Download Macrocytic Anemias


Recognize normal/abnormal results and
understand their implications

Interpret abnormal results, identify
possible underlying disease states and
perform additional evaluation

Identify critical results and take
appropriate action

Series of tests used to evaluate the
composition and concentration of
various cellular components of blood
› Red Cell Parameters
 Hemoglobin, RBC, MCV, MCHC, MCH, RDW
› White Cell Parameters
 Differential Count
› Platelet Count
Automated instruments using anticoagulated whole blood
 Clots consume platelets and can trap
other cells artificially decreasing values
 Incomplete filling of tubes with blood
can cause artifacts by exposing cells to
toxic quantities of the tube’s anticoagulants

WBC Parameters
RBC Parameters
Platelet Count

Red Cell Disorders
› Anemia
› Polycythemia

White Cell Disorders
› Leukocytosis
› Leukopenia

Platelet Disorders
› Thrombocytosis
› Thrombocytopenia
Biconcave disk
 Clinical significance:
transport hemoglobin,
measure of the
oxygen carrying
capacity of blood
 Regulated by
erythropoietin
 Life span of ~120 days


Normal Values are
dependent on:
› Age

Adult Male: 13.516.5 g/L

Adult Female: 1215.5 g/L
› Gender
› Altitude
› Tobacco use
› Drugs

Hematocrit – packed cell volume
› Ratio of volume of RBC to volume of blood

MCV (mean corpuscular volume)
› Normal 80-100
› Microcytic <80
› Macrocytic >100

MCHC (mean corpuscular hemoglobin
concentration)
› Hemoglobin/RBC
› Low = hypochromic

MCH (mean corpuscular hemoglobin)
› Hemoglobin/Hematocrit

RDW (red cell distribution width)
› Correlates with the degree of anisocytosis

Reticulocyte Count
› Young RBC
› Normal: 1-2%

Red Cell Disorders
› Anemia
› Polycythemia

White Cell Disorders
› Leukocytosis
› Leukopenia

Platelet Disorders
› Thrombocytosis
› Thrombocytopenia
Most common hematologic disorder
 Decrease in the number of circulating
red blood cells causing a decrease in
oxygen carrying capacity of blood
 Usually a secondary underlying cause

Shortness of Breath
 Chest Pain
 Tachycardia
 Skin/Mucosal Pallor
 Bleeding
 Fatigue

Blood Loss Anemia
 Anemia of Decreased RBC Production
 Anemia with Increased RBC Destruction

Microcytic: MCV <80
 Normocytic: MCV 80-100
 Macrocytic: MCV >100


Microcytic Anemias
› Iron Deficiency Anemia
› Thalassemia
› Sideroblastic Anemia
› Chronic Disease
Macrocytic Anemias
 Normocytic Anemias

Iron Deficiency
 Thalassemia
 Sideroblastic
 Chronic Disease

1. Dietary Deficiency
› Meat deficient diets
› Pregnancy
2. Malabsorption
› Partial gastrectomy (hypochlorhydria)
› Celiac
› Chronic diarrhea
3. Chronic Blood Loss
›
›
›
›

GI Tract - Ulcerative disease, Gastritis,
Cancer, Hemorrhods, AV Malformations
Menorrhagia
Hematuria – Bladder/Kidney Cancers
Frequent blood donation/inpatient
phlebotomy
Diagnosis of Iron deficiency in an adult
mandates an evaluation to rule out
malignancy

Gold Standard: Bone Marrow Biopsy

Iron Studies (Fe, Ferritin, TIBC)
Iron
Iron
Saturation
Ferritin
TIBC
Peripheral Smear
Low
Low
Low
High
Microcytic (low MCV) and
Hypochromic (low MCHC) Red Cells

Oral Iron Replacement
› Ferrous Sulfate 325mg PO TID
› Ascorbic Acid can increase absorption
› Can cause GI upset/constipation

Parenteral Iron
› Indicated in cases of intolerance to PO Fe or
failure to respond to PO Fe

