Anemia

Август 12, 2022

Содержание

2. Initial Laboratory Evaluation Complete blood count with indices: MCV – indication of RBC size. RDW –
3. Additional Labs Vitamin levels: iron profile, ferritin, Vitamin B12, folate. LDH, bilirubin, haptoglobin. Coomb’s test Hemoglobin
4. Definition of Anemia Reduction in the volume of RBC’s (hematocrit) or concentration (hemoglobin) when compared to
5. Morphology Classification Microcytic (MCV Iron deficiency, thalassemia, chronic disease/inflammation, sideroblastic anemia, lead poisoning. Normocytic (MCV 80-100
6. Case 1 A 35 year old woman has a history of pleurisy and has been told
7. Case 1 Initial Labs: Hemoglobin 7.9 gm/dL HCT 23.9% WBC 4000/mm3 with a normal differential Platelet
8. Case 1 MCV 114 Uncorrected Retic count 14.2% LDH 2343 U/L Bilirubin 4.3mg/dL Direct bili .8mg/dL
9. Case 1
10. Case 1 You suspect an autoimmune hemolytic anemia based on her history, Physical Exam, labs, and
11. Case 1 Direct Coombs Test (AKA direct antiglobulin test): RBC’s are washed, removing serum and then
12. Case 1 Direct Coombs test results are as follows: DAT: Positive 3+ IgG: Positive 3+ Complement:
13. Case 1 You diagnose a warm-antibody hemolytic anemia and suspect an underlying autoimmune disorder. Etiology: Idiopathic
14. Case 1 You decide to avoid blood transfusion because of: The difficulties in obtaining cross match
15. Case 1 Treatment: Prednisone Splenectomy Rituximab (monoclonal antibody) Immunosuppressive agents Cytoxan, imuran, cyclosporin Danazol Plasma exchange
16. Case 1 You begin her on 60 mg Prednisone and she has a good response. Upon
17. Case 1 She responds well to splenectomy, but still requires very low maintenance doses of Prednisone.
18. Case 2 You are referred a pleasant 34 year old African American woman who has been
19. Case 2 Labs: HCT 31-34% Hgb 10.6-11.4gm/dL PLT 232-312K/mm3 WBC 6500-8000/mm3 with a normal differential MCV
20. Case 2 Differential Diagnosis: Iron deficiency anemia Noncompliance, inadequate dosing, incorrect formulation. Beta thalassemia Alpha thalassemia
21. Case 2 Iron studies are normal. Chemistries, liver function tests, thyroid studies are normal. No history
22. Case 2
23. Case 2 ASH image bank
24. Case 2 You also request a hemoglobin electrophoresis. Hgb A = 97.5% Hgb A2 = 2.1%
25. Case 2 Alpha thalassemia with a double gene deletion. No treatment is necessary. Anemia is not
26. Case 3 A 32 year old previously healthy woman with no prior medical history presents to
27. Case 3 Physical exam confirms an ill appearing woman. T = 38.6, pulse 122, BP 123/54
28. Case 3 Routine labs: WBC = 1700/mm3 Hgb = 5.6 gm/dL HCT 18.2% Platelet – 12,000/mm3
29. Case 3 Differential of the white blood cell count reveals at least 50% of young white
30. Case 3
31. Case 3
32. Case 3
33. Case 3 Hematopathology evaluation revealed AML subtype M1. Chromosomal studies were normal. What should you do
34. Case 3 The patient tolerated induction chemotherapy well and remains in remission 4 months after completing
35. Case 4 You are asked to see a 43 year old previously healthy woman who presented
36. Case 4 The ER attending notes: The patient to be ill appearing T 38.3, HR 123,
37. Case 4 Labs: WBC 5600/mm3, normal differential HCT 16.3% Hgb 5.3 gm/dL Platelets 21,000/mm3 PT 11
38. Case 4 Labs: Creatinine 2.4 mg/dL LDH 3000 U/L Bili 3.2 mg/dL, mostly indirect Reticulocyte count
39. Case 4
40. Case 4 What is your differential diagnosis based on the history, physical, labs and blood smear?
41. Case 4 You diagnosis TTP based on the classic pentad and consistent blood smear: Microangiopathic hemolytic
42. Case 4 You begin daily plasma exchange procedures using FFP as your replacement fluid. Her mental
43. Case 4 Pathophysiology: Typically an inhibitor against ADAMTS- 13, a vWF cleaving to protease leading to
44. Case 4
45. Case 5 A 36 year old Caucasian man with a history of progressive renal failure over
46. Case 5 Physical exam is significant for pale sclera and an AV shunt in his left
47. Case 5 Prior labs reveal a hematocrit that was normal 4 years ago, but has steadily
