TBL3 Hematology Oncology 2025 Blood Loss Anemia PDF

Hematology Oncology, Spring 2025, Prework for TBL3 Red Blood Cell Disorders III— Blood loss and diminished/impaired erythropoiesis Talal El-Hefnawy, M.D., Ph.D. Professor, CHSU-College of Osteopathic Medicine Objectives 1. Discuss the clinical significance...

Hematology Oncology, Spring 2025, Prework for TBL3 Red Blood Cell Disorders III— Blood loss and diminished/impaired erythropoiesis Talal El-Hefnawy, M.D., Ph.D. Professor, CHSU-College of Osteopathic Medicine Objectives 1. Discuss the clinical significance of abnormal MCV, MCH, MCHC, ferritin, TSAT, transferrin values 2. List the corpuscular volume-based classification for the various types of anemias 3. Review iron metabolism as it pertains to absorption, transport, storage and erythropoiesis, with special emphasis on key molecules (ferroportin, hepcidin, transferrin and ferritin) 4. List the etiology, pathogenesis, stages, clinical representation and laboratory findings for iron deficiency anemia 5. Describe the etiology, pathogenesis, key inflammatory cytokines, clinical representation and laboratory findings for anemia of chronic disease (anemia of inflammation) 6. Describe the etiology, pathogenesis, clinical representation, key responsible enzyme deficiencies/inhibition, and laboratory findings for sideroblastic anemia 7. Discuss the etiology, pathogenesis, clinical representation and laboratory findings for megaloblastic anemias due to folate deficiency and vitamin B12 8. Describe the clinical consequences and associated pathogenesis of the non-hematologic of vitamin B12 deficiency 9. Discuss the etiology of normocytic leukemia due to reduced production 10. Explain the pathogenesis of how parvovirus B19 infection can result in low reticulocyte count and transient aplastic crisis References Atlas of diagnostic hematology Pathophysiology of Blood Disorders, 2e | AccessMedicine | McGraw Hill Medical Robbins and Cotran Pathologic Basis of Disease-10th ed Williams Hematology 9th edition Fundamentals of Pathology by Hussain A, sattar (Pathoma 2015) Anemia Anemia is characterized by a reduction of the RBC total mass Patients typically have hypoxia-related symptoms and signs: Weakness, dyspnea and fatigue Pale skin, lips and conjunctiva Headache, lightheadedness Myocardial ischemia (angina pain) especially when associated with coronary conditions Because the total RBC mass is difficult to assess, the following are used as surrogates: Blood Hb ( 5 lobes) Glossitis Low serum folate High serum homocysteine (increases risk for thrombosis) Normal methylmalonic acid (dd for B12 deficiency) II. b. Vitamin B12 Vitamin B12 is a water-soluble vitamin that is present in some foods and is available as a dietary supplement and medication. Because vitamin B12 contains the mineral cobalt, compounds with vitamin B12 activity are collectively called cobalamins Vitamin B12 is required for the development, myelination, and function of the central nervous system; healthy red blood cell formation; and DNA synthesis Vitamin B12 is bound to protein in food and must be released before it is absorbed by salivary enzymes  the freed B12 binds to salivary haptocorrin More B12 is released by the gastric HCl and protease  bind to haptocorrin In the duodenum, B12 is released from haptocorrin and binds to intrinsic factor (from parietal cells)  absorption in the ileum by receptor- mediated endocytosis Robbins and Cotran, pathologic basis of disease II. b. Vitamin B12 deficiency B12 has a large hepatic storage (acute changes do not cause anemia) Pernicious anemia (due to autoimmune destruction of the parietal cells) is the most common cause for vit B12 deficiency due to reduced intrinsic factor Other causes Pancreatic insufficiency Damages to the terminal ileum (Crohn’s, resection, Diphyllobothrium latum fish tapeworm  competes with the intrinsic factor binding) Dietary deficiency is rare (except in vegans) Patients have general S&S of anemia, plus Causes impairment of DNA synthesis  ineffective hematopoiesis jaundice, glossitis II. b. Vitamin B12 and folate deficiency (microscopic findings) Macrocytic (and oval) RBCs with hypersegmented neutrophils (see next slide) Cells are hyperchromatic (ample Hb/cell)  some RBCs lack central pallor… Note, MCHC is NOT elevated Increased variation in RBC sizes (anisocytosis) and occasional pencil cells (poikilocytosis) Low reticulocyte count Megaloblastic changes (clumped nuclear chromatin) in bone marrow erythroid precursors Bone marrow hyperplasia (effect of EPO) From Robbins and Cotran From Williams hematology, 9th edition II. b. Vitamin B12 deficiency (clinical and lab findings) Subacute combined degeneration of the spinal cord Vitamin B12 is a cofactor for the conversion of methylmalonic acid to succinyl CoA (important in fatty acid metabolism). Vitamin B12 deficiency  ↑↑methylmalonic acid, which impairs spinal cord myelinization, Neurological damage results in poor proprioception and vibratory sensation (posterior column) and spastic paresis (lateral corticospinal tract). ↓ serum vitamin B12 ↑ serum homocysteine (same as folate deficiency)  higher risk for thrombosis ↑ methylmalonic acid (unlike folate deficiency) III. NORMOCYTIC ANEMIA Anemia with normal-sized RBCs (80-100 nm3) Results from increased destruction, or reduced production of RBCs The circulating reticulocytes help in distinguishing the above two types Reticulocytes (immature RBCs released from the bone marrow) identified with bluish cytoplasm due to the presence of residual RNA Normal reticulocyte count is 1-2% of the RBCs Corrected reticulocyte (percentage of RBCs x hematocrit vale/45) values in normocytic anemias: > 3% Increased destruction < 3% poor BM response (underproduction) III. a. hemolytic anemia (Discussed in TBL2) Predominant extravascular hemolysis Accelerated destruction of RBCs by the reticuloendothelial macrophages in the liver, spleen and lymph nodes due to: Hereditary spherocytosis Sickle cell anemia (Hb-S) Hemoglobin C Predominant intravascular hemolysis Paroxysmal nocturnal hemoglobinuria Glucose-6-phosphate dehydrogenase (G6PD) deficiency Immune hemolytic anemia Microangiopathic hemolytic anemia III. b. Normocytic anemia due to reduced production Renal failure (low EPO production by the peritubular interstitial cells) Hepatocellular disease  folate and iron deficiency, and bleeding tendencies Damage to bone marrow erythroid precursor cells (pure red cell aplasia) Parvovirus B19 (acute, and typically transient) Temporarily halting erythropoiesis (self-limited) Causes transient aplastic crisis and transient erythroblastopenia of childhood More significant if it occurs in other pre-existing pathologies, e.g. sickle cell anemia Chronic conditions Thymoma Large granular lymphocytic leukemia Neutralizing antibodies against EPO Autoimmune disorders Aplastic anemia (covered in other TBL) Parvovirus B19 Small DNA virus, which commonly infects humans Most adults have IgG against B19 (children are more susceptible) The erythroid progenitor cells’ P antigen is the receptor for B19 entry  lysis Because of this, very low number of reticulocytes is seen in all infected persons (due to the transient nature, it really depends on the stage during which the disease was diagnosed) Anemia only occurs if significant reduction in RBCs occurs, or in the presence of other hematological pathologies that impact RBCs (for example sickle cell anemia) Light infection  Symptoms and signs of a typical “slapped cheek” cutaneous eruption and arthralgia or arthritis are secondary to antibody–virus immune complex deposition With high concentration of the virus  transient aplastic crisis and erythroblastopenia Poorly understood mechanism