Hematology Notes PDF

# HEMATOLOGY ## Erythropoiesis - A process produces red blood cells (erythrocytes) from hematopoietic stem cells (derived from pluripotent stem cells) - committed stem cells (progenitor cells)→ specific types of blood cells. - Hematopoietic growth factors control Growth and differentiation of stem cells - Committed stem cells colony forming unit-erythrocytes (CFU-E) (give erythrocytes) and CFU-GM (WBCs). - Hemoglobin is the oxygen carrying pigment of red blood cells. Structurally it contains & globular chains, each of which is wrapped around an iron-containing heme group ### Site of production: | Organ | Production Site | |---|---| | Fetal | Bone marrow of all bones, Spleen and liver | | Childhood | Bone marrow of compact bones | | Adulthood | Bone marrow of the sternum and the pelvic bone | | Pathologic hematopoiesis (extramedullary) | Spleen and liver | ## Anemia - Reduction of the red blood cell (RBC) volume or Hb concentration below the range of values occurring in healthy persons (male: > 15yrs = 13 g/dl - female: > 15yrs = 12 g/dl-pregnant: 11 g/dl) ### Symptoms: - Asymptomatic and symptoms are according to severity and Onset. - Symptoms of underlying cause ### Signs: - Most common symptoms are fatigue and poor concentration. - In severe anemia, Palpitations, angina (especially with CAD), intermittent claudication, and symptoms of heart failure. - Pallor (pale skin, mucosa, conjunctiva & nail beds), but not a reliable sign. - Signs of causes of anemia, e.g. jaundice, fatigue. ## Anemia Classification ### According to mean corpuscular: | MCV | Anemia | |---|---| | Less than 75 FL | Microcytic Anemias | | 75-100 FL | Normocytic Anemias | | More than 100 FL | Macrocytic (megaloblastic) Anemias | ### According to etiology of anemia: #### Excessive destruction (hemolytic anemias) → 1st type - Intrinsic RBCs abnormalities (congenital and acquired) - Extrinsic RBCs abnormalities (immune and non-immune) #### Inadequate production of RBCs 2nd type - Deficiency of specific factors (nutritional anemia) - Decreased production with normal precursors in bone marrow - Decrease RBCs precursors: (BMF): - Single cell line failure (pure red cell anemia) - Multiple cell line failure (Aplastic anemia) #### Blood loss (hemorrhage) → 3rd type - Internal - External ## Common causes of anemia (MCV Differential in-CBC) | MCV | Anemia | |---|---| | Microcytic hypochromic | - Iron Deficiency - Thalassemia syndromes - Sideroblastic anemia - Anemia of malignancy (20%) - Anemia of chronic disease (15%) | | Normocytic normochromic | - Acute post hemorrhagic anemia - Hemolytic anemia (most types) - Anemia of Chronic diseases (85%) - Anemia of malignancy (80%) - Bone marrow failure disorders | | Macrocytic | - Megaloblastic anemia: (folic acid/B12 deficiency) - Non megaloblastic: - Liver disease - Alcoholism - Obstructive Jaundice - Myelodysplastic syndrome - Alcoholism - Reticulocytosis - Pregnancy - Drugs (AZT/Trimethoprim sulfate) | ## Warm Autoimmune Anemia ### Characters: - IgG active at 37-40°C - Do not require complement for activity - Most common form of AIHA - More common among women ### Etiology: - Idiopathic - Secondary or symptomatic (with infections, lymphoma, drugs (methyl dopa and _L-_dopal and 5-FU) ### C/P: - Acute transient - Chronic ### Investigation: - CBC - Coomb's test - Retics - IgG at 37-40°C-warm - IgM at low temperatures → cold ## Cold Autoimmune Anemia ### Characters: - IgM active at low temp - Require complement for activity ### Notes: - Cold agglutinin disease manifests as acute or chronic hemolytic anemia. Other cytopathic Symptoms or be acrocyanosis, Raynaud syndrome, cold associated occlusive changes! ### Etiology: - Idiopathic - Secondary to infections specially EB virus, Mycoplasma pneumoniae, or lymphoreticular malignancy ### C/P: - Severe hemolysis after exposure to cold ## Chronic Hemolytic Anemia ### Characters: - Persistent/recurrent anemia not responding to hematinic pallor and