Haemolytic anaemias Dr. Suhair Abbas Ahmed

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.

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.

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.

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

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

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.

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.

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

Approach to the diagnosis of haemolytic anaemias.

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

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

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

Skeletal changes in patients with b thalassaemia.

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.

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).

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

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.

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

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

Intravascular haemolysis

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.

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

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

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

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.