patient problems in anemia

Patient Problems in AnemiaPatient Problems in Anemia

Mary S. Muscato, M.D., FACP

Missouri Cancer Associates

Mary S. Muscato, M.D., FACP

Missouri Cancer Associates

59 y/o woman with RA59 y/o woman with RA

59 y/o woman with a 4-year history of RA was referred for persistent anemia. She has been treated with NSAIDs, Plaquenil and methotrexate. She complains of fatigue and epigastric burning. She denied any change in bowel habits.

59 y/o woman with a 4-year history of RA was referred for persistent anemia. She has been treated with NSAIDs, Plaquenil and methotrexate. She complains of fatigue and epigastric burning. She denied any change in bowel habits.

Physical ExamPhysical Exam

Mildly weak, VS normal

Pale conjunctivae

Several actively inflamed joints

Stool heme (+)

Mildly weak, VS normal

Pale conjunctivae

Several actively inflamed joints

Stool heme (+)

WBC 4.1

Hb 8.3

Hct 24.6

MCV 78

Plt 528

Neut 77

Bands

Lymph 15

Mono 6

Eos 2

Baso

Other

MorphAniso,

poik, hypo

59 y/o woman with RA 59 y/o woman with RA


Retic count 0.7% WESR 64 CRP 1.05 (elevated) LDH 140

Retic count 0.7% WESR 64 CRP 1.05 (elevated) LDH 140

How Should we Look at this Problem?How Should we Look at this Problem?

Technically, hypochromic, “normocytic” anemia, but slide shows poik, aniso

MCV a little on the small side: consistent with iron deficiency and anemia of chronic disease (ACD)

Heme(+) stool Known RA, CRP elevated On methotrexate

Technically, hypochromic, “normocytic” anemia, but slide shows poik, aniso

MCV a little on the small side: consistent with iron deficiency and anemia of chronic disease (ACD)

Heme(+) stool Known RA, CRP elevated On methotrexate

More DataMore Data

Ferritin 36 Fe 6, TIBC 224, Sat 3% Upper endo: gastritis Soluble Transferrin Receptor (STfR) 6.1

(normal <4.5)

Ferritin 36 Fe 6, TIBC 224, Sat 3% Upper endo: gastritis Soluble Transferrin Receptor (STfR) 6.1

(normal <4.5)

DiagnosesDiagnoses

Iron deficiency (low normal ferritin, but elevated STfR)

Anemia of chronic disease Gastritis

Are we done?

Iron deficiency (low normal ferritin, but elevated STfR)

Anemia of chronic disease Gastritis

Are we done?

Try Not to Make Assumptions!Try Not to Make Assumptions!

Colonoscopy: Large adenocarcinoma in the ascending colon

Colonoscopy: Large adenocarcinoma in the ascending colon


The patient underwent a right colectomy and no other cancer was found. She did not require adjuvant chemotherapy.

She was treated with four months of oral iron on an empty stomach. Her repeat Hb rose to 10.4 and the MCV was now 85.

She still has active RA; she was started on infliximab (Remicade).

The patient underwent a right colectomy and no other cancer was found. She did not require adjuvant chemotherapy.

She was treated with four months of oral iron on an empty stomach. Her repeat Hb rose to 10.4 and the MCV was now 85.

She still has active RA; she was started on infliximab (Remicade).


Infliximab is a monoclonal antibody that binds to α-TNF (tumor necrosis factor).

Her inflammatory arthritis rapidly improved.

Over the next 2 months her Hb rose to 13.1, The MCV rose to 91, her platelets fell to 320,000, WESR and CRP fell to normal.

Infliximab is a monoclonal antibody that binds to α-TNF (tumor necrosis factor).

Her inflammatory arthritis rapidly improved.

Over the next 2 months her Hb rose to 13.1, The MCV rose to 91, her platelets fell to 320,000, WESR and CRP fell to normal.

ANEMIA OF CHRONIC DISEASE ACD is Cytokine Driven

ANEMIA OF CHRONIC DISEASE ACD is Cytokine Driven

Production of pro-inflammatory cytokines, like TNF and gamma interferon, damage erythroid progenitors

Changes in iron homeostasis

Decreased proliferation of erythroid progenitor cells

Decreased production of Epo and shortened lifespan of RBC’s

Production of pro-inflammatory cytokines, like TNF and gamma interferon, damage erythroid progenitors

Changes in iron homeostasis

Decreased proliferation of erythroid progenitor cells

Decreased production of Epo and shortened lifespan of RBC’s

Changes in Hb with RemicadeChanges in Hb with Remicade

16 y/o girl with rapid-onset anemia16 y/o girl with rapid-onset anemia


Moderately pale young woman

VS T=100.6, pulse 110

No adenopathy, splenomegaly

Petechiae on LE’s

Mildly lethargic

Moderately pale young woman

VS T=100.6, pulse 110

No adenopathy, splenomegaly

Petechiae on LE’s

Mildly lethargic

WBC 12.3

Hb 7.1

Hct 22.7

MCV 103

Plt 14

Neut 79

Bands 10

Lymph 6

Mono 3

Eos 1

Baso 1

Other3 NRBC

2 metas

MorphPoik,

aniso, 2+ schisto



Creatinine 1.3 LDH 2,800 Retic 18% PT, PTT, fibrinogen normal Haptoglobin absent Bili 2.3, mostly indirect U/A 2+ protein

