1. Haemolytic anaemias
Dr. Suhair Abbas Ahmed

2. Haemolytic anaemias (HAs)
HAs are defined as those anaemias which result from an increase in the rate of red cell destruction.
any condition which leads to a reduction in the mean lifespan of the red cell is a haemolytic disorder.

3. Because of erythropoietic hyperplasia and anatomical extension of bone marrow, red cell destruction may be increased several fold before the patient become anaemic --- compensated haemolytic anaemia.
The normal adult marrow, after full expansion, is able to produce red cells at 6-8 times the normal rate.
Therefore HA may not be seen until the red cell lifespan is less than 30 days.

4. Classification of HA
The HA can be classified in several different ways:
1- Site of haemolysis:
Extravascular haemolytic disorders -macrophages of the RES
Intravascular haemolytic disorders- within the circulatory system
In many of the cases there is a combination of both extra and intravascular haemolysis.

5. Extravascular haemolysis
Red cell destruction usually occurs in the cell of the RES.

6. Intravascular haemolysis
Destruction of red cells occur inside the blood vessels.

7. Classification of HA 2- Site of defect:
Intrinsic defect (intracorpuscular)- structural or functional defect within the red cell.
Extrinsic defect (extracorpuscular)- an abnormality in the red cell environment.

8. Classification of HA 3- Inherited or acquired:
Inherited HA are usually caused by intrinsic defect.
While acquired HA are caused by an extrinsic defect.
However there are some exceptions: Paroxysmal nocturnal haemoglobinuria (PNH) which is an acquired intrinsic defect, and severe hereditaryG6PD enz deficiency which requires the presence of an extrinsic trigger such as the antimalarial drug for the intrinsic defect to manifest.

9. Inherited & acquired HA
Hereditary HA
Membrane defects e.g hereditary spherocytosis
Metabolic defect e.g G6PD deficiency.
Haemoglobin defects e.g sickle cell disease.
Acquired HA
Immune
-Autoimmune eg AIHA
-Alloimmune e.g HDN, HTR
Red cell fragmentation syndromes
March haemoglobinaemia
Infections
Chemical and physical agents.
PNH

10. Approach to the diagnosis of haemolytic anaemias.

11. Patient’s history
Good history is essential to provide guidance for the diagnosis of haemolytic disorders. The following points should not be neglected:
Family history--- hereditary conditions, mode of inheritance.
Ethnic origin--- G6PD deficiency is most common in Mediterranean and Chinese populations.
Past history--- NNJ may be indicative of congenital conditions as HS or G6PD deficiency.
Triggering events--- history of drugs, infections

12. Clinical features Pallor of the mucous membranes
Mild fluctuating jaundice
Splenomegaly
Dark urine
Pigment gall stones.
Ulcers around the ankle
Aplastic crisis may complicate viral infections.
Growth retardation
Hypertrophic skeletal changes

13. Leg ulcers in patients with severe congenital haemolytic disorders. e
Leg ulcers in patients with severe congenital haemolytic disorders. e.g sickle cell anaemia

14. Skeletal changes in patients with b thalassaemia.

15. Laboratory findings The lab. Findings are divided into 3 groups:
1- Features of increased red cell breakdown.
2- Features of increased red cell production.
3- Damaged red cells.

16. Laboratory findings 1-Features of increased red cell breakdown:
Raised S.bilirubin, unconjugated and bound to albumin.
Increased urine urobilinogen.
Increased faecal stercobilinogen.
Absent S.haptoglobins (saturated with Hb and removed by the RE cells).

17. Laboratory findings 2-Features of increased red cell production:
Reticulocytosis
Bone marrow erythroid hyperplasia.

18. Laboratory findings 3-Damaged red cells:
Morphology– microspherocytes, elliptocytes, fragments, etc.,….
Special tests: Osmotic fragility, autohaemolysis…..
Red cell survival is shortened; this is best shown by 51Cr labelling with study of the sites of destruction.

21. Reticulocytosis is a feature of increased red cell production.
New methylene blue is used to stain the reticulocytes

22. Fragmented cells, and bitten cells are sings of damaged cells occurring in haemolysis

23. Intravascular haemolysis

24. Intravascular haemolysis
Free Hb will be released from damaged red cells.
This free Hb will rapidly saturates plasma haptoglobins. The complex will be removed by the liver.
The excess free Hb is filtered by the glomerulus, and free Hb will enter the urine, as iron is released, the renal tubules become loaded with haemosiderin.
Methaemalbumin and haemopexin are also found in the process of IV haemolysis.

25. The process of intravascular haemolysis
Liberation of free Hb
Filtered through the kidney
Appear in urine as haemoglobinuria

26. Lab features of intravascular haemolysis
Haemoglobinaemia & haemoglobinuria.
Haemosiderinuria (iron storage protein in the spun deposit of urine).
Methaemalbumin (detected by Schumm’s test).

27. Haemoglobinuria
Notice the dark colour of urine compared to the normal colour in the other container.
This is a sign of intravascular haemolysis.

28. Conclusion
Good history taking is essential in guiding the physician towards the correct diagnosis.
Clinical findings seldom are sufficient to enable a definitive diagnosis of a particular haemolytic condition to be made.
Lab investigations play a central role in the accurate diagnosis of haemolysis.