9.5: Paroxysmal Nocturnal Hemoglobinuria (PNH)

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Paroxysmal Nocturnal Hemoglobinuria is an acquired clonal disorder that starts at the stem cell level. Cells produced become susceptible and are destroyed by chronic complement-mediated hemolysis.^1,2

Cause(s):^1,2

Deficiency in glycosylphosphatidylinositol anchor proteins (GPIs). Normally, CD55 and CD59 act as complement regulators to prevent autologous complement-mediated hemolysis. Without GPIs, cells lack CD55 and CD59 and undergo spontaneous intravascular hemolysis.

Hemolytic episodes (Paroxysms) can be exacerbated by stressors such as inflammation or infections.

Complications:²

Hemolytic Anemia

Bone Marrow Failure

Thrombophilia

Laboratory Results for PNH:^1,3,4

CBC:

RBC: Decreased

WBC: Decreased

PLT: Decreased

Hb: Decreased

MCV: Increased

RETIC: Increased

PBS:

May see:

-nRBCs

-Polychromasia

If Iron Deficiency Present:

-Hypochromic

-Microcytic

If Folate Deficiency Present:

-Oval Macrocytes

If BM Failure Present:

-Pancytopenia

BM:

If BM Failure:

-Impaired hematopoiesis

-Hypocellular

If not BM Failure, may be:

-Normo to hypercellular

-Erythroid hyperplasia

Iron stores: Decreased, or absent

Note: Any dysplastic findings may be indicative of MDS.

Iron Studies:

Same as iron deficiency anemia if patient becomes iron deficient.

Other Tests:

Sucrose Hemolysis Test: Positive for hemolysis

Ham’s (Acidified Serum Lysis) Test: Positive

Flow cytometry (for CD55 and CD59)

DAT: Negative

Osmotic Fragility: Normal

Tests for IVH:

Indirect bilirubin: Increased

Haptoglobin: Decreased

LD: Increased

Hemoglobinemia

Hemoglobinuria

Hemosiderinuria

References:

1. DeZern AE, Brodsky RA. Paroxysmal Nocturnal Hemoglobinuria. A Complement-Mediated Hemolytic Anemia. Hematol Oncol Clin North Am [Internet]. 2015 Jun 7 [cited 2018 Jun 26];29(3):479–94. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695989/

2. Mastellos DC, Ricklin D, Yancopoulou D, Risitano A, Lambris JD. Complement in paroxysmal nocturnal hemoglobinuria: Exploiting our current knowledge to improve the treatment landscape. Expert Rev Hematol [Internet]. 2014 Oct 2 [cited 2018 Jun 26];7(5):583–98. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383744/

3. Cochran-Black D. Hemolytic anemia: membrane defects. In: Clinical laboratory hematology. 3rd ed. New Jersey: Pearson; 2015. p. 317-33.

4. Keohane EM. Intrinsic defects leading to increased erythrocyte destruction. In: Rodak’s hematology clinical applications and principles. 5th ed. St. Louis, Missouri: Saunders; 2015. p. 367–93.