Anemia- General aspectsDepartment of HematologyRui Jin Hospital

AnemiaMost importantRelated to many diseasesDiagnosed properlyTreated properly

What is anemia?A reduction below normal in the- concentration of hemoglobin- red blood cells in the blood- hematocrit The blood hemoglobin concentration often preferred- accuracy and reproducibility- value most indicative of the patho-physiologic consequences of anemia

Normal range - adult

RBC1012L HGBg/LHemotocrit

M 4.0-5.5 (400-550mm3) 120-160 (12-16g/dl) 0.4-0.5 (40-50) F 3.5-5.0 (350-500mm3) 110-150 (11-15g/dl) 0.37-0.45 (37-45)

Conditions associated with a significant disproportion between the hematocrit and RBC?Spurious anemia ()- relative increase in plasma volumehydremia of pregnancyoverhydration in oliguric renal failure or congestive heart failurechronic diseases and hypoalbuminemiacongestive splenomegalyrecumbency ()

NormoblastsPronormoblast

Regulation of erythropoiesisHow many are produced?25 billion /24 hoursThe entering cells are reticulocytes which should be 1% of the total population of circulating erythrocytesErythrocytes last 120 days and are destroyed by the spleen Red cell production should equal red cell destruction

Anemia: EtiologiesProduction defectsBlood loss

Blood destruction

RBC loss without RBC DestructionHemorrhage- Due to trauma- Due to disorders: e.g. cancer, ulcers, tuberculosis, and irritable bowel syndrome (including ulcerative colitis and Crohns disease) Menstrual flowGynecological disorders (e.g. endometriosis)Pregnancy, especially at gestationParasitism- Hookworms

RBC DestructionIntrinsic Abnormalities ThalassemiaG6PDSickle Cell AnemiaHereditary SpherocytosisExtrinsic AbnormalitiesInfectionsMalaria (Plasmodiumm species)Mycoplasma (Disseminated Intravascular CoagulationLead poisoning

Conditions Associated with Anemias Due to Reduced Erythrocyte ProductionAnemias due to decreased erythropoietin production Renal disease Endocrine deficiency (pituitary, adrenal, thyroid, testis) Starvation Hemoglobinopathy (reduced oxygen affinity) Anemias due to inadequate marrow response to erythropoietin Deficiency state (iron, vitamin B12, folate) Anemia of chronic disease (inflammation, infection, or malignancy) Sideroblastic anemia Primary marrow disorders-pure red cell aplasia, myelodysplasia, myelofibrosis, leukemia metastasis to bone marrow, osteogenic sarcoma

(pathophysiology of anemia) RBC Hb1.34ml

RBC

RBC2323DPG23DPGHbHb O2

Clinical manifestationFirst symptom- decreased work tolerance- shortness of breath- palpitations- other signs of cardiorespiratory adjustments to anemia- at times, they feel fine, but their friends or family notes the pallor

The manifestations depend onThe reduction in the oxygen-carrying capacity of the bloodThe degree of change in total blood volumeThe rate at which these two factors developedThe capacity of the cardiovascular and pulmonary systems to compensate for the anemiaThe associated manifestations of the underlying disorder

Cardiorespiratory system Noticeable only after exertion or excitementDyspnea and awareness of vigorous or rapid heart action noted at restShortness of breath, tachycardia, dizziness or faintness, and extreme fatigueCongestive heart failure, angina pectoris, intermittent claudication

Cardiorespiratory systemLeft ventricular hypertrophy Heart murmurs- systolic in pulmonic areaElectrocardiographic changes- depression of the ST junction- U-shaped deformation of the S-T segment- inverted T waves

The skinPallor most evident sign- dilation of the peripheral vessels- degree and nature of the pigmentation- nature and fluid content of the subcutaneous tissues- jaundice, cyanosisDetected most accurately in the mucous membranes of the mouth and pharynx, conjunctivae, lips, and the nail beds, palms of the hands

Tell anemia from the color of the skinA waxy, dead whiteness- acute blood lossA distinctly sallow color- chronic anemiaA lemon-yellow pallor- pernicious anemiaMarked pallor associated with petechiae or ecchymoses- acute leukemia

Neuromuscular systemHeadacheVertigoTinnitusFaintnessScotomata Lack of mental concentrationDrowsinessRestlessnessMuscular weakness

Gastrointestinal systemUnderlying diseases: ulcer, cancerGlossitis and atrophy of the papillae of the tonguePainful, ulcerative, and necrotic lesions in the mouth and pharynx (aplastic anemia, acute leukemia)Dysphagia (chronic iron-deficiency anemia)

OthersRetinopathy: 20%- flame-shaped hemorrhagesSlight proteinuria Fever of mild degreeHemolytic anemia- jaundice- hemoglobinemia, pain in the abdomen or back

Evaluation and diagnosisMedical HistoryPhysical examinationLaboratory testsMorphologic features

Medical historyThe duration of the symptoms and their onset (insidious/acute)Family history of jaundice, splenectomy, bleeding disorders, and hemoglobin-associated abnormalitiesOccupation, drugs, solvents and other chemicals

OthersStool habits: neoplasms of the colon and rectum, hemorrhoidsWomen: blood lost during menstruationChild or adolescent: growth rateDietary historyFever: infection, lymphoma, collagen disease, etc.Bruises, ecchymoses, and petechiae

Physical examinationIcterus (hemolytic)Sternal tenderness (leukemia)Lymph nodes enlargements (infection, lymphoma, leukemia, metastatic carcinoma)Cardiac murmurs (bacterial endocarditis)Liver, spleen, and kidneys

Morphologic featureBlood smear

Bone marrow examination

ClassificationImpaired erythrocyte production- hypoproliferativeiron-deficient erythropoiesiserythropoietic deficiencyhypoplastic anemiainfiltration- ineffectivemegaloblasticmicrocyticIncreased erythrocyte production- hemolytic anemia

Anemia?Production?SurvivalDestruction?The key test is the ..

The reticulocyte countIncreased reticulocytes (greater than 2-3% or 100,000/mm3 total) are seen in blood loss and hemolytic processes, although up to 25% of hemolytic anemias will present with a normal reticulocyte count due to immune destruction of red cell precursors. Retic counts are most helpful if extremely low (

Another step of diagnosisAnemia

Erythrocyte indicesblood smear

MCV>100 MCV 80-100MCV

Macrocytic anemiasVitamin B12 or folate deficiencyAccelerated erythropoiesis- hemolytic anemia Erythroleukemia ()Increased membrane surface- hepatic disease, obstructive jaundiceRefractory anemias- myelodysplastic anemias

Normal, RBC's. They have a zone of central pallor about 1/3 the size of the RBC.). A few small fuzzy blue platelets are seen. In the center of the field are a band neutrophil on the left and a segmented neutrophil on the right.

Note the hypersegmented neurotrophil and also that the RBC are almost as large as the lymphocyte. Finally, note that there are fewer RBCs.

Vitamin B12 deficiencyDietary deficiency (rare)Lack of intrinsic factor- pernicious anemia- gastric surgeryFunctionally abnormal intrinsic factorBiologic competition- small-bowel bacterial overgrowthDrug-induced vitamin B12 malabsorptionChronic disease of the pancreasZollinger-Ellision syndromeHemodialysis

Folate deficiencyDietary deficiencyIncreased requirements- alcoholism and cirrhosis- pregnancy- infancyCongenital folate deficiencyExtensive intestinal resection

DiagnosisSmear- Macrocytic (High MCV) RBCs, +/- hypersegmented neutrophils, +/- modest neutropeniaB12- Low serum B12 levelFolate- Serum folate level -- can normalize with a single good meal

Neurological presentation of B12 deficiencyParesthesias of fingers & toesReduced vibration sense (256-Hz)Ataxia (Combined system disease)Perversion of taste & smell Optic atrophyDementia (), Memory Loss & DepressionMegaloblastic Madness Paranoid SchizophreniaSpecific MRI abnormalities

TreatmentB12 deficiency- B12 1 mg/month IM, or 1-2 mg/day poFolate deficiency- Improved diet, 5mg tabletsMonitor for a response to therapyPernicious Anemia monitor for GI cancers

FoodB12 deficiencyMeatEggsFolate deficiencyGreen vegebablesNutsCerealFruitYeast

Microcytic anemiasDisorders of iron metabolism- iron-deficiency anemia- anemia of chronic disordersDisorders of globin synthesis- thalassemias- hemoglobin E and C diseaseSideroblastic anemia

The RBC's here are smaller than normal and have an increased zone of central pallor. This is indicative of a hypochromic (less hemoglobin in each RBC) microcytic (smaller size of each RBC) anemia. There is also increased anisocytosis (variation in size) and poikilocytosis (variation in shape).

Iron Deficiency Anemia vs. anemia of chronic disordersSmear- hypochromic and microcytic (low MCV) RBCs, usually not seen unless Hct 30%- platelet count is often elevatedFerritin: a measure of total body iron stores, but also an acute phase reactant-

ThalassemiasGenetic defect in hemoglobin synthesis- synthesis of one of the 2 globin chains ( or )- Imbalance of globin chain synthesis leads to depression of hemoglobin production and precipitation of excess globin (toxic)- Ineffective erythropoiesis- Ranges in severity from asymptomatic to incompatible with life (hydrops fetalis)- Found in people of African, Asian, and Mediterranean heritage

ThalassemiasDiagnosis- Smear: microcytic/hypochromic- -thal will have an abnormal Hgb electrophoresis (HbA2, HbF)- The more severe -thal syndromes can have HbH inclusions in RBCs- Fe stores are usually elevatedTreatment- Mild: None- Severe: RBC transfusions + Fe chelation, Stem cell transplants

Sideroblastic AnemiasHeterogenous grouping of anemias defined by presence of ringed sideroblasts in the BMEtiologies- Hereditary (rare)- Myelodysplasia- EtOH- Drugs (INH, Chloramphenicol )Treatment- Trial of pyridoxine for hereditary or INH induced sideroblastic anemia

Normocytic anemiasAssociated with appropriately increased erythrocyte production- posthemorrhagic anemia- hemolytic anemiaAssociated with impaired marrow response- intrinsic bone marrow diseasehypoplasiainfiltration of the bone marrow- decreased erythropoietin secretionrenal

TherapyEtiologyB12

TherapyDrug treatment1.Iron2.Folic acid and VitaminB12

Therapy3. Vitamin B6 100mg 23/d4.Glucocorticoid() 5. Androgen() 36 6. EpoetinEPO

TherapyTransfusion support

TherapySplenectomy

TherapyMarrow transplantation- - -

Anemia is not a diagnosis in itself, but merely an objective sign of disease.A subnormal concentration of RBC resulting from expansion of the plasma volume.1. The initial cell is a BFU-E (burst forming unit erythroid)2. BFU-E in the presence of interleukin-3 and erythropoietin forms CFU-E (colony forming units erythroid).3. CFU-E in the presence of a high concentration of erythropoietin forms a pronormoblast.The pronormoblast large nucleated cell but NO hemoglobin4.The pronormoblast large nucleated cell but NO hemoglobin5.Normoblast characterized by increased hemoglobin synthesis.During this stage, cytoplasmic organelles are lost.6. The reticulocyte (arrow)Has no nucleusHas no organelles

Mean corpuscular volume