Red Cell Haemolysis

Question 1

Define:
(a) haemolysis
(b) haemolytic disorder
(c) haemolytic anaemia

Answer 1

(a) haemolysis: the process by which red blood cells are destroyed and their contents, such as haemoglobin, are released into the surrounding fluid
(b) haemolytic disorder: This refers to any condition that leads to the premature destruction of red blood cells. [This can result from various causes, including genetic defects, autoimmune reactions, infections or exposure to certain drugs or toxins.]
(c) haemolytic anaemia: This is a type of anaemia that occurs when the rate of red blood cell destruction exceeds the rate of their production in the bone marrow.

Question 2

Briefly discuss the pathophysiology of extravascular haemolysis.
What is the fate of the iron produced?

Answer 2

🩸 This is the process by which damaged or abnormal red blood cells are removed and destroyed by macrophages, primarily in the spleen and liver, and sometimes in the bone marrow.
🩸 When RBCs are broken down, haemoglobin is released. The iron from hemoglobin is recycled and transported back to the bone marrow.

Question 3

Briefly discuss the pathophysiology of intravascular haemolysis.

Answer 3

🩸 This refers to the destruction of red blood cells within the blood vessels, leading to the release of their contents directly into the plasma.
🩸 This may be as a result of mechanical trauma, complement fixation and activation and infectious agents e.g. plasmodium.
🩸 The free haemoglobin released from lysed RBCs can be filtered by the kidneys and excreted in the urine, leading to hemoglobinuria. This can cause urine to appear dark or red.
🩸 Some of the haemoglobin is broken down to hemosiderin, an iron-storage complex, which can also be excreted in the urine, leading to haemosiderinuria.

Question 4

Compare hemoglobinuria and hemosiderinuria in terms of duration.

Answer 4

🩸 Hemoglobinuria typically lasts for a short period, usually a few days, depending on the underlying cause and the effectiveness of treatment. It resolves once the acute hemolysis is controlled.
🩸 Hemosiderinuria can persist for several weeks or longer, as it indicates chronic or ongoing intravascular hemolysis. The presence of hemosiderin in the urine reflects the body’s longer-term response to hemolysis.

Question 5

Briefly discuss the pathogenesis of haemosiderinuria.

Answer 5

🩸 Excress haemoglobin released from RBCs in circulation is filtered by the kidney.
🩸 In cells of the proximal tubule, the iron is removed and stored as hemosiderin.
🩸 When the cells slough off, they are excreted into the urine, producing a brownish/dirty color due to the haemosiderin within.

Question 6

List four red cell membrane defects associated with hemolysis [and indicate whether it is associated mainly with intravascular or extravascular hemolysis].

Answer 6

(a) hereditary spherocytosis [extravascular]
(b) hereditary elliptocytosis and ovalocytosis [extravascular]
(c) hereditary stomatocytosis [extravascular]
(d) paroxysmal nocturnal haemoglobinuria [acquired, intravascular]

Question 7

What are two broad categories of haemoglobin disorders that may result in red cell haemolysis.

Answer 7

(a) structural variants e.g. HbS, HbC, HbE and unstable haemoglobins
(b) imbalance in globin chain synthesis e.g. thalassemia syndromes

Question 8

List red cell enzyme defects that may contribute to abnormal haemolysis.

Answer 8

🩸 G6PD deficiency
🩸 pyruvate kinase deficiency
🩸 hexokinase deficiency
🩸 glutathione synthetase deficiency
🩸 phosphoglycerate kinase deficiency

Question 9

List some non-immune causes of abnormal red cell haemolysis.

Answer 9

(1) infections e.g. malaria, bacterial sepsis, clostridial infections
(2) toxins, chemicals, drugs
(3) red cell fragmentation syndromes e.g. DIC, prosthetic cardiac valves
(4) hypersplenism

Question 10

List some causes of immune-mediated haemolysis.

Answer 10

🩸 autoimmune haemolytic anaemia (AIHA)
🩸 alloimmune haemolytic anaemia: (1) haemolytic transfusion reaction, (2) haemolytic disease of the newborn, (3) allograft associated haemolytic anaemia
🩸 drug induced immune haemolytic anaemia

Question 11

List signs and symptoms of anaemia.

Answer 11

Sign: pallor [Image 1] [Image 2] [Image 3]
Symptoms: dyspnea, fatigue, weakness, oedema, angina, cardiopulmonary decompensation

Further notes:
dyspnea: shortness of breath
angina: chest pain or discomfort caused by reduced blood flow to the heart muscle
cardiopulmonary decompensation: worsening of heart failure symptoms

Question 12

List clinical feature of abnormal red cell haemolysis.

Answer 12

🩸 anaemia
🩸 jaundice
🩸 splenomegaly
🩸 dark urine, haemoglobinuria and haemosiderinuria [indicative of intravascular haemolysis]

Question 13

Painful occlusive crisis reflects what underlying haemolytic condition?

Answer 13

Sickle Cell Disease (SCD)

Question 14

Leg ulcers may reflect what underlying haemolytic condition?

Answer 14

Sickle Cell Disease (SCD)

[Image 1] [Image 2]

Further notes:
Here’s an interesting read:
Sickle cell: Nigerian Surgeon develops compression therapy for leg ulcers

Question 15

Skull and skeletal deformities e.g. skull bossing may reflect what underlying haemolytic conditions?

Answer 15

Sickle Cell Disease, Thalassemias, other chronic haemolytic anaemias