Paroxysmal Nocturnal
Haemoglobinuria
Title
Ñ
Paroxysmal Nocturnal
Haemoglobinuria
Definition
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A rare acquired red cell defect
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Creates a clone of red cells
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Particularly sensitive to:
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Destruction by activated
complement
Aetiology
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Mutation in X-linked pig-A
gene
Pathogenesis
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PNH cells cannot make
glycosylphosphatidyinositol
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This anchors CD 55 and CD 59
which are involved in complement degradation
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Absence of these factors allows
the haemolytic action of complement to continue
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Tendency to develop venous
thrombosis is increased in PNH
Clinical Features
History
Age
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Presents in adults
Sex
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Females > Males
HS
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Anaemia
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Jaundice
GIT
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Recurrent abdominal pains
KUS
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Voiding of dark urine:
Night
Morning on waking
Examination
CVS
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Venous thrombosis:
Deep venous thrombosis
Budd-Chiari syndrome
Mesenteric vein thrombosis
Cerebral vein thrombosis
Investigations
Fluids
Blood
Haematology
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Anaemia
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Thrombocytopaenia
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Neutropaenia
Biochemistry
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Haptoglobin:
Low
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Methaemalbumin:
Seen as a characteristic band on
spectrophotometry of plasma:
·
Schumm’s test
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Iron deficiency;
Loss of iron in urine as haemoglobinuria and
haemosiderinuria
Immunology
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Deficient antigen expression:
Red cells CD 59, CD55
Urine
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Haemosiderinuria
Tissue Diagnosis
Bone marrow
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May be hypoplastic
Management
Support
Biological Agents
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Blood transfusion:
Leucocyte depleted blood to prevent
transfusion reactions causing complement activation
Control
Drugs
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Long term anticoagulation:
Venous thrombosis
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Immunosuppression with
ciclosporin for bone marrow failure
Biological Agents
Ñ
Immunosuppression with
antilymphocyte globulin:
Bone marrow failure
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Eculizumab:
Prevents cleavage of complement C5 and thus
prevents formation of the membrane attack complex
Cure
Biological Agents
Ñ
Bone marrow transplantation
Prognosis
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Median survival 10 years from
diagnosis
Ñ
PNH may transform into aplastic
anaemia or acute leukaemia
