Hematology for Family

Practice
When to treat and when to
refer
Karen deGenevieve MSN, FNP,BC OCN
 Objectives:
1. Identify types of anemia's by
analyzing indices, and appropriate
tests.
2. Understand manual differential and
terminology.
3. Discuss abnormalities in platelets and
white cells, and determine
appropriate testing.
 Objectives continued:
4. Discuss treatment options for
hematologic conditions and
medication management.

5. Know when to refer.

1. Anemia's and
Erythrocytosis

2. Low platelets and High

platelets

3. Leukopenia's and
Leukocytosis
 How long do cells live?
• Red blood cells live approximately 120
days.

• Platelets live 8 -11 days.

• White blood cells live about 4 days.

 There are millions of RBCs in just
one drop of blood. People who
live at higher altitudes have more
(like in the mountains of Peru).
They are produced in the bone
marrow of large bones at a rate of
2 million per second. In the minute
it took you to read this, you made
120 million of them!
 Anemia’s
And Erythrocytosis
First thing to do with an abnormal CBC is to repeat it
and get a smear to pathology, manual diff, and
reticulocyte count.

MICROCYTOSIS:

Low MCV (mean corpuscular volume) under 80.

Low MCH (mean corpuscular hemoglobin) under 27.
Low MCHC (mean corpuscular hemoglobin concentration) under 30.

MACROCYTOSIS:
High MCV over 93
High MCH over 33
High MCHC over 37

NORMOCYTIC ANEMIA: NOMAL INDICIES

 DEFINITIONS
Reticulocyte: The youngest of the circulating red cells,
normally they comprise about 1% of the red cell population.
They are increased in response to bleeding, or hemolysis, or
in response to treatment with B 12, iron, of folic acid.
Decreased in the presence of a suppressed or otherwise
abnormal bone marrow, aplastic anemia, pure red cell
aplasia or following chemotherapy.

Nucleated red blood cells: Are NORMOBLASTS. Are not

normally seen in peripheral blood. They usually indicate the
presence of severe degrees of hemolysis, profound stress,
hypoxemia, or myelofibrosis.

Erythrocyte: A mature red blood cell that contains

hemoglobin, confined within a lipid membrane, it’s main
purpose is to transport oxygen.
Leukocyte: Is a white blood cell. 5 types of leukocytes are
classified by the presence or absence of granules in the cytoplasm
of the cell. The agranulocytes are lymphocytes and monocytes.
The granulocytes are neutrophils, basophils, and eosinophil's.

Leukocytes function as phagocytes of bacteria, fungi, and viruses,

detoxifiers of toxic proteins that may result from allergic reactions
and cellular injury, and immune system cells.

Platelet: The smallest cells in the body, they are formed in the
bone marrow and some are stored in the spleen, they do not
contain hemoglobin and are essential for the coagulation of blood
and in maintenance of hemostasis.
 Anemia Testing
Click here for topics associated with this algorithm

INDICATIONS FOR TESTING

Fatigue, weakness, pallor, dizziness, fainting

ORDER
CBC with Platelet Count and Automated
Differential (including RBC indices and
morphology on manual differential)
Reticulocytes, Percent & Number

Anemia present on CBC (males Hgb <13g/dL,

females Hgb <12g/dL)
AND
Corrected reticulocyte index ≥2.5

No Yes

Classify by RBC indices Fragmented cells on

peripheral smear

Normocytic, normochromic Microcytic, hypochromic Macrocytic Yes

(normal MCV, MCHC) (low MCV, MCHC) (high MCV) No
(suggests hemolysis)
(suggests hypoproliferation) (suggests maturation defects) (suggests maturation defects)

B12 deficiency, (less Suggests Metabolic defect (see PNH

Bone marrow disorder acute blood Consult topic)
(infiltration, aplasia) commonly folate
deficiency) – see loss (eg, Hemoglobinopathies (eg,
Inflammation Iron deficiency hemmorhage) sickle cell) – see Hemolytic
Autoimmune disease Megaloblastic Anemia
Chronic disease Testing Algorithm Anemias Testing Algorithm
Chronic renal disease Thalassemia – see Autoimmune destruction
Critical illness Drug effect
Hemoglobinopathies topic Excessive alcohol use Splenic sequestration
Chronic endocrine Sideroblastic anemia RBC membrane defect – see
disorders Hypothyroidism
Lead toxicity Myelodysplasia – see Hemolytic Anemias Consult
Aplastic anemia, pure topic
red cell aplasia Myelodysplastic
Syndromes Consult topic Intravascular hemolysis –
see Hemolytic Anemias
Consult topic
Abnormal peripheral smear

