Paroxysmal Nocturnal Haemoglobinuria Flashcards
What is Paroxysmal nocturnal haemoglobinuria?
Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired, clonal disorder of marrow stem cells in which there is deficient synthesis of the glycosylphosphatidylinositol (GPI) anchor, a structure that attaches several surface proteins to the cell membrane.
What is the clinical triad of PNH?
- Chronic intravascular haemolysis
- Venous thrombosis
- Bone marrow failure.
Fill in the blanks. “ PNH arises from the acquired mutations in the X chromosome gene coding for _____________.”
Phosphatidylinositol glycan protein class A (PIGA), which is essential for the formation of the GPI anchor
What are examples of GPI linked proteins?
Decay-activating factor (DAF, CD55)
Membrane inhibitor of reactive lysis (MIRL, CD59)
What Is a constant feature of PNH?
Haemosiderinuria
What are the clinical features of PNH?
- Haemosiderinuria - ( can give rise to iron deficiency )
- Haptoglobins are ABSENT !
- Free Hb can damage kidney
- Oesophageal spasm
- Dysphagia
- Erectile dysfunction
- Pulmonary hypertension
- VENOUS THROMBOSIS
- Stroke
- MI
- Bone marrow Hypoplasia
Fill in the blanks. “ PNH is diagnosed by ______________”
Flow cytometry which shows loss of expression of the GPI-linked proteins CD55 and CD59 or the fluorescent aerolysin (FLAER).
Fill in the blanks. “ ______________ are humanized antibody against complement C5.”
Eculizumab and Ravulizumab which inhibit the activation of terminal components of complement and reduce haemolysis, transfusion requirements and the incidence of thrombosis.
What is Red Cell Aplasia ?
This is a rare group of syndromes characterized by anaemia with normal leucocytes and platelets and grossly reduced or absent erythroblasts in the marrow .
Fill in the blanks. “ A congenital form of Red cell aplasia is known as ___________.”
Diamond– Blackfan anaemia
When is Diamond- Blackman anaemia typically diagnosed?
In the first 2 years of life.
What is Congenital dyserythropoietic anaemias?
Congenital dyserythropoietic anaemias (CDAs) are a group of hereditary refractory anaemias characterized by ineffective erythropoiesis and often erythroblast multinuclearity
What are the clinical features of Congenital dyserythropoietic anaemias (CDAs)?
- Jaundice with bone marrow expansion.
- Normal WBC & Platelet
- Reticulocyte count is LOW
- The anaemia is of variable severity and is usually first noted in infancy or childhood
- Iron Overload
- Splenomegaly is common
Fill in the blanks “ Congenital Dyserythropoietic anaemias type 1 is due to mutation of the gene _________.”
CDAN1 active during the S phase of the cell cycle
Congenital Dyserythropoietic anaemias type 2 aka HEMPAS (hereditary erythroblast multinuclearity with a positive acidified serum lysis test) is due to mutation in which gene ?
SEC23B
