Haemolytic anaemias Flashcards

Question

What can go wrong with the structure of hemoglobin?

Answer 1

What can go wrong? • Quantitative - thalassaemias: • Production increased/ decreased amount of a globin chain (structurally normal) • Qualitative – variant haemoglobins: • Production of a structurally abnormal globin chain

Answer 2

* Imbalanced alpha and beta chain production * Excess unpaired globin chains are unstable * precipitate and damage RBC and their precursors * Ineffective erythropoiesis in bone marrow * Haemolytic anaemia

Answer 3

* Beta thalassemia is a blood disorder that reduces the production of haemoglobin * Low levels of hemoglobin lead to a lack of oxygen in many parts of the body * People with beta thalassemia trait have both normal hemoglobin A and the abnormal beta thalassemia(β) hemoglobin in their red blood cells. Beta thalassemia is common in people of African, Mediterranean, Asian and Middle Eastern descent * Beta thalassemia major (also called Cooley's anemia). People with beta thalassemia major have severe symptoms and life-threatening anemia. They need regular blood transfusions and other medical treatment

Answer 4

* Asymptomatic * Microcytic hypochromic anaemia * Low Hb, MCV, MCH * Increased RBC * Often confused with Fe deficiency * HbA2 increased in b-thal trait –(diagnostic) * a-thal trait often by exclusion * globin chain synthesis (rarely done now) * DNA studies (expensive)

Answer 5

* Transfusion dependent in 1st year of life * If not transfused: * Failure to thrive * Progressive hepatosplenomegaly * Bone marrow expansion – skeletal abnormalities * Death in 1st 5 years of life from anaemia * Side effects of transfusion: Get 200mg from a single blood transfusion * Iron overload * Endocrinopathies * Heart failure * Liver cirrhosis * But iron chelators bind excess iron in the circulation and in organs from blood transfusions

Answer 6

Sickle Cell Disease (SCD) • Lot of different genes that can cause it • Commonest are SS and SC • You get an insoluble Hb that wants to polymerise, and it distorts the shape of the RBC Blood film • Some normal cells • Some sickle cells • Nucleated red ells • Howell-jolly bodies as they are hypersplenic • Some polychromasia • More common than thalassaemia in the UK • Autosomal recessive

Answer 7

* A vascular disease * Abnormal shaped RBCs irritate the lining of the capillaries * Changes on the surfaces of the White cells * Problems due to the intravascular haemolysis  alters the vascular tone * SC disease is the commonest cause of child stroke * They get narrowing of main arteries in the brain * Older patients will have pulmonary hypertension and leg ulceration * Pain is the most well-known symptom * Sickling in the chest causes problem with oxygenation * Also, effects in blood supply to the bone, causing necrosis * Well known for causing acute pain or vaso-occlusive crises – most common symptom, has biggest impact of quality of life in patients * Get occlusion in blood vessels of sickle cell disease. Particularly in places like bones where you get infarction of small areas of the bone * Can cause sickling in many organs, e.g. in the chest, getting acute chest syndrome. In the tissue, can get leg ulcers. Sickling in blood vessel in penis causing priapism. Sickling in brain causing stroke * These are associated with other blood cell abnormalities particularly the stenosis or vasodilatation due to NO and increased changes in the tone of blood ve

Answer 8

* Children get dactylitis first (sickling of the small bones in the hand) * Also have painful, puffy hands * Trouble with blood flow through the spleen in children * Spleen enlarges largely and can cause death * As they get older the vessels in the back of the eye change, they can bleed and cause a hemorrhage or a retinal detachment

Answer 9

* Changes to blood vessels means you produce new blood vessels which are prone to bleeding  intra-cranial bleeds * Chronic changes to vessels at the back of the eye that can results in a loss of vision * Pulmonary hypertension * Chronic renal failure is quite common

Answer 10

``` Clinical • Painful crises • Aplastic crises • Infections • Acute sickling: • Chest syndrome • Splenic sequestration • Stroke • Chronic sickling effects: • Renal failure • Avascular necrosis bone Laboratory • Anaemia • Hb often 65-85 • Reticulocytosis • Increased NRBC • Raised bilirubin • Low creatinine ```

Answer 11

* Sickle Hb is insoluble * Solubility test * Expose blood to reducing agent * Hb S precipitated * Positive in trait and disease * Electrophoresis * Structure * Separate out Hb over an electric current

Answer 12

* HPLC is not definitive * Need a sickle solubility test * Because other Hbs can run at exactly the same time point * Many different mutations you can get in beta chains, most of which aren’t clinically significant and that’s the problems with these assays as you pick up stuff which interfere with what you’re looking for * Separates out the Hb, hPLC * Different proteins can also separate out where we expect to see sickle Hb, so we always do a second test just to make sure

Answer 13

``` Autoimmune • Idiopathic • Usually warm • IgG, IgM • Drug-mediated • Cancer associated • LPDs Alloimmune • Transplacental transfer: • Haemolytic disease of the newborn: • D, c, L • ABO incompatability • Transfusion related • Acute haemolytic transfusion reaction • ABO • Delayed haemolytic transfusion reaction • E.g Rh groups, Duffy ``` ``` Non-immune acquired haemolysis • Paroxysmal nocturnal haemoglobinuria • Fragmentation haemolysis: • Mechanical • Microangiopathic haemolysis • Disseminated intravascular coagulation • Thrombotic thrombocytopenic purpura • Other: • Severe burns • Some infections: e.g. malaria ```

Haemolytic anaemias Flashcards

(37 cards)