48. Case 5
49. Case 5 Differential Diagnosis: Anemia of renal failure Iron deficiency anemia Thalassemia Lead poisoning Myelodysplasia Mixed
50. Case 5 You order an erythropoietin level which returns at 12 IU ( 4.1-19.5 ) within
51. Case 5 You place the patient on 10,000 units of EPO SQ tiw with dialysis. He
52. Case 5 He continues on his EPO injections for four months. Soon after he again becomes
53. Case 5
54. Case 5 You suspect with his increased reticulocytosis and hgb/hct over the last few months he
55. Case 5 He again feels much improved and is tolerating the iron fairly well. His hematocrit
56. Case 5: Anemia of Chronic Inflammation Mild to moderate anemia that is persistent for greater than
57. Case 5: Pathophysiology Epo production is inhibited or decreased, so inappropriately low levels. Increased levels of
58. Case 5: Laboratory Abnormalities ASH SAP 5th edition
59. Case 5 ACI does not usually require treatment. Iron replacement is typically not necessary. Erythrocyte-stimulating agent
60. Case 6 A 53 year-old female complains of fatigue for 3 months. She falls and breaks
61. Case 6 What is the most likely diagnosis? How do you want to proceed with your
62. Case 6 Serum protein electrophoresis (SPEP) M- spike of 4.2 gm/dl Immunofixation (IFE) IgG lambda noted
63. Case 6 Skeletal survey Multiple lytic lesions throughout the skeleton Bone Marrow aspirate and biopsy Sheets
64. Case 6 An M-protein is usually seen as a discrete band on agarose gel electrophoresis in
65. Case 6: SPEP
66. Case 6: SPEP NORMAL
67. Case 6: Myeloma + - α1 α2 β γ *
68. Case 6: Density Scan + - Albumin α-1 α-2 β
69. Case 6 When to order an SPEP: When you suspect multiple myeloma, Waldenstrom’s macroglobulinemia or amyloidosis.
70. Case 6 Immunofixation (IFE): Proteins are fractioned on electrophoretic strips: Each lane overlaid with monospecific antisera
71. Case 6: Normal IFE gamma alpha mu kappa lambda SPE
72. Case 6 When to order an IFE: To type the paraprotein (M spike) identified on SPEP
73. Case 6: Quantitative Immunoglobulins Useful to quantitate: The amount of monoclonal protein Suppression of uninvolved immunoglobulins
74. Case 6 Serum light chain assays are newer and a very sensitive technique for measuring serum
75. Case 6: Quantitative Immunoglobulins + - Albumin “M-spike”, “Paraprotein” or “M- α-1 α-2 β Note loss
76. Case 6 Our patient
77. Case 6
78. Case 6: Stage III Multiple Myeloma The patient is started on systemic chemotherapy and an autologous
79. Case A A 45 yo white male presents to his physician complaining of tiredness and fatigue
80. Case A Progression of symptoms Blood in stool Other medications or toxins, including EToH Prior history
81. Case A The patient does note he has had black tarry stools for a few weeks
82. Case A You order a CBC which shows the following results: Hbg 8.2 gm/dL HCT 26%
83. Case A
84. Case A Iron studies: Fe 14 ug/dL TIBC 426 ug/dL % sat 3% Ferritin 10ng/mL Corrected
85. Case A You confirm iron deficiency likely secondary to NSAID use. An endoscopy confirms a H.pylori
86. Case A He feels much better and has experienced resolution of his fatigue and lethargy. Hgb
87. Case A
88. Case B A 67 year old woman with a history of IDDM and treated hypothyroidism is
89. Case B Current Labs: 2 years ago: How do you interpret these values?
90. Case B *Hypersegmented neutrophil, macroovalocytes
91. Case B What tests or procedures do you want to perform to further evaluate this patient?
92. Case B You diagnose B12 deficiency and prescribe B12 injections 1000ug weekly x4 then 1000ug a
93. Case B: Vitamin B12 Deficiency Found primarily in animal meats. Large hepatic reservoir. Deficiency from decreased
94. Case B: Vitamin B12 Deficiency Clinical findings: Insidious onset. Glossitis, weight loss, pale yellow skin. Neurologic
95. Case B: Vitamin B12 Deficiency Lab findings: Cobalamin If low-normal (200-350ng/L), check homocysteine and MMA. Both
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Initial Laboratory Evaluation
Complete blood count with indices:
MCV – indication of

