Paroxysmal Nocturnal Hemoglobinuria

Algorithm(s)

PDF algorithm(s) available at www.arupconsult.com.

Hemolytic Anemias Testing Algorithm

Clinical Background

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hemolytic disorder caused by a stem cell mutation which results in deficient cell surface glycol phosphatidylinositol anchoring proteins, including complement pathway regulatory proteins

Epidemiology

Incidence - 1-4/1,000,000
Sex - equal gender distribution
Age of onset - teens to 20s

Classification

Classic PNH
PNH associated with marrow abnormality
Subclinical PNH

Pathophysiology

Consequence of nonmalignant clonal expansion of one or more stem cells that have acquired a mutation of glycol phosphatidylinositol, resulting in the absence of GPI-anchored cell membrane proteins (CD55, CD59)
An association exists between acquired aplastic anemia and PNH - virtually all patients with PNH develop bone marrow dysfunction at some point in the disease
Pathophysiology of bone marrow failure involves abnormal red blood cell sensitivity to complement lysis

Clinical Presentation

Chronic hemolysis
Thrombophilia with anemia
- Thromboses at various sites; most common sites are central nervous system and abdominal veins
- Thromboses are leading cause of death
Bone marrow failure
Other signs and symptoms may include abdominal pain, iron deficiency anemia, jaundice and smooth muscle dysfunction

Treatment

Minimal signs and symptoms - folic acid and thrombosis prophylaxis
Severe signs and symptoms - allogeneic transplants
Moderate disease - humanized monoclonal antibody

See Also

Hemoglobinopathies

Hemolytic Anemias

Algorithm(s)

PDF algorithm(s) available at www.arupconsult.com.

Hemolytic Anemias Testing Algorithm

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: Sugar Water Test

ARUP #: 0049005

Methodology: Visual Identification of Hemolysis

Use:

Screen for paroxysmal nocturnal hemoglobinuria (PNH)

Follow-up:

Follow with Ham Test or Flow Cytometry to confirm PNH

Test name: Acid Hemolysin (Ham Test)

ARUP #: 0049010

Methodology: Visual Identification of Hemolysis

Use:

Confirm PNH and congenital dyserythropoietic anemia (CDA)

Limitations:

Follow-up:

Test name: CBC with Platelet Count & Automated Differential

ARUP #: 0040003

Methodology: Automated Cell Count with Flow Cell Differential

Use:

Definitive test for the diagnosis of PNH

Test name: Reticulocytes, Percent & Number

ARUP #: 0040022

Methodology: Flow Cytometry

Use:

Aid in diagnosis of PNH

Test name: Lactate Dehydrogenase, Serum or Plasma

ARUP #: 0020006

Methodology: Enzymatic

Use:

Aid in diagnosis of PNH

Test name: Bilirubin, Total, Serum or Plasma

ARUP #: 0020032

Methodology: Spectrophotometry

Use:

Aid in diagnosis of PNH

Test name: Haptoglobin

ARUP #: 0050280

Methodology: Immunoturbidimetric

Use:

Aid in diagnosis of PNH

Test name: Paroxysmal Nocturnal Hemoglobinuria Profile, High Resolution - WBC

ARUP #: 0096666

Methodology: Flow Cytometry

Use:

Confirm PNH

Panel detects the absence of phosphatidylinositol-linked membrane proteins CD55 (DAF-decay accelerating factor) and CD59 (MIRL-membrane inhibitor of reactive lysis) on neutrophils (CD16, CD24, CD55 and CD59)

The expression of CD55 and CD59 is decreased or absent in a subpopulation of RBCs in patients with paroxysmal nocturnal hemoglobinuria

Limitations:

Follow-up:

Test name: Paroxysmal Nocturnal Hemoglobinuria Profile, High Resolution - RBC

ARUP #: 0095864

Methodology: Flow Cytometry

Use:

Confirm PNH

Panel detects the absence of phosphatidylinositol-linked membrane proteins CD55 (DAF-decay accelerating factor) and CD59 (MIRL-membrane inhibitor of reactive lysis) on erythrocytes

The expression of CD55 and CD59 is decreased or absent in a subpopulation of RBCs in patients with paroxysmal nocturnal hemoglobinuria

Limitations:

Follow-up: