Anemia and Abnormalities of Red Blood Cells: Approach to Diagnosis and Treatment Section of Hematology- Section of Hematology- Oncology Oncology Department of Medicine Department of Medicine University of Santo Tomas University of Santo Tomas Faculty of Medicine and Faculty of Medicine and Surgery Surgery
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Anemia and Abnormalities of Red Blood Cells: Approach to
Diagnosis and Treatment
Section of Hematology-OncologySection of Hematology-OncologyDepartment of MedicineDepartment of Medicine
University of Santo TomasUniversity of Santo TomasFaculty of Medicine and SurgeryFaculty of Medicine and Surgery
Case 1-01-01: 35 year old pre-menopausic female with menorrhagia
housewife housewife complains of progressive easy fatigability of complains of progressive easy fatigability of
about 3 months duration.about 3 months duration.(-) epigastric pain, (-) hematochezia nor (-) epigastric pain, (-) hematochezia nor melenamelenamenses – 28 days cycle, 7 days duration,menses – 28 days cycle, 7 days duration,3 days profuse flow , 5-6 fully soaked 3 days profuse flow , 5-6 fully soaked
pads/daypads/day (-) bruises/ecchymoses(-) bruises/ecchymoses P.E. Pale, no jaundiceP.E. Pale, no jaundice (-) hepatosplenomegaly(-) hepatosplenomegaly
Case 1-01-01
1.1. What other questions should you What other questions should you ask of this patient who presents ask of this patient who presents with pallor? with pallor?
2.2. What other findings should you What other findings should you look for in the physical look for in the physical examination?examination?
Case 1-01-01
3. What laboratory examinations 3. What laboratory examinations would you request in this case?would you request in this case?
4. What are red cell indices?4. What are red cell indices?
5. What information can you get from 5. What information can you get from the examination of the peripheral the examination of the peripheral smear?smear?
6. What is the significance of the 6. What is the significance of the reticulocyte count?reticulocyte count?
Serum iron lowSerum iron low TIBC normalTIBC normal Transferrin saturation lowTransferrin saturation low Serum ferritin lowSerum ferritin low
Iron deficiency anemiaIron deficiency anemia
Anemia Reduction below normal in the Reduction below normal in the
concentration of hemoglobin or concentration of hemoglobin or RBC’s in the bloodRBC’s in the blood
Anemia is Anemia is not a diagnosisnot a diagnosis in itself, but in itself, but merely an merely an objective signobjective sign of disease of disease
First step in its diagnosis is detection of its First step in its diagnosis is detection of its presencepresence
Symptoms of moderate to severe anemia
FatigueFatigue BreathlessnessBreathlessness Loss of staminaLoss of stamina Palpitations, especially with physical exertionPalpitations, especially with physical exertion HeadacheHeadache VertigoVertigo Lack of mental concentrationLack of mental concentration DrowsinessDrowsiness TinnitusTinnitus ParesthesiasParesthesias PicaPica
History
Symptoms depend on:Symptoms depend on:1.1. Severity of the anemiaSeverity of the anemia2.2. Rapidity of onsetRapidity of onset3.3. Patient’s age and CV statusPatient’s age and CV status
- capacity of the CV & pulmonary system - capacity of the CV & pulmonary system to compensate for the anemiato compensate for the anemia4.4. Associated manifestations of the underlying Associated manifestations of the underlying
Hemic murmurs: mid or Hemic murmurs: mid or holosystolic often in the pulmonic holosystolic often in the pulmonic or apical area, due to increased or apical area, due to increased blood flow and turbulenceblood flow and turbulence
Gallop rhythmsGallop rhythms Tachycardia/CardiomegalyTachycardia/Cardiomegaly Strong peripheral pulses with wide Strong peripheral pulses with wide
pulse pressurepulse pressure
Pallor: <8 to 10 mg/dL hemoglobinPallor: <8 to 10 mg/dL hemoglobinAffected by:Affected by:
state of vasoconstriction/vasodilatationstate of vasoconstriction/vasodilatation degree & nature of pigmentationdegree & nature of pigmentation nature & fluid content of the nature & fluid content of the
subcutaneous subcutaneous tissuestissuesMost constantly detected in:Most constantly detected in: mucous membranes of the mouth, pharynx, mucous membranes of the mouth, pharynx,
Red cell indices IndexIndex Normal Value Normal Value
Mean Cell Volume(MCV)Mean Cell Volume(MCV) (hematocrit x 10)/(red cell ct. x 106)(hematocrit x 10)/(red cell ct. x 106) 90 90 ++ 8 fL 8 fL Mean Cell Hemoglobin (MCH)Mean Cell Hemoglobin (MCH) (hemoglobin x 10)/ (red cell ct. x 106)(hemoglobin x 10)/ (red cell ct. x 106) 30 30 ++
3 pg3 pg
Mean Cell Hemoglobin ConcentrationMean Cell Hemoglobin Concentration 33 33 ++ 2% 2% (hemoglobin x 10)/ hematocrit, (hemoglobin x 10)/ hematocrit, or MCH/MCVor MCH/MCV
Back to questions
Morphology
Morphology
APPROACH TO THE DIAGNOSIS OF ANEMIA
Reticulocyte count Measure of bone marrow Measure of bone marrow
compensation for anemiacompensation for anemia Normal ValueNormal Value
0.5 – 1.5% (old)0.5 – 1.5% (old) 5 – 15 x 105 – 15 x 10-3-3 (SI) (SI)
Corrected Reticulocyte Corrected Reticulocyte ctct==Patient’s HctPatient’s Hct x x
Severity and cause determine Severity and cause determine approach to treamentapproach to treament Elderly+/- cardiovasular Elderly+/- cardiovasular
instability: RBC transfusionsinstability: RBC transfusions Younger individuals with Younger individuals with
compensated anemia: iron compensated anemia: iron replacementreplacement
Optimal response occurs when about Optimal response occurs when about 200 mg of elemental iron given per day200 mg of elemental iron given per day
Absorption more complete on empty Absorption more complete on empty stomachstomach
With or after a meal, absorption With or after a meal, absorption decreases by 40 to 50%decreases by 40 to 50%
However gastric irritation is common, However gastric irritation is common, hence, advisingpt to take tablet hence, advisingpt to take tablet immediately after a meal may increase immediately after a meal may increase compliancecompliance
Optimal response occurs when about Optimal response occurs when about 200 mg of elemental iron given per day200 mg of elemental iron given per day
Absorption more complete on empty Absorption more complete on empty stomachstomach
With or after a meal, absorption With or after a meal, absorption decreases by 40 to 50%decreases by 40 to 50%
However gastric irritation is common, However gastric irritation is common, hence, advisingpt to take tablet hence, advisingpt to take tablet immediately after a meal may increase immediately after a meal may increase compliancecompliance
Oral Iron TherapyOral Iron Therapy
Absorption enhanced by orange juice, Absorption enhanced by orange juice, meat, poultry, fishmeat, poultry, fish
Absorption inhibited by cereals, tea, milkAbsorption inhibited by cereals, tea, milk Side Effects of Oral Iron: Side Effects of Oral Iron:
gastrointestinal: heartburn, nausea, gastrointestinal: heartburn, nausea, abdominal cramps, diarrheaabdominal cramps, diarrhea Related to doseRelated to dose
Continue iron treatment 3 to 6 months Continue iron treatment 3 to 6 months after anemia resolvesafter anemia resolves Allows repletion of iron storesAllows repletion of iron stores
Absorption enhanced by orange juice, Absorption enhanced by orange juice, meat, poultry, fishmeat, poultry, fish
Absorption inhibited by cereals, tea, milkAbsorption inhibited by cereals, tea, milk Side Effects of Oral Iron: Side Effects of Oral Iron:
gastrointestinal: heartburn, nausea, gastrointestinal: heartburn, nausea, abdominal cramps, diarrheaabdominal cramps, diarrhea Related to doseRelated to dose
Continue iron treatment 3 to 6 months Continue iron treatment 3 to 6 months after anemia resolvesafter anemia resolves Allows repletion of iron storesAllows repletion of iron stores
Oral Iron TherapyOral Iron Therapy
PreparationPreparation SizeSize Iron Iron ContentContent
Indications for Parenteral Iron Unable to tolerate iron compounds orallyUnable to tolerate iron compounds orally Poor compliancePoor compliance Persistent loss of blood or iron at a rate too Persistent loss of blood or iron at a rate too
rapid for oral intake to compensate for the lossrapid for oral intake to compensate for the loss Disorder of GI tract e.g. ulcerative colitisDisorder of GI tract e.g. ulcerative colitis Malabsorption of ironMalabsorption of iron Inability of maintain iron balance during Inability of maintain iron balance during
treatment with hemodialysistreatment with hemodialysis Donating large amounts of blood for Donating large amounts of blood for
autotransfusionautotransfusion
Unable to tolerate iron compounds orallyUnable to tolerate iron compounds orally Poor compliancePoor compliance Persistent loss of blood or iron at a rate too Persistent loss of blood or iron at a rate too
rapid for oral intake to compensate for the lossrapid for oral intake to compensate for the loss Disorder of GI tract e.g. ulcerative colitisDisorder of GI tract e.g. ulcerative colitis Malabsorption of ironMalabsorption of iron Inability of maintain iron balance during Inability of maintain iron balance during
treatment with hemodialysistreatment with hemodialysis Donating large amounts of blood for Donating large amounts of blood for
autotransfusionautotransfusion
Computing for the dose of parenteral iron
= Body weight (kg) x 2.3 x (15 – = Body weight (kg) x 2.3 x (15 – patient’s Hgb, g/dL) + 500 or 1000 patient’s Hgb, g/dL) + 500 or 1000 mg (for stores)mg (for stores)
Case 1-02-01 75 year old female consulted because of progressive weakness 75 year old female consulted because of progressive weakness