RBC size.
RDW – indication of RBC size variation.
Examination of the peripheral blood smear.
Reticulocyte count:
Measurement of newly produced young RBC’s.
Considered a measure of bone marrow responsiveness.

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Additional Labs
Vitamin levels: iron profile, ferritin, Vitamin B12, folate.
LDH, bilirubin,

haptoglobin.
Coomb’s test
Hemoglobin electrophoresis
SPEP
Creatinine
TSH
Urinalysis
Stool guaiac
Consider bone marrow examination

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Definition of Anemia
Reduction in the volume of RBC’s (hematocrit) or concentration

(hemoglobin) when compared to similar values from a reference population.
Hgb = expression of amount (g/dL).
Hct = expression of volume (% or decimal fraction).
RBC = expression of number (#/mm3).

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Morphology Classification
Microcytic (MCV <80 µ3):
Iron deficiency, thalassemia, chronic disease/inflammation, sideroblastic

anemia, lead poisoning.
Normocytic (MCV 80-100 µ3):
Acute blood loss, chronic disease, hypersplenism, bone marrow failure, hemolysis.
Macrocytic (MCV >100 µ3):
B12 or folate deficiency, hemolysis with reticulocytosis, chemotherapy, hypothyroidism, MDS.

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Case 1
A 35 year old woman has a history of pleurisy

and has been told she may have SLE.
Previous CBC’s have been normal.
She presents to your office with complaints of exertional dyspnea, fatigue, and yellowing of her eyes.
Physical exam is normal except for mild scleral icterus and moderate splenomegaly.

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Case 1
Initial Labs:
Hemoglobin 7.9 gm/dL
HCT 23.9%
WBC 4000/mm3 with a normal

differential
Platelet 138,000/mm3
What other labs would you like to see?

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Case 1
MCV 114
Uncorrected Retic count 14.2%
LDH 2343 U/L
Bilirubin 4.3mg/dL
Direct bili

.8mg/dL
The peripheral blood smear reveals macrovalocytes, polychromasia, and an occasional nucleated red blood cell.

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Case 1

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Case 1
You suspect an autoimmune hemolytic anemia based on her history,

Physical Exam, labs, and smear.
What further tests would you like to order?

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Case 1
Direct Coombs Test (AKA direct antiglobulin test):
RBC’s are washed,

removing serum and then incubated with antihuman globulin (Coombs reagent).
This binds immunoglobulin or complement factors fixed on the RBC surface, causing agglutination and therefore a positive DAT.

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Case 1
Direct Coombs test results are as follows:
DAT: Positive 3+
IgG:

Positive 3+
Complement: Negative
What type of autoantibody is this?
What conditions are typically associated with this type of antibody?

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Case 1
You diagnose a warm-antibody hemolytic anemia and suspect an underlying

autoimmune disorder.
Etiology:
Idiopathic
Autoimmune
Lymphoproliferative Disorder
Viral
Immunodeficiency
Medications

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Case 1
You decide to avoid blood transfusion because of:
The difficulties

in obtaining cross match compatible blood, AND
The expected short half life of transfused blood.
What treatment do you recommend?

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Case 1
Treatment:
Prednisone
Splenectomy
Rituximab (monoclonal antibody)
Immunosuppressive agents
Cytoxan, imuran, cyclosporin
Danazol
Plasma exchange

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Case 1
You begin her on 60 mg Prednisone and she has

a good response. Upon several attempts at tapering the prednisone she has a relapse with worsening of the hemolytic anemia.
You are concerned about the long term side effects of Prednisone, thus you send her for a procedure.

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Case 1
She responds well to splenectomy, but still requires very low

maintenance doses of Prednisone.
Over the years she occasionally requires higher doses of Prednisone when she is ill or has a lupus flare.

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Case 2
You are referred a pleasant 34 year old African American

woman who has been known to have a mild microcytic anemia, which was picked up some years ago on routine blood work. She is entirely asymptomatic. She has been prescribed iron several times over the years without a response.
What data would you like to review?

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Case 2
Labs:
HCT 31-34%
Hgb 10.6-11.4gm/dL
PLT 232-312K/mm3
WBC 6500-8000/mm3 with a normal differential
MCV

72-74 cubic microns
What is in your differential diagnosis?

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Case 2
Differential Diagnosis:
Iron deficiency anemia
Noncompliance, inadequate dosing, incorrect formulation.
Beta

thalassemia
Alpha thalassemia
Anemia of chronic inflammation/disease
Sideroblastic anemia
Lead
What additional lab tests would you like to order?

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Case 2
Iron studies are normal.
Chemistries, liver function tests, thyroid studies

are normal.
No history of lead exposure.
You ask to see a peripheral blood smear and one other study. What is it?

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Case 2

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Case 2
ASH image bank

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Case 2
You also request a hemoglobin electrophoresis.
Hgb A = 97.5%
Hgb

A2 = 2.1%
Hgb F = 0.6%
What is your diagnosis of exclusion?

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Case 2
Alpha thalassemia with a double gene deletion.
No treatment is

necessary.
Anemia is not progressive.
No other systemic problems.
Often mistaken for iron deficiency and treated with iron or for anemia of chronic disease.

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Case 3
A 32 year old previously healthy woman with no prior

medical history presents to your office stating that she has felt “unwell” for the past month. In the past 3 days she has experienced fevers, a “rash” on her legs, weakness, and shortness of breath. She has been too weak to get out of bed the last 24 hours and has experienced spontaneous nose bleeds.

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Case 3
Physical exam confirms an ill appearing woman.
T = 38.6,

pulse 122, BP 123/54
Dried blood in the nares, pale conjunctiva
Dried mucous membrane
Tachycardia and tachypnea
Petechiae over the lower extremities

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Case 3
Routine labs:
WBC = 1700/mm3
Hgb = 5.6 gm/dL
HCT 18.2%
Platelet –

12,000/mm3
What important piece of laboratory information is missing from the WBC?

