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4 major groups

• Vascular (mechanical damage). gg • Chemical damage.

• Physical damage.

Infection

Malaria—especially falciparum. Causes anaemia through marrow suppression, hypersplenism and RBC sequestration. In addition there is haemolysis due to destruction of parasitised RBCs by RES and intravascular haemolysis when sporozoites released from infected RBCs. Blackwater fever refers to severe acute intravascular haemolysis with haemoglobinaemia, 5 Hb, haemoglobinuria and ARF.

Babesiosis—Babesia (RBC protozoan). Rapid onset of vomiting, diarrhoea, rigors, jaundice, TT°. Haemoglobinaemia, haemoglobinuria, ARF and death.

Clostridium perfringens—septicaemia and acute intravascular haemolysis.

Viral—especially viral haemorrhagic fevers e.g. dengue, yellow fever. Mechanical

Cardiac—turbulence and shear stress following mechanical valve replacement. General feature of haemolysis: T reticulocytes, LDH, plasma Hb, with 5 haptoglobins ± platelets. Urinary haemosiderin +ve.

March haemoglobinuria—with severe strenuous exercise e.g. running. Destruction of RBCs in soles of feet. Worse with hard soles and uneven hard ground. Mild anaemia. No specific features on film. May be associated GIT bleeding and 5 ferritin (lost in sweat).

Chemical & physical

Oxidative haemolysis —chronic Heinz body intravascular haemolysis with dapsone or salazopyrine in G6PD deficient people or unstable Hb (and normals if dose high enough). Film: bite cells (RBC). Heinz bodies not prominent if intact spleen. Haemolysis well compensated.

MetHb—see p110.

Lead poisoning—moderate 5 RBC lifespan. Anaemia mainly due to block in haem synthesis although lead also inhibits 5' nucleotidase (NT). Basophilic stippling on film. Ring sideroblasts in BM.

O2—haemolysis in patients treated with hyperbaric O2.

Insect bites—e.g. spider, bee-sting (not common with snake bites). gy

Heat—e.g. burns—^severe haemolysis due to direct RBC damage.

Liver disease—reduced RBC lifespan in acute hepatitis, cirrhosis, Zieve's syndrome is an uncommon form of haemolysis—intravascular associated with acute abdominal pain (ffl p54).

Wilson's disease—autosomally inherited disorder of copper metabolism, with hepatolenticular, hepatocerebral degeneration.

Hereditary acanthocytosis—a-|3-lipoproteinaemia. Rare, inherited. Associated with retinitis pigmentosa, steatorrhoea, ataxia and mental retardation.

Most common inherited RBC membrane defect characterised by variable degrees of haemolysis, spherocytic RBCs with 4 osmotic fragility.

Pathophysiology gg Abnormal RBC cytoskeleton: partial deficiency of spectrin, ankyrin, band 3 or protein 4.2 (leads to 5 binding to band 4.1 protein and ankyrin). Loss of lipid from RBC membrane—^spherical (cf biconcave) RBCs with reduced surface area—>get trapped in splenic cords and have reduced lifespan. RBCs use more energy than normal in attempt to maintain cell shape. RBC membrane has 4 Na+ permeability (loses intracellular Na+) and energy required to restore Na+ balance. Red cells are less deformable than normal.

Epidemiology

In Northern Europeans 1:5000 people are affected. In most cases inheritance is autosomal dominant although autosomal recessive inheritance has been reported.

Clinical features

Presents at any age. Highly variable from asymptomatic to severely anaemic, but usually there are few symptoms. Well-compensated haemolysis; other features of haemolytic anaemia may be present e.g. splenomegaly, gallstones, mild jaundice. Occasional aplastic crises occur, e.g. with parvovirus B19 infection.

Diagnosis

• Positive family history of HS in many cases.

• Blood film shows 44 spherocytic RBCs.

