Hemolytic Anemia PDF

Hemolytic Anemia Haemolytic anaemias are defined as those anaemias that result from an increase in the rate of red cell destruction. Intravascular hemolysis: hemolysis occurs in the circulation Extravascular hemolysis: hemolysis occurs inside reticuloenothelial system Mechanism Of Hemolysis Clinical...

Hemolytic Anemia Haemolytic anaemias are defined as those anaemias that result from an increase in the rate of red cell destruction. Intravascular hemolysis: hemolysis occurs in the circulation Extravascular hemolysis: hemolysis occurs inside reticuloenothelial system Mechanism Of Hemolysis Clinical Features - Pallor of the mucous membranes fluctuating jaundice Splenomegaly. Pigment (bilirubin) gallstones. Ulcers around the ankle. Aplastic crises. Laboratory Findings 1. Features of increased red cell breakdown: >Serum Bilirubin ↑ >Urine urobilinogen ↑, faecal stercobilinogen↑ >Serum Haptoglobins Absent 2. Features of increased red cell production: > Reticulocytosis > bone marrow erythroid hyperplasia 3. Damaged red cells: >Morphology (microspherocytes, elliptocyte,fragmented cells) > Red cell survival study > Specific enzymes, proteins or DNA tests. 4. Features of intravascular hemolysis: > Haemoglobinaemia and haemoglobinuria > Haemosiderinuria > Methaemalbuminemia Hereditary spherocytosis Is the most common hereditary hemolytic anemia in Northern Europeans. It is caused by a defect in the proteins involved in the interactions between the membrane cytoskeleton and the lipid bilayer of the red cell: ankyrin, spectrin (mostly) and pallidin. Autosomal dominant inheritance usually. Clinical Features - May be asymptomatic The anaemia can present at any age. Jaundice is typically fluctuating. splenomegaly occurs in most patients. Pigment gallstones are frequent. Aplastic crises Laboratory Findings Anaemia is usual. Reticulocytosis 5-20% Microspherocytes are seen in the blood film. (densely staining with smaller diameters than normal red cells). Osmotic Fragility test: Increased Autohaemolysis is increased and corrected by glucose. Direct coombs test : Negative Flow cytometry There is increased haemolysis in the patient in comparison with the control. Glucose has given partial correction Hereditary elliptocytosis Has similar clinical and laboratory features to HS apart from morphology. Usually clinical milder disorder. Intrinsic defect in the membrane cytoskeleton. Glucose-6-phosphate dehydrogenase deficiency G6PD functions to reduce nicotinamide adenine dinucleotide phosphate (NADP) while oxidizing glucose-6-phosphate. NADPH is needed for the production of reduced glutathione (GSH) which is important to defend the red cells against oxidant stress. Reduced glutathione (GSH) acts as a scavenger for dangerous oxidative metabolites in the cell. GSH converts harmful hydrogen peroxide to water catalyzed by the enzyme, glutathione peroxidase (catalase enzyme also detoxifies H2O2). G6PD deficiency More than 400 variants due to point mutations or deletions of the enzyme G6PD have been characterized which show less activity than normal. Worldwide over 400 million people are G6PD deficient in enzyme activity. The inheritance is sex-linked, affecting males, and carried by females. The main races affected are in West Africa, the Mediteranean, the Middle East, and South East Asia. Clinical Features G6PD deficiency is usually asymptomatic. Acute haemolytic anaemia in response to oxidant stress(In most cases, the hemolytic crisis is self-limiting once exposure to the trigger is stopped) Neonatal jaundice. Rarely a congenital non-spherocytic hemolytic anemia favism : hemolysis after ingestion of fava beans Agents that may cause hemolysis in G6PD deficiency Laboratory finding Between crises blood count is normal. The enzyme deficiency is detected by One of a number of screening tests or By direct enzyme assay on red cells. During the crisis, the blood film may show contracted and fragmented cells, bite and blister cells. Heinz bodies (oxidized denatured hemoglobin) may be seen in reticulocyte preparation. There are features of intravascular haemolysis Acquired Hemolytic Anemias Immune Hemolytic Anemias Antibody mediated hemolysis is an important cause of acquired hemolytic anemia. Antibodies may be: Autoantibodies produced by the patiet’s own immune system & directed against his own red cell antigens. Alloantibodies produced by the patient & directed against antigens not present on his own red cells but introduced either by transfusion or secondarily acquired as in drug induced hemolysis. Autoimmune hemolytic anemia (AIHA) Characterized by a positive Coombs test or DAT, which detects antibody, with or without