Page 2266 - Williams Hematology ( PDFDrive )

2240 Part XII: Hemostasis and Thrombosis Chapter 131: The Antiphospholipid Syndrome 2241

for prothrombin should be performed when the prothrombin time is OTHER MANIFESTATIONS
prolonged. Other causes of bleeding in APS include acquired throm- Acute adrenal failure secondary to bilateral infarction of the adrenal
bocytopathies, thrombocytopenia (see “Thrombocytopenia,” above), glands has been reported as the first manifestation of primary APS.
254
acquired inhibitors against specific coagulation factors, such as factor Adrenal hemorrhage has been reported. aPL antibodies have been
255
VIII, and the acquired von Willebrand syndrome (AVWS).
associated with marrow necrosis. 256
RETINAL ABNORMALITIES
The diagnosis of aPL antibody retinopathy should be suspected in LABORATORY FEATURES
patients with diffuse retinal vasoocclusion, particularly when char- Diagnosis of APS requires the demonstration of antibodies against
acterized by involvement of arteries and veins, neovascularization at phospholipids and/or relevant protein cofactors (Table 131–6). The cur-
presentation, and symptoms of systemic rheumatologic disease. aPL rent tests for APS recommended by the most recent consensus on inves-
237
antibodies were present in 5 to 33 percent of patients with retinal vein tigational criteria and the Scientific Standardization Committee of the
18
occlusion. 238,239 Cilioretinal artery occlusion, optic neuropathy, and International Society of Thrombosis and Hemostasis are aCL, anti-β
241
240
severe vasoocclusive retinopathy have been described with APS. GPI (IgG and IgM), and LA. The laboratory diagnosis of APS fre- 2
242
257
quently is problematic, with limitations that have been detailed. 258,259
KIDNEY DISEASES aCL IgG and IgM assays are the most sensitive, but the least specific.
APS may affect the renal system. Patients may present with renal artery Anti-β GPI IgG and IgM assays are more specific but less sensitive.
2
stenosis and/or thrombosis, renal infarction, renal vein thrombosis, and LA assays, of which the dilute Russell viper venom time (dRVVT) is
glomerulonephritis that is distinct from vasoocclusive disease. 200,243 An the most common, generally tend to be the least sensitive but the most
entity named “APS nephropathy” has been described, which consists specific. The current recommended tests are less than ideal because
244
of a vasoocclusive disease of small-size intrarenal vessels. This neph- they are empirically derived tests and do not yet measure antibodies
ropathy features fibrous intimal hyperplasia, focal cortical atrophy, and directed against disease specific epitopes or functional parameters that
thrombotic microangiopathy. A review of 29 consecutive renal biopsies correlate with disease mechanisms. Despite these limitations, positiv-
from patients with primary APS, performed at two institutions over ity for all three criteria assays (“triple positivity”) has been correlated
144
22 years, described 20 cases of APS nephropathy and nine cases with with an increased risk for a future thrombotic event (see Fig. 131–5).
243
other distinct pathologic features. These features included membra- Investigational criteria have been developed to identify patients with
nous nephropathy, minimal change disease/focal segmental glomeru-
lonephritis, mesangial C3 nephropathy, and pauci-immune crescentic
glomerulonephritis. TABLE 131–6. Diagnostic Tests for Antiphospholipid
Syndrome
ANTIPHOSPHOLIPID SYNDROME AND AIDS Immunoassays
Although patients with HIV-1 infection frequently have elevated aPL anti- Anticardiolipin IgG and IgM antibodies*
body levels, they do not often have thrombotic manifestations. A review Anti-β GPI IgG and IgM antibodies*
indicated that approximately 50 percent of HIV-1 patients test positive 2
for aPL antibodies, most of which are not cofactor dependent. HIV- Serologic test for syphilis (“biologic false-positive”)
221
infected patients with manifestations of APS have also presented with Antiphosphatidyl serine antibodies
avascular bone and cutaneous necrosis. 222 Antiprothrombin antibodies
Coagulation Tests †
ANTIPHOSPHOLIPID SYNDROME IN CHILDREN Dilute Russell viper venom time with mixing incubations and neu-
Increasingly, APS has become recognized in children, in whom tralization with excess phospholipid
245
diverse clinical features are common. The results of a European regis- aPTT with mixing incubation and neutralization with excess
246
try have been reported. Review of 121 cases indicated that although phospholipids
the thrombotic manifestations were similar to adults with APS, there aPL-sensitive and -insensitive reagents and platelet neutralization
was a difference between children with primary APS and the secondary procedure
APS; the children with primary APS were younger and had a higher fre- Kaolin clotting time
quency of arterial thrombotic events, whereas the children with second- Dilute prothrombin time (a.k.a tissue thromboplastin inhibition
ary APS patients had a higher frequency of venous thrombotic events test)
associated with hematologic and skin manifestations. CAPS has been Hexagonal phase array test
reported in children, but is rare. 247,248
Thrombosis is rare in newborns delivered from mothers with APS, Textarin/ecarin test
and only a few cases are reported, mostly associated with other proth- aPL, antiphospholipid; APS, antiphospholipid syndrome; aPTT, acti-
rombotic factors. aPL antibodies have been found in up to 30 percent vated partial thromboplastin time; β GPI, β -glycoprotein I; Ig, immu-
249
of offspring of mothers with APS. 250 noglobulin; LA, lupus anticoagulant. 2 2
In a recent European prospective study, 17 percent of neonates *Recommended by the International Society on Thrombosis and
born to APS mothers were premature; however, no specific complica- Haemostasis (ISTH) Scientific and Standardisation Committee (SSC)
251
tions were found during the 5-year followup. The study did show a Subcommittee on Lupus Anticoagulants and Antiphospholipid
higher rate of neurodevelopmental abnormalities with learning dis- Antibodies. 258
abilities similar to two retrospective reports where learning disabilities † The committee recommended that two coagulation assays be per-
without other neurodevelopmental abnormalities were present in 15 to formed if LA or APS are suspected, preferably the dilute Russell viper
20 percent of cases. 252,253 venom time (dRVVT) and aPTT.

Kaushansky_chapter 131_p2233-2252.indd 2241 9/18/15 5:10 PM