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Haemotology > Anemia (Taylor) > Flashcards

Anemia (Taylor) Flashcards

1
Q

Evaluation of Anemia

A

Erythron: Circulating RBCs and erythroid marrow (5 day maturation from BFU-E).

• 2L RBCs and 90mL marrow in 70kg male •

Reticulocyte – no nucleus – retains mitochondria, rRNA and hemoglobin synthesis 24-36 hours in circulation • Loss of these organelles in sinusoids of spleen

Mature RBC – 120 day lifespan until marked for destruction. Steady state, daily replacement of 0.83% of erythron (17 mL)

Oxygen Sensing-Hypoxia stimulates erythropoietin synthesis; done in the kidney

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2
Q

Erythropoiesis

A

Epo is made in the kidney and released in the blood stream then the bone marrow.

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3
Q

Hemoglobin

A

measured by absorption at 540 nM after cell lysis, the best measure of O2 carrying

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4
Q

RBC count

A

automated rbc counting when alter electrical conductance through aperture (x109/μL). Cells > 36 femtoliters in size and density of the cell

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5
Q

Hematocrit

A

volume blood composed of

RBCs. Calculated by RBC x MCV/10 and

reported in %. This is a calculated value!

aka packed cell volume

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6
Q

MCV (mean cell vol)

A

RBC size measured directly and

reported as a histogram. The mean rbc size is

reported as the mean cellular volume.

• Normocytic, microcytic (<80) or macrocytic (>100)

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7
Q

Mean Cellular Hemoglobin (MCH)

A

Calculated = hgb/RBC x 10. Few clinical uses.

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8
Q

Mean Cellular Hemoglobin concentration (MCHC)

A

Calculated = hgb/HCT x 100.

Normal 32-36 g/dL.

  • MCHC < 32 = hypochoromic
  • MCHC elevated in heretitary spherocytosis
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9
Q

Red cell distribution width (RDW)

A

Calculated value with normal range = 11.5% - 14.5%.

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10
Q

Reticulocyte count

A

% of all RBC (normal 0.8-1.5%)

Absolute reticulocyte count

– Relative reticulocyte count x RBC count

– Normal 25,000-90,000/μl

– Examples:

1.1% x 4.96 x106 = 55,000/μl

12.2% x 2.05 x106 = 250,000/μl

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11
Q

Anemia by Etiology

A

External blood loss – acute or chronic

• Increased destruction (hemolysis) – long

differential including toxin, RBC defect,

extra-erythrocytic damage (antibody, etc.),

splenic destruction

• Decreased production (hypoplastic) –

primary marrow failure, insufficient Epo,

injury (radiation), replacement (malignancy)

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12
Q

Classification of Anemia:

RBC Kinetics and Size 1

A

Macrocytic = MCV >100 fL

  • Microcytic = MCV < 80 fL
  • Hypochromic = MCHC < 32 g/dL
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13
Q

Classification of Anemia:

RBC Kinetics and Size 2

Macrocytic, normochromic anemia vs Normocytic, normochromic anemia

A

Macrocytic, normochromic anemia

– MCV >100 fL

– Megaloblastic (B12 or folate def., chronic AZT)

– Non-megaloblastic (drugs, liver disease,

hypothyroidism) – often with reticulocytosis

• Normocytic, normochromic anemia

– Acute blood loss, acute hemolysis, bone marrow

failure, chronic disease, hypersplenism

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14
Q

Microcytic, hypochromic anemia

A

MCV < 80 fL; MCHC <32 g/dL

– Iron deficiency

– Lead poisoning

– Thalassemia (can be normochromic)

– Chronic disease

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15
Q

Case 1:

19-year old male admitted hospitalized for an elective cholecystectomy.

  • A consultation is requested to evaluate anemia noted with pre-operative testing. “Always been told by physicians has mild anemia”.
  • Past medical history: Negative.
  • Vitals signs normal. Mild icteric sclerae and palpable mass in the left upper quadrant below the costal margin. Remainder normal
A

cholecystectomy - hemoglobin is broken down to billirubin and excreted by the gall bladder

LUQ- spleen, destruction of red blood cells

Normocytic Anemia

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16
Q

Case 1 labs

Hemoglobin 11.2 g/dl

  • Hematocrit 34%
  • WBC 9.0, normal diff
  • Platelet count 295,000/ul
  • MCV 89 fl

• Absolute reticulocyte count 200,000 (29,500-87,300)

• Blood Smear Polychromasia, microspherocytes

A

micrspherocytes - HS or something causing hemolysis

normocytic

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17
Q

Case 1: Which of the following tests is most likely to help confirm the diagnosis?