fatigue. - Hemolysis release Hb→ indirect bilirubin jaundice and GB stones - Chronic disease there is available time for compensation. - Hemosiderosis-Iron overload ### Cause: - Chronic hemolysis. - Increase iron absorption from intestine due to increase erythropoietin. - Repeated blood transfusion. ### Compensation: - Extra medullary hematopoiesis - Hepatosplenomegaly: - Traumatic rupture of spleen. - Hypersplenism: increase of destructive power of spleen → Pancytopenia. ### Result: - Leading to iron deposition in: - Liver: cirrhosis and HSM. - Pancreas: OM - Heart: cardiomyopathy - Skin: bronzed color and leg ulcer. - Endocrine: decrease pituitary and gonads. - BM medullary hematopoiesis - Medulla expansion/ hyperplasia - Mongoloid Facies - Prominent forehead - Cortex thinning - Osteoporosis - Pathological fracture - Prominent cheek bones - Prominent maxilla ### Treatment: - Follow infection - Acute pallor, jaundice fever and hemoglobinuria (as in G6PD def) - Good response to steroids (3 months) full recovery. - Mostly secondary cause - Variable response to steroids, - CBC decrease Hb and RBCs count (anemia). - Coomb's test positive autoimmune - Retics: increase - Irreversible antibody disease, C3 is present while IgG is usually absent. - Steroids(2-6mg/kg/dav) - IVIG - RBCs transfusion - Plasmapheresis - Splenectomy (in resistant causes) - Immune-suppressive drugs (as cyclosporine) ## 2 Phase Hemolytic Anemia ### Characters: - Persistent/recurrent anemia not responding to hematinic pallor and fatigue. - Hemolysis release Hb→ indirect bilirubin jaundice and GB stones - Chronic disease there is available time for compensation. - Hemosiderosis-Iron overload ### Cause: - Chronic hemolysis. - Increase iron absorption from intestine due to increase erythropoietin. - Repeated blood transfusion. ### Compensation: - Extra medullary hematopoiesis - Hepatosplenomegaly: - Traumatic rupture of spleen. - Hypersplenism: increase of destructive power of spleen → Pancytopenia. ### Result: - Leading to iron deposition in: - Liver: cirrhosis and HSM. - Pancreas: OM - Heart: cardiomyopathy - Skin: bronzed color and leg ulcer. - Endocrine: decrease pituitary and gonads. - BM medullary hematopoiesis - Medulla expansion/ hyperplasia - Mongoloid Facies - Prominent forehead - Cortex thinning - Osteoporosis - Pathological fracture - Prominent cheek bones - Prominent maxilla ### Treatment: - Follow infection - Acute pallor, jaundice fever and hemoglobinuria (as in G6PD def) - Good response to steroids (3 months) full recovery. - Mostly secondary cause - Variable response to steroids, - CBC decrease Hb and RBCs count (anemia). - Coomb's test positive autoimmune - Retics: increase - Irreversible antibody disease, C3 is present while IgG is usually absent. - Steroids(2-6mg/kg/dav) - IVIG - RBCs transfusion - Plasmapheresis - Splenectomy (in resistant causes) - Immune-suppressive drugs (as cyclosporine) ## Normally (HMP shunt) - **NADP** + **Glucose 6-phosphate** →**Glucose 6- phosphate dehydrogenase** → **6-phospho gluconolactone** + **NADPH + H** → **Lactonase** → **6-phospho gluconate** → **6-phospho glucona dehydrogenase** → **CO2** + **NADPH + H** → **D-Roulose 5-phosphate** → **Phospho penbisomerase** → **D-Ribose 5-phosphate** + **NADP+H** - **NADPH + H** (Protect RBCs from oxidizing agents). ## G6PD Deficiency ### Etiology: - Responsible for only 5-10% of glucose metabolized by RBCs. - It is the only source of NADPH+H - Abnormally, In G6PD deficiency, exposure to oxidizing agent RBCs destruction (most of glutathione will be in oxidized form (GSH-GS5G). - Complexing of GSSG + HbHb is irreversibly denatured precipitation as Heinz bodies hemolysis (oxidation of Hb). ### C/P: - Oxidizing agents: - Food: fava beans "favism" - Infection: HBV and hepatitis - Chemicals and Phenyl-hydrazine (Benzene, Naphthalene) - Antipyretic: aspirin - Antipain "analgesics - Antibacterial: "sulphadrugs" - Antimalarial: primaquine - Exposure to these triggering factors (1-2 