18. Haemolytic anaemia Flashcards
Causes of anaemia
- failure to make RBC
- marrow problem - lack of haematinics: iron, B12, folate
- dietary deficiency
- malabsorption - increased loss of RBC
- bleeding - increased destruction of RBC
- haemolysis - chronic disease
What is haemolytic anaemia
anaemia due to excess breakdown of RBC with marrow compensation
- increased LDH (lactate dehydrogenase) and bilirubin
- high reticulocyte count
Where does destruction of cells occur
- Circulation (intravascular haemolysis)
2. Spleen-by splenic macrophages
Why is there an elevated reticulocyte count in haemolytic anaemia
reticulocyte = immature RBC that is nucleated
Lack of red cell -> Bone marrow going into overdrive -> Bone marrow pushes reticulocyte to compensate
Causes of immune-acquired haemolytic anaemia
- autoimmune self-antigens cause an immune destruction of RBC
-in warm temp (around 37°C), IgG
-in cooler temp (around 20°C), IgM
binds to surface of RBC, tags it & when it passes through the spleen, the splenic macrophages will take it out (opsonisation) - alloimune non-self antigens cause immune destruction of RBC
-haemolytic transfusion reaction
-haemolytic disease of newborn
-post bone marrow transplant rejection of graft (mixed blood group due to change in bone marrow) - drug associated
-dapsone - other autoimmune disease
-systemic lupus erythematosus (STE) - lymphoma
- infection
-mycoplasma
How to test for immune haemolysis
Direct Antiglobulin Test
- Coomb’s test
1. Wash RBC
2. Add anti-IgM and anti-IgG
3. Look for agglutination
4. Antibodies (IgG +IgM) bind to RBC
5. RBC membrane phagocytosed
Causes of non-immune acquired haemolytic anaemia
- red cell fragmentation syndrome
- eclampsia
- sepsis
- disseminated intravascular coagulation (excess thrombi and bleeding) - mechanical heart valve
Examples of congenital haemolytic anaemia
- membrane abnormalities
- hereditary spherocytosis
- hereditary elliptocytosis
- defect in structural protein of RBC membrane: spectrin - enzyme abnormalities
- G6PD deficiency
- pyruvate kinase deficiency - haemoglobin abnormalities
How does G6PD deficiency cause congenital haemolytic anaemia
This enzyme participates in the pentose phosphate pathway, a metabolic pathway that supplies reducing energy to cells (such as RBC) by maintaining the level of the NADPH.
The NADPH in turn maintains the level of glutathione in these cells that helps protect the RBC against oxidative damage
How does pyruvate kinase deficiency cause congenital haemolytic anaemia
Pyruvate kinase transfer phosphate group from phosphenolpyruvate (PEP) to ADP resulting in both ATP and pyruvate.
Pyruvate kinase deficiency in the red blood cells results in an inadequate amount of or complete lack of the enzyme, blocking the completion of the glycolytic pathway. Therefore, all products past the block would be deficient in the red blood cell. These products include ATP and pyruvate.
Mature erythrocytes lack a nucleus and mitochondria. Without a nucleus, they lack the ability to synthesize new proteins so if anything happens to their pyruvate kinase, they are unable to generate replacement enzymes throughout the rest of their life cycle. Without mitochondria, erythrocytes are heavily dependent on the anaerobic generation of ATP during glycolysis for nearly all of their energy requirements.
With insufficient ATP in an erythrocyte, all active processes in the cell come to a halt. Sodium potassium ATPase pumps are the first to stop. Since the cell membrane is more permeable to potassium than sodium, potassium leaks out. Intracellular fluid becomes hypotonic, water moves down its concentration gradient out of the cell. The cell shrinks and cellular death occurs. The body is deficient in red blood cells as they are destroyed by lack of ATP at a larger rate than they are being created.
How does haemoglobin defects cause congenital haemolytic anaemia
abnormal genetic code in Hb
- accumulation of abnormal chains leads to structural defects
1. sickle cell disease - can make Hb but wrong shape
2. thalassemia - can make Hb but cannot make enough
How does sickle cell anaemia occur
- autosomal recessive
- valine -> glutamic acid
- inherits two abnormal copies of the β-globin gene that makes haemoglobin
- increased HbS with RBC aggregation at low O2 tensions
- offers resistance to malaria
Pathogenesis of sickle cell anaemia
- chronic
- HbS in deoxygenated state is less soluble than HbA
- insoluble chains crystallise in RBC with distortion of membrane
- cells become crescent shaped
- sickle cell last for 10-20 days only
- deformed cells are more rigid and cannot pass through microcirculation
- causes vascular occlusion
- structural change and increase blood viscosity -> venous stasis -> local obstruction -> tissue hypoxia -> more sickling -> tissue infarction
Sickle cell anaemia can be precipitated by
- hypoxia
- acidosis
- hypotension
- infection
- dehydration
- hypothermia
Other complications of sickle cell anaemia
- osteomyelitis
- blood supply to bone is cut off
- micro part of bone has no blood supply, bacteria can accumulate (usually in long bones of the leg)
- present with horrible pain until the bone heals - gall stones
- produced from excess bilirubin, which is caused by the constant breakdown of RBC
- biliary sludge (formed when excess bile settles in the duct) can also lead to gallstones forming - renal failure
- cardiac failure
- constantly anaemic, heart has to pump harder - chronic leg ulcer
- mechanical obstruction by dense sickled red cells
