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Hemolytic Anemias (Paroxysmal Nocturnal Hemoglobinuria (Investigations…
Hemolytic Anemias
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Membrane
Hereditary Spherocytosis
- most common inherited haemolytic anaemia
- autosomal dominant
- due to defects in the red cell membrane
- unable to pass through the splenic microcirculation so they have a short- ened lifespan.
Clinical features
- jaundice at birth (can be delayed)
- Asymptomatic
- splenomegaly and ulcers on the leg.
- may be interrupted by aplastic (after infections with erythro (parvo) virus), haemolytic and megaloblastic crises (folate depletion).
- Chronic haemolysis leads to the formation of pigment gallstones
Investigations
- Anaemia: mild, but can be severe.
- Blood film. shows spherocytes and reticulocytes.
- LD, bilirubin are High
- Osmotic fragility
- Direct antiglobulin (Coombs’) test is negative in hereditary spherocytosis, ruling out autoimmune haemolytic anaemia where spherocytes are also commonly present.
Treatment
- Splenectomy: best to postpone splenectomy until after childhood, as sudden overwhelming fatal infections, usually due to encapsulated organisms such as pneumococci
followed by lifelong penicillin prophylaxis
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Immune
Autoimmune
- acquired disorders resulting from increased red cell destruction due to red cell autoantibodies.
- characterized by the presence of a positive direct antiglobulin (Coombs’) test.
- divided into ‘warm’ and ‘cold’ types, depending on whether the antibody attaches better to the red cells at body temperature (37°C) or at lower temperatures.
Warm antybodies ( IgG )
Clinical features
- occur at all ages and in both sexes (frequent in middle-aged females)
- short episode of anaemia and jaundice
- splenomegaly
- Infections or folate deficiency may provoke fall in the haemoglobin.
- primary (Idiopathic) or secondary (CLL, NHL, autoimmune disorders) (blood transfusions and infections, drugs or vaccination).
- commonest underlying cause is a lymphoproliferative disorder
- Extravascular hemolysis
Investigations
- Haemolytic anaemia.
- Spherocytosis
- Direct antiglobulin test is positive
- Autoantibodies may have specificity for the Rh blood group system
- Autoimmune thrombocytopenia and/or neutropenia may also be present (Evans’ syndrome).
- Abdominal CT scan for the detection of splenomegaly or abdominal lymphoma.
Treatment
- Corticosteroids.
- Splenectomy
- immunosuppressive drugs, such as azathioprine and rituximab
- Blood transfusion
Cold antibodies ( IgM, IgA)
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- primary (Idiopathic)
- secondary to infections (mycoplasma, EBV), NHLParoxysmal cold haemoglobinuria (IgG)
- Extravascular and intravascular haemolysis
Drug-induced
- rare
- interaction between a drug and red cell membrane may produce:
Antibodies to the drug: e.g. quinidine, rifampicin. intravascular haemolysis.
Antibodies to the cell membrane: e.g. methyldopa, fludarabine. extravascular haemolysis
Antibodies to part-drug, part-cell membrane: e.g. penicillin.
- Confirmation of the diagnosis requires:
Recovery after withdrawal of the drug
direct antiglobulin test should be positive
Alloimmune
- occurs in haemolytic disease of the newborn, haemolytic transfusion reactions
Haemoglobinopathies
sickle cell disease
Sickle cell anaemia
Investigations
- hemoglobin electrophoresis is the most specific test (no HbA, 80–95% HbSS and 2–20% HbF.)
- Blood films can show features of hyposplenism and sickling.
- normal MCV, reticulocytosis, LDH and bilirubin are elevated.
Treatment
- Acute chest syndrome:
pain relief, high-flow supplemental oxygen and antibiotics (cefotaxime and clarithromycin)
- red blood cell transfusions if the hematocrit is low, and exchange transfusion if the hematocrit is high.
