Page 602 - Williams Hematology ( PDFDrive )

576 Part VI: The Erythrocyte Chapter 40: Paroxysmal Nocturnal Hemoglobinuria 577

Normal Control Patient
PNH03.002 PNH02.002
10 4 3 10 4 3

10
GLYCOPHORIN PE 10 1 10 1 72%

RBCs 10 2 GLYCOPHORIN PE 10 2

10

10 0 10 0 0 1 2 3 4
10 0 10 1 10 2 10 3 10 4 10 10 10 10 10
CD55 FITC + CD59 FITC CD55 FITC + CD59 FITC

PNH06.002 PNH05.002
10 4 10 4

10 3 10 3

PMNs CD11b PE 10 2 CD11b PE 10 2 96%

10 1 10 1

10 0 10 0
10 0 10 1 10 2 10 3 10 4 10 0 10 1 10 2 10 3 10 4
CD55 + CD59 CD55 + CD59
Figure 40–5. Diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) by flow cytometry. Erythrocytes (RBCs) and neutrophils (PMNs) from a
healthy volunteer and a patient with PNH were analyzed by flow cytometry using anti–glycophorin A (top row, vertical axis) to identify RBCs and
anti-CD11b (bottom row, vertical axis) to identify PMNs. Glycosylphosphatidylinositol-anchored protein (GPI-AP) expression was detected using a
combination of anti-CD55 and anti-CD59 (top and bottom rows, horizontal axis). PNH cells are deficient in both CD55 and CD59 (upper left quadrant of
each histogram). The percentage of GPI-AP–deficient (PNH) cells is shown for each sample.

TABLE 40–3. Basic Evaluation for Paroxysmal Nocturnal these cases, the proportion of GPI-AP–deficient blood neutrophils is
38
Hemoglobinuria less than 25 percent of the total. Those patients with very small popu-
lations of GPI-AP–deficient erythrocytes (designated PNH-sc) have no
Flow cytometric evidence of a population of erythrocytes and clinical or biochemical evidence of hemolysis and require no specific
granulocytes partially or completely deficient in multiple glycosyl- treatment for PNH (see Table 40–2).
phosphatidylinositol-anchored proteins (GPI-APs) * Studies have investigated the natural history of PNH clones in the
Complete blood count, reticulocyte count, serum concentration setting of marrow failure. 38,40,41 The threshold that separates PNH-sc from
of lactate dehydrogenase, bilirubin (fractionated) and haptoglobin, clinical PNH is reached when the neutrophil clone size is in the range
†
determination of iron stores of 20 to 25 percent with a corresponding GPI-AP–deficient erythrocyte
Marrow aspirate, biopsy, and cytogenetics ‡ population of 3 to 5 percent. Longitudinal studies indicate that clonal
40
* Paroxysmal nocturnal hemoglobinuria (PNH) clone size is deter- expansion occurs in 15 to 50 percent of cases. 38,40,41 In 10 to 25 percent
mined by the percentage of GPI-AP–deficient polymorphonuclear of cases the clone disappears, and in 25 to 60 percent of cases the clone
cells. size persists unchanged. 38,40,41 Available evidence indicates that patients
† The most important surrogate marker for intravascular hemolysis. who present with PNH-sc do not progress to clinical PNH. 38,40,41 Among
‡ Marrow aspirate and biopsy are used to distinguish classic PNH from patients who present with clinical PNH in the setting of marrow fail-
PNH in the setting of another marrow failure syndrome. Nonrandom ure, treatment for complications of PNH (eculizumab for hemolysis or
karyotypic abnormalities are rare in PNH. anticoagulation for thrombosis) is required in approximately 50 percent

Kaushansky_chapter 40_p0571-0582.indd 577 9/17/15 6:22 PM