Approach to

Anemia
Group 5
Dr. Madelaine Cosing
Patient C.S.
71/M, hypertensive,
known Prostate CA St. IV
(bone)
Chief Complaint: Hematuria
 History of Present Illness

No trauma, fever,
dysuria, frequency,
urgency, flank pain,
lightheadedness,
mucosal bleeding,
melena, hematochezia,

Hypogastric pain (7/10)

Hematuria

3 weeks
 History of Present Illness

No trauma, fever,
dysuria, frequency, Decreasing appetite
urgency, flank pain,
lightheadedness, Easy fatigability
mucosal bleeding,
melena, hematochezia, Decreasing urine output

Hypogastric pain (7/10)

Hematuria

3 weeks Interim
 History of Present Illness
ER Consult
Clearing of UO
No trauma, fever, via FC
dysuria, frequency, Decreasing appetite UA: Blood
urgency, flank pain, 3+/Leuk
lightheadedness, Easy fatigability trace/R42 W5
mucosal bleeding, E1 C2 B0
melena, hematochezia, Decreasing urine output DAMA

Hypogastric pain (7/10) Dysuria

Hematuria

3 weeks Interim 4 days

 History of Present Illness
ER Consult
Clearing of UO
No trauma, fever, via FC
dysuria, frequency, Decreasing appetite UA: Blood
urgency, flank pain, 3+/Leuk
lightheadedness, Easy fatigability trace/R42 W5
mucosal bleeding, E1 C2 B0
melena, hematochezia, Decreasing urine output DAMA

Hypogastric pain (7/10) Dysuria

Hematuria

3 weeks Interim 4 days DAY OF

CONSULT
 Past Medical History
● HASCVD s/p ACS NSTEMI s/p PCI 2 vessels (2019)
○ UBP 120/80, HBP 140
○ Enalapril 5mg BID, Carvedilol 6.25mg BID, Atorvastatin 40mg OD,
Aspirin 80mg OD (last dose 5 days PTA)
● Prostate adenocarcinoma Stage IV (bone) (2020) s/p TURP
(07/2020), orchiectomy, bilateral (09/2020)
● No DM, Bronchial Asthma, PTB, Blood dyscrasia, Nephrolithiasis
● No recent hospitalization
● No recent antibiotic use
● No chronic NSAID use
 Family History
● Prostate CA, Breast CA, Colon CA (cousins)
● Hypertension (mother)
● No DM, kidney disease, blood dyscrasia
 Personal & Social History
● Non smoker
● Non alcoholic beverage drinker
● Jehovah’s witness
 Review of Systems
(+) Palpitations
Generally unremarkable
Physical Exam
Vital Signs:
HR78 BP 110/70 Temp 37.5 RR 20 O2sat: 99% @RA

Anthropometric Measure
Height: 163cm Weight: 54 kg BMI: 20.3 = Normal

General: Patient is a alert, conscious, coherent, not in respiratory distress. Thought

processes are coherent, insight is good. The patient is oriented to person, place, and
time.
 Physical Exam
● Pale palpebral conjunctivae, Additional Assessment:
anicteric sclera
● Eyes: sunken?
● No neck vein distention
● Skin & Mucous membranes:
● Clear breath sounds dry? Pale? Skin turgor?
● Normal rate, regular rhythm ● Genital exam
● Peripheral pulses: absent,
● Abdomen soft nontender
thready, strong?
● (+) foley catheter in place with ● Capillary refill time
dark red urine output
● No bipedal edema
Salient Features
 SUBJECTIVE OBJECTIVE

● 71/M ● (+) dark red urine output on FC

● Hypertensive, known Prostate CA St. IV, ● Pale palpebral conjunctivae
s/p TURP, orchiectomy, bilateral (2020) ● Urinalysis at ER: hematuria
● Jehovah’s witness
● 3 week history of hematuria
○ Associated with hypogastric pain,
oliguria, and dysuria
● (+) Easy fatigability, palpitations
● On Aspirin 80 mg OD

● No trauma, fever, frequency, urgency, flank ● Alert, conscious, coherent, not in

pain, dizziness, lightheadedness, mucosal respiratory distress
bleeding, melena, hematochezia ● VS: 110/70, 78, 20, 37.5C, 99%
● No personal history and family history of
blood dyscrasia
Approach to
Anemia
 Anemia
Reduction in one or more of the major red blood cell
measurements obtained as a part of the complete blood count:
hemoglobin concentration, hematocrit or RBC count