A. Hemoglobin Electrophoresis

B. Osmotic Fragility Test

C. Direct and Indirect Antiglobulin (Coombs) test (autoimmunity)

D. Bone Marrow Aspiration and Biopsy (cancer maybe)

A

B. Osmotic Fragility Test

Hereditary spherocytosis

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18
Q

Normocytic anemia classifications

A

DETERMINE IF ADEQUATE BONE MARROW RESPONSE RELATIVE TO DEGREE OF ANEMIA

(ABSOLUTE RETICULOCYTE COUNT OF > OR = 100K)

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19
Q
A

normal BM

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20
Q
A

myelophistic anemia

absence space and fat globules

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21
Q
A

aplastic anemia

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22
Q

NORMOCYTIC ANEMIA:

WITH ADEQUATE RESPONSE

choice with reticulocytosis

A

acute blood loss or hemolysis

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23
Q

methylene blue stain: residual RNA

A

POLYCHROMASIA: INCREASED

RETICULOCYTES ON PERIPHERAL

SMEAR

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24
Q

NORMOCYTIC ANEMIA: HEMOLYSIS: extravascular

A
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25
Q

NORMOCYTIC ANEMIA: HEMOLYSIS

Intravascular

A

COMPLEMENT FIXATION

Example: PNH or paroxysmal

nocturnal hemoglobinuria. Acquired

somatic mutation in PIGA gene = no

GPI-linked membrane proteins like

CD55 (DAF or decay accelerating

factor). Complement fixation and

intense intravascular hemoloysis.

MECHANICAL FIXATION

EXOGENOUS TOXIC FACTORS

HB PRODUCTS IN BLOODSTREAM

Heme ring to biliverdin to bilirubin

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26
Q

extravascular vs intravascular hemolysis

A
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27
Q

NORMOCYTIC ANEMIA: CLASSIFICATION

WITH RETICULOCYTOSIS

A
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28
Q

Case 2:

42-year-old female with Systemic Lupus

Erythematosus (SLE) presents with fatigue

•Has been on Anti-TNF therapy and doing well

from lupus standpoint. However, she has

recently experienced worsening fatigue.

•Vital signs normal. Face and conjunctiva are

both jaundiced; she has a fading butterfly

rash on her face. The spleen is palpable on

deep inspiration.

HEMOGLOBIN 7.8 G/dL

  • HEMATOCRIT 27%
  • MCV 95 FL
  • WBC COUNT 4.5, NORMAL DIFF
  • PLATELET COUNT 450,000 /UL
  • ABSOLUTE RETICULOCYTE 170,000 (29-87)
  • ESR 25 MM/HR
  • LDH 400 U/L (140-280)
  • T. BILIRUBIN 3.5 MG/DL ((0.1-1.0)
  • I. BILIRUBIN 3.0 MG/DL
A

Normocytic anemia

elevated reticulocyte count

LDH - some type of hemolysis is going on

neutrophils and spherocytes present= hemolysis

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29
Q

CASE #2

• WHICH OF THE FOLLOWING IS THE BEST

INTREPRETATION OF THE DATA?

A. The hemolysis is predominately intravascular.

B. The bone marrow is not responding to the anemia.

C. Direct Coombs testing should be positive.

D. Urine hemoglobin testing should be positive.

A

D. Urine hemoglobin testing should be positive. (Combs positive)

DIAGNOSIS: WARM AUTOIMMUNE HEMOLYTIC ANEMIA

ASSOCIATED WITH LUPUS

• EXTRAVASCULAR PROCESS

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30
Q

NORMOCYTIC ANEMIA: EXTRINSIC

IMMUNE: AIHA

A

Warm antibody type

  • Active at 37C (body temp)
  • IgG and RARELY complement
  • Monospecific Coombs’ test
  • Primary (Idiopathic)
  • Secondary
  • Lymphoma/CLL
  • Autoimmune disorders

(LUPUS)