days) causes → acute hemolysis then RBCs rupture, extracellular Hb causes Bloody urine → ATN Pain in loin. - Fever and rigors (Hb act as Pyrogens) - Pallor and fatigue (anemia) - Jaundice (conversion of Hb to Bilirubin) ### Investigations: - CBC: Hb, RBCs count (anemia) - Blood film shows: 1) fragmented RBCs 2) Heinz inclusion bodies - Hb in urine - Increase indirect bilirubin - Electrophoresis-G6PD variant - The diagnostic test: enzyme activity assay: 4-6 weeks after attack, why? - Coomb's test - GGPD assay and Glutathione stability test-Decrease sensitivity - PCR-To reveal genetic abnormality (Florescent labelled probes are used to detect mutant G6PD alleles ### Treatment: - reduced glutathione - Preventive: - Avoid oxidizing agents and treatment of infection - Neonatal screening if suspected - Antipyretic: Paracetamol - During attack: - TTT of the cause and stop oxidant exposure - Rare: if chronic: splenectomy ## Enumerate genetic variant of G6PD: | Variant | Activity | Disease Severity | |---|---|---| | B+ | Commonest normal | | | A+ | Normal in blacks | | | B- | Mediterranean < 5% activity | Severe in whites | | A- | Genetic variant in black 5-15% activity | | | Canton type | In Asians | Severe disease| ## Diagnosis of hemolytic anemia - Is anemia hemolytic? - if so, is it intravascular/Extravascular haemolysis? - What is etiology? - What is the severity of anemia? ## Acute Immune Hemolytic Anemia (AIHA) - Group of disorders characterized by a malfunction of the immune system that produces autoantibodies, which attack red bleed cells - May be primary (idiopathic) or result from an underlying disease or medication - The condition may develop gradually or occur suddenly - Etiology: Caused by abnormalities extrinsic to RBC and has two main types of autoimmune hemolytic anemia: Warm antibody and Cold antibody hemolytic anemia ## Excess RBC Destruction (Hemolytic Anemia) ### Definition: - Accelerated erythrocyte destruction together with those of vigorous blood regeneration/shortened life span of RBCs (15-20 days) / elevated erythropoietin / accumulation of hemoglobin degradation products ### Site of RBCs destruction: - **Intravascular:** Red cells rupture within the vasculature releasing free hemoglobin into circulation - **Extravascular:** Liver and Spleen - **Intramedullary:** Bone marrow ### Suggestive features of haemolysis: - Anemia/Jaundice/Bony pain HSM in some cases / Fever in some cases ### According to causes: - **Extra corpuscular** - Infection - Hypersplenism - Infection/toxin - Drugs - PNH - **Intrinsic(corpuscular)** - **Defects:** - **Congenital** - **Immune** - **Infection:** - Immune (RH, ABO incompatibility) - **Autoimmune:** - AIHA - **Drug associated** - **Membrane defect:** - **Hereditary** - Spherocytosis- malaria - Hereditary pyropoikilcoytosis- - Hereditary stomatocytosis - **Hb defect** - **Quantity:** - Thalassemia - **Quality:** - Sickle cell anemia - **Enzyme defect:** - G6PD - HiP - MA - **Acquired** - **Non-immune** - Fragmentation syndromes: - DIC-TTP-MAHA ## According to onset: ### Acute - DD acute hemolytic anemia - G6PD. - Acute autoimmune hemolytic anemia (AIHA) - Micro-angiopathic hemolytic anemia (MAHA) - Hemolytic crisis in chronic hemolytic anemia. - Acute hemolytic reaction in incompatible blood transfusion. - Infection "viral, sepsis, malaria ### Chronic: - Membrane defect: spherocytosis. - Hb defect: - Quality: sickle cell anemia. - Quantity: thalassemia. ## Hemoglobinopathies - **Thalassemia** - Thalassemia major - Sickle cell disease - Sickle thalassemia - Hemoglobin C disease - **Unstable haemoglobinopathies** ## G6PD deficiency (enzymatic defects) ### Etiology: - XLR genetic Defect ### Pathophysiology: - X-linked Recessive - It's an enzyme of HMP pathway that Protects against oxidative stress - Deficiency results into Impaired NADPH production Accumulation of oxidants in cell and oxidative stress leads to Heinz body formation & hemolysis - Increase in males, why? Because