated in patients with chronic
liver diseases. In one prospective study of patients with liver disease, Fig. 141.4 LIVEDO RETICULARIS IN A WOMAN WITH ANTIPHOS-
approximately half of patients with alcoholic liver disease and one- PHOLIPID SYNDROME. (From Ruiz-Irastorza G, Crowther M, Branch W,
third of patients with chronic hepatitis C virus had elevated aPL Khamashta MA: Antiphospholipid syndrome. Lancet 376:1498, 2010.)