ORDER No
Iron and Iron Binding
No Yes
Capacity
Ferritin
Vitamin
B12 &
Folate
High TIBC Low/normal TIBC Workup based on
Low iron Normal/high ferritin smear
Low ferritin Low/normal iron characteristics

Abbreviations and Formula

Suggests Bone marrow MCV = mean cell volume

Iron deficiency
Inflammation biopsy may be MCHC = mean cell hemoglobin concentration
anemia
Chronic disease necessary TIBC = total iron binding capacity
Thalassemia
Reticulocyte correction for anemia:

If no obvious chronic disease present, Hgb 1 _

consider bone marrow biopsy; for ReticCount% x Htc x Maturation time correction
Thalassemia suspicion, consider (use 2% for most patients)
hemoglobin electrophoresis

© 2006 ARUP Laboratories. All Rights Reserved. 02/09/2015 www.arupconsult.com

 Red Cell Morphology and associated Conditions

Auer Rods: observed in Blasts associated with AML

Acanthocytosis (spur cells): Alcoholic cirrhosis, post splenectomy,
hemolytic anemia
Anisocytosis: Various types of anemia
Basophilic Stippling: Fine: various anemias Course: lead toxicity
and thalassemias
Bite Cells: Chemical poisoning, G-6PD deficiency, hemolytic
anemia
Burr Cells: Myeloproliferative states, heparin therapy, uremia,
Chronic renal disease, bleeding, peptic ulcers
Howell-Jolly bodies: Post Splenectomy, megaloblastic and
hemolytic anemias
Hypochromia: Iron deficiency and thalassemia
Hypersegmented neutrophils: megaloblastic anemias, pernicious,
B12, and folate deficiencies
Heinz bodies: G-6PD deficiency, thalassemia
Pelger-Huet: myelogenous leukemia
Dohle bodies: (toxic granulation are usually seen together) Acute
infection, pneumonia, scarlet fever, measles,
septicemia, pregnancy, burns
Reactive lymphocytes: (Downey cells) mono, CMV, viral hepatitis,
chronic inflammatory disease
Smudge Cells: atypical lymphocytosis, CML
Schistocytosis: cardiac valve disease, DIC, severe burns, uremia
Spherocytes: (helmet cells) hereditary spherocytosis, thermal
injuries, immune and hemolytic diseases, TTP, DIC
Rouleaux: multiple myeloma, elevated protein
Target cells: chronic liver disease, iron deficiency, post splenectomy
Tear drop cells: Thalassemias, pernicious anemia, Myeloproliferative
disorders.

Band Neutrophils: normal 5-11% increased # = LEFT SHIFT (stress,

infection, Myeloproliferative disease)
Basophils: <2% are normal. Allergic reaction, hypothyroid, chronic
hemolytic anemia, post splenectomy
Eosinophils: increased in asthma, hay fever, extensive skin lesions,
parasitic infections. Decreased in shock, severe burns,
and severe infections.
Metamyelocyte: Myelocytic hyperplasia
Myelocyte: CML, AML
Plasma cells: Not usually seen in peripheral blood. Chronic
infections, autoimmune disorders, alcoholic liver disease.
Monocytes: increased in chronic neutropenia, IBD, chronic infection,
CMV, TB an can be elevated in AMML.

Evaluating Anemia

Number one reason for microcytic anemia is bleeding, either GU

or GI. Ask the right questions. A good physical exam and a
good history is essential to your investigation. Don’t forget family
history.
 Megaloblastic Anemia Testing
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INDICATIONS FOR TESTING

Patient presents with megaloblastic anemia and/or neurologic symptoms

ORDER
Vitamin B12
Folate (for patient with known risk factors)

Vitamin B12 >400 pg/mL Vitamin B12 100-400 pg/mL Low folate levels only Low or normal folate
Vitamin B12
levels and high suspicion
<100 pg/mL
for deficiency

Folate deficiency Low

ORDER
Occasionally, clinician may Methylmalonic Acid, Serum
find normal levels of B12 in ORDER
or Plasma (Vitamin B12
symptomatic patients (usually Folate, RBC
Status)
neurologic symptoms) No
B12 deficiency Normal
folate deficiency
MMA and homocysteine may
be appropriate to confirm B12 <0.4 µmol/L >0.4 µmol/L
deficiency, as homocysteine
may have a role in detecting
folate or B12 deficiency Not
pernicious
anemia

ORDER Optional antibody testing when MMA >0.4 µmol/L

Methylmalonic Acid, Serum or
(MMA >0.4 µmol/L confirms B12 deficiency )
Plasma (Vitamin B12 Status)
Homocysteine, Total
ORDER
Intrinsic Factor Blocking Antibody

Both elevated
Positive Negative

Pernicious ORDER
Confirmed B12 anemia Gastric Parietal Cell
deficiency Antibody, IgG

Positive Negative

Pernicious ORDER
anemia Gastrin

<100 pg/mL >100 pg/mL

Not pernicious Pernicious anemia

anemia (indirect confirmation)

© 2006 ARUP Laboratories. All Rights Reserved. Revised 02/09/2015 www.arupconsult.com

Iron preparations:
Ferrous gluconate orally is less likely to cause GI upset and is
more tolerated than ferrous sulfate. It is equally absorbable with
less side effects. Comes in may strengths and is generally OTC.
Severe iron deficiency may require 325 mg TID. Most patients
don’t take it as directed for a variety of reasons. Nausea and
constipation are the biggest reasons.

I never order ferrous sulfate, for those reasons.

There are many conditions that can interfere with oral iron
absorption and or cause iron deficiency:

Being older, poor tolerance of oral iron preparations

Inflammatory bowel disease, ulcerative colitis
Gastric surgery and gastric bypass
H. Pylori, autoimmune gastritis and celiac disease.
Chronic kidney disease and dialysis
Cancer patients
IV iron preparations: (use them when patients cannot tolerate oral)

AVOID IM: It’s painful, stains the buttocks, and has variable
absorption. Case reports have also described development of
sarcomas.

Iron Dextran (Infed): Black Box warnings for anaphylaxis, requires pre
medications and takes long to give. Usually including premeds and
test dose, 4-6 hours. Dosing is by weight and Hgb. (Chart) can be up
to 1.5 Gms. More than a Gram doesn’t work any better.

Ferumoxytol (Feraheme): Given in 2 doses, one week apart. 510 mg

Often given with premeds and has an increase in second dose
reactions.

Iron sucrose (Venofer): Should have a test dose. Given in multiple

doses, not over 300 mg. Used in CKD, and in the setting of dialysis.

Ferric carboxymaltose (Injectafer): is a colloidal iron hydroxide

complex with a tighter binding of elemental iron. It’s a 15 minute
infusion and doesn’t require premeds and is given in NSS 750 mg in 2
doses, one week apart.
 Monitoring:
For chronic iron deficiency anemia patients that require
ongoing IV iron treatments, monthly CBC’s and iron studies
including ferritin. Treat again when ferritin goes below 50.

Oral iron treatment F/U should be checked monthly during

replacement until repleted. Continue oral iron up to 3-6
months after normalization of iron levels to replete iron stores.
When ferritin is normalized, a trial off iron for 3 months and
recheck CBC, iron, TIBC and ferritin.

If the cause of the iron deficiency has been treated, no further

iron should be necessary. (normalization of periods, post
uterine oblation, GI bleed is successfully treated, etc.)
Case Study:
71 year old female with a history of macrocytic anemia over 2
years. Supplementation with B 12 shows adequate B 12 levels
and folate. She has hypothyroidism and upper and lower
endoscopies were completed in 2013 and she was found to
have a single benign colon polyp and mild gastritis that was
treated. ECOG performance status is 0.

MCV = 125.7 (81.6 -98.3)

MCH = 43.5 (25.6-32.2)
Hgb = 9.3
Hct = 26.9
WBC 3.30 (3.98-10.04)
Retic count = 1.71% (0.50-1.70)
Ferritin = 912 (11.1-264)
Iron = 188 (37-170)
Question:
What tests do you do next?

1. Repeat Upper and lower endoscopies, as she

had a polyp 3 years ago.

2. Bone Marrow Biopsy with Cytogenetics.

3. She has had this for 2 years and is stable, no

further work up is necessary.

4. Consider hypothyroid as a reason for her

macrocytosis and follow closely.
71 Y/O female with megaloblastic anemia

Bone Marrow Biopsy showed:

Severely increased iron stores present, ringed sideroblasts present.

Increased cellularity, no evidence of metastatic neoplasm.

Comment: On BMB from pathologist

The patient developed anemia starting in 2013. She is not B 12 or

folate deficient, and she is taking levothyroxine. Hypothyroidism
may be associated with megaloblastic anemia; however, there is
increased particulate iron without blast increase in her marrow.
Cytogenetics was negative for myelodysplastic syndrome.