WHO:
Adult Males - Hgb <13 g/dL or Hct <39%
Adult Females - <12 g/dL or Hct <37%
Approach to
Anemia
History and Physical
Examination
Approach to
Anemia
Laboratory Evaluation
Approach to
Anemia
Approach to
Anemia
Approach to
Anemia
Approach to
Anemia
CBC ON ADMISSION
CBC: 6.4/18.6/2.16/6710/N72-L16-E3-M9/419k/86-30-34/14.7

Low hemoglobin

Low hematocrit

Low RBC

Normal WBC

Normal Platelet

Normocytic

Normochromic
Approach to Anemia
Differential
Diagnosis
 Anemia Secondary
Blood loss
MORE LIKELY LESS LIKELY

● Hematuria ● Normal RDW

● (+) dark red urine output on FC
● Normocytic normochromic
● Prostate Cancer Stage IV
 Anemia of Chronic
Disease
MORE LIKELY LESS LIKELY

● Normocytic, normochromic
● Normal RDW
● Prostate Cancer Stage IV
● Elderly
● Hospitalized
 Anemia Secondary to
poor oral intake
MORE LIKELY LESS LIKELY

● (+) Decreased appetite ● Normocytic

● (+) Easy fatigability, ● Normochromic
palpitations
● (+) increased requirement
secondary to hematuria
 Anemia Secondary to
Infection
MORE LIKELY LESS LIKELY

● Hematuria ● Not elevated WBC

● Dysuria
● Normocytic normochromic
 Anemia s/t
Acute Blood Loss
with contributory

Anemia of Chronic Disease

& poor oral intake
PRIMARY IMPRESSION
Diagnostics
 Complete blood count
● Hemoglobin
● Hematocrit
● RBC count
● Red blood cell indices
○ MCV
○ MCHC
○ MCH
● WBC count and differential
● Platelet count
 CBC of the patient
6/18 6.5/ 18.9/ 2.16/ 9340/ N77 L15 E1 M7/ 446k/ 88-30-34/ 15.2
6/15 PM 7.2/ 22.3/ 2.49/ 8500/ N75 L13 E4 M8/ 425k/ 90-29-32/ 15.7
6/15 AM 6.4/18.6/2.16/6710 N72 L16 E3 M9/ 419k/86-30-34-14.7
6/14 6.9/19.2/2.29/6,430/N71 L17 E1 M11/358k/84-30-36/13.7
6/13 6.9/19.9/2.35/6380/N74 L16 E2 M8/383k/85-29-35/14.4
●
Reticulocyte count
Reticulocyte Production Index:
○ Correction #1: corrected reticulocyte count
■ cRC = reticulocyte% x (Hgb/15) OR
(Hct/45)
○ Correction #2: Reticulocyte Production Index
■ Need to examine peripheral blood smear
for prematurely released reticulocytes or
“shift cells”
■ RPI = cRC/maturation time correction
(usually 2)
 Peripheral Blood Smear
● Defects in red cell production
● Variations in cell size (anisocytosis)
● Variations in shape (poikilocytosis)
 Iron supply studies

Serum Iron Transferrin Saturation

Topic of the section
(Tsat)
Topic of the section

Total Iron-binding Serum Ferritin

Capacity Topic of the section
Topic of the section
 ● Represents the amount of circulating iron bound to
Serum Iron ●
transferrin.
Normal range: 50-150 ug/dL

● An indirect measure of the circulating

transferrin.
Total Iron-binding ● Normal range: 300-360 ug/L

Capacity
 ● Calculated by (serum iron / TIBC) x100
T-saturation ●
●
Normal range: 25-50%
Iron deficiency states associated with levels <20%

● Correlates with the total body iron stores under

steady-state conditions.
○ The most convenient test to estimate iron stores
Serum Ferritin ● Men: 100 ug/L, Women: 30 ug/L
● Acute phase reactant
Hematologic studies
Urinalysis and ● Complicated UTI
Urine culture

Renal (Creatinine, ● Possible acute kidney injury

secondary to hypoperfusion
BUN)