and loss of balanceand loss of balance numbness and tingling sensation in all extremitiesnumbness and tingling sensation in all extremities no gastrointestinal complaintsno gastrointestinal complaints hypertensive on Felodipine 5 mg per day, but not a diabetichypertensive on Felodipine 5 mg per day, but not a diabetic Diet consists of vegetables and fish because of poor dentitionDiet consists of vegetables and fish because of poor dentition P.E. Vital signs: BP: 150/90, PR: 80/min, regular, RR: 21/min., P.E. Vital signs: BP: 150/90, PR: 80/min, regular, RR: 21/min.,
regular, Temp: 35.5’Cregular, Temp: 35.5’C pale, has slightly icteric scleraepale, has slightly icteric sclerae smooth, red tonguesmooth, red tongue no lymph nodes, nor anterior neck mass. no lymph nodes, nor anterior neck mass. regular rate and rhythm, no murmursregular rate and rhythm, no murmurs Lung examination is normalLung examination is normal no abdominal masses palpatedno abdominal masses palpated some problems with gait but has an otherwise normal some problems with gait but has an otherwise normal
neurologic examination neurologic examination
Case 1-02-01
1.1. What other questions should you What other questions should you ask of this patient who presents ask of this patient who presents with pallor? with pallor?
2.2. What other findings should you What other findings should you look for in the physical look for in the physical examination?examination?
• deficiency of Vit. B12, Folate• disorders of DNA synthesis - drug-induced - inherited
YES NO• hypothyroidism• hypoplastic marrow and misc.
INCREASED NORMAL/DECREASED
Back to Questions
Diagnostic Tests: Megaloblastic Anemia Reticulocyte indexReticulocyte index Unconjugated bilirubin may be increasedUnconjugated bilirubin may be increased LDH may be increasedLDH may be increased Serum levels of Serum levels of
Folate (6 – 20 mg/mL)Folate (6 – 20 mg/mL) Red cell folate levels Red cell folate levels
not subject to fluctuations in folate intakenot subject to fluctuations in folate intake better indication of folate storesbetter indication of folate stores
Bone marrow findings: Megaloblastic anemia
HypercellularHypercellular Decreased Decreased
myeloid/erythroid ratiomyeloid/erythroid ratio Abundant stainable ironAbundant stainable iron RBC precursors abnormally RBC precursors abnormally
large, nuclei less mature large, nuclei less mature (nuclear-cytoplasmic (nuclear-cytoplasmic asynchrony)asynchrony)
Nuclear chromatin more Nuclear chromatin more disperse and condenses in disperse and condenses in a fenestrated patterna fenestrated pattern
MCV high (macrocytic)MCV high (macrocytic) MCH high (hyperchromic)MCH high (hyperchromic) PS: macrocytic red cells, some PS: macrocytic red cells, some
hyperchromic red cells, hyperchromic red cells, hypersegmented neutrophilshypersegmented neutrophils
disorder caused by impaired DNA disorder caused by impaired DNA synthesissynthesis
Cells primarily affected: blood Cells primarily affected: blood cells, GI epithelial cellscells, GI epithelial cells
slowed nuclear cell division with slowed nuclear cell division with normal progression of cytoplasmic normal progression of cytoplasmic maturation maturation megaloblastosis megaloblastosis in bone marrowin bone marrow
Treatment of Megaloblastic anemia Treat the causeTreat the cause Cobalamin deficiencyCobalamin deficiency
IM cyanocobalamin: 1000 mcg IM cyanocobalamin: 1000 mcg per week for 8 weeks then per week for 8 weeks then monthlymonthly
Oral cobalamin: 2 mg crystalline Oral cobalamin: 2 mg crystalline B12 per dayB12 per day
Folic acid: 1 mg/day poFolic acid: 1 mg/day po
Case 1-03-01 50 year old female was referred for evaluation of 50 year old female was referred for evaluation of
anemiaanemia easy fatigability about 5 weeks easy fatigability about 5 weeks cough and fever and was diagnosed to have cough and fever and was diagnosed to have
pneumonia. She was given antibiotics which included pneumonia. She was given antibiotics which included Cefuroxime 500 mg BIDCefuroxime 500 mg BID
other symptoms other symptoms passage of highly colored urinepassage of highly colored urine weight loss of about 5 lbs in the last 2 monthsweight loss of about 5 lbs in the last 2 months
P.E. Vital signs: BP: 120/70, PR: 110/min, regular, RR: P.E. Vital signs: BP: 120/70, PR: 110/min, regular, RR: 23/min, regular, Temp: 37’C23/min, regular, Temp: 37’C pale palpebral conjunctivae, icteric sclerae, small pale palpebral conjunctivae, icteric sclerae, small
cervical lymph nodes on both sides, cervical lymph nodes on both sides, no hepatomegaly and slight splenomegalyno hepatomegaly and slight splenomegaly
Reticulocyte count: Reticulocyte count: 80 x 1080 x 10-3-3/L/L
Case 1-03-01
1.1. What other questions should you What other questions should you ask of this patient who presents ask of this patient who presents with pallor? with pallor?