• Drugs

31
Q

NORMOCYTIC ANEMIA: HEMOLYSIS

EXTRINSIC DEFECTS: NON-IMMUNE

A

TTP= cleaving vWF factor by metalloproteinase

32
Q
A

MICROANGIOPATHIC ANEMIA

33
Q

NORMCYTIC ANEMIA: HEMOLYSIS

intrinsic RBC defects

A

MEMBRANE:

  • HEREDITARY SPHEROCYTOSIS
  • HEREDITARY ELLIPTOCYTOSIS
  • PNH

HEMOGLOBIN:

  • SICKLE CELL ANEMIA
  • THALASSEMIAS
  • UNSTABLE HEMOGLOBINS

ENZYME DEFECTS:

-G6PD DEFICIENCY (CHECK

LEVELS BETWEEN ATTACKS)

-PRYVATE KINASE DEFICIENCY

34
Q

NORMOCYTIC ANEMIA: INTRINSIC

HEMOLYSIS: MEMBRANE DEFECTS

A

HER. SPHEROCYTOSIS and HER. ELLIPTOCYTOSIS

Diagnostic tests: osmotic fragility test

Hereditary spherocytosis frequent pigment gallstones

35
Q
A

Her. spherocytosis

36
Q
A

Her. Elliptocytosis

37
Q

ENORMOCYTIC ANEMIA: INTRINSIC

HEMOLYSIS: MEMBRANE DEFECTS

A

Extravascular hemolysis: Kupffer cells phagocytose rbcs in the spleen

and liver.

38
Q

CASE #3

•28-year-old male with sickle cell disease

present to ER with abdominal pain, chest

pain, and shortness of breath (SOB).

  • His dyspnea evolved over 36 hours after a visit with his kids.
  • History of 2 ER visits per year
  • He takes Hydroxyurea intermittently.

VITALS SIGNS: PULSE: 116, B/P: 138/76 and

resp rate: 18 and T: 38.3

  • Pulse oximeter: 85% on room air; 90% on 4L of O2
  • Lungs: Inspiratory crackles in RML.
  • Spleen is not palpable
  • Rest of exam normal

HEMOGLOBIN 7.9 G/DL

  • HEMATOCRIT 25%
  • MCV 80 FL
  • WBC 16.0 (70% PMNs; 15% LYM)
  • PLATELET 490,000
  • CXR: RML INFILTRATE -
  • SpO2 = 60% on room air
A

some type of pneumonia

39
Q

Case 3

A

Howell Jolly body = nuclear remnants, normally removed by the spleen

40
Q

CASE #3

• WHICH OF THE FOLLOWING SHOULD YOU ORDER?

A. HYDROXYUREA

B. ERYTHROCYTE EXCHANGE TRANSFUSION

C. PLASMA EXCHANGE

D. ANTICOAGULATION WITH UNFRACTIONATED HEPARIN

E. AGGRESSIVE IV HYDRATION

A

ANSWER: B. ERYTHROCYTE EXCHANGE TRANSFUSION

  • DIAGNOSIS: Sickle cell anemia ACUTE CHEST SYNDROME
  • When do you do acute exchange transfusion?
  • Acute Chest Syndrome
  • Acute Stroke
  • NOT FOR AN UNCOMPLICATED PAIN CRISIS – transfusion has no

role in uncomplicated pain crisis unless severe anemia!

41
Q

SICKLE CELL DISEASE VS TRAIT

A

SICKLE CELL DISEASE

• BOTH ALLELES FOR β-GLOBIN

GENE MUTATED (SS)

  • LOW HGB (anemia): 8-10
  • SICKLING WITH HEMOLYSIS 6

MONTHS OF AGE ONWARDS

due to decline in HbF

• VASO-OCCULSION (pain)

SICKLE CELL TRAIT

• ONE SICKLE β-GLOBIN CHAIN

MUTATED (AS)

  • <50% HbS
  • NOT ANEMIC (normal Hb)
  • NO SICKLED CELLS
  • RARELY SYMPTOMATIC
  • Risk w severe hypoxia,etc.
42
Q

PATHOPHYSIOLOGY OF SCD

43
Q

SICKLE CELL DISEASE

A

CLINICAL MANIFESTATIONS

  • CHRONIC HEMOLYTIC ANEMIA
  • LIFESPAN OF RBC IS 20 DAYS VS. 120 DAYS
  • EXTRAVASCULAR >>>>>>>> INTRAVASCULAR
  • OCCULUSION SMALL VESSELS
  • TRAPPING SICKLED CELLS
  • DELAYED CIRCULATION TIME
  • EXPOSURE TO LOWER OXYGEN STATES
  • PAIN DUE TO HYPOXIA
44
Q