Assesses hydration, kidney, heart,

Electrolytes ●
and other metabolic conditions.
 Course in
the Wards
06-14-2021: Patient admitted under the service of Dr. Perez. Consents signed and secured for contemplated procedure.
Patient hooked to IV and laboratories done. Noted bloody output on catheter initially which cleared once started on
cystoclysis. Noted fever of 38.1C at 2000H.
CXR: 6/14 No focal opacities | CBC: 6.9/19.2/2.29/6,430/N71 L17 E1 M11/358k/84-30-36/13.7
Bleeding time 5 min (N); PT 11.6/12.3 INR 1.03 PTT 35.7 | Na 132 K 4.2 | Crea 0.80 (0.88) BUN 8 | NT-proBNP 179
ECG: SR (HR=83) ; NSSTWC

06-15-2021: Patient seen awake, comfortable no in distress. No difficulty breathing, chest pain, abdominal pain, no recurrence
of epigastric pain. Cystoscopy, fulguration of bleeders and transverse urethral resection of intravesical prostate done. Patient
tolerated the procedure well.
Procedure: Cystoscopy, Fulguration of Prostatic Bleeders; Transurethral Resection of Prostate in Saline
OR Time: 33min
EBL: 5ml
BP Range 130-90/65-85 | HR Range: 80-100
No episodes of hypotension, arrhythmia or desaturations.
IOF: Smooth urethral mucosa; enlarged poorly define prostatic lobe with TURP defect and areas of bleeding from the
intravesical extension of known prostatic tumor; moderately trabeculated bladder walls; no intravesical lithiasis seen.

CBC: 6.4/18.6/2.16/6710/N72-L16-E3-M9/419k/86-30-34/14.7
CBC: 7.2/ 22.3/ 2.49/ 8500/ N75 L13 E4 M8/ 425k/ 90-29-32/ 15.7 | Na 133 K 4.0 (0400H) | Na 139 K 3.8 | Crea 0.77

06-16-2021: Day 1 s/p cystoscopy, fulguration of bleeders with transurethral resection of prostate. Patient seen awake,
comfortable, soft abdomen with noted flatus. Still with no bowel movement hence started on lactulose. No recurrence of
febrile episode. Foley catheter in place with clear output on slow clysis.
06-17-2021: Day 2 s/p cystoscopy, fulguration of bleeders with transurethral resection of prostate. Patient seen awake, not in
distress. No nausea, vomiting. Noted flatus and bowel movement. Stable vital signs. Abdomen soft, nontender. Foley catheter in
place with clear output on moderate to slow clysis. Noted febrile episode of 38C at 2000H

06-18-2021: Day 3 s/p cystoscopy, fulguration of bleeders with transurethral resection of prostate. Patient seen awake, comfortable
with good pain control. Continued monitoring for fever episodes and present management.
CBC: 6.5/ 18.9/ 2.16/ 9340/ N77 L15 E1 M7/ 446k/ 88-30-34/ 15.2
CXR: No acute infectious process or consolidation. Atheromatous aorta. Degenerative osseous changes
Total testosterone: <10.00 | Total PSA: 170.80
Histopath: Prostatic adenocarcinoma, Gleason score 4+4=8, prognostic grade group IV/V, involving 100% of the tissues examined

06-19-2021: Day 4 s/p cystoscopy, fulguration of bleeders with transurethral resection of prostate. Patient seen awake, comfortable,
not in distress. Good pain control. Last fever 12 midnight (38C). Started on Forgram 2g IV.
UA: Smokey red/Cloudy/1.007/6.5 (acidic)/Total protein 30mg/dl (1+)/Blood large (3+)/Leukocytes small (1+)/NUBKG Negative/R485
W11 E1 C0 B146 Isomorphic

06-20-2021: Day 5 s/p cystoscopy, fulguration of bleeders with transurethral resection of prostate. Seen awake, comfortable, with
good pain control. D1 Afebrile since 12 midnight last June 19. Foley catheter clear output and off clysis. Patency assured. No
recurrence of leak from midnight and no clots noted. Patient remained stable hence deemed fit for discharge. Advised on follow up
schedule and medications.
 Anemia s/t
1) Hematuria s/t tumoral bleed
2) Chronic Disease
FINAL DIAGNOSIS
 Case
Discussion
 Normal Red Cells
● O2 is transported to tissues bound to Hb within circulating red cells
● Mature red cell:
○ 8 μm diameter
○ anucleate, discoid in shape
○ extremely pliable
● Daily replacement of 0.8-1%
● Average lifespan 100-120 days
Hematopoiesis and Red Cell Production
Hematopoiesis
● Process by which formed elements in
blood are produced
Erythropoietin (EPO)
● Key regulator for red cell production
● Produced and released in kidneys
(majority) and hepatocytes
● Requires adequate nutrients (iron,
folate, B12)
 WHO Definition of Anemia
● Hemoglobin level <130 g/L (13g/dL) in men
● Hemoglobin level <120 g/L (12g/dL) in women