complement, on the red blood cell surface. AIHA is classified into warm and cold types, depending on whether the antibody reacts more strongly with red blood cells at 37°C or at 4°C and whether IgG (warm) or IgM (cold) autoantibody predominates. Warm autoimmune hemolytic anemia >The autoantibodies are polyclonal & IgG in type. >They react best at 37C. >Red cells coated with IgG are taken up by macrophages especially in the spleen which have receptors for the Fc fragment. Part of the coated membrane is lost so the cell becomes progressively more spherical and prematurely destroyed predominantly in the spleen. Causes 1. Idiopathic : 2. Secondary: in association with other disorders including autoimmune disorders, lymphomas,CLL and some drugs. Clinical features >The disease can occur at any age in both sexes & presents as a hemolytic anemia of variable severity. >The spleen is often enlarged. >Presentation is variable and depends on the speed with which anemia develops, the capacity of the bone marrow to compensate and the effects of any associated disease. >It tends to remit and relapse. Laboratory Finding Features of extravascular hemolysis Anemia Reticulocytosis High bilirubin. Direct Coomb’s test is positive. Blood film shows Spherocytosis, polychromasia & nucleated red cells Cold autoimmune hemolytic anemia The cold autoantibody attaches to red cells mainly in the peripheral circulation where blood temperature is cooled. The antibody is usually IgM & binds to red cells best at 4C. Both intravascular and extravascular hemolysis can occur Causes 1. Idiopathic. 2. Secondary : in association with lymphomas and certain infections like Mycoplasma pneumonia, infectious mononucleosis. Clinical Features The patient may have chronic hemolytic anemia aggravated by cold & often associated with intravascular hemolysis. The patient may develop acrocyanosis (purplish skin discoloration) at the tip of the nose, ears, fingers & toes due to the agglutination of red cells in small vessels. Mild jaundice & splenomegaly may be present. Laboratory Finding Features of hemolytic anemia. Direct Coomb’s test is positive. Blood film shows red cell autoagglutination. Red cell fragmentation syndromes These arise through physical damage to red cells due to: Passing of cells on abnormal surfaces like prosthetic heart valves, grafts, arteriovenous malformations. Passing through abnormal small vessels (microangiopathic hemolytic anemia): TTP/HUS, Malignant disease Vasculitis, HELLP, Renal vascular disorders, DIC Features of intravascular hemolysis Blood film : many deep staining red cell fragments Aplastic Anemia Aplastic anemia is defined as pancytopenia resulting from aplasia of the bone marrow. Pancytopenia: reduction of all major cells lines of blood from various causes as aplasia, leukemia, myelodysplasia, myeloma, megaloblastic anaemia, myelofibrosis, marrow infiltration. Causes Primary: Congenital e.g. Fanconi’s anemia Idiopathic Acquired Secondary: Ionizing radiation Chemicals: benzene & other organic solvents, insecticides, hair dyes Drugs: Which regularly cause marrow depression e.g. busulphan, cyclophosphamide, chloramphenicol, sulfonamides, anti-inflammatory, antidepressant drugs. Infection: viral hepatitis (non-A non-B),EBV Autoimmune diseases as SLE Transfussion associated Mechanism The underlying defect in all cases appears to be a substantial reduction in the number of stem cells & a fault in the remaining stem cells or an immune reaction against them. This makes them unable to divide & differentiate sufficiently to populate the bone marrow. Clinical Features The onset is at any age with bimodal peak incidence at 10-25 and over 60 years & a slight male predominance. It can be insidious or acute with symptoms & signs resulting from anemia, neutropenia or thrombocytopenia. Infections, particularly of the mouth & throat, are common. Generalized infections are frequently life threatening. Bruising, bleeding gums, epistaxis & menorrhagia are the most frequent hemorrhagic manifestations & the usual presenting features. Symptoms of anemia. The lymph nodes, liver& spleen are not enlarged. Laboratory Finding Anemia is usually normochromic normocytic. The retic count is extremely reduced. Leucopenia. There is selective neutropenia usually but not always to below 1.5 x 109/L. The neutrophils appear normal. Thrombocytopenia is always present & in severe cases is less than 50x109/L. There are no abnormal cells in the peripheral blood. Bone marrow shows hypoplasia with loss of hemopoietic tissue & replacement by fat cells >75%. Bone marrow biopsy is essential & may show patchy cellular areas in a hypocellular background. Thank You