Creatinine 1.3 LDH 2,800 Retic 18% PT, PTT, fibrinogen normal Haptoglobin absent Bili 2.3, mostly indirect U/A 2+ protein

Diagnosis: Thrombotic Thrombocytopenic Purpura (TTP)

Diagnosis: Thrombotic Thrombocytopenic Purpura (TTP)

Treatment begun with emergent daily plasmapheresis, aspirin, folic acid

Mental status deteriorated initially, minimal seizure activity

LDH & retic gradually dropped, plt count improved, remained with significant hemolysis

After two weeks, plasmapheresis switched to every other day. She eventually recovered and made it to the prom.

Treatment begun with emergent daily plasmapheresis, aspirin, folic acid

Mental status deteriorated initially, minimal seizure activity

LDH & retic gradually dropped, plt count improved, remained with significant hemolysis

After two weeks, plasmapheresis switched to every other day. She eventually recovered and made it to the prom.

TTPTTP

TTP is caused by a deficiency of ADAMTS-13, a metalloprotease which normally cleaves the large multimers of VWF.

The enzyme deficiency (often acquired) results in an overabundance of ultralarge VWF multimers (ULVWF).

These ULVWF bind platelets to endothelium, leaving platelet-rich microvascular thrombosis unchecked, leading to micro-thrombi and intravascular hemolysis.

TTP is caused by a deficiency of ADAMTS-13, a metalloprotease which normally cleaves the large multimers of VWF.

The enzyme deficiency (often acquired) results in an overabundance of ultralarge VWF multimers (ULVWF).

These ULVWF bind platelets to endothelium, leaving platelet-rich microvascular thrombosis unchecked, leading to micro-thrombi and intravascular hemolysis.

Alcoholic with AnemiaAlcoholic with Anemia


42 y.o. man, alcoholic, history of GI bleeds Recently drinking, presents with abd pain PMH: total gastrectomy 20 years before for

hemorrhagic gastritis PE: Anicteric, spiders, liver 14 cm, spleen

down 3 cm Stool heme (+)

42 y.o. man, alcoholic, history of GI bleeds Recently drinking, presents with abd pain PMH: total gastrectomy 20 years before for

hemorrhagic gastritis PE: Anicteric, spiders, liver 14 cm, spleen

down 3 cm Stool heme (+)

WBC 3.4

Hb 9.8

Hct 30

MCV 94

Plt 71

Neut 67

Bands 3

Lymph 18

Mono 10

Eos 2

Baso

Other

MorphMacro, aniso, targets

CBCCBC


Retic 1.6% Ferritin 133 Folate 2.6 RBC Folate 122 (nl 200-700) Creat 1.3 Bili 1.8 LDH 1100

Retic 1.6% Ferritin 133 Folate 2.6 RBC Folate 122 (nl 200-700) Creat 1.3 Bili 1.8 LDH 1100


Because of the pancytopenia, confusing MCV, and concern re mixed anemia, a bone marrow aspirate and biopsy was done.

Bone marrow showed

–megaloblastic changes

– absent iron stores

– normal megakaryocytes

Because of the pancytopenia, confusing MCV, and concern re mixed anemia, a bone marrow aspirate and biopsy was done.

Bone marrow showed

–megaloblastic changes

– absent iron stores

– normal megakaryocytes


Colonoscopy normal B12 level 153 (nl 211-911) Causes of anemia:

– History of bleeding: iron loss

– Gastrectomy: loss of IF, loss of iron absorption, change in mucosa

– Folate lack from not eating broccoli

RX: B12, folate, iron and stop drinking!

Colonoscopy normal B12 level 153 (nl 211-911) Causes of anemia:

– History of bleeding: iron loss

– Gastrectomy: loss of IF, loss of iron absorption, change in mucosa

– Folate lack from not eating broccoli

RX: B12, folate, iron and stop drinking!

57 y.o. Man with Erythrocytosis57 y.o. Man with Erythrocytosis


A 57 y.o. man is referred for erythrocytosis. His history is pertinent for malaise and pruritis. His wife has noticed that he appears plethoric. He has smoked 1 ½ ppd for 35 years.

P.E. Plethoric. Decreased breath sounds. Cardiac exam normal. No hepato-splenomegaly.

A 57 y.o. man is referred for erythrocytosis. His history is pertinent for malaise and pruritis. His wife has noticed that he appears plethoric. He has smoked 1 ½ ppd for 35 years.

P.E. Plethoric. Decreased breath sounds. Cardiac exam normal. No hepato-splenomegaly.