it's XLB - females if the two alleles affected (less common) ## Hereditary Spherocytosis (membrane defects) ### Etiology: - Genetic defect (AD) → defect in spectrin (contractile protein) loss of biconcave shape cell permeability to Na increase water inside RBCs spherocytic cell deformed RBCs - Increase phagocytosis (premature destruction) (trapped and destroyed in spleen) ### Pathophysiology: - Overwork of Na/K pump to keep Na out of the cell decrease ATP and glucose consumption- premature aging of RBCs ### C/P: - General of chronic hemolytic anemia - Genetic: positive family history (75%) - Crises: - Fatigue, hemolysis, hemosiderosis - May start from birth (50%) neonatal anemia Neonatal jaundice, dark urine and dark stool/ - Hemolytic or aplastic crisis - Gall stones ### Investigation: - General: scheme+(Anemia: Hb 6-10-gro/di, with reticulocytosis/Hyperbilirubinemia) - Specific - Spherocytes in-blood film (the hall mark) - Spectrin deficiency in membrane composition test - Cellosmotic fragility test: spherocytes (already swollen) break down in higher concentration compared to normal. - Cell auto hemolysis test ## Iron Deficiency Anemia ### Etiology: - Inadequate intake: - A diet not supplemented with iron (6- 24-month age) - Cow's milk: allergy - occult blood loss - less bioavailable than Fe in breast milk - Mal absorption: - (Celiac disease-diarrhea - increase of phytate and tannate in diet - antacid) - Decreased iron stores: - (preterm pregnant with iron deficienc) - Increased iron loss: (blood loss) - (Ankylstoma-peptic ulcer - cow milk allergy) - Increased requirements: - Rapid rate of growth (preterm, 1 year age and adolescence) and low birth weight - Perinatal hemorrhage ### Stages and clinical findings of IDA: - **Iron stores depletion:** - No C/P / Hb: normal / Ferritin: decrease - **Iron deficient erythropoiesis:** - C/P: decrease work capacity - Hb: normal low iron and transferrin saturation - **Iron deficiency anemia: (Microcytic Hypochromic anemia):** - Hb (6-10g/dl) - Hb (<5g/dl) ### Symptoms: - Anorexia - Fatigue - Dyspnea - Pica: eating non-food martials e.g., soil, chalk and dirt ### Signs: - Pallor (the most important sign) in lips, oral mucosa, nail beds and conjunctiva - Spooning nails (koilonychias) - Irritability - Signs of atrophic glossitis - Cheilitis (inflammation around the lips) - Intellectual, concentration affection - Immune system suppression - Murmur (Hyperdynamic circulation) - Muscle weakness - Splenomegaly in servere persistent cases ### Investigations: - CBC: Hb < 11 gm/dl-(Microcytic Hypochromic anemia) and 3-4 gm/dl in severe cases - MCV: <75-microcytic - MCH. MHCH: decrease hypochromic - RDW: increase (red blood cells distribution width) > 145 - Iron profile: - Serum iron decrease - Ferritin decrease - Transferrin saturation decrease - TIBC increase - Free erythrocyte protoporphyrin (FEP) increase - Investigate the cause: - Stool analysis: parasites and occult blood - Urine analysis: Hematuria ### Treatment: - Preventive: - Iron intake to pregnant mothers - Breast feeding - Iron fortified milk and cereals after 3-4 months - Curative: - Treatment of cause (e.g. anti parasitic) - Blood transfusion (packed RBCs) if Hb less than 4gm/dL, anemic heart failure and infection interfering with iron therapy. - Fe Therapy: - Oral: (Fe sulphate) 3-6 mg/kg/day - Given between meals. - Given for 4-6 weeks after correction of hematological values. - Side effects: GIT upset, constipation and dark stool. - Parenteral ## *Sickle Cell Disease* ### Pathophysiology: - Genetic: AR/types (homozygous/Heterozygous) - Substitution of valine for glutamic acid in B-globin chain resulting in (structural hemoglobinopathies) - HbS Can't withstand Hypoxia valine polymers HbS polymer distort RBCs shape (sickle)→ clogged in the small blood vessels (vascular occlusion) and therefore do not deliver oxygen to the tissues - Sickle cells trapped and destroyed in spleen ### Clinical pictures and complications of crisis (in chronic anemia) - **Spleen infarction.