CBC: 6.4/18.6/2.16/6710/N72-L16-E3-M9/419k/86-30-34/14.7
Normocytic Normochromic Anemia
 Compensatory Response to Anemia
Anemia developing over a period of days or weeks

● Total blood volume normal or slightly inc.

● Compensation from CO and regional blood flow

With chronic anemia

- Intracellular levels of 2,3-DPG rise

- Shift to the right for O2 unloading
- Only maintain normal O2 delivery in deficit of Hb 2-3 g/dL

Further protection to vital organs

- Blood shunted away from organs with rich blood supply

 Clinical Manifestations
Acute anemia with acute blood loss

Total Blood Volume Loss Manifestations

10-15% ● Hypotension
● Decreased organ perfusion

>30% ● Prefer supine position

● Postural hypotension
● Tachycardia

>40% ● Signs of hypovolemic shock

 Clinical Manifestations
Symptoms of moderate anemia
● Fatigue
● Loss of stamina
● Breathlessness
● Tachycardia (w/ physical exertion)
May not be associated with signs or symptoms until anemia is
severe (Hb 7-8 g/dL)
Mechanisms of Anemia in Cancer
● Blood loss that is either intrinsic or iatrogenic
● Nutritional deficiencies involving primarily iron or folic acid
● Hemolysis (autoimmune, traumatic, or drug-induced)
● Bone marrow failure due to tumor encroachment,
myelofibrosis, or marrow necrosis
● Infection
● Inflammation
● Presence of a cancer elsewhere in the body

Patients with cancer have anemia that is typically normocytic and

normochromic.
Spivak JL. Cancer-related anemia: its causes and characteristics. Semin Oncol. 1994 Apr;21(2 Suppl 3):3-8. PMID: 8202724
 Mechanisms of Anemia in Cancer
Prostate Adenocarcinoma Stage IV
(2020) (bone) initially presenting as
difficulty voiding s/p TURP and
Surgical orchiectomy, bilateral
(2020), no prior RT or chemotherapy

May be due to production of

inflammatory cytokines→ blunt
ability of bone marrow to respond
to the available circulating EPO

Spivak JL. Cancer-related anemia: its causes and characteristics. Semin Oncol. 1994 Apr;21(2 Suppl 3):3-8. PMID: 8202724
 Mechanisms of Anemia in Cancer

Busti F, Marchi G, Ugolini S, Castagna A, Girelli D. Anemia and Iron Deficiency in Cancer Patients: Role of Iron Replacement Therapy. Pharmaceuticals (Basel).
2018;11(4):94. Published 2018 Sep 30. doi:10.3390/ph11040094
 Anemia s/t hematuria sec to tumoral bleed
● Hematuria and other sources of slow blood loss can also
contribute to anemia in men with advanced prostate cancer.

● Hematuria is caused by internal growth of the prostate into

the urethra or growth of metastatic deposits within the wall
of the bladder

Nalesnik JG, Mysliwiec AG, Canby-Hagino E. Anemia in men with advanced prostate cancer: incidence, etiology, and treatment. Rev Urol. 2004;6(1):1-4.
 Anemia s/t chronic disease
● Anemia of chronic disease (ACD) or anemia of chronic
inflammation is the most common cause of anemia in
admitted patients

● ACD in cancer results from activation of the immune and

inflammatory systems, leading to excessive release of
several cytokines and acute-phase proteins

● Low serum iron and a normal or increased serum ferritin

 Anemia s/t chronic disease
Overproduction of cytokines:
● (1) iron metabolism abnormalities
and impaired iron utilization
● (2) inadequate erythropoietin (EPO)
production and a blunted erythroid
progenitor response to EPO
● (3) reduction in red-cell survival
● (4) impaired proliferation and
differentiation of erythroid
progenitor cells