Treatment:
For now, she should be followed frequently with blood counts and
no treatment is needed at this time. Should she continue to drop
her blood counts or become symptomatic, then a trial of
erythropoietin could be initiated.
 Hemolytic Anemias Testing
Click here for topics associated with this algorithm

ORDER Presence of the following may provide clues to the etiology of the anemia
CBC with Platelet Count and Increased reticulocyte count
INDICATIONS FOR TESTING Automated Differential Abnormal peripheral smear
Patient with anemia and Reticulocytes Polychromasia, spherocytes, schistocytes, sickle cells,
evidence of hemolysis Lactate Dehydrogenase stomatocytes, Heinz bodies, basophilic stippling, unusual red cell
Haptoglobin inclusions, and agglutination
Bilirubin Note: lack of any of the above does not rule out hemolytic anemia

Consider
DIC Proceed based on above findings
TTP
DIC Increased Consider Sickle cell disease –
HELLP High-performance liquid
ORDER HUS Microangiopathic Schistocytes, Sickle cells diverse genotypes: SS, SC, chromatography (HPLC)
Normal D-Dimer Mechanical RBC destruction thrombocytopenia SE, Sβ thalassemia, S Lepore
Clinical presentation cardiac valve
consistent with TMA Vasculitis
Congenital 5'
Malignant Consider 5'
No nucleotidase
hypertension nucleotidase testing
deficiency
Basophilic
Pregnant Acquired
stippling
ORDER
ADAMTS13 Activity
Consider Consider serum
Consider OR Yes lead lead level testing
HELLP E. coli Shiga-like Toxin by EIA
If infection suspected, poisoning
(dependent on presentation)
consider Unusual red
Polychromasia
malaria, bartonella cell inclusions
only with or Consider ORDER
(oroya fever), babesia
ADAMTS13 Positive without platelet PNH PNH, High Sensitivity, RBC and WBC testing
Normal decrease
activity <10% Shiga toxin

Consider one or more

Atypical Consider of the following tests
TTP HUS Polychromasia without
HUS Pyruvate kinase Pyruvate kinase
other reproducible deficiency Hexokinase
morphologic abnormality Hexokinase deficiency
ORDER Glucose phosphate
Other enzyme defects isomerase
RBC Band 3
Consider Consider
Protein
molecular No RBC membrane
Reduction in ORDER
testing disorder Warm
Hereditary Osmotic Spherocytes, ORDER
(hereditary Consider No autoimmune
Spherocytosis Fragility, pyropoikilocytes, Direct
Acquired spherocytosis, cold Positive for hemolytic anemia
Erythrocyte elliptocytes or Agglutination Coombs
(usually hereditary acanthocytes agglutinins complement
Direct Coombs disease (Anti-Human
positive) elliptocytosis,
(Anti-Human Yes Globulin)
autoimmune
Globulin) Cold Cold
hemolysis)
Yes agglutinins agglutinins
testing disease

IgG+ +C3 Consider Consider one or more of

Glucose-6-Phosphate the following tests
dehydrogenase Isopropanol heat
No Yes For hemoglobin
deficiency stability testing
Cold agglutinins disease, paroxysmal disorders,
Heinz Unstable hemoglobin Glucose-6-
cold hemoglobinuria (PCH) consider
bodies defects Phosphate
Recluse spider Autoimmune hemolytic anemia HPLC, genetic
Glutathione Dehydrogenase
venom, clostridium (consider drug induced, testing
metabolism defects (G6PD) 2 Mutations
sepsis hemolytic disease of the Hemoglobin H Enzymes of
Confirm PCH with Donath
newborn, autoimmune disease) disease glutathione cycle
Landsteiner testing

© 2006 ARUP Laboratories. All Rights Reserved. Revised 05/14/2015 www.arupconsult.com

Hemolytic Anemia:

Tests: CBC, with manual diff, reticulocyte count, LDH, Haptoglobin,

Bilirubin.

Findings:
Elevated reticulocyte count
Elevate LDH
Decreased Haptoglobin < 25 (if LDH and Haptoglobin are normal, 90%
probability it’s not hemolytic anemia)
Positive Direct Coombs test
Increased indirect Bilirubin

Peripheral smear:
Fragmented RBC (schistocytes or helmet cells
Spherocytes seen in hereditary scherocytosis
Spur cells seen in liver disease
Tear drop RBC’s with circulating nucleated RBC indicating the
presence of marrow involvement.
 Treatment for Hemolytic Anemia (Autoimmune):