SCD:THERAPY PRINCIPLES

A
  • THERAPY
  • PREVENTING INFECTIONS (ANTIBIOCTIC

PROPHYLAXIS IN CHILDREN,

PNEUMOCOCCAL VACCINATIONS)

•PREVENTING SICKLING EPISODES (STAY

HYDRATED; AVOID STRESS)

  • ANALGESIA FOR ACUTE PAINFUL CRISES
  • INCREASING HbF WITH HYDROXYUREA
45
Q

FDA approved therapies for SCD

A

L-Glutamine (Endari) – precursor for NAD –

an rbc antioxidant. Reduces pain, increases

hemoglobin.

•Voxelotor (Oxbryta) – small molecule that

shifts P50 curve (oxy-hemoglobin saturation

curve) to the LEFT like HbF. INCREASES

Hb but no effect on pain.

•Crizanlizumab (Adakveo) - monoclonal

antibody blocking post-vaso-occlusion

inflammation (blocks P-selectin). ↓ pain 50%.

46
Q

experimental SCD therapies

A

HLA matched sibling donor stem cell

transplant

•Lentivirus mediated gene therapy (insert

modified HbA into stem cells ex vivo followed

by transplant). Recombinant HbA modified

with anti-sickling mutations (axial and lateral sickle β contact sites from M1 lecture)

•CRISPR/CAS9 gene editing/mutation of

BCL11A to increase HbF (BCL11A repressor

of HbF synthesis)

NOT ON TEST

47
Q

EVALUATION ALGORITHM:

NORMOCYTIC ANEMIA

48
Q

CASE #4

• 46-year-old female with progressive numbness.

Initially, she has tingling of her toes and now she

has decreased sensation to the level of her thighs

and has trouble buttoning her shirts.

• Physical exam: Objective decreased sensation

greatest in the lower extremities with markedly

diminished proprioception.

• Labs: Hgb 9.5 g/dl, Hct 27%, MCV 113, WBC 3600,

Platelets 398,000

A

microcytic anemia

small lymphocyte

Huge red blood cells

49
Q

CASE #4

• THE NEXT MOST APPROPRIATE TESTS IN THIS

PATIENT WOULD BE:

A. Serum folic acid, AST, ALT, and TSH

B. Bone marrow biopsy to look for dysplasis and ringed sideroblasts

C. Flourescent in situ hybridization (FISH) for BCRABL on the peripheral blood (Philadelphia chromosome)

D. Serum Vitamin B12 and Folic acid, plasma homocysteine and methylmalonic acid

A

D. Serum Vitamin B12 and Folic acid, plasma homocysteine and methylmalonic acid

Serum Vitamin B12 and Folic acid, plasma homocysteine and methylmalonic acid

  • Diagnosis: Megaloblastic anemia (likely B12 deficiency)
  • Etiology: pernicious anemia (anti-parietal antibodies and no intrinsic factor made to absorb

B12 in terminal ileum); gastric bypass surgery (no IF in gut); GI surgery (resection terminal ileum)

50
Q

MACROCYTIC ANEMIA:

MEGALOBLASTIC

A

has to do with cell cycle arrest

51
Q

MACROCYTIC ANEMIA: CLASSIFICATION

52
Q

Testing for B12 and folate deficiency

A

in b12 methylmalonic acid is elevated and in folate the methylmalonic acid will be normal or low

homocysteine is elevated in both

53
Q
A

megaloblastic anemia

54
Q

MACROCYTIC ANEMIA:

CLASSIFICATION

55
Q

MACROCYTIC ANEMIA

A

LIVER DISEASE

Target cells + echinocytes

HYPOTHYROIDISM

Round macrocytes and other cells

56
Q
A

liver disease- microcytic anemia

57
Q
A

microcytic anemia

hypothyroidism

58
Q

MACROCYTIC ANEMIA ALGORITHM

59
Q

CASE #5

•58-year-old female with active rheumatoid

arthritis, presents with fatigue and joint pain

•She is taking Prednisone 10 mg daily and

weekly Methotrexate

• Vital signs are normal. Conjunctiva are pale and active synovitis affecting both knees.

