Hemolytic Anemia PDF

‫ُه‬ ‫َّل‬ « ‫ْم ْج َع ل‬ ‫َن‬ ‫َل‬‫َأ‬ «‫َو ِلَس اًنا‬ ‫»َع ْي َن ْي ِن‬ ‫َت‬ ‫َف‬ ‫َش‬ ‫»َو‬ ‫ْي ِن‬ « ‫َو َه َد ْي َن اُه‬ ‫»الَّن ْج َد ْي ِن‬...

‫ُه‬ ‫َّل‬ « ‫ْم ْج َع ل‬ ‫َن‬ ‫َل‬‫َأ‬ «‫َو ِلَس اًنا‬ ‫»َع ْي َن ْي ِن‬ ‫َت‬ ‫َف‬ ‫َش‬ ‫»َو‬ ‫ْي ِن‬ « ‫َو َه َد ْي َن اُه‬ ‫»الَّن ْج َد ْي ِن‬ HEMOLYTIC ANEMIA Dr.F.Tajikrostami Hematology and Medical Oncology ANEMIA 1- decreased production of red cells 2- increased destruction of red cells 3-acute blood loss. overconsumption of red cells from the peripheral blood supply of cells from the bone marrow is normal (indeed, it is usually increased ) Acute or Chronic Intravascula or Extravascular Hemolysis Retic Bone marrow responces Intravascular hemolysis Intravascular hemolysis describes hemolysis that happens mainly inside the vasculature the contents of the red blood cell are released into the general circulation leading to hemoglobinemia urinary hemoglobin , or hemosiderin serum or urine may be pink or darker ᵇʳᵒʷᵐ ᵐᵉᵗʰᵉᵐᵒᵍˡᵒᵇᶦⁿ Free Hᵇ or hem damage to the kidney, AKI , trigger DIC OR increased risk of thrombosis ᵒˣʸʰᵉᵐᵒᵍˡᵒᵇᶦⁿ hyperbilirubinemia red blood cells are targeted by autoantibodies, leading to complement fixation or by damage by parasites such as Babesia Free Hb binds to haptoglobin (complex) removed by the liver Extravascular hemolysis hemolysis taking place in the liver, spleen, bone marrow, and lymph nodes little hemoglobin escapes into blood plasma The macrophages of the reticuloendothelial system in these organs engulf and destroy structurally-defective red blood cells or antibodies attached, and release unconjugated bilirubin into the blood plasma circulation spleen destroys mildly abnormal red blood cells or those coated with IgG-type antibodies severely abnormal red blood cells or those coated with IgM-type antibodies are destroyed in the circulation or in the liver NL:red blood cell survives 90 to 120 days in the circulation about 1% of human red blood cells break down each day The spleen (part of the reticulo-endothelial system) is the main organ that removes old and damaged RBCs from the circulation NL:the breakdown and removal of RBCs from the circulation is matched by the production of new RBCs in the bone marrow In conditions where the rate of RBC breakdown is increased, the body initially compensates by producing more RBCs breakdown of RBCs can exceed the rate that the body can make RBCs, and so anemia can develop Bilirubin, a breakdown product of hemoglobin, can accumulate in the blood, causing jaundice intravascular hemolysis: the release of RBC contents into the blood stream Free hemoglobin can bind to haptoglobin, and the complex is cleared from the circulation; thus, a decrease in haptoglobin can support a diagnosis of hemolytic anemia Alternatively, hemoglobin may oxidize and release the heme group that is able to bind to either albumin or hemopexin The heme is ultimately converted to bilirubin and removed in stool and urine Hemoglobin may be cleared directly by the kidneys resulting in fast clearance of free hemoglobin but causing the continued loss of hemosiderin loaded renal tubular cells for many days  2 1 3 INHERITED HEMOLYTIC ANEMIAS The red cell has three essential components: (1) hemoglobin (2) the membrane-cytoskeleton complex (3) the metabolic machinery The red cell membrane and cytoskeleton  HEREDITARY SPHEROCYTOSIs autosomal dominant red cells were abnormally susceptible to lysis in hypotonic media osmotic fragility became the main diagnostic test for HS some of the most severe forms are instead autosomal recessive Severe cases may present in infancy with severe anemia mild cases may present in young adults or even later in life main clinical findings are jaundice, an enlarged spleen, and often gallstones variability in clinical manifestations ? due to the different underlying molecular lesions milder cases, hemolysis is often compensated intercurrent conditions (e.g., pregnancy, infection) may cause decompensation anemia is usually normocytic (MCHC >34) RDW >14% normal or slightly decreased MCV spleen plays a key role in HS through a :major site of destruction Red cells in HS are less deformable, transit through the splenic circulation makes them more prone to vesiculate, thus accelerating their demise family history pos. easy to make a diagnosis family history may be negative for at least two reasons First: the patient may have a de novo mutation Second: the patient may have a recessive form of HS extensive laboratory osmotic fragility investigations acid glycerol lysis test eosin-5’-maleimide (EMA)–binding test SDS-gel electrophoresis of membrane proteins mutation in one of the genes TREATMENT splenectomy splenectomy at the age of 4–6 years in severe cases Before splenectomy, vaccination Neisseria meningitidis Streptococcus pneumonia) penicillin prophylaxis controversial cholecystectomy “? clinically indicated. laparoscopic approach HEREDITARY ELLIPTOCYTOSIS HE is at least as heterogeneous as HS no direct correlation between the elliptocytic morphology and clinical severity diagnosis of HE is generally incidental, hemolysis may be compensated and there may be no anemia cases of HE with the most severe HA are those with biallelic mutations of one of the genes involved are said to have pyropoikilocytosis (HPP) decreased MCV: 50–60 bizarre poikilocytes are seen on the blood smear HPP patients have splenomegaly and often benefit from splenectomy Eliptocytosis pyropoikilocytosis  Channelopathies abnormalities in red cell ion content and alteration of erythrocyte volume Cation leak can cause hyperkalemia this leak is accelerated in the cold dehydrated stomatocytosis (xerocytosis) : macrocytic hemolytic disorder Increased MCHC overhydrated stomatocytosis (OHS): this too is macrocytic (MCV >110 fL), but the MCHC is low (