4- haemolytic anaemias.pdf

‫بسم هللا الرحمن الرحيم‬ Haemolytic anaemias (HA)  Introduction The life span of the RBC is 120 days after which the cells are removed extravascularly by the macrophages of the reticuloendothelial system, (spleen)  Haemolytic anaemias (HA) are defined as those anaemia...

‫بسم هللا الرحمن الرحيم‬ Haemolytic anaemias (HA)  Introduction The life span of the RBC is 120 days after which the cells are removed extravascularly by the macrophages of the reticuloendothelial system, (spleen)  Haemolytic anaemias (HA) are defined as those anaemias that result from an increase in the rate of red cell destruction.  Clinical features pallor of the mucus membranes, jaundice splenomegaly Splenectomy may be indicated if hypersplenism is symptomatic  + Pigment (bilirubin) gall stones may complicate the condition ulcers around the ankle. (Sickle cell anaemia) Mongoloid appearance  Laboratory findings 1. Features of increased red cell breakdown: 2. Features of increased red cell production: 1-Features of increased red cell breakdown: (a) serum bilirubin is raised (unconjugated);  (b) urine urobilinogen is increased (c) faecal stercobilinogen is increased; 2. Features of increased red cell production: (a) reticulocytosis (b) bone marrow erythroid hyperplasia  Classification 1- Hereditary HA 2- Acquired HA 1-Hereditary haemolytic anaemia: Membrane defects Metabolism defects Haemoglobin defects  2- Acquired : Immune Infections Chemical and physical agents  1-Hereditary HA: Membrane defects: 1-Hereditary spherocytosis, 2-hereditary elliptocytosis  Metabolism defect: 1-G6PD deficiency, 2-pyruvate kinase deficiency  Haemoglobin (Haemoglobinopathies): thalassaemia, sickle cell anaemia.  Acquired HA: 1-Immune 2-Infections (malaria) 3-chemical & physical agents (drugs)  Immune HA: Autoimmune Alloimmune Drug associated Hereditary haemolytic anaemias due to membrane defects Hereditary spherocytosis is due to abnormality in the red cell membrane, leading to formation of spherocytes.  These spherocytes undergo haemolysis prematurely on passing through the spleen.  Investigations: Blood smear shows spherocytes. RBCs show increased osmotic fragility. (osmotic fragility test) Treatment: Splenectomy.  Hereditary elliptocytosis This has similar clinical and laboratory features to hereditary spherocytosis except for the appearance of the blood film  PATHOLOGICAL RBC ABNORMALITIES Ellipto-cytosis Or Ovalo-cytosis  Hereditary haemoglobinopathies This is due to abnormal Hb structure. 1-Thalassaemias 2-Sickle cell syndromes  1-Thalassaemias Thalassaemias are a heterogenous group of genetic disorders that result from absent or reduced rate of synthesis of α or β chains. Normal haemoglobin in adult blood Hb A Hb F Hb A2 structure α2 β2 α2 γ 2 α2 δ 2 Normal % 96-98 0.5- 0.8 1.5- 3.2 2 types of thalassaemia: 1-Alpha thalass. (reduced or absent α chains) 2-Beta thalass. (reduced or absent β chains)  Severity of disease depends on number of genes affected Thalassaemia major ( homozygous) Thalassaemia minor ( heterozygous)  Thalassaemia major ( homozygous) severe hypochromic, microcytic anaemia, great enlargement of spleen and liver skeletal abnormalities due to marrow expansion. Regular blood transfusions are needed which lead to progressive iron deposition in the tissues. (Haemosiderosis) (Iron over load)  Haemosiderosis is the main cause of death and leads to dysfunction of glands and other organs (heart, liver, spleen …).  Thalassaemia minor causes mild microcytic anaemia but is asymptomatic  Investigations 1. CBC & blood picture : Microcytic hypochromic anaemia. 2. Reticulocytosis. 3. High serum iron.  4. Hb-electrophoresis: (confirmatory) *Increased Hb-F (in cases of β- thalassaemia major) *increased Hb-A2 (in cases of β-thalassaemia minor),  Treatment (5) 1-Repeated blood transfusion. 2-Iron chelating agents are used to prevent iron overload (e.g. desferrioxamine). 3- Folic acid to meet increased demand. 4-Splenectomy: If hypersplenism develops. 5-Bone marrow transplantation is curative.  Sickle cell syndromes What is it? Haemolytic anaemia due to production of structurally abnormal Hb → HbS. Autosomal recessive.  HbS The abnormality is caused by substitution of valine for glutamic acid in position 6 in the β chain.  Sickle cell syndrome can be: *sickle cell trait * sickle cell anaemia  Sickle cell trait ( AS) It is the heterozygous type of the disease Hb-S is less than 50%.  Mostly no clinical symptoms or signs as there is enough Hb-A in RBCs Hb-electrophoresis is essential for diagnosis.  Sickle cell anaemia Autosomal recessive It is the homozygous form of the disease (SS) (inherited from both parents), Hb-S is more than 50%.  What is the problem with HbS? Hb-S is less soluble than Hb A& under low O2 tension, undergoes polymerization resulting in: Hb-S is less soluble in the de-oxygenated form precipitation & polymerization inside RBC crescent-shaped rigid sickle cells vaso-occlusion & haemolysis  Block capillaries (vaso-occlusion) Haemolysis & chronic anaemia. Sickling crises Leg ulcers  Factors that can precipitate sickling crises: 1-Hypoxia as in high altitudes & anaesthesia. 2- Dehydration 3- Infections  Sickling crisis: Painful crisis Aplastic crisis Sequestration crisis  Investigations: 1- blood smear: sickle cells 2-Screening tests: Sickling test Solubility test 3-Confirmatory test: Hb-electrophoresis Inherited haemolytic anaemias due to RBCs enzymatic abnormalities Glucose 6 phosphate dehydrogenase (G6PD) deficiency) 1-It is a sex-linked disease 2- affects males only 3-females are carriers. It is due to deficiency of the enzyme G6PD in RBCs (which is important in regenerating reduced glutathione which protects the red cells against oxidative stress).  usually asymptomatic. Acute haemolytic anaemia develops in response to oxidant stress resulting in intravascular haemolysis →  jaundice, anaemia haemoglobinuria.(intravascular haemolysis) → dark urine. haemosiderinuria  What causes acute haemolysis? drugs, fava beans or infections.  In between crises complete blood count (CBC) is normal, but the enzyme is always low  Investigations: 1- screening tests. 2-Direct enzymatic assay.  Treatment: Avoid oxidants agents Examples: *nitrofurans and chloramphenicol). *Analgesics (e.g. aspirin). *Antihelminths (e.g. stibophen).  *Miscellaneous (e.g.vitamin K analogue) *Fava beans (possibly other vegetables)  Main drugs that may cause haemolytic anaemia in G6PD deficiency are: 1-Antimalarials (e.g. primaquine, pamaquine and chloroquine). 2-Sulphonamides (e.g.cotrimoxazole, and dapsone).  Acquired haemolytic anaemia Autoimmune haemolytic anaemia autoantibodies against the red cell antigens  Causes: Systemic lupus, drugs, certain lymphomas, Infections idiopathic.  Investigations: Blood smears: microspherocytes Coombs’ test: detects antibodies that result in haemolysis of RBCs