Important to not only treat the iron
deficiency, but you must discover and
treat the underlying disorder
Spectrum of diseases characterized by
decreased or lack of production of one or
more globulin chains
 Normal hemoglobin contains four alpha
and two beta chains
 Alpha thalassemias – alpha chain
production problem leading to an excess of
beta globin chains
 Beta thalassemias – beta chain production
problem leading to excess alpha chains

More common in Mediterranean, African
and Southeast Asian populations
 Beta Thalassemia Major – complete lack
of production of Beta Globin Chains
 Beta Thalassemia Minor – loss of one of
the two alleles coding for the Betaglobulin gene

Complete lack of hemoglobin A production
 Microcytic (low MCV) hypochromic (low
MCHC) red cells
 Complications:

› Bone deformities (EPO stimulated expansion of
bone marrow)
› Hepatosplenomegaly (extramedullary
hemoatopiesis)
› Secondary Iron Overload (increased iron
absorption and repeated transfusions)
Asymptomatic condition
 Microcytosis and a normal RDW
 If anemia is present, usually mild


Hemoglobin electrophoresis
› Beta Thalassemia and Severe Alpha
Thalassemia

Mild alpha thalassemia detection
› Alpha:Beta Ratio
› Molecular testing
› Neither test is widely available
Depends on the severity of the genetic
defect and the clinical sequelae
 Minor Thalassemias

› Often asymptomatic and require no therapy

Major Thalassemias
› Chronic transfusions
› Iron chelation
› Splenectomy

Avoid Routine Iron Supplementation

Characterized by ineffective
erythropoiesis and presence of ringed
sideroblasts in the bone marrow

“Ringed” – accumulation of iron in the
mitochondria that surround the periphery
of the nucleus
Hereditary
 Ideopathic
 Drug-Associated

› Alcohol, INH, Chloramphenicol

Lead Poisoning
› Basophilic Stippling
No cure for hereditary condition
 Prevent iron overload/chelation
 Drug induced

› Often resolves when offending agent
discontinued

Isoniazid associated – can be overcome
with high dose pyridoxine
supplementation
› Can reverse anemia and allow for
continuation of drug
Microcytic Anemias
 Macrocytic Anemias

› Vitamin B12 Deficiency
› Folate Deficiency
› Drug Induced

Normocytic Anemias
MCV >100
 Can be categorized based on features
seen on peripheral smear
 Megaloblastic – oval macrocytes;
hypersegmented polymorphonuclear
lymphocytes (PMN)

› >5 lobes

Non-Megaloblastic
Megaloblastlc



Vitamin B12
Deficiency
Folic Acid Deficiency
Drug induced
Non-Megaloblastic




Liver Disease
Hypothyroidism
Alcohol Induced
Reticulocytosis
(hemolysis)

Etiologies:
›
›
›
›

Pernicious Anemia
Gastrectomy/Gastric Bypass
Ileal disorders
Inadequate intake
Additional Symptoms:
›
›
›
›
›
Diarrhea/abdominal pain
Numbness/paresthesia
Glossitis
Motor weakness/spasticity
Decreased proprioception
Vitamin B12 level
 Serum Methylmalonic Acid and
Homocystine levels
 Anti-intrinsic Factor or Anti-parietal Cell
Antibodies
 Endoscopic evaluation
 Surgical History


Vitamin B12 1mg IM or SC
› Daily x7 days, then
› Weekly for 4 weeks, then
› Monthly thereafter
Hematologic abnormalities take about 2
moths to resolve
 Neurologic abnormalities can take up to
18 months to resolve; however, may be
permanent

Inadequate intake
 Decreased absorption

› Celiac, bacterial overgrowth, drugs (dilantin)

Increased requirement
› Hemolytic Anemia, Pregnancy, Hemodialysis

Iatrogenic – Folic Acid Antagonists
› Methotrexate, Trimethoprim

Appears similar to Vitamin B12 deficiency;
however, no neurologic symptoms
Folic Acid 1mg PO daily
 Hematologic abnormalities should
resolve in about 2 months