** - **Liver function impairment (sickle cell hepatopathy)** - **Penis-priapism (Sustained erection)** - Can result in death - **Vaso-occlusion/painful crisis (sickle cell vascular occlusion ischemia and infarction)** ### N.B: Functional Asplenia: - Due to auto splenectomy - Decrease phagocytic function (hyposplenism) - Increase susceptibility to capsulated bacterial infection, Salmonella, _H. influenza_, meningococci and _St. Pneumonia_) ### Investigation: - Peripheral blood exam as general + blood film: Sickle cell during attacks - Chemistry tests, as general + increased LDH - Ante natal, amniocentesis: DNA technology - Sickling test (Sodium metabisulfite test), reducing agent induce D, decrease induce sickling - HbS in Hb electrophoresis - BM exam: erythroid hyperplasia ### Treatment: - **Preventive:** - Conditions enhance sickling: (Acidosis - fever-decrease of O2 tension - Shock/Dehydration) - **During attacks:** - Eliminate conditions that precipitate vaso-occulsion - Rest in bed/Hydration - Sedation/Antibiotics - Blood Transfusion - **Between attacks:** - **For spleen:** - No splenectomy if auto splenectomy - **For Hyposplenism:** - Vaccination against capsulated organism - Prophylactic penicillin - **For aplastic crisis:** - Blood transfusion - Bone marrow transplantation - Hydroxyurea: increase HbF synthesis and decrease disease activity - **For sequestration crisis:** - Plasma expanders, - Blood transfusion - **Treatment of cause (hypoxia by O2 , acidosis by NaHCO3, shock by good hydration)** - **Exchange transfusion in life-threatening conditions to decrease HbS** - **Marrow Stem Cell Transplantation/Gene Therapy** ## Thalassemia - The most common chronic hemolytic anemia in Egypt - Quantitative abnormality secondary to decreased rates of globin chain synthesis: - beta-thalassemia: reduced beta chain synthesis (Time of appearance: 6-12 months) - alpha-thalassemia: reduced alpha chain synthesis ### Etiology and Pathogenesis: #### a) β-Thalassemia - **Incompatible with life (Hydrops fetalis)** - **Genetic defect AR in B-globin chain production decrease of HbA1, increase of HbAZ and HbF-intercellular deposition of a-chain in RBCs intramedullary/ splenic destruction → hemolytic anemia erythropoietin production Hyperactive bone marrow → Marrow expansion.** - **Severe anemia also stimulates extra medullary hematopoiesis with enlargement of liver and spleen** - (Beta): complete absence of 3 chain production (no Hb A synthesis HbF + Hb A2) - (Beta+): partial reduction (Hb A + HbF+HbA2) ##### **B-thalassemia major:** - **Most common of chronic hemolytic anemia in Egypt** - The 2 genes on chromosome 17 are both affected (Homozygous) - Presented after 6 months (why?) - Have all general clinical picture: - Severe pallor-jaundice (muddy face) - dark urine - Mongoloid face - growth retardation-delayed puberty - Splenomegaly - hepatomegaly - gall stone - pathological fractures ##### **B-thalassemia minor/trait:** - **Heterozygous** - Asymptomatic or minimal pallor and mild splenomegaly/discovered accidentally - Very mild anemia (microcytic hypochramic) - There is increased level of Hb A2 and Hb F ##### **B-thalassemia intermedia:** - Homozygous/double heterozygous - No symptoms or signs: till 2-3 years then pallor and jaundice general C/P - Growth is relatively uncompromised and Skeletal changes are more manifest - Hb can be kept at 6-8 gm/dl without blood transfusion ### Investigations: - General + - Antenatal: amniocentesis, genetic study - CBC: microcytic hypochromic anemia - Iron profile: increase of serum-iron, decrease of ferritin and decrease of TIBC (iron overload) to (differ from IDA) - BM exam: Erythroid hyperplasia - Hb electrophoresis: decrease of HbA, increase of HbA2 and HbF - Alkaline denaturation test: Resistant - Radiological Investigations: X-Ray skull - Wide diploic space and flair on end appearance - Long bones: widen medullary cavities Trabeculations ### Treatment: - B-thalassemia trait (thalassemia minor): No treatment except genetic counseling - B-thalassemia intermedia: - Folic acid - Tron chelators - Blood transfusion is not needed except in cases of circulatory decompensation - Chronic transfusion in cases of poor growth - A splenectomy may be done - Treatment of complications e.g. cardiac and endocrinal - Hydroxyurea to induce synthesis of Hb F decreasing unmatched a chain - **B-thalassemia major:** - **Step 1 (Blood transfusion):** when Hb less than 6 gm% / Keep Hb more than 10 gm% (hyper transfusion)/Keep more than Hb 12 gm% (super transfusion) - **Chelation of iron: Step 2** - Started when ferritin exceeds 1000 ng/ml to avoid hemosiderosis. #### b) a-thalassemia - & genes (Chromosome 16); a chain ### Pathophysiology: - Defect in 1 gene: silent carrier no C/P - 2 gene: a-thalassemia trait mild hemolysis. - 3 gene: HbH disease - Hemolytic anemia at birth - 4 gene fetal hydrops severe hemolysis in utero ### Investigation: - General electrophoresis - HbH (4 8 chain): hemolysis-neonatal jaundice - Decrease of HbF and HbA ### Treatment: - General - a-thalassemia trait: no treatment - HbH disease: blood transfusion + folic acid - Antenatal diagnosis ## *Hereditary Elliptocytosis* ### Etiology: - Genetic defect (AD) → defect in Spectrin, Band 3 protein (transmembrane protein) that carries - Anion exchange protein) and protein 4.1 - Red cell membranes become elliptical in shape - - Elliptocytes are rigid less deformable and can be prematurely removed from circulation ### Pathophysiology: - Red cell membranes become elliptical in shape - Elliptocytes are rigid, less deformable and can be prematurely removed from circulation ### C/P: - General: - Anemia - Jaundice - Splenomegaly - **Clinical features** - Age 2-3 weeks: may have the first hemolytic crisis - Severe anemia in some patients, - Splenectomy in some cases ### Investigations: - General + - Blood film → elliptocytes - Osmotic fragility test - Increased in H. Elliptocytosis because of decrease of SA - Normal in thalassemia and iron deficiency anemia - Electron microscopy reveals defects in the cell membrane. ## *Iron Regulation* - Iron balance is regulated by: - amount of iron ingested, and amount of iron absorbed - red blood cell formation using recycled and new iron - iron stores and iron loss through blood loss or other sources - Iron metabolism - Dietary iron is absorbed by gut mucosal cells used in the formation of Hb, myoglobin, iron-containing enzymes. - Storage iron exists in 2 forms: Ferritin and Hemosiderin. It is stored in the liver, spleen, and bone marrow. - Ferritin can be measured in plasma, while hemosiderin is more often identified in the urine or stained through the bone marrow. - In the adult, approximately 95% of recycled iron is used for red cell production. ### Bioavailability of Fe: - Fe in breast milk is more bio-available than in cow's milk. - Decrease absorption occurs with phytates, phosphate, and tannate. - Normal-term infants are born with sufficient iron stores to prevent iron deficiency for the first 4 months of life. So nutritional iron deficiency is most common between 6 and 24 months of life. - Iron deficiency beyond 24 months is mostly blood loss. - Daily requirements of Fe = 2-3 mg/kg/day ## *Megaloblastic Anemia* ### Definition: - Macrocytic anemia with presence of megaloblasts in bone marrow caused by deficiency of Vit B12 or folic acid or both - Morphological classification of anemias that have an MCV of greater than 100 fL and divided into two categories: Megaloblastic and non-megaloblastic ### Pathogenesis: - Folic acid and vit B12 DNA synthesis in RBCs, WBCs, and platelets (stem cells) so if decrease → impaired nucleus division and maturation Megaloblasts - **DNA synthesis:** depend on a key structure (thymidine triphosphate) (TTP) that can’t be formed unless it receives methyl group from methyl tetrahydrofolate (folic acid) that also need Vitamin B12 as a cofactor, so If vitamin B12 