Diagnosis – Accurate diagnosis of warm agglutinin autoimmune

hemolytic anemia (AIHA) requires documentation of the presence of
red cell destruction (hemolysis) along with demonstration of the
presence of an autoantibody or complement on the surface of the
patient's red cells.
Indications for treatment – Most patients with AIHA present with an
acute onset of severe hemolysis with symptomatic anemia, requiring
immediate treatment. In patients with underlying cardiac disease,
AIHA can present as a medical emergency, requiring immediate
packed red cell transfusion.
Initial treatment – Once the diagnosis of symptomatic warm agglutinin
AIHA is confirmed, we recommend immediate institution of treatment
with glucocorticoids over splenectomy,

Poorly responsive, severe, or resistant disease

Second-line treatment – For symptomatic patients not responding to
glucocorticoids, or for those who require large doses to maintain their
response (eg, >15 mg/day)
CONTINUED

For adults, it is preferred splenectomy over Rituximab, as it is the only

modality with potential for long-term cure, while rituximab is the
treatment of choice for adults who either are not surgical candidates or
refuse surgery.

Third-line treatment – For those who have failed treatment with both
splenectomy and rituximab, should institute immunosuppressive or
cytotoxic agents such as azathioprine (Imuran), cyclophosphamide, or
cyclosporine.

Obviously you have already referred to Hematology!

 Erythrocytosis

Polycythemia

Primary or Secondary
QUESTION:

You have a patient, age 50ish, that you have followed for many years,
who comes in complaining of fatigue, weight gain, depression, and
tells you their spouse complains of their snoring is getting worse. You
check labs and find that they are not anemic, in fact over the past few
years, their Hgb has risen to the level of polycythemia. No other indices
are abnormal. What tests do you do next?

1. Repeat CBC, with smear to path, CMP, Hgb A1c, and lipid panel.

2. Set them up for a sleep study.

3. Repeat CBC with diff and draw erythropoietin level, and make sure
they are well hydrated.

4. Discuss with them about their sleep habits and activity levels, and
dietary considerations, and family history of hereditary syndromes.
You find out the EPO level is elevated, now what?

Over night oximetry shows O2 saturations are under 85% frequently

during testing and multiple events of apnea are noted.

Patient feels unrested upon arising, and sluggish during the day.

Exercise tolerance is poor. Diet is rich in starchy carbs and Hgb A1c
is elevated at 8.0, along with high triglycerides and LDL.

Ultrasound of abdomen shows fatty liver but spleen is normal.

WHAT IS YOUR DIAGNOSIS?

How many patients in your practice fit this pattern?

You’ve got work to do…........

Let’s Talk White Cells
 Chronic Lymphocytic Leukemia

Can this be managed by primary care providers? YES!

You have a patient that has an elevation in lymphocytes, and

you are following them over the years and now you notice a
small increase in the total WBC and the lymphocyte % is higher
than the neutrophil %.

What is the next test to be drawn if you suspect CLL?

Flow Cytometry.

It can confirm the diagnosis without a BMB.

Usually they will be CD 20 positive.
You can follow these patients.
 Platelets, Thrombocytes
those tiny little critters that
keep us from bleeding out!
 CAUSES OF REACTIVE THROMBOCYTOSIS

NON MALIGNANT HEMATOLOGIC CONDITIONS:

ACUTE BLOOD LOSS

ACUTE HEMOLYTIC ANEMIA
ACUTE IRON DEFICIENCY ANEMIA
TREATMENT OF VITAMIN B DEFICIENCY
REBOUND EFFECT AFTER TREATMENT OF IMMUNE THROMBOCYTOPENIA
REBOUND EFFECT AFTER ETHANOL-INDUCED THROMBOCYTOPENIA

MALIGNANT CONDITIONS:

METASTATIC CANCER
LYMPHOMA
REBOUND EFFECT FOLLOWING USE OF MYELOSUOORESSIVE AGENTS

ACUTE AND CHRONIC INFLAMMATORY CONDITIONS:

RHEUMATOLOGIC CONDITIONS, VASCULITIS, IBS, CELIAC DISEASE

TISSUE DAMAGE:

THERMAL BURNS
MYOCARDIAL INFARCTION
SEVERE TRAUMA
ACUTE PANCREATITIS
POST-SURGICAL PERIOD, ESPECIALLY POST-SPENECTOMY
CORONARY ARTERY BYPASS PROCEDURES

INFECTIONS:

CHRONIC INFECTIONS AND TUBERCULOSIS

EXERCISE

ALLERGIC REACTIONS

FUNCTIONAL AND SURGICAL ASPLENIA

REACTION TO MEDICATIONS:

VINCRISTINE
EPINEPHERINE, GLUCOCORTICOIDS
INTERLEUKIN-1B
ALL-TRANS RETINOIC ACID
THROMBOPOIETIN, THROMBOPOITIN MIMETICS
LOW MOLECULAR WEIGHT HEPARINS (ENOXAPARIN)
MEDICATIONS

THOSE
PESKY
DRUGS
Hydroxyurea:

Used mostly these days for Essential Thrombocythemia. It can be

used in CML.
Dosing is 500 mg tablets titrated to keep the platelet count below
400K.
Monitoring CBC’s should be weekly at first and then changed to
every 2 weeks until stabilization occurs.
It can drop Hgb and WBC’s so titration can be tricky.
Usually changes in dosing shouldn’t be sooner than every 2 weeks as
it takes that long to stabilize on a new dose.

