Paroxysmal Nocturnal Hemoglobinuria (PNH)
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Transcript of Paroxysmal Nocturnal Hemoglobinuria (PNH)
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Section 5 HA
Definition
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 pancytopenia with a dysplastic or aplastic marrow morphology.
Definition
GPI - glycosylphosphatidylinositol glycan
mutations of pig-A gene in HSC
complete or partial failure in the production of GPI anchor protein
Loss of several GPI-anchored membrane proteins
CD59 : membrane inhibitor of reactive lysis, CD55 ( decay accelerating factor CD58CD16CD14
Neutrophilsdecrease
infection
anemia
increased sensitivity to C-mediated lysis
Intravascular hemolysis
hemoglobinuria
Marrow damage
pancytopenia
thrombosis
Platelet falls, bleeding
complement-driven activation of platelets, impaired fibrinolysis
Hypercoagulabe state
Clinical features of PNH
1. Severity of anemia is variable .
Severe anemia : fatigue, weakness, pallor, dyspnea
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.)
Complement activation
PNH I : GPI-negative cells(normal)
PNH II : Partial deficiency
PNH III:Complete deficiency
3. Splenomegaly in some patients
Clinical features of PNH
Some die of thrombotic diseases, some die of leukemia, some develop(or revert to AA.
4. Venous thrombosis (hepatic, portal, splenic mesenteric veins) or DIC
5. Major bleeding or infection.
1. Blood:
• Ret serum bilirubin
• RBC, Hb
usually hypochromic and normochromic anemia
dimorphic
• 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)
Lab findings of PNH
A. intermittent hemoglobinuria
hemosiderinuria
B. sideropenia (secondary to iron deficiency)
C. marrow insufficiency
Why the patien with hypochromic anemia?
3. Urine: sometimes hemoglobinuria, URO + constant hemosiderinuria (Rous test +)
Lab findings of PNH
5. Immunophenotype : decreased CD55, CD59
4. Specific tests --- Sugar water test: screening test for PNH --- Ham test: definitive test for PNH
SUGAR WATER TEST
【 Method 】
control serum ( or same blood type)
Red cells suspension(patient)
sucrose room temperature 1h
no hemolysis
exclude PNHPNH(lysis>5%)
hemolysis
MA, IHA or some leukemia
HAM’S TEST
【 Principle 】 The complement present in serum is responsible for lysis of PNH cells with sensitivity to acidifiction.
patient’s red cells suspension
mixed with fresh complement
( same type control serum or patient’s own serum)
acidified pH6.5 , 37℃1h
lysis: no lysis:
PNH normal or lack of PNH cells
Red cells suspension
+
inactivated serum (56℃, 30’)
pH6.5 , 37 1h℃
no lysis:
Control tubes for excluding false negative
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.
Progressive Studies
Clinical featrues
Plus
Plus exclude AA.(exp. hypoplasia)
Diagnosis for PNH :
two of the following or
Sugar water test: (+)Ham test: (+)
Rous test +
one of the following
•> twice +,•Hemoglobinuria +•evidence of intravascular hemolysis•Exclude HS,IHA,G-6PD deficiency and PCH
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:
Questions: 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 :
1.What is the etioloy of PNH?
2.How to diagnose PNH?
3.How to differentiate PNH and AA?
4. How to differentiate PNH and IDA?