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Case 3
Differential of the white blood cell count reveals at least

50% of young white cells, the lab thinks are blasts.
Reticulocyte count = 0.4%
Electrolytes are consistent with dehydration, potassium and creatinine are slightly elevated.

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Case 3

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Case 3

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Case 3

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Case 3
Hematopathology evaluation revealed AML subtype M1.
Chromosomal studies were normal.

What should you do prior to beginning chemotherapy in this patient?

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Case 3
The patient tolerated induction chemotherapy well and remains in remission

4 months after completing induction and consolidation therapy. Her blood counts have all now normalized.
If she was to relapse what therapy would you recommend?

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Case 4
You are asked to see a 43 year old previously

healthy woman who presented to the ER complaining of fevers, weakness, and bleeding from her gums.
Her only significant past history is a recently resolved viral syndrome. Her family notes she has been somewhat confused over the last 24 hours.

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Case 4
The ER attending notes:
The patient to be ill appearing
T

38.3, HR 123, BP 126/76, RR 26
Dried blood in the nares and mouth
Petechiae on lower extremities
Patient slightly confused, but no focal neurologic findings.
Before you arrive in the ER she has a seizure.

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Case 4
Labs:
WBC 5600/mm3, normal differential
HCT 16.3%
Hgb 5.3 gm/dL
Platelets 21,000/mm3
PT 11

sec
PTT 29 sec

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Case 4
Labs:
Creatinine 2.4 mg/dL
LDH 3000 U/L
Bili 3.2 mg/dL, mostly indirect
Reticulocyte

count 6.2%
Haptoglobin <10mg/dL
Urine: 2+ hemoglobin, neg RBC

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Case 4

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Case 4
What is your differential diagnosis based on the history, physical,

labs and blood smear?
What else could give you a similar blood smear?

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Case 4
You diagnosis TTP based on the classic pentad and consistent

blood smear:
Microangiopathic hemolytic anemia
Thrombocytopenia
Fever
Renal Failure
MS changes
What is the first line treatment of TTP?

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Case 4
You begin daily plasma exchange procedures using FFP as your

replacement fluid. Her mental status improves by the next day. Her platelet count normalizes and LDH decreases over the next week. Her anemia slowly improves as does her renal failure. She is weaned off plasma exchange and has a single relapse, which responds to similar therapy.

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Case 4
Pathophysiology:
Typically an inhibitor against ADAMTS- 13, a vWF cleaving

to protease leading to accumulation of High Molecular Weight vWF multimers leading to small vessel thrombosis and microangiopathic hemolytic anemia.
Plasmapheresis:
Removes the offending antibody
Supplies the deficient ADAMTS-13

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Case 4

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Case 5
A 36 year old Caucasian man with a history of

progressive renal failure over the last 4 years comes to you for work up of weakness and progressive anemia. He has recently begun dialysis. His renal failure initially appeared after an acute febrile illness and the etiology was never determined.

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Case 5
Physical exam is significant for pale sclera and an AV

shunt in his left arm.
CBC:
WBC 6400/mm3
Hgb 7.6 gm/dL
HCT 23.8%
Platelet 242,000/mm3
MCV 78/mm3

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Case 5
Prior labs reveal a hematocrit that was normal 4 years

ago, but has steadily declined as his renal function worsened.
Reticulocyte count corrected= 0.7%
Fe 26 mcg/dL
TIBC 224 mcg/dL
Iron saturation 11%
Ferritin 145 ng/mL
What is in your differential diagnosis?

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Case 5

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Case 5
Differential Diagnosis:
Anemia of renal failure
Iron deficiency anemia
Thalassemia
Lead poisoning
Myelodysplasia
Mixed microcytic

and macrocytic anemia.
You request one more study to support your suspicion?

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Case 5
You order an erythropoietin level which returns at 12 IU

( 4.1-19.5 ) within the normal limits.
What do you make of this value?
Should you proceed to a bone marrow exam?

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Case 5
You place the patient on 10,000 units of EPO SQ

tiw with dialysis. He comes to see you in one month feeling better.
Labs:
HCT 34%
Hgb 11.2 gm/dL
MCV 83/mm3
Retic 3.2%

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Case 5
He continues on his EPO injections for four months. Soon after

he again becomes fatigued, but otherwise doing well. Labs reveal:
WBC 6200/mm3
Hgb 8.9 gm/dL
Platelet 234,000/mm3
MCV 76 cubic microns
Retic .6%

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Case 5

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Case 5
You suspect with his increased reticulocytosis and hgb/hct over the

last few months he has become iron deficient. You confirm this with lab assay.
You give him 1 gram of intravenous iron and ask him to come back in 2 weeks.

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Case 5
He again feels much improved and is tolerating the iron

fairly well. His hematocrit has increased to 33%, corrected reticulocyte count to 3.2%, and the MCV is now 80 cubic microns.
He continues on Iron and EPO injections and is considering renal transplant.