It is an antineoplastic agent and is carcinogenic. Advise sun

protection and monitor for malignancies.

Adjustments for lower Creatinine clearance.

Most people tolerate it without side effects.
Causes macrocytosis
Eltrombopag (Promacta):

Colony stimulating Factor; Hematopoietic Agent; Thrombopoietic

Agent.
Used for Chronic immune idiopathic Thrombocytopenia (ITP)
Max dose is 150 mg daily.
Titrate to maintain platelets with lowest dose.
Weekly CBC monitoring until Platelets get up to 30K and you are
seeing an upward trend, the CBC’s every 2 weeks.
Pricing:
12.5 mg tabs # 30 = $4124.09
75 mg tabs # 30 = $11,509.09
Monitor liver functions
Should be taken on an empty stomach
Can be used in Hepatitis C for thrombocytopenia with caution.
Dosing is usually tolerated well.
SE: fatigue, nausea, diarrhea, elevated LFT’s are the most
common.
Anagrelide (Agrylin):

Antiplatelet Agent, used for Essential Thrombocythemia (ET)

Well tolerated, and can be used with Hydroxyurea on tough cases.
Caution in Hepatic impairment.
Initial dosing is 0.5 mg 1 to 4 times daily Max daily dose of 10 mg
Titrate up slowly, must not be increase by more than 0.5 mg a day in
any one week. Most patients will stabilize between 1.5 and 3 mg
daily.
Generic form available

Pricing:
0.5 mg (100) = $585.70 (generic)
1 mg (100) =$1171.35 (generic)
Monitoring parameters CBC Q 2 days during the first week with
pretreatment EKG and CMP frequently during treatment.
Monitor for interstitial lung disease.
SE: palpitations, chest pain, CHF, fatigue, edema, rash, diarrhea,
nausea, elevated LFT’s
 Hematopoietic Growth Factors:

Erythropoietin, Granulocyte and granulocyte-macrophage

colony stimulating factors (G-CSF and GM-CSF), Thrombopoietin

The family of glycoproteins known as the hematopoietic growth

factors (HGFs) plays a major role in the proliferation,
differentiation, and survival of primitive hematopoietic stem and
progenitor cells, as well as in functional activation of some
mature cells. These effects are mediated by high affinity binding
of the HGFs to specific receptors expressed on the surface of
the target cells.
Recombinant HGFs are administered in the following clinical
settings:

Transient bone marrow failure following chemotherapy

Hematopoietic stem cell and progenitor cell mobilization
Recovery from hematopoietic cell transplantation
Myelodysplastic syndrome
Aplastic anemia
Some forms of neutropenia
Inherited bone marrow failure syndromes
Human immunodeficiency virus (HIV) infection-associated
neutropenia
Chronic anemias (eg, renal failure, prematurity, chronic disease/
inflammation, HIV infection)
Reducing the need for perioperative blood transfusion
Potential toxicities of the recombinant HGFs include the following (see
'Toxicity of colony-stimulating factors' above and 'Toxicity of
erythropoietin' above):

Transient leukopenia

Systemic reactions (eg, flu-like symptoms, capillary leak, hypertension,

thrombosis)

Production of deleterious neutralizing antibodies

Possible stimulation of malignancy

Possible enhancement of HIV replication

Multiorgan failure when used in sickle cell syndromes

 PEARLS:
1. ANC (absolute neutrophil count) is the neutrophil # on the
differential of a CBC. Always order CBC with diff so you
can find this number. If it is < 1.5 or below 1500 you have
neutropenia.
2. Thrombocytopenia alone, may be due to platelet
clumping. Have the lab do a manual diff to verify if there is
clumping. If so have the next CBC, have drawn in a
sodium citrate tube. Clumping can be seen with EDTA
tube.
Case Study:

73 Y/O female with anemia, severe monocytosis, elevated

WBC, low platelets. Hx of DM, HTN, multiple UTI’s.