- splenectomy
- Hydroxycarbamide (hydroxyurea) is the first drug which has been widely used as therapy for sickle cell anaemia.
increases HbF concentrations
- Bone marrow transplantation can be curative in severe cases.
- Avoid high altitudes (low oxygen tension can precipitate crisis).
- Folic acid supplements (due to chronic hemolysis).
Clinical features
- Vaso-occlusive crises causes pain and fever.
- Pulmonary hypertension: ssociated with an increased mortality
- Acute chest syndrome:
pulmonary hypertension and chronic lung disease are the commonest causes of death in adults with sickle cell disease
caused by infection, fat embolism from necrotic bone marrow or pulmonary infarction due to sequestration of sickle cells.
shortness of breath, chest pain, hypoxia and new chest X-ray changes due to consolidation.
- Anaemia.
- Splenic sequestration ( Sudden pooling of blood into the spleen results in rapid development of splenomegaly and hypovolemic shock.).
- Bone marrow aplasia: commonly occurs following infection with erythro- virus B19
Long-term problems
- Low Growth and development.
- Bones:
common site for vaso-occlusive episodesleading to chronic infarcts.
Avascular necrosis, compression of vertebrae, Osteomyelitis
- Infections, Leg ulcers, cardiomegaly, arrhythmias, MI.
- Neurological: transient ischaemic attacks, fits, cerebral infarction, cerebral haemorrhage and coma.
- Cholelithiasis, hepatomegaly and liver dysfunction, Chronic tubulointerstitial nephritis
- Priapism: painful erection occurs from vaso- occlusion.
- retinopathy, vitreous haemorrhages and retinal detachments
- Impaired placental blood flow causes spon- taneous abortion, intrauterine growth retardation, pre- eclampsia and fetal death.
- results from a single-base mutation of adenine to thymine
- In the homozygous state (sickle cell anaemia), both genes are abnormal (HbSS), whereas in the heterozygous state (sickle cell trait, HbAS)
- characterized by irreversibly sickled cells and recurrent painful crises.
- autosomal recessive hereditary disease.
Sickle cell trait
- no symptoms unless extreme circumstances cause anoxia, such as flying in non-pressurized aircraft.
- gives some protection against Plas- modium falciparum malaria
- there is 60% HbA and 40% HbS.
- blood count and film of a person with sickle cell trait are normal
- diagnosis is made by a positive sickle test or by Hb electrophoresis
- Abnormalities occur in:
Globin chain production (e.g. thalassaemia)
Structure of the globin chain (e.g. sickle cell disease)
Combined defects of globin chain production and structure, e.g. sickle cell β-thalassaemia.
Causes
Hereditary
- Membrane: heriditary spherocytosis, hereditary elliptocytosis.
- Metabolism: G6PD deficiency, pyruvate kinase deficiency,
- Hemoglobin: genetic abnormalities (Hb S, Hb C, unstable), Thalassaemia, Sickle cell
Acquired
- Immune:
• Autoimmune: warm antibody type, cold antibody type
• Alloimmune: transfusion reactions, hemolytic disease of the newborn, allografts (especially stem cell transplantation)
• Drug-associated
- Red Cell Fragmentation Syndromes
- Infections: malaria, clostridia
- Chemical and Physical Agents
- Secondary: liver and renal disease
- Paroxysmal Nocturnal Hemoglobinuria
- Mechanical heart valves
haemolysis
Extravascular (common)
- LD, bilirubin are High
- haptoglobin is absent
- hemoglubinuria, Free Hb in plasma, urine hemosidrin are absent
Intravascular
- LD, bilirubin are High
- haptoglobin is absent
- hemoglubinuria, Free Hb in plasma, urine hemosidrin are present
- presence of methaemalbumin (positive Schumm’s test)
- occurs when rate of destruction exceeds production, in the blood vessels (intravascular) or extravascular, inside the spleen.
- Symptoms: Jaundice, splenomegaly