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Case 5: Anemia of Chronic Inflammation
Mild to moderate anemia that is

persistent for greater than 1-2 months in patients with infectious, inflammatory, or neoplastic diseases.
Other causes have been excluded.
Hypoproliferative, low reticulocyte count.
Normocytic-MCV 80-100:
May be microcytic in later stages.
Iron studies show low serum iron, low percent saturation, and normal to elevated ferritin.
Adequate reticuloendothelial iron stores.

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Case 5: Pathophysiology
Epo production is inhibited or decreased, so inappropriately low

levels.
Increased levels of inflammatory cytokines:
IL-1, TNF α.
IL-6 causes induction of hepcidin synthesis (decreased iron absorption).
Alterations in iron metabolism.
Suppression of erythropoiesis.
Moderate decrease in RBC survival.

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Case 5: Laboratory Abnormalities
ASH SAP 5th edition

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Case 5
ACI does not usually require treatment.
Iron replacement is typically

not necessary.
Erythrocyte-stimulating agent can be given in the setting of renal disease however caution regarding hypertension and thrombosis.
Treat the underlying cause!

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Case 6
A 53 year-old female complains of fatigue for 3 months.

She falls and breaks her left femur.
On reviewing her labs the creatinine is 1.3 mg/dl, calcium 10.1 mg/dL. Comprehensive metabolic panel is otherwise normal.
Hematocrit is 25%. White blood count and platelet counts are mildly depressed at 3.9K/mm3 and 147K/ mm3.

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Case 6
What is the most likely diagnosis?
How do you want to

proceed with your evaluation?

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Case 6
Serum protein electrophoresis (SPEP)
M- spike of 4.2 gm/dl
Immunofixation (IFE)
IgG lambda

noted in serum.
Free lambda light chains in urine.
Quantitative immunoglobulins
Moderately suppressed levels of IgM (31 mg/dL) and IgA (32 mg/dL).
IgG elevated at 3875 mg/dL

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Case 6
Skeletal survey
Multiple lytic lesions throughout the skeleton
Bone Marrow aspirate and

biopsy
Sheets of malignant appearing plasma cells identified

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Case 6
An M-protein is usually seen as a discrete band on

agarose gel electrophoresis in the γ,β,α2 region of the densitometry tracing.
Immunoglobulins primarily in γ component, but also in β and α2 region
A polyclonal response produces a broad band or a broad-based peak limited to the γ region

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Case 6: SPEP

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Case 6: SPEP
NORMAL

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Case 6: Myeloma
+
-
α1
α2
β
γ
*

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Case 6: Density Scan
+
-
Albumin
α-1
α-2
β

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Case 6
When to order an SPEP:
When you suspect multiple myeloma,

Waldenstrom’s macroglobulinemia or amyloidosis.
With unexplained:
Weakness, fatigue, anemia, back pain, fractures, hypercalcemia, renal insufficiency.
Recurrent infections.
Sensorimotor neuropathy, carpal tunnel syndrome, CHF, syncope.

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$Case 6 Immunofixation (IFE): Proteins are fractioned on electrophoretic strips: Each$

Case 6
Immunofixation (IFE):
Proteins are fractioned on electrophoretic strips:
Each lane overlaid

with monospecific antisera against IgG, IgA, IgM, and light chains
Immunoglobulins are precipitated by antisera
Wash away nonprecipitated proteins
Precipitated proteins are stained

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Case 6: Normal IFE
gamma
alpha
mu
kappa
lambda
SPE

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Case 6
When to order an IFE:
To type the paraprotein (M

spike) identified on SPEP
Further evaluate an equivocal SPEP
To search for a low level paraprotein with a negative SPEP:
clinical suspicion of a lymphoplasmacytic disorder is high
unexplained symptoms such as neuropathy, renal failure, etc..
When searching for Bence-Jones proteinuria
In treated myeloma patients with a negative SPEP

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Case 6: Quantitative Immunoglobulins
Useful to quantitate:
The amount of monoclonal protein
Suppression

of uninvolved immunoglobulins in a monoclonal disorder
Identify a congenital or acquired deficiency state of an individual immunoglobulin

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Case 6
Serum light chain assays are newer and a very sensitive

technique for measuring serum light chains.
Either an adjunct to or replacement of urine protein electrophoresis.

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Case 6: Quantitative Immunoglobulins
+
-
Albumin
“M-spike”, “Paraprotein” or “M-
α-1
α-2
β
Note loss of normal “polyclonal”

immunoglobulins

component”

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Case 6
Our patient

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Case 6

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Case 6: Stage III Multiple Myeloma
The patient is started on systemic

chemotherapy and an autologous bone marrow transplant is planned.
Multiple new and effective agents exist for MM:
Thalidomide or Revlimid and other anti-angiogenic agents.
Proteosome inhibitors (velcade)
Double autologous transplant
Mini allogeneic transplant
Remains non-curative except possibly for allogeneic transplant

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Case A
A 45 yo white male presents to his physician complaining

of tiredness and fatigue over the last several months. He is otherwise healthy. His only other complaint is vague abdominal discomfort. The only medications he takes are daily NSAIDS for a knee injury he sustained while playing tennis.
You are concerned he might be anemic. What questions should you ask in the H & P?