Important to rule out concurrent Vitamin
B12 deficiency
› Folic Acid may improve the hematologic
parameters in Vitamin B12 deficiency but
wont correct any underlying neurologic
symptoms




Purine Analogs
(azathioprine)
Pyrimidine Analogs
(5-FU, ARA-C)
Hydroxyurea
Anticonvulsants
(dilantin,
phenobarbital)

Treatment:
› Stop offending
agent
› Tolerate mild
anemia if
therapeutic benefit
of drug is justified
Microcytic Anemias
 Macrocytic Anemias
 Normocytic Anemias

› Hemolytic Anemias
 G6PD Deficiency
 Spherocytosis
 Microangiopathic Hemolytic Anemia
(DIC/TTP/HUS)
› Malignancy/Bone Marrow Infiltration
› Myelodysplastic Syndrome
› Anemia of Chronic Kidney Disease

Elevated Reticulocyte Count
› Hemolytic Anemia
› Acute Bleeding

Decreased Reticulocyte Count
› Malignancy/Marrow infiltration
 Leukemia/lymphoma, Myeloma, Granulomatous
Disease
› Stem Cell Disorders
 Myelofibrosis, Aplastic Anemia/Pure RCB Aplasia,
Myelodysplasia
› Medical Conditions
 Chronic Kidney Disease, Anemia of Chronic
Disease
Anemias with increased RBC destruction
 Jaundice, splenomegaly, brown/red urine
 Laboratory abnormalities:

› Increased LDH
› Decreased Haptoglobin
› Increased unconjugated bilirubin
› Increased reticulocyte count
› Positive Direct Coombs Test

Disordered Hemoglobin Synthesis
› Sickle Cell

RBC Membrane Disorders
› Spherocytosis
› Elliptocytosis

RBC Enzyme Disorders
› G6PD Deficiency
› Pyruvate Kinase Deficiency
› Hexokinase Deficiency
X-linked disorder that leads to hemolysis
in the presence of an oxidative stress
 Hemoglobin loses its ability to maintain a
reduced state and precipitates within
the RBC and cells lyse
 Leads to Heinz Body formation and
hemolysis
 Bite cells

Precipitants of hemolysis:
 Infection – E. coli, salmonella, S.
pneumoniae, vital hepatitis
 Drug Induced

› Antimalarials (primaquine and chloroquine)
› Antibiotics (sulfonamides, nitrofurantoin)
Fava Beans
 Napthalene


Diagnosis made by measuring G6PD
activity level
› Should be checked 3-4 weeks after
hemolytic episode for accurate results
› Measuring during hemolytic episode will give
false negative results certain subtypes

Treatment is supportive
› Transfusions/Folic Acid supplementation
› Avoiding precipitants of hemolysis

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
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Autosomal Dominant, mostly commonly in
people of Northern European decent
Defect in a membrane cytoskeletal protein
leading to spherocyte formation
Physical Examination: splenomegaly
secondary to extravascular hemolysis
Peripheral blood smear: Spherocytes
Diagnosis: Osmotic fragility test
Treatment: splenectomy (corrects anemia,
not underlying defect) and supportive
transfusions
Small, dark, dense, hyperchromic red
blood cells lacking central pallor
 Increased MCHC


Immune Related
› Transfuision Reactions
› Cold Agglutinin
› Warm Auto Antibody

Non-immune related
› Microangiopathic Hemolytic Anemia
› Infection
› PNH
› Prosthetic Heart Valves

Potential Causes
› TTP/HUS
› DIC
› Malignant Hypertension
› Metastatic Malignancy





Malfunction of coagulation/secondary hemostasis
Usually secondary (Infection, trauma, immunemediated reactions, obstetric complications)
Inappropriate systemic thrombosis of small/mid-sized
vessles
Depleted clotting factors leading to potential for lifethreatening hemorrhage
Labs: in addition to anemia
›
›
›
›