2.2. What other findings should you What other findings should you look for in the physical look for in the physical examination?examination?
Case 1-03-01
3. What is the most likely problem 3. What is the most likely problem in this patient?in this patient?
4. What diagnostic tests are 4. What diagnostic tests are important in this patient?important in this patient?
Diagnostic tests for hemolytic anemia Peripheral smearPeripheral smear Direct Coomb’s test (antiglobulin test)Direct Coomb’s test (antiglobulin test)
Clue to immune (antibody-mediated) Clue to immune (antibody-mediated) hemolysis of RBChemolysis of RBC
Ham’s test (acid hemolysis); sucrose Ham’s test (acid hemolysis); sucrose hemolysis test screens for paroxysmal hemolysis test screens for paroxysmal nocturnal hemoglobinurianocturnal hemoglobinuria Flow cytometry diagnosticFlow cytometry diagnostic
Osmotic fragility testOsmotic fragility test Hemoglobin electrophoresis for Hemoglobin electrophoresis for
Immune-mediated hemolysis Usually due to IgG or IgM antibodies with Usually due to IgG or IgM antibodies with
specificity to antigens on red cell specificity to antigens on red cell membrane(autoantibodies) or with membrane(autoantibodies) or with alloantigens on transfused RBC alloantigens on transfused RBC (alloantibodies)(alloantibodies)
Diagnostic tool: Coomb’s antiglobulin testDiagnostic tool: Coomb’s antiglobulin test Direct: ability of anti-IgG or anti-C3 sera Direct: ability of anti-IgG or anti-C3 sera
to agglutinate patient’s RBCto agglutinate patient’s RBC Indirect: serum of patient incubated with Indirect: serum of patient incubated with
normal RBC & antibody is detected with normal RBC & antibody is detected with anti-IgGanti-IgG
Hemolysis due to Antibodies Warm-Antibody Warm-Antibody
Immunohemolytic Immunohemolytic anemiaanemia IdiopathicIdiopathic LymphomasLymphomas SLE & other collagen SLE & other collagen
Treatment: Autoimmune hemolytic anemia Glucocorticoids: PrednisoneGlucocorticoids: Prednisone SplenectomySplenectomy Immunosuppressive drugsImmunosuppressive drugs Blood transfusion for severe Blood transfusion for severe
anemiaanemia
Case 1-04-01
48 year old male farmer with 48 year old male farmer with progressive weakness and pallorprogressive weakness and pallor
no jaundice nor no jaundice nor hepatosplenomegaly hepatosplenomegaly
petechiae noted on both L.E.’spetechiae noted on both L.E.’s
ALG or ATG + cyclosporineALG or ATG + cyclosporine ModerateModerate
AndrogensAndrogens
Summary History and Physical examination are essential in the History and Physical examination are essential in the
assessment of a patient who may have anemiaassessment of a patient who may have anemia CBC, done and reported correctly is an important tool in CBC, done and reported correctly is an important tool in
anemiaanemia Confirms presence of anemiaConfirms presence of anemia Clues to the type and possible etiology of anemiaClues to the type and possible etiology of anemia
Additional tests indicated depending on type of anemiaAdditional tests indicated depending on type of anemia Bone marrow examinationBone marrow examination Iron studiesIron studies Hemoglobin electrophoresisHemoglobin electrophoresis Blood chemistriesBlood chemistries Vitamin levels: B12, folic acidVitamin levels: B12, folic acid Coomb’s testCoomb’s test OthersOthers
Treatment depends on the causeTreatment depends on the cause
Acknowledgements:
This presentation has been the This presentation has been the collective effort of the following collective effort of the following members of the staff of the members of the staff of the Section:Section:
Gina V. Panuncialman, MDGina V. Panuncialman, MD Priscilla B. Caguioa, MDPriscilla B. Caguioa, MD Irene D. Castillo, MDIrene D. Castillo, MD