HLS- Pathology Anemia – lecture 3 Ayah Fraihat Anemia of Diminished production Pathogenesis Laboratory findings Notes Aplastic anemia * Extrinsic factor: * decreased - Most cases are idiopathic Activated T- hematopoietic cells in - other associated factors lymphocytes destroy BM (with residual fat) are drugs , some viruses and stem cells due to pregnancy antigen cross reactivity * pancytopenia - immunosuppressive (BM Failure) therapy restores bone * Intrinsic factor: marrow in inherited defects in *normochromic or 70% of cases Telomerase. macrocyctic anemia. - stem cells might (Note: problems with *Special types of AA: express abnormal stem cells give - Fanconi anemia: rare, Antigens attracting T- macrocystic anemias) defect in DNA repair cells proteins>>>mutations. Can lead to leukemia Myelophthisic anemia * Infiltration of bone * pancytopenia *patient comes with skin marrow>>>damaging * Peripheral blood: bleeding hematopoietic cells Immature precursors of (Thrombocytopenia) (Could be Cancer, TB, RBC’s+ granulocytes Storage diseases, * Neutropenia may lead to infections & death Anemia of Renal Deficiency in kidney *increased serum * uremia leads to abnormal disease function>> Low EPO>> creatinine platelets function (due to Decreased RBC * Low EPO change in blood production * low reticulocyte count environment), but doesn’t * Uremia in advanced affect their count. cases (urea nitrogen in blood) *Burr cells (echinocytes) are الخﻻيا secondary to uremia الشوكية Anemia of Liver *multifactorial : *low transferrin *morphology: spur cells Disease - bleeding (varices, (Acanthocytes) decreased synthesis of [due to abnormal lipid clotting factors) metabolism] Anemia of * Hypothyroidism>> *normocytic anemia (can Hypothyroidism decreased levels of be macrocytic like AA) thyroid hormones>> decreased erythropoiesis& EPO production Myelodysplastic * RBCs are macrocytes *the only neoplastic disease syndrome (Stem cells problem) in this group * Acquired *relatively common *mainly old age *anemia doesn’t respond to treatment ( iron, folic acid,…) anemia of increased destruction cause main site of hemolysis extracorpuscular intracorpusclar extravascular: intravascular: (extrensic) (intrensic) spleen inside blood stream due to : aquired : *infections hereditary *Paroxysmal *antibodies nocturnal *mechanical damage hematuria membranopthies: hemoglobinopathies enzymopathies: spherocytosis thalassemia & G6PD-Deficiency sickle cell anemia Anemia of increased destruction Pathogenesis Genetics Symptoms Laboratory Diagnosis findings Thalassemia *Genetic 1) α-chain: * Thalassemia *low Hb >>> * Hemoglobin disorders that *encoded by 2 minor>>asymptomatic Hypochromic electrophoresis cause a genes on microcytic test decrease in chromosome 16 * Thalassemia anemia the synthesis * deletion of 1 or 2 intermedia and HgH * increase in of α/β chains. genes >> silent disease >>moderate * Reticulocytosis HgA2 and HgF carrier anemia. No need for percentages * deficiency in * Deletion of 3 regular blood * poikelocytosis more than one globin genes>> transfusions. &nucleated 3.5%>> β-thal chain results Hemoglobin H RBCs in in relative disease *Thalassemia major>> peripheral blood * absent or increase in *Deletion of 4 symptoms begin after decreased the other one genes >> hydrops age of 6 months( Β- *hemosiderosis HgA>> leading to fetalis chain replaces y- & ↑↑ β-thal major instability and chain). They require normoblasts in β 0 /β 0 hemolysis blood transfusions BM 2) Β-chain: *HbH and Hb * Most *organ damage due to Barts bands>> mutations in * encoded by a iron overload(2nd or HbH disease(α- α-thalassemia single gene on 3rd decade of life thal m, severe are deletions chromosome 11 anemia) while most * β 0 : no mutations in production of β- *genetic testing β-thal are chain is available for α- point * β+: decreased thal carrier and mutations production of β- minor chain Many combinations are found : .β/β+:silent carrier or mild anemia (thal- minor) . β+/β+: thalassemia intermedia . β 0 /β 0 or β 0 /β+: thalassemia major (Cooley anemia) Notes * Mode of inheritance: autosomal recessive * Resistant to infection by malaria falciparum * Reticulocytosis differentiates between hemolytic anemia and anemia of diminished production .