WBC 43.81 HH
RBC 3.09 L
HGB 9.2 L
HCT 28.7 L
MCV 92.9 H
MCH 29.8
PLTS 20 LL
ANC# 0.34 LL
Lymph # 9.78 H
MONO# 33.53 HH
EOS # 0.01 L

BUN 24 (7 – 17)
Creatinine 2.5 (0.7 – 1.2)

Blood sugar and electrolytes were normal

Bone Marrow Biopsy:

Peripheral Blood:

Normocytic, normochromic anemia with anisocytosis. Atypical

monocytosis with dysplastic morphology. Few monoblasts. Few
variant lymphocytes.

Bone Marrow:

Acute myeloid leukemia with monocytic differentiation with

infiltration of marrow about 85% cellularity of the marrow is close to
100%

Flow Cytometry:

Markedly increased immunophenotypically atypical monocytes

detected. Blast count is 3.4%. Manual count with 5% immature
monocytes noted.
Monocytosis:

A number of conditions which cause neutrophilia can also cause

monocytosis, making this combination a relatively nonspecific finding.
These include pregnancy, the asplenic state, inflammatory (eg,
sarcoidosis, inflammatory bowel disease) and autoimmune conditions,
depression, and treatment with corticosteroids or colony stimulating
factors. Monocytosis may also accompany conditions associated with
neutropenia, presumably as a compensatory mechanism.

A large number of infections have been associated with monocytosis

including brucellosis, varicella-zoster, bacterial endocarditis, tuberculosis,
malaria, typhoid fever, syphilis, and trypanosomiasis.

Monocytosis may also be seen in certain malignancies, such as Hodgkin

lymphoma. Neutrophilia with monocytosis may also suggest chronic
myelomonocytic leukemia, one of the myelodysplastic disorders.
Additional associated findings in this condition are anemia,
thrombocytopenia and abnormal cellular maturation (eg, macrocytic red
cells, defective lobulation in neutrophils, and abnormal size and
granulation in platelets).
In this case study, at the time of the BMB, she had declining platelets
and she was quite weak. She was instructed to be very careful
about injuries and falls!

Within 2 days she was in the ER and transported to Albuquerque.

She neglected to tell anyone she had fallen and hit her head.
She became obtunded and a CT revealed a subdural hematoma.

She went into a blast crisis with her Acute myelomonocytic leukemia
and passed.
Case Study:

63 Y/O male with elevated LFT’s, macrocytosis, Hx of colon cancer,

in to F/U on colon cancer.

WBC 8.75
RBC 3.92
HGB 14.6
HCT 40.2
MCV 102.6 H
MCH 37.2 H
PLTS 175 (163-369)

Glucose 111.0 non fasting

BUN 5 L
Creat 0.7 L
Sodium 131 L

AST 106 H (17-59)

ALT 89 H (13-69)
CEA 7.9 H
Ordered the following:

Restaging CT Chest, Abd, and pelvis

Hepatitis panel
Colonoscopy

All were negative.

Patient smokes 2 pks per day

Patient drinks 12 pk beer per day

CEA is elevated in smokers

Macrocytosis and elevated liver functions from
alcohol intake.
Case Study:

67 Y/O male who had orthopedic surgery and required 2 units

of blood post op. He was discharged and 6 weeks later
returned to the ER with purpura lower extremities, blood blisters
in his mouth. Platelet count was 4K, Hgb was 11.4 The next day
platelet count was 0.
He has a Hx of high risk prostate cancer and is on Lupron
injections every 6 months. Otherwise he is healthy for his age.

Post transfusion purpura

He was first treated with plasmaphoresis which failed. Then

treated with steroids and IVIG which also failed. He was then
placed on Eltrombopag (Promacta).

Started at 50 mg daily, CBC’s followed weekly platelets took

about 4 weeks to recover to 79 K.
Discontinued Promacta in February when his Platelets were
265K.
 Hemochromatosis Testing
Click here for topics associated with this algorithm

INDICATIONS FOR TESTING

Suspicion of hemochromatosis (family history, compatible symptoms)

ORDER
Iron and Iron Binding Capacity
Note: Test includes serum transferrin saturation (STS)
AND
Ferritin (SF)

STS <45% and STS ≥45% and/or

normal SF elevated SF

No further Repeat STS and SF

testing at tests
this point

STS ≥45%
Repeat STS and
SF: elevated for age and sex
SF tests at 2-
(esp. if >2x normal)
year intervals

Secondary
If both elevated, iron
do liver biopsy overload

No
Yes

FOR ADULTS, ORDER Treat

FOR PEDIATRICS,
Hemochromatosis (HFE) 3 underlying
CONSIDER
Mutations cause
HJV (HFE2) gene sequencing
(accounts for >90% of mutations in
(accounts for >90% of cases)
Caucasians)