HEMOGLOBIN 9.0 G/DL

  • HEMATOCRIT 30%
  • MCV 80
  • WBC 11,500 WITH 80% NEUTROPHILS
  • PLATELET 500,000/UL
  • ESR 50 MM/HR
  • ERYTHROPOIETIN 15 MU/ML (0-19)
A

normocytic macrocytic anemia

60
Q

CASE #5

• WHICH OF THE FOLLOWING LABORATORY FINDINGS ARE

CONSISTENT WITH THIS CONDITION?

A. Elevated hepcidin, elevated ferritin, elevated TIBC, elevated

serum iron

B. Elevated hepcidin, elevated ferritin, decreased TIBC, elevated serum iron

C. Decreased hepcidin, elevated ferritin, decreased TIBC, elevated serum iron

D. Elevated hepcidin, elevated ferritin, decreased TIBC, normalserum iron

A

Elevated hepcidin, elevated ferritin, decreased TIBC, normal serum iron

  • Answer: D
  • Clinical Diagnosis: Anemia of Chronic Disease
61
Q

MICROCYTIC ANEMIA: HEMOGLOBIN

SYNTHESIS DEFECT

62
Q

Hemoglobin Ontology

A

Adult hemoglobin:

  • A: α2β2
  • F: α2ϒ2
  • A2: α2δ2
  • β-Thalassemia
  • Increased HbA2 and F
  • β-globin: Chromosome 11
  • α-globin: Chromosome 16
63
Q
A

microcytic anemia

64
Q

β-Thalassemia

A

β-Thalassemia Minor (β/β0 or β/β+)

  • Single gene defect
  • Trait (heterozygote)
  • Microcytosis
  • Asymptomatic but mild anemia

β-Thalassemia Intermedia (β+/β+)

  • 2 genes abnormal
  • Anemic: No transfusion needed

β-Thalassemia Major (β0/β0 or β+/β0)

  • 2 abnormal genes
  • Severe anemia (extramedullary

hematopoiesis; Hb 2-3 gm/dL)

•Transfusion dependent (monthly)

65
Q

a-THALASSEMIA

A
  • Normal:
  • 4 a globin genes
  • Abnormal:
  • 0-3 alpha globin genes
  • Small DNA deletions (meiotic crossover events)
  • Large DNA deletions (Southeast Asian)
  • Less common point mutations (Hb Constant

Spring)

Hemoglobin Electrophoresis: NORMAL Diagnosis: DNA Testing for mutation

66
Q

a-THALASSEMIA DNA DELETIONS

A
  • Small DNA deletions: Remove 1 a gene
  • 3.7 kb deletion, rightward (z box); ( - a3.7)
  • 4.2 kb deletion, leftward (x box); ( - a4.2)
  • Nonreciprocal homologous recombination

event: -a / aa and aaa / aa

67
Q

a-THALASSEMIA DNA DELETIONS- large

A

Large DNA deletions:

  • Remove 2 a genes, gives rise to a0 phenotype
  • Southeast Asian variant (SEA; D20 kb), deletions

common in Asia only

68
Q
A

Genotypes in red are only observed in Southeast Asia (why?) – Cis 2 gene

deletion alleles only seen in Asia

69
Q

a-thallassemia

A
  • 29% of African Americans are silent carriers
  • 1-2 % of African Americans have a-thal trait
  • Note again that only 1 gene deletion alleles are

observed in Africa (so no HbH or hydrops in Africa)

70
Q

IRON STUDIES IN MICROCYTIC

ANEMIA

71
Q

IRON DEFICIENCY ANEMIA

A

LOW FERRITIN

  • HIGH EPO
  • HIGH TIBC
  • LOW SERUM IRON
  • What is the cause? Typically chronic blood loss or inadequate

dietary intake.

• Common causes of chronic blood loss: GI bleeding (colon cancer),

menorrhagia (females), poor diet (children ~4-5 years of age)

72
Q

ANEMIA OF CHRONIC DISEASE

A

HYPOPROLIFERATIVE ANEMIA

  • ELEVATED INFLAMMATORY MARKERS
  • MOST COMMON CAUSES OF ANEMIA

AMONG HOSPITALIZED PATIENTS

73
Q

MICROCYTIC ANEMIA ALGORITHM

74
Q

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Haemotology (15 decks)

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