Working Problem 9- Anaemia Flashcards

Question

Low Haemoglobin,normal to mildly low MCV,moderate reticulocyte?

Answer 1

Iron deficiency-early stages | anaemia of chronic disease

Answer 2

* Normal adults red cell contains 96% HbA (α2β2), 3% HbA2 (α2δ2), and 1% fetal Hb (HbF, α2γ2). * HbS is produced by the substitution of valine for glutamic acid at the sixth amino acid residue of β-globin. * In homozygotes all Hb A is replaced by HbS, whereas in heterozygotes only about half is replaced Deoxygenation causes HbS to sickle(by distortion) which is initially reversible but on repeated sickling causes membrane to be damaged and eventually result in irreversible sickling and cause hemolysis

Answer 3

Severe chronic haemolytic anaemia The increased breakdown of heme to bilirubin Microvascular obstruction which provoke tissue ischemia and infarction There is a compensatory hyperplasia of erythroid progenitors in the BM Cellular proliferation→ bone resorption and secondary bone formation→prominent cheek bones and changes in skull resembling crewcut in radiographs Splenomegaly and auto splenomegaly(where spleen becomes fibrotic due to hypoxic damage from chronic splenic erythrostasis) and this leads to more likelihood of infection vasoocclusive pain crisis

Answer 4

* Blood count-Level of Hb is in the range from 60-80g/L with a high reticulocyte count (10-20%) * Blood films- features of hyposplenism and sickling * Sickle solubility test-Hb S presence gives the solution a turbid appearance * Hb electrophoresis-always needed to confirm diagnosis

Answer 5

• Give intravenous fluids and adequate analgesia to treat acute pain crisis • In extremely painful situations give morphine • Milder pain can sometimes be relieved by codeine, paracetamol and NSAIDS • Manage other symptoms such as constipation with laxatives ,vomiting with antiemetic, pruritus with anti-pruritic • Folic acid given to patients with haemolysis • Vaccination given against pneumococcal and Haemophilus influenzae type B vaccine Treating anaemia • Hydroxcarbamide (hydroxyurea)-: the first drug that has been used widely as therapy for sickle cell anaemia. - Acts by increasing HbF concentration→takeover the HbS role and reduce the episodes of pain, the acute chest syndrome and the need for blood transfusions • Stem cell transplantation: has been used to tx sickle cell anaemia in fewer cases then thalassemia. - Children and adolescents younger than 16 years of age who have severe complications(recurrent chest syndrome or refractory pain) and have HLA-matched donor are the best candidate for transplantation

Answer 6

• Hb A is a tetramer composed of two α chains and two β chains. • The α chains are encoded by two α-globin genes, which lie in tandem on chromosome 16, • While the β chains are encoded by a single β-globin gene located on chromosome 11. • Clinical features vary according to the specific mutant alleles that are inherited by parents Beta Thalassemia • In beta thalassemia it is important to note that the HbA2 will increase to make up for the defect in HbA due to decreased B globin production, globin replaced by delta globin in Hb A2 • The mutations associated with β-thalassemia fall into two categories: (1) β 0, in which no β-globin chains are produced; and (2) β + , in which there is reduced (but detectable) β-globin synthesis. Alpha Thalassemia • Unlike B thalassemia, A thalassemia is caused mainly by deletion involving one or more of the alpha globin genes • The severity is dependent on the number of genes missing • Single gene loss→silent carrier • Deletion of all 4 gene→lethal and life non-compatible as virtually no oxygen delivering capacity

Answer 7

* B thalassemia minor and alpha thalassemia trait(2 genes deletion),abnormalities confined to peripheral blood * In smears cells are microcytic and hypochromic * Target cells are seen=Cell with ↑ area to volume ratio that allows the cytoplasm to collect in a central dark red puddle * In B thalassemia major there is microcytosis,hypochromia,poikilocytosis(variation in size and anisocytosis(variation in shape) in peripheral smear * B thalassemia intemedia→findings lie b/n the 2 spectrums * Anatomical changes in B thalassemia major=skeletal deformities(due to hyperplasia of erythroid progenitor), * splenomegaly ,hepatomegaly and lymphadenopathy(extramedullary haematopoiesis and hyperplasia of mononuclear phagocytes in them) * Cachexia and Hemosiderosis(↑ consumption of nutrient by erythropoeitic precursors and ↑Fe accumulation)

Answer 8

Aim is to suppress ineffective erythropoiesis, prevent bony deformities and allow normal activity and development * Long term folic acid * Regular transfusions should be given to keep the Hb above 100g/L * Blood transfusions may be required every 4-6 weeks * Transfusion requirements increase splenectomy would help but must delay till age of 6 as there is a risk of infection and prophylaxis is required for those undergoing splenectomy * Iron overload(due to repeated transfusions)which can damage the heart, liver and pancreas →Desferrioxamine should be given(iron chelating agent)+ascorbic acid should be given to increase urinary excretion of iron * Bone marrow transplantation * Prenatal dx and gene therapy * Patient’s partner should be tested if both partners have β-thalassaemia trait, there is a one in four chance of such pregnancy resulting in a child having β-thalassaemia major. Therefore, couples in this situation must be offered prenatal diagnosis

Answer 9

It is due to deletion of 3 alpha globin alleles(remember there is 2 genes for alpha and one for beta) The excess β chains form unstable tetramers (called Hemoglobin H or HbH of 4 beta chains) which have abnormal oxygen dissociation curves Unstable hemoglobin have a higher affinity for oxygen than normal hemoglobin, resulting in poor oxygen delivery to tissues. There is a microcytic hypochromic anemias with target cells and Heinz bodies (precipitated HbH) on the peripheral blood smear, as well as hepatosplenomegaly. The disease may first be noticed in childhood or in early adult life, when the anemias and hepatosplenomegaly are noted. Heinz bodies are inclusions within the red blood cells composed of denatured hemoglobin

Answer 10

It is the reticulocyte which is 10- 20% bigger than normal red blood cells(super big misconception)reticulocytes are called that because they contain residual strands of ribosomal material called “reticulum” that remains following the extrusion of the nucleus from the bone marrow normoblasts. They persist in the circulation 1-2 days after they are made in the bone marrow