WBC 13.1

Hb 19.8

Hct 59.5

MCV 91

Plt 450

Neut 78

Bands 1

Lymph 12

Mono 4

Eos 2

Baso 3

Other

Morph Normal

CBCCBC


Retic 2.3% ABG: pH 7.41, pO2 85, pCO2 38, O2 sat 94% B12 level 1235 LAP 112 Red cell mass: 34 ml/kg, plasma volume

normal Erythopoetin: 2 (nl 4-19)

Retic 2.3% ABG: pH 7.41, pO2 85, pCO2 38, O2 sat 94% B12 level 1235 LAP 112 Red cell mass: 34 ml/kg, plasma volume

normal Erythopoetin: 2 (nl 4-19)


Diagnosis: Polycythemia Vera Confirmatory genetic testing: JAK2, positive (Official Symbol: JAK2 and Name: Janus

kinase 2 (a protein tyrosine kinase) -Chromosome: 9; Location: 9p24)

Treatment: phlebotomy to normal hematocrit, aspirin, possibly hyrdoxyurea

Diagnosis: Polycythemia Vera Confirmatory genetic testing: JAK2, positive (Official Symbol: JAK2 and Name: Janus

kinase 2 (a protein tyrosine kinase) -Chromosome: 9; Location: 9p24)

Treatment: phlebotomy to normal hematocrit, aspirin, possibly hyrdoxyurea

56 y/o with intermittent anemia56 y/o with intermittent anemia


A 56 y/o woman presents with a mild anemia. History reveals that she was once told by a doctor that she might have had some jaundice. Generally healthy, no infections.

FH + for her 86 y/o mother diagnosed last year with massive splenomegaly and Hb 6. Thought to be MDS, but she clinically improved.

PE normal except spleen tip palpable.

A 56 y/o woman presents with a mild anemia. History reveals that she was once told by a doctor that she might have had some jaundice. Generally healthy, no infections.

FH + for her 86 y/o mother diagnosed last year with massive splenomegaly and Hb 6. Thought to be MDS, but she clinically improved.

PE normal except spleen tip palpable.

WBC 4.6

Hb 10.7

Hct 33.1

MCV 104

Plt 152

Neut 67

Bands

Lymph 18

Mono 10

Eos 3

Baso 2

Other

MorphMacro,

polychromasia

CBCCBC

Peripheral SmearPeripheral Smear

Some polychromasia seen. Hematologist noted normocytic spherocytes. No poikilocytosis.

Some polychromasia seen. Hematologist noted normocytic spherocytes. No poikilocytosis.


Retic count 11.2% MCHC elevated Bili 2.2, 1.8 Indirect LDH 317 Haptoglobin normal Nuclear Medicine liver-spleen scan shows

only minimal splenomegaly Direct Coombs negative

Retic count 11.2% MCHC elevated Bili 2.2, 1.8 Indirect LDH 317 Haptoglobin normal Nuclear Medicine liver-spleen scan shows

only minimal splenomegaly Direct Coombs negative


Osmotic fragility ordered. Returns showing increased osmotic fragility, consistent with hereditary spherocytosis.

The patient’s mother had come with her; she was re-examined. Spleen now only 6 cm and Hb back up to 11.0! Peripheral smear: spherocytes.

Her son was also in the exam room. His smear also showed spherocytes.

(This is a true story!)

Osmotic fragility ordered. Returns showing increased osmotic fragility, consistent with hereditary spherocytosis.

The patient’s mother had come with her; she was re-examined. Spleen now only 6 cm and Hb back up to 11.0! Peripheral smear: spherocytes.

Her son was also in the exam room. His smear also showed spherocytes.

(This is a true story!)

29 y.o. G3P2 woman with anemia29 y.o. G3P2 woman with anemia


29 y.o. African-American woman is referred during the 5th month of her 3rd pregnancy.

Pregnancy has been uncomplicated, as have her previous pregnancies.

She has been faithfully taking her prenatal vitamins.

P.E. normal; uterine size 22 weeks.

29 y.o. African-American woman is referred during the 5th month of her 3rd pregnancy.

Pregnancy has been uncomplicated, as have her previous pregnancies.

She has been faithfully taking her prenatal vitamins.

P.E. normal; uterine size 22 weeks.

WBC 6.5

Hb 8.8

Hct 24

MCV 78

Plt 340

Neut 65

Bands

Lymph 24

Mono 9

Eos 2

Baso

Other

MorphMicro, targets

CBCCBC


Retic 2.1% Ferritin 140 Fe/TIBC 110/290 STfR 2.9 (normal) Hb electrophoresis normal: A2 and F not

elevated Cord blood at time of delivery showed Hb

Bart’s (tetramers of γ-chains)

Retic 2.1% Ferritin 140 Fe/TIBC 110/290 STfR 2.9 (normal) Hb electrophoresis normal: A2 and F not

elevated Cord blood at time of delivery showed Hb

Bart’s (tetramers of γ-chains)

Globin Chain DimersGlobin Chain Dimers

A1 A2 F

α

β

γ

δ

Summary: Anemia for M3sSummary: Anemia for M3s

Always pay attention to:

– History, PE: do they fit?

– Peripheral smear

– Retic

–MCV

– LDH, bili

– Blood in stool or urine

Always pay attention to:

– History, PE: do they fit?

– Peripheral smear

– Retic

–MCV

– LDH, bili

– Blood in stool or urine

patient problems in anemia

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