Grotto HZ. Anaemia of cancer: an overview of mechanisms involved in its pathogenesis. Med Oncol. 2008;25(1):12-21. doi: 10.1007/s12032-007-9000-8. Epub 2007
Sep 2. PMID: 18188710
 s/p Surgical orchiectomy, bilateral (2020)
● Castration is a well-documented cause of anemia
○ Testosterone is required for the enhancement of erythropoietin
formation in the kidney, as well as for the marrow action of
erythropoiesis
● Red blood cell mass decreases 10%, red blood cell diameter
decreases 40%, and osmotic fragility increases

Nalesnik JG, Mysliwiec AG, Canby-Hagino E. Anemia in men with advanced prostate cancer: incidence, etiology, and treatment. Rev Urol. 2004;6(1):1-4.
 Complications
● AKI at risk sec to renal hypoperfusion from anemia
● Cardiovascular complications
Treatment
 Oral vs IV
ORAL IRON INTRAVENOUS IRON
● Only form of iron available in ● Patients who are unable to tolerate
under-resourced areas gastrointestinal side effects of oral
● Avoids the need for IV access and iron
monitored infusion ● Severe/ongoing blood loss
● Eliminates the potential for infusion ● Gastric surgery (bypass, resection)
reactions or anaphylaxis that reduces gastric acid
● Generally used for infants, children, ● Malabsorption syndromes
and adolescents
 Treatment

Intravenous (IV) iron administration

Oral iron provides an inexpensive
helps in correction of anemia, in the
and effective means of restoring
prevention of exacerbation of
iron balance in a patient with iron
anemia, in decreasing blood
deficiency without complicating
transfusion rates, and in increasing
comorbid conditions
survival of cancer patients

Iron Sucrose Infusion Ferrous Sulfate

 Therapeutic
Approach to
Anemia
Secondary to
Blood Loss
 Transfusion Investigation
Ideal first step
Especially in severe anemia Determine cause of
( Hb <7) anemia
1 pRBC= 1g/dL rise in Treat underlying condition
hemoglobin
NOT allowed in the patient
Treatment Dilemmas

What to do if we cannot transfuse blood?

Should we still give iron supplements even if

ferritin levels are high?

What is our long term treatment plan for the

patient’s anemia in the context of prostate
cancer?
What if we can’t transfuse blood?
Jehovah’s Witness with
Severe Anemia
Hb < 7 g/dL

Evaluate for critical anemia Initiate Anemia

● ABG (lactate and base deficit) Protocol
● Hemodynamic instability
(shock, hemorrhage)
● Check for cardiac ischemia

Critical Anemia
Hemoglobin Based
Non Critical but Hb <5
Oxygen Carrier (HBOC)
HBOC Treatment
treatment + Hemopure
(1 unit IV over 4 hrs)

Posluszny, J. A., & Napolitano, L. M. (2014). How do we treat life-threatening anemia in a Jehovah’s Witness patient?
Transfusion, 54(12), 3026–3034. doi:10.1111/trf.12888
 ANEMIA PROTOCOL
Erythropoietin B12
Stimulating Oral or IV

Agent Folate
1 mg PO or IV QD
Epoetin alfa
40,000 units IV or SQ daily until Hb > 7 g/dL
Then weekly
Vitamin C
Iron 500 mg TID
Except in renal failure
100 mg iron sucrose IV daily for 10 days min
Then convert to oral iron supplementation
Should we Yes!
Optimizes hematologic response
give iron?
 How do we NO CHANGE IN
manage anemia MANAGEMENT
ESA
secondary to
cancer?
 MANAGEMENT PRINCIPLES
• Monitor Hb and methemoglobin daily with blood gas
(0.3 ml)

• Control any bleeding + correct coagulopathy

(tranexamic acid, recombinant factor VIIa,
prothrombin complex concentrate)
 MANAGEMENT PRINCIPLES
• Reduce oxygen consumption (control fever,
tachycardia, agitation, work of breathing, etc.)

• Supplemental oxygen to maintain saO2 > 95%

 MANAGEMENT PRINCIPLES
• Optimize ionized calcium (1.2-1.3)

• Avoid hemodilution, diuresis if possible to

achieve hemoconcentration