• Anaemia, 4 reticulocytes, 4 LDH, unconjugated bilirubin, urinary urobilinogen with 5 haptoglobins. DAT -ve.

Osmotic fragility test—RBCs incubated in saline at various concentrations. Results in cell expansion and eventually rupture. Normal RBCs can withstand greater volume increases than spherocytic RBCs. Positive result (i.e. confirms HS) when RBCs lyse in saline at near to isotonic concentration, i.e. 0.6-0.8g/dL (whereas normal RBCs will simply show swelling with little lysis). Osmotic fragility more marked in patients who have not undergone splenectomy, and if the RBCs are incubated at 37°C for 24h before performing the test.

Autohaemolysis test—since spherocytic RBCs use more glucose than normal RBCs (to maintain normal shape) red cells incubated in buffer or serum for 48h show lysis and release of Hb into solution, which can be measured. In HS RBCs release greater amounts of Hb cf normal RBCs (3% vs. 1% in normal).

Complications

• Aplastic crisis (e.g. parvovirus B19 infection, but may be any virus); see temporary 55 reticulocytes, Hb and Hct.

• Megaloblastic changes in folate deficiency.

• 4 haemolysis during intercurrent illness e.g. infections.

• Gallstones (in 50% patients; occur even in mild disease).

• Extramedullar/ haemopoiesis.

• Iron overload if multiply transfused.

Exclude

Other causes of haemolytic anaemia e.g. immune-mediated, unstable Hbs and MAHA, which can give rise to spherocytic RBCs.

Treatment

Supportive treatment is usually all that is required, e.g. folic acid (5mg/d). In parvovirus crisis Hb drops significantly and blood transfusion may be required. Splenectomy is 'curative' but is reserved for patients who are severely anaemic or who have symptomatic moderate anaemia. Best avoided in patients <10 years old due to risk of 4 fatal infection post-splenectomy.

^ Remember pre-splenectomy vaccines and post-splenectomy antibiotics (O p582).

% Saline

Osmotic fragility assay: note control red cells (red) lyse at lower % saline since they are able to take up more water than spherocytic red cells before lysis occurs.

Blood film in hereditary spherocytosis: note large numbers of dark spherical red cells.

Heterogeneous group of disorders with elliptical RBCs.

3 major groups

• Hereditary elliptocytosis. 100 • Spherocytic HE.

• South East Asian ovalocytosis.

Pathophysiology

Mutations in a or |3 spectrin. There may be partial, complete deficiency, or structural abnormality of protein 4.1, or absence of glycophorin C.

Epidemiology

In Northern Europeans 1:2500 are affected. Inheritance is autosomal dominant. More common in areas where malaria is endemic.

Clinical features

Most are asymptomatic. Well-compensated haemolysis. A few patients have chronic symptomatic anaemia. Homozygote more severely affected.

Diagnosis

• May have positive family history.

• Blood film shows 44 elliptical or oval RBCs.

• Anaemia, 4 reticulocytes, 4 LDH, unconjugated bilirubin, urinary urobilinogen with 5 haptoglobins. DAT is -ve.

• Osmotic fragility usually normal (unless spherocytic HE).

• Transient increase in haemolysis if intercurrent infection.

Complications

Usual complications of haemolytic anaemia e.g. gallstones, folate deficiency, etc.

Treatment

Supportive care: folic acid (5mg/d). Most patients require no treatment. In more severe cases consider splenectomy. Remember pre-splenectomy vaccines and post-splenectomy antibiotics (ffl p582).

Spherocytic HE

Elliptical and spherical 'sphero-ovalocytes' in peripheral blood. Haemolysis and 4 osmotic fragility distinguish it from common hereditary elliptocy-tosis. Molecular basis is unknown.

Southeast Asian ovalocytosis

Caused by abnormal band 3 protein. RBCs are oval with 1-2 transverse ridges. Cells have 4 rigidity and 5 osmotic fragility. RBCs are more resistant to malaria than normal RBCs.

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