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Case A
Progression of symptoms
Blood in stool
Other medications or toxins, including EToH
Prior

history of anemia, prior CBC’s
Other constitutional symptoms, recent illness
Family history
Diet
Craving ice, starch, or dirt

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Case A
The patient does note he has had black tarry stools

for a few weeks prior to his visit. You suspect GI blood loss induced by NSAID use.
What should you key in on the physical exam?

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Case A
You order a CBC which shows the following results:
Hbg

8.2 gm/dL
HCT 26%
RBC count 3.82 million/mm3
MCV 73 cubic microns
Platelet count 516,000/mm3
WBC 7,000/mm3
What is your interpretation of these values?

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Case A

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Case A
Iron studies:
Fe 14 ug/dL
TIBC 426 ug/dL
% sat 3%
Ferritin 10ng/mL
Corrected

reticulocyte count 1.1%
Are any other studies (bone marrow) needed?

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Case A
You confirm iron deficiency likely secondary to NSAID use. An endoscopy

confirms a H.pylori negative ulcer with chronic bleeding. He is started on Omeprazole and his NSAID is stopped.
You prescribe oral Fe Sulfate 325 mg titrated to TID which he tolerates fairly well.
He comes back to see you in 4 weeks.

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Case A
He feels much better and has experienced resolution of his

fatigue and lethargy.
Hgb 12gm/dl
HCT 35%
MCV 82 cubic microns
Retic count 4.2%
Why do you think his retic count is elevated?
Can you stop his Fe sulfate when his hgb/hct become normal?

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Case A

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Case B
A 67 year old woman with a history of IDDM

and treated hypothyroidism is referred to you for evaluation of anemia. Her complaints leading to this diagnosis included weakness, fatigue, weight loss, and mild numbness in her feet bilaterally.
Physical exam was essentially normal except for mild loss of proprioception in her feet bilaterally.

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Case B
Current Labs:
2 years ago:
How do you interpret these values?

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Case B
*Hypersegmented neutrophil, macroovalocytes

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Case B
What tests or procedures do you want to perform to

further evaluate this patient?

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Case B
You diagnose B12 deficiency and prescribe B12 injections 1000ug weekly

x4 then 1000ug a month indefinitely.
In 1 month the patient feels remarkably better and her blood counts have all improved.

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Case B: Vitamin B12 Deficiency
Found primarily in animal meats.
Large hepatic

reservoir.
Deficiency from decreased oral intake takes many years.
In the duodenum cobalamin binds to intrinsic factor produced by parietal cells of the stomach.
In the terminal ileum, cobalamin-IF complex is transported through the enterocyte into the blood.
Almost always due to malabsorption:
Pernicious anemia, achlorhydria, IBD, celiac disease, pancreatic insufficiency, bacterial overgrowth, alcohol.

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Case B: Vitamin B12 Deficiency
Clinical findings:
Insidious onset.
Glossitis, weight loss, pale

yellow skin.
Neurologic manifestations:
Loss of position or vibratory sense.
Can progress to spastic ataxia.
May occur with mild anemia and may be irreversible.
Psychiatric disorders can occur without evidence of hematologic abnormalities.
Hallucinations, dementia, psychosis, “megaloblastic mania”.
May be irreversible.

Слайд 95

Case B: Vitamin B12 Deficiency
Lab findings:
Cobalamin <200ng/L.
If low-normal (200-350ng/L), check

homocysteine and MMA.
Both elevated in Vitamin B12 deficiency.
Methylmalonic acid level is more sensitive than low-normal cobalamin alone.
Pernicious anemia:
Autoantibodies to parietal cells or intrinsic factor (50-70% sensitive, 100% specific).

Anemia

Содержание

Initial Laboratory EvaluationComplete blood count with indices: MCV – indication of

Additional LabsVitamin levels: iron profile, ferritin, Vitamin B12, folate. LDH, bilirubin,

Definition of AnemiaReduction in the volume of RBC’s (hematocrit) or concentration

Morphology ClassificationMicrocytic (MCV <80 µ3): Iron deficiency, thalassemia, chronic disease/inflammation, sideroblastic

Case 1A 35 year old woman has a history of pleurisy

Case 1Initial Labs: Hemoglobin 7.9 gm/dLHCT 23.9%WBC 4000/mm3 with a normal

Case 1MCV 114 Uncorrected Retic count 14.2%LDH 2343 U/LBilirubin 4.3mg/dLDirect bili

Case 1

Case 1You suspect an autoimmune hemolytic anemia based on her history,

Case 1Direct Coombs Test (AKA direct antiglobulin test): RBC’s are washed,

Case 1Direct Coombs test results are as follows: DAT: Positive 3+IgG:

Case 1You diagnose a warm-antibody hemolytic anemia and suspect an underlying

Case 1You decide to avoid blood transfusion because of: The difficulties

Case 1Treatment: PrednisoneSplenectomyRituximab (monoclonal antibody)Immunosuppressive agentsCytoxan, imuran, cyclosporinDanazolPlasma exchange

