Blood-RBC&Anaemia II 2024.PDF

RBC and anaemia (II) Anaemia of chronic diseases Aplastic anaemia Haemoglobin abnormality Red cell enzyme deficiency Learning outcomes To explain the difference between anaemia of chronic diseases and aplastic anaemia To show knowledge of major haemoglobin abnormalities To understand the pathogenesi...

RBC and anaemia (II) Anaemia of chronic diseases Aplastic anaemia Haemoglobin abnormality Red cell enzyme deficiency Learning outcomes To explain the difference between anaemia of chronic diseases and aplastic anaemia To show knowledge of major haemoglobin abnormalities To understand the pathogenesis of red cell enzyme deficiency RBC and anaemia (II) Anaemia of chronic diseases Aplastic anaemia Haemoglobin abnormality Red cell enzyme deficiency Anaemia of chronic diseases One of the most common anaemias Associated with reduced RBC proliferation and impaired Fe utilisation Associated chronic diseases: − Chronic microbial infections (e.g. osteomyelitis) − Chronic immune disorders (e.g. rheumatoid arthritis) − Neoplasm (e.g. Hodgkin’s lymphoma, lung carcinoma) Anaemia of chronic diseases Pathogenesis - Cytokine-driven inhibition of RBC production Chronic inflammatory /neoplastic diseases Cytokines Hepcidin synthesis ↓Iron release from storage pool ↓EPO production ↓RBC production Anaemia of chronic diseases Laboratory feature: Serum iron↓ and total iron binding capacity↓ Increased storage iron in marrow macrophages Red cells: − Normocytic and normochromic or − Microcytic and hypochromic as in iron deficiency anaemia Recent advance: soluble transferrin receptor to differentiate anaemia of chronic disease from pure Fe deficiency Anaemia of chronic diseases Clinical feature: − Anaemia not severe, Hb ≥ 8g/dl − Dominant symptoms: those of the underlying diseases Treatment: − Only successful treatment of the underlying condition corrects the anaemia − Many patients benefit from EPO RBC and anaemia (II) Anaemia of chronic diseases Aplastic anaemia Haemoglobin abnormality Red cell enzyme deficiency Aplastic anaemia Defined as pancytopenia (anaemia, neutropenia, thrombocytopenia) with hypocellularity of bone marrow Uncommon but serious condition May be inherited; more commonly acquired Probably results from failure or suppression of pluripotent stem cells Very occasionally, defect of the erythroid series only - “pure red cell aplasia” Major causes of aplastic anaemia Idiopathic − Primary stem cell defect − Immune mediated Chemical agents − Dose related (alkylating agents, benzene) − Idiosyncratic (chloramphenicol) Physical agents − Whole body irradiation Viral infections − Hepatitis (unknown virus) − Cytomegalovirus infection Miscellaneous − Infrequently, many other drugs and chemicals Aplastic anaemia Clinical features Symptoms - results of the deficiency of − Red blood cells (anaemia) − White blood cells (susceptibility to infection) − Platelets (bleeding) Physical findings − Bruising, bleeding gums and epistaxis − Mouth infection common Aplastic anaemia Investigations Blood count − Pancytopenia − Low or absent reticulocytes Bone marrow examination − A hypocellular marrow with increased fat spaces Normal bone marrow Aplastic anaemia Aplastic anaemia Differential diagnosis: – Other causes of pancytopenia – Bone marrow biopsy: bone marrow cellularity Treatment: – Withdrawal of offending agent – Supportive care (infection control) – Specific treatment (bone marrow transplantation; immunosuppressive therapy) RBC and anaemia (II) Anaemia of chronic diseases Aplastic anaemia Haemoglobin abnormality Red cell enzyme deficiency Anaemia - Haemoglobin abnormality Mostly caused by single point mutation Abnormal globin chain structure Imbalanced globin chain production Sickle cell disease A disease of abnormal ß globin chains Common in people of African origin Cause: homozygous inheritance of a gene coding for a haemoglobin variant (HbS) Molecular basis:  single-base mutation adenine → thymine glutamine → valine 2 2s (2 26 glu→val) Sickle cell disease Pathogenesis: HbS crystalline at low O2 tension Clinical Shortened RBC survival Impaired passage through microcirculation feature: Characterized by tissue infarction and chronic haemolysis − Vaso-occlusive crises (acute pain in hands/feet; severe pain in other bones) − Anaemia (chronic haemolysis or acute fall in Hb ) − precipitated by other factors (infection, dehydration, cold, acidosis, hypoxia) Heterozygous state (sickle cell trait): no symptoms Sickle cell disease Investigations: − Blood count: Hb range 6-8 g/dl, reticulocytes 10-20% − Blood film: sickled RBC Management: − Asymptomatic: no treatment − Avoid precipitating factors − Acute painful attacks: supportive therapy − Severe haemolysis: folic acid − Infection: prophylaxis (antibiotics, vaccine) − Anaemia as indicated (transfusion, hydroxycarbamide) Thalassaemias Cause: abnormalities of globin chain ( or ) synthesis Pathogenesis: ‘imbalanced’globin chain production globin chains in RBC Blood picture: Microcytic, hypochromic ineffective erythropoiesis & haemolysis Thalassaemias - main types -thalassaemia major ( chain production↓): Severe anaemia from infancy, Splenomegaly, Marrow expansion -thalassaemia minor: Clinically mild -thalassaemia ( chain production↓): Range from severe anaemia to clinically insignificant diseases Thalassaemias Laboratory test: Blood count and film: − Hypochromic/microcytic anaemia − Reticulocytes ↑ − Nucleated red cells ↑ Diagnosis by haemoglobin electrophoresis: e.g. Hb F ↑, Hb A ↓ RBC and anaemia (II) Anaemia of chronic diseases Aplastic anaemia Haemoglobin abnormality Red cell enzyme deficiency Red cell enzyme deficiency - Glucose-6-phosphate dehydrogenase (G6PD) deficiency Red cell enzyme deficiencies may produce haemolytic anaemia, The most common: G6PD deficiency G6PD deficiency is the chief RBC enzyme defect Affecting 100million people, mainly male A common heterogeneous X-linked trait, predominantly in Africa, Mediterranean and Middle East G6PD deficiency - Pathogenesis G6PD is a vital enzyme in hexose monophosphate shunt, which maintains glutathione in the reduced state (GSH) GSH protect against oxidant injury in RBC G6PD deficiency reduces the ability of RBC to protect against oxidative injuries This leads to haemolysis Glucose-6-phosphate Glutathione reductase G6PD NADPH 6-phosphogluconate H2O2 GSH NADP Glutathione oxidase GSSG H2O G6PD deficiency Genetics Over 400 G6PD variants; mostly single AA substitutions The most common types have normal activity: Type B+, almost all Caucasians and 70% black Africans Type A+, about 20% of black Africans Two common variants with reduced activity : African (A-) type, mild deficiency and more marked in older cells. Haemolysis is self-limiting Mediterranean type, both young and old red cells have very low enzyme activity; serious clinical consequences. G6PD deficiency Clinical manifestations Most are asymptomatic, but may get oxidative crisis when precipitated Neonatal jaundice Chronic haemolytic anaemia Acute haemolysis, precipitated by − Ingestion of broad beans − Administration of oxidising drugs (quinine, sulphonamides) − Infection and acute illness G6PD deficiency Investigations: Blood count normal between attacks During an attack: Blood film – bite cells, blister cells Haemolysis (serum bilirubin↑) Measurement of G6PD levels Bite cells Blister cells G6PD deficiency Treatment Avoid precipitating factors Transfusion if necessary Treat the underlying infection Which of the following is a feature of anaemia of chronic diseases? a) An uncommon anaemia b) Stimulated RBC proliferation c) Impaired Fe utilisation d) Increased haemolysis e) None of the above Clinical presentation of aplastic anaemia includes: a) Anaemia b) Neutropenia c) Thrombocytopenia d) Bone marrow hypocellularity e) All the above