is deficient, TTP can't be synthesized and replaced by deoxyridine triphosphate (DTP)→ nuclear fragmentation and destruction of cells and impaired cell division - Megaloblastic precursor cells hemolyze before their maturation cycle is completed. - So, Reticulocytes aren’t delivered from the bone marrow as they normally would in response to anemic stress, so the reticulocyte count is low and also peripheral destruction leading to elevated bilirubin and LOH ## *Sources and Deficiency of B12* ### Sources: - Microorganisms and fungi are the main producers of vitamin B12, a group of vitamins known as cobalamins may also be in liver, meat, fish, eggs, and dairy products ### Deficiency: - Dietary requirements will increase during pregnancy and lactation - **B12 deficiency:** Dietary deficiencies are rarely the cause of vitamin B12 deficiency, except vegetarians or infants nursed by vegetarian mothers. - Blind loop syndrome, in which there is an overgrowth of bacteria in a small pocket of malformed intestine ## *Folic Acid Deficiency* - Increase requirement in the elderly or alcoholic persons because of lack of availability - Tropical sprue is one of the most common malabsorption syndromes that contributes to folic acid deficiency - Last, folic acid deficiency may be expected in individuals taking methotrexate or other chemotherapy drugs ## *Vitamin B12 Deficiency* ### Etiology: - **Decrease intake:** - Vegetarian mother or decrease intake - **Decrease absorption (malabsorption):** - Bacterial overgrowth of the small bowel (e.g. diverticula) - Infection with the fish tapeworm (_Diphyllobothrium latum_ - tapeworm) - After surgical resection of the terminal ileum - Patients with inflammatory diseases (e.g. regional enteritis) - **Parasitic (_Diphyllobothrium latum_):** - **Pernicious anemia (decrease intrinsic factor):** - Congenital AR - inability to secrete IF - Acquired antibodies against Parietal cells and IF ### N.B: Intrinsic factor: - Is the single most important ingredient to the absorption and delivery of vitamin B12 to the circulation and problem in it called pernicious anemia. - Factors as partial or whole gastrectomy, atrophic gastritis decreases intrinsic factor. - Genetic and immune factors: antibodies against intrinsic factor and parietal cells as pernicious anemia/there is a higher frequency of pernicious anemias with diabetes, thyroid conditions, and other autoimmune processes ### C/P: | Deficiency | Symptoms | |---|---| | Folic acid deficiency | - Manifestation of Vit. C deficiency (Scurvy and bleeding) - Age: 4-7 months - Anemia, irritability - Diarrhea, failure to thrive. - Thrombocytopenia - anemia and pallor | | Vitamin B12 deficiency | - Red and painful tongue (glossitis) - Vomiting and diarrhea - Neurological symptoms: - Posterior column degeneration: sensory ataxia - Pyramidal tract degeneration: delayed motor milestones - Peripheral nerve degeneration, paresthesia - SCD (subacute combined degeneration of cord): - Abnormal gait - Paresthesia | ## *Investigations* - CBC: decrease HCT and Hb (anemia) / Pancytopenia in advanced cases - MCV > 100 fl→ macrocytic - MHCH: normal → normochromic - Peripheral smear: hyper segmented neutrophil? / Megaloblasts? Megaloblastic - Folic acid deficiency - Decrease serum folate - Increase formamino glutamic acid - BM: Megaloblastic changes - Vit B12 deficiency - Decrease serum vit B12 - Increase homocysteine - Hematologic features: There is a low reticulocyte count (less than 1%) - Gastric analysis to determine achlorhydria or lack of hydrochloric acid in the stomach - Tests to denote intrinsic factor or parietal cell antibodies performed by ELISA - Schilling test ## *Treatment* - **Folic acid deficiency:** Folic acid supplement 2-5 mg/day + Vit. C + vit B12 - **Vit B12 deficiency:** - If with SCD: - Parental B12 1 mg IM/day 2 weeks - Maintenance therapy: 1 mg IM/month/life

Hematology Notes PDF

Document Details

Tags

Related

Summary

Full Transcript

Upgrade to continue