Thrombocytopenia
Abnormal coagulation tests
Elevated fibrin split products
Decreased fibrinogen
Peripheral Smear: Schistocytes
Treatment aimed at underlying disorder
› Patients are usually gravely ill
Microangiopathic hemolytic anemia
and thrombocytopenia
 Neurologic changes, Fever, Renal
Dysfunction (Predominates in HUS)
 Involves microvascular damage and
platelet destruction/aggregation; high
shear stress and endothelial damage
 Typically sporadic; HUS can be
associated with verotoxin and E. coli
O157:H7 (typically in children)


Classis Pentad of Findings
› Thrombocytopenia (typically <40,000)
› Microangiopathic Hemolytic Anemia
 Elevated LDH, Decreased Haptoglobin, elevated
reticulocyte count, peripheral smear schistocytes
› Neurologic Changes
› Renal Dysfunction
 Elevated Creatinine, Decreased Urine output
› Fever

Bleeding
› Coagulation studies typically normal

Abdominal Pain/Nausea/Vomiting/Diarrhea

Additional Potential Etiologies:
› Drug exposure: Quinine, Mitomycin C,
Bleomycin, Cisplatin, Cyclosporine, Plavix
› HIV infection
› Systemic Lupus Erythematosis
› Metastatic Adenocarcinoma

Treatment: Urgent Plasmapheresis
Metastatic Cancer to the Bone Marrow
 Leukemias/Lymphomas/Myelomas


Peripheral smear: Nucleated RBC,
teardrop cells, immature WBC

Bone marrow biopsy core usually
needed for diagnosis; often a “dry tap”
Heterogeneous group of clonal
hematopoietic stem cell disorders with
the presence of dysplastic changes in
one or more cell line
 Associated with inappropriate apoptosis
and excessive bone marrow proliferation
 Peripheral cytopenias and dysplastic
changes in the bone marrow

Mean age of diagnosis: 68
 Slight male predominance
 Environmental Links:

› Smoking, benzene, organic chemicals,
herbicides, pesticides, fertilizers, petroleum
and diesel derivatives

Prior Chemotherapy or Radiation
› Melphalan, chlorambucil,
cyclophosphamide
Refractory cytopenias
 Anemia and fatigue

› Macrocytic or normocytic

Infections, bleeding

Symptoms depend on cytopenias
present and their severity
CBC: Macrocytic anemia (other
cytopenias)
 Low reticulocyte count
 Peripheral Smear: macrocytic red cells,
hypogranular granulocytes with pseudoPelger-Huët anomaly, giant platelets
 Bone Marrow Biopsy

Type of MDS
Peripheral
Blood Blasts
OR Bone Marrow
Blasts
Refractory Anemia (RA)
≤1%
<5%
Refractory Anemia with Ringed
Sideroblasts (RARS)
≤1%
<5%
Refractory Anemia with Excess
Blasts (RAEB)
<5%
5-20%
(1:5-9%; 2:9-19%)
Refractory Anemia with Excess
Blasts in Transformation (RAEB-T)
≥5%
21-30%
Chronic Myelomonocytoc
Leukemia (CMML)
<5%
≤20% with >1000
Monocytes/microL
Usually supportive
 Dependent on degree/severity of
findings

Erythropoietin support
 Transfusion support
 Chemotherapy
 Bone Marrow Transplantation

Due to Erythropoietin Deficiency
 Generally anemia begins when the
creatinine clearance in <45 mL/min and
worsens with increasing renal failure
 Treat underlying CKD and cause
 Can support with subcutaneous
erythropoietin with adjustment in dose
based on response


Red Cell Disorders
› Anemia
› Polycythemia

White Cell Disorders
› Leukocytosis
› Leukopenia

Platelet Disorders
› Thrombocytosis
› Thrombocytopenia

Laboratory finding of increased RBC
number and subsequently hemoglobin
and hematocrit

Can be primary (Polycythemia Vera) or
secondary

Initial evaluation: determine underlying
cause and minimize potential
complications

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



Hypertension
Thrombosis
Pruritus
Erythromelalgia
Joint Pain
Headache
Weakness
Visual disturbance
Weakness

Palpable
splenomegaly

Gout/Kidney stones
(increased cellular
turnover)
Suspected when hematocrit elevated
Can also have associated elevation in
platelets or white blood cells
 