Case 1You begin her on 60 mg Prednisone and she has

Case 1She responds well to splenectomy, but still requires very low

Case 2You are referred a pleasant 34 year old African American

Case 2Labs: HCT 31-34%Hgb 10.6-11.4gm/dLPLT 232-312K/mm3WBC 6500-8000/mm3 with a normal differentialMCV

Case 2Differential Diagnosis: Iron deficiency anemiaNoncompliance, inadequate dosing, incorrect formulation. Beta

Case 2Iron studies are normal. Chemistries, liver function tests, thyroid studies

Case 2

Case 2ASH image bank

Case 2You also request a hemoglobin electrophoresis. Hgb A = 97.5%Hgb

Case 2Alpha thalassemia with a double gene deletion. No treatment is

Case 3A 32 year old previously healthy woman with no prior

Case 3Physical exam confirms an ill appearing woman. T = 38.6,

Case 3Routine labs: WBC = 1700/mm3Hgb = 5.6 gm/dLHCT 18.2%Platelet –

Case 3Differential of the white blood cell count reveals at least

Case 3

Case 3

Case 3

Case 3Hematopathology evaluation revealed AML subtype M1. Chromosomal studies were normal.

Case 3The patient tolerated induction chemotherapy well and remains in remission

Case 4You are asked to see a 43 year old previously

Case 4The ER attending notes: The patient to be ill appearingT

Case 4Labs: WBC 5600/mm3, normal differentialHCT 16.3%Hgb 5.3 gm/dLPlatelets 21,000/mm3PT 11

Case 4Labs: Creatinine 2.4 mg/dLLDH 3000 U/LBili 3.2 mg/dL, mostly indirectReticulocyte

Case 4

Case 4What is your differential diagnosis based on the history, physical,

Case 4You diagnosis TTP based on the classic pentad and consistent

Case 4You begin daily plasma exchange procedures using FFP as your

Case 4Pathophysiology: Typically an inhibitor against ADAMTS- 13, a vWF cleaving

Case 4

Case 5A 36 year old Caucasian man with a history of

Case 5Physical exam is significant for pale sclera and an AV

Case 5Prior labs reveal a hematocrit that was normal 4 years

Case 5

Case 5Differential Diagnosis: Anemia of renal failureIron deficiency anemiaThalassemiaLead poisoningMyelodysplasiaMixed microcytic

Case 5You order an erythropoietin level which returns at 12 IU

Case 5You place the patient on 10,000 units of EPO SQ

Case 5He continues on his EPO injections for four months. Soon after

Case 5

Case 5You suspect with his increased reticulocytosis and hgb/hct over the

Case 5He again feels much improved and is tolerating the iron

Case 5: Anemia of Chronic InflammationMild to moderate anemia that is

Case 5: PathophysiologyEpo production is inhibited or decreased, so inappropriately low

Case 5: Laboratory AbnormalitiesASH SAP 5th edition

Case 5ACI does not usually require treatment. Iron replacement is typically

Case 6A 53 year-old female complains of fatigue for 3 months.

Case 6What is the most likely diagnosis?How do you want to

Case 6Serum protein electrophoresis (SPEP)M- spike of 4.2 gm/dlImmunofixation (IFE)IgG lambda

Case 6Skeletal surveyMultiple lytic lesions throughout the skeletonBone Marrow aspirate and

Case 6An M-protein is usually seen as a discrete band on

Case 6: SPEP

Case 6: SPEPNORMAL

Case 6: Myeloma+-α1α2βγ*

Case 6: Density Scan +-Albuminα-1α-2β

Case 6When to order an SPEP: When you suspect multiple myeloma,

Case 6Immunofixation (IFE): Proteins are fractioned on electrophoretic strips:Each lane overlaid

Case 6: Normal IFEgammaalphamukappalambdaSPE

Case 6When to order an IFE: To type the paraprotein (M

Case 6: Quantitative ImmunoglobulinsUseful to quantitate: The amount of monoclonal proteinSuppression

Case 6Serum light chain assays are newer and a very sensitive

Case 6: Quantitative Immunoglobulins+-Albumin“M-spike”, “Paraprotein” or “M-α-1α-2βNote loss of normal “polyclonal”

Initial Laboratory Evaluation
Complete blood count with indices:
MCV – indication of

Additional Labs
Vitamin levels: iron profile, ferritin, Vitamin B12, folate.
LDH, bilirubin,

Definition of Anemia
Reduction in the volume of RBC’s (hematocrit) or concentration

Morphology Classification
Microcytic (MCV <80 µ3):
Iron deficiency, thalassemia, chronic disease/inflammation, sideroblastic

Case 1
A 35 year old woman has a history of pleurisy

Case 1
Initial Labs:
Hemoglobin 7.9 gm/dL
HCT 23.9%
WBC 4000/mm3 with a normal

Case 1
MCV 114
Uncorrected Retic count 14.2%
LDH 2343 U/L
Bilirubin 4.3mg/dL
Direct bili

