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Section 5 HA. Paroxysmal Nocturnal Hemoglobinuria (PNH). Definition Etiology and pathogenesis Characteristics of PNH ( clinical and lab ) Diagnostic process. Definition.

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Section 5 HA

Paroxysmal Nocturnal Hemoglobinuria (PNH)


Etiology and pathogenesis

Characteristics of PNH (clinical and lab)

Diagnostic process


PNH is a clonal disorder of hematopoietic stem cells caused by a somatic mutation of the pig-A gene on the short arm of the X chromosome . And the patients with it may present either with a HA( with intravascular hemolysis and episodes of nocturnal hemoglobinuria) or pancytopeniawith a dysplastic or aplastic marrow morphology.

GPI - glycosylphosphatidylinositol glycan

Marrow damage

complete or partial failure in the production of GPI anchor protein

Loss of several GPI-anchored membrane proteins

increased sensitivity to C-mediated lysis



complement-driven activation of platelets, impaired fibrinolysis

Intravascular hemolysis

Platelet falls,bleeding

Hypercoagulabe state






mutations of pig-A gene in HSC

CD59 : membrane inhibitor of reactive lysis,

CD55(decay accelerating factor




Severe anemia:fatigue, weakness, pallor, dyspnea

Clinical featuresof PNH

2. Dark urine : paroxysmal or on awakening or no.

(hemolysis episode after infection, transfusion, acid food or drugs, stress, fatigues or after aplastic or hypoplastic anemia.)

PNH I : GPI-negative cells(normal)

PNH II : Partial deficiency

PNH III:Complete deficiency

Complement activation

Clinical featuresof PNH

3. Splenomegaly in some patients

4. Venous thrombosis (hepatic, portal, splenic mesenteric veins) or DIC

5. Major bleeding or infection.

Some die of thrombotic diseases, some die of leukemia, some develop(or revert to AA.

  • Blood:

  • Ret serum bilirubin

  • RBC, Hb

  • usually hypochromic andnormochromic anemia


Lab findings of PNH

  • WBC : neutropenia, low LAP score or absence.

  • BPC: fall, abnormal platelet function

Lab findings of PNH

  • 2. Bone marrow

  • hyperplasia or hypoplasia (aspiration site)

  • hypochromic and normochromic erythrone

  • Iron stain is often absent.(iron deficiency)

PNH: hypercellularity

Why the patien with hypochromic anemia?

A. intermittent hemoglobinuria


B. sideropenia (secondary to iron deficiency)

C. marrow insufficiency

Lab findings of PNH

3. Urine: sometimes hemoglobinuria,URO +

constanthemosiderinuria (Rous test +)

4. Specific tests

--- Sugar water test: screening test for PNH

--- Ham test: definitive test for PNH

5. Immunophenotype:decreased CD55, CD59

3. Urine: URO +

room temperature 1h

no hemolysis



exclude PNH

MA, IHA or some leukemia



Red cells suspension(patient)

control serum ( or same blood type)



【Principle】 The complement present in serum is responsible for lysis of PNH cells with sensitivity to acidifiction.

patient’s red cells suspension

acidified pH6.5 , 37℃1h

mixed with fresh complement

( same type control serum or patient’s own serum)

lysis: no lysis:

PNH normal orlack of PNH cells

Control tubes for excluding false negative

Red cells suspension


inactivated serum(56℃, 30’)

pH6.5 , 37℃1h

no lysis:

Progressive Studies

1. kinetic studies with 51Cr labeled ,the red cells show a double population:

A. with a short half-life

B. with a subnormal survival

2. A cytometric assay of CD16 and CD66b on granulocytes in patients with equivocal red cell

3. GPI anchor protein and PIG-A gene.

Diagnosis for PNH

Clinical featrues


two of the following or

one of the following

  • > twice +,

  • Hemoglobinuria +

  • evidence of intravascular hemolysis

  • Exclude HS,IHA,G-6PD deficiency and PCH

Sugar water test: (+)

Ham test: (+)

Rous test +


exclude AA.(exp. hypoplasia)

Case assay:

A 30-year-old male came to see the physician because of increasing fatigue over the previous few months.

PE : a pale but otherwise normal-appearing adult male, the liver and spleen slightly enlarged.

The patient reported noticing that his first urine of the morning was occasionally brown.

Case assay:


Hb:85 g/L

Hematocrit 0.25 l/L

RBC 2.6×1012/L

WBC 4.4×109/L

Blood smear

Ret 13%

Case assay:

Rous test

Case assay:


1. What is the most probably diagnosis of this patient? List your evidence of the diagnosis.

2. If you want to have an exact diagnosis of this patient, which tests are supposed to be done and what are the expected results?

3. Can you explain the following results with the patient?

Serum iron: 8.1umol/L, TIBC: 66umol/L

  • Questions :

  • What is the etioloy of PNH?

  • How to diagnose PNH?

  • 3.How to differentiate PNH and AA?

  • 4. How to differentiate PNH and IDA?




AA and PNH:

AA-PNH syndrome

AA crisis


Clinical features of AA

Ham test positive or Hburia,Rous test positive