H63D/H63D C282Y/H63D
C282Y/wt C282Y/C282Y Positive Negative
H63D/S65C C282Y/S65C

Hemochromatosis CONSIDER
Monitor STS Hemochromatosis confirmed confirmed HAMP (HEPC) gene
Consider liver biopsy sequencing
Consider alternative gene (accounts for <10% of cases)
testing (TFr2, FPN) ORDER
Ferritin
AND
Aspartate Aminotransferase, Serum or
Plasma

Ferritin ≥1000 μg/L Ferritin <1000 μg/L

Aspartate aminotransferase (AST) abnormal Aspartate aminotransferase (AST) normal

Liver biopsy with hepatic iron concentration Phlebotomy

Monitor STS

Family screening

© 2006 ARUP Laboratories. All Rights Reserved. Revised 01/18/2012 www.arupconsult.com

 Plasma Cell Dyscrasias
Click here for topics associated with this algorithm

INDICATIONS FOR TESTING

Bone pain, recurrent infections, anemia,
lytic lesions on plain film

Perform baseline screening

Rule out
CBC with Platelet Count and Automated Differential
Chronic infections such as HIV
Metabolic profile, which should include
Immunoglobulin deficiencies such as
Calcium, Serum or Plasma AND Common Variable Immunodeficiency (CVID)
BUN/Creatinine, Serum or Plasma
Chronic inflammatory processes such as
Protein, Total, Serum or Plasm
systemic lupus erythematous, liver disease
Albumin, Serum or Plasma by Spectrophotometry
Other malignancies
Lactate Dehydrogenase, Serum or Plasma
If negative for
other diseases

ORDER
Protein Electrophoresis with Reflex to Immunofixation Electrophoresis Monoclonal Protein Detection, Quantitation
and Characterization, IgA, IgG, and IgM, Serum
24 hr urine protein electrophoresis
AND
Monoclonal Protein Detection Quantitation & Characterization, SPEP, IFE, IgA, IgG, IgM, Serum (Protein
electrophoresis with reflex testing may occasionally miss IgA MGUS or multiple myeloma [MM])
Immunofixation Electrophoresis, Qualitative, Gel

Serum M protein ≥3 g/dL

No Yes

Abnormal baseline testing or

suspicion for multiple myeloma (MM)
ORDER
Bone marrow biopsy
Skeletal survey

No Yes

ORDER
Serum free light chain ratio (Kappa/Lambda Quantitative
Free Light Chains with Ratio, Serum) to diagnose
oligosecretory myeloma and non-secretory myeloma ≥10% plasma cells*
<10% plasma cells
Bone lesions present
No bone lesions present
Monoclonal Abnormal baseline
Normal baseline testing
gammopathy of testing
Normal Abnormal
undetermined
FLC ratio FLC ratio
significance
(MGUS)
ORDER
Asymptomatic MM
Bone marrow biopsy
(smoldering)
Repeat Skeletal survey
MM
evaluation in
3-6 months Bone lessions

No Repeat
Yes
evaluation in
3 months

MM
<10% plasma cells ≥10% plasma cells

Likely Asymptomatic
MGUS (smoldering) MM *This criterion is unnecessary
if bone lesions are present

Repeat evaluation in Repeat evaluation in

3-6 months 3 months

© 2006 ARUP Laboratories. All Rights Reserved. 02/17/2015 www.arupconsult.com

RESCOURCES :

UP TO DATE has apps for cell phone, expensive but

great!

ARUP Consult apps for cell phone, great reference for

algorithms.

iHematology apps for cell phone, quick reference to

describe smear morphology.

Medical Lab Tests for cell phones

labtestsonline.org
 WHEN TO REFER
1. PANCYTOPENIA
2. PLATELETS TREND DOWN OVER TIME AND ARE STAYING
UNDER 100 K
3. YOU CAN’T FIND A REASON FOR IRON DEFICIENCY
4. UNEXPLAINED LEUKOCYTOSIS
5. UNEXPLAINED ADENOPATHY…. GET IT BIOPSIED!
6. INTOLERANCE TO ORAL IRON AND PERSISTANCE OF
IRON DEFICIENCY WITH NEGATIVE WORKUP
7. YOU HAVE A BAD FEELING AND TOO MAY ABNORMALS
ON THE SMEAR...

MY ADVICE:
GET TO KNOW YOUR LOCAL HEMATOLOGIST AND ASK FOR
ADVICE. THEY MAY HAVE A FRIENDLY NP TO TALK TO. SHE
OR HE MAY HAVE GOOD ADVICE!!!