Case 1
You suspect an autoimmune hemolytic anemia based on her history,

Case 1
Direct Coombs Test (AKA direct antiglobulin test):
RBC’s are washed,

Case 1
Direct Coombs test results are as follows:
DAT: Positive 3+
IgG:

Case 1
You diagnose a warm-antibody hemolytic anemia and suspect an underlying

Case 1
You decide to avoid blood transfusion because of:
The difficulties

Case 1
Treatment:
Prednisone
Splenectomy
Rituximab (monoclonal antibody)
Immunosuppressive agents
Cytoxan, imuran, cyclosporin
Danazol
Plasma exchange

Case 1
You begin her on 60 mg Prednisone and she has

Case 1
She responds well to splenectomy, but still requires very low

Case 2
You are referred a pleasant 34 year old African American

Case 2
Labs:
HCT 31-34%
Hgb 10.6-11.4gm/dL
PLT 232-312K/mm3
WBC 6500-8000/mm3 with a normal differential
MCV

Case 2
Differential Diagnosis:
Iron deficiency anemia
Noncompliance, inadequate dosing, incorrect formulation.
Beta

Case 2
Iron studies are normal.
Chemistries, liver function tests, thyroid studies

Case 2
ASH image bank

Case 2
You also request a hemoglobin electrophoresis.
Hgb A = 97.5%
Hgb

Case 2
Alpha thalassemia with a double gene deletion.
No treatment is

Case 3
A 32 year old previously healthy woman with no prior

Case 3
Physical exam confirms an ill appearing woman.
T = 38.6,

Case 3
Routine labs:
WBC = 1700/mm3
Hgb = 5.6 gm/dL
HCT 18.2%
Platelet –

Case 3
Differential of the white blood cell count reveals at least

Case 3
Hematopathology evaluation revealed AML subtype M1.
Chromosomal studies were normal.

Case 3
The patient tolerated induction chemotherapy well and remains in remission

Case 4
You are asked to see a 43 year old previously

Case 4
The ER attending notes:
The patient to be ill appearing
T

Case 4
Labs:
WBC 5600/mm3, normal differential
HCT 16.3%
Hgb 5.3 gm/dL
Platelets 21,000/mm3
PT 11

Case 4
Labs:
Creatinine 2.4 mg/dL
LDH 3000 U/L
Bili 3.2 mg/dL, mostly indirect
Reticulocyte

Case 4
What is your differential diagnosis based on the history, physical,

Case 4
You diagnosis TTP based on the classic pentad and consistent

Case 4
You begin daily plasma exchange procedures using FFP as your

Case 4
Pathophysiology:
Typically an inhibitor against ADAMTS- 13, a vWF cleaving

Case 5
A 36 year old Caucasian man with a history of

Case 5
Physical exam is significant for pale sclera and an AV

Case 5
Prior labs reveal a hematocrit that was normal 4 years

Case 5
Differential Diagnosis:
Anemia of renal failure
Iron deficiency anemia
Thalassemia
Lead poisoning
Myelodysplasia
Mixed microcytic

Case 5
You order an erythropoietin level which returns at 12 IU

Case 5
You place the patient on 10,000 units of EPO SQ

Case 5
He continues on his EPO injections for four months. Soon after

Case 5
You suspect with his increased reticulocytosis and hgb/hct over the

Case 5
He again feels much improved and is tolerating the iron

Case 5: Anemia of Chronic Inflammation
Mild to moderate anemia that is

Case 5: Pathophysiology
Epo production is inhibited or decreased, so inappropriately low

Case 5: Laboratory Abnormalities
ASH SAP 5th edition

Case 5
ACI does not usually require treatment.
Iron replacement is typically

Case 6
A 53 year-old female complains of fatigue for 3 months.

Case 6
What is the most likely diagnosis?
How do you want to

Case 6
Serum protein electrophoresis (SPEP)
M- spike of 4.2 gm/dl
Immunofixation (IFE)
IgG lambda

Case 6
Skeletal survey
Multiple lytic lesions throughout the skeleton
Bone Marrow aspirate and

Case 6
An M-protein is usually seen as a discrete band on

Case 6: SPEP
NORMAL

Case 6: Myeloma
+
-
α1
α2
β
γ
*

Case 6: Density Scan
+
-
Albumin
α-1
α-2
β

Case 6
When to order an SPEP:
When you suspect multiple myeloma,

Case 6
Immunofixation (IFE):
Proteins are fractioned on electrophoretic strips:
Each lane overlaid

Case 6: Normal IFE
gamma
alpha
mu
kappa
lambda
SPE

Case 6
When to order an IFE:
To type the paraprotein (M

Case 6: Quantitative Immunoglobulins
Useful to quantitate:
The amount of monoclonal protein
Suppression

Case 6
Serum light chain assays are newer and a very sensitive

Case 6: Quantitative Immunoglobulins
+
-
Albumin
“M-spike”, “Paraprotein” or “M-
α-1
α-2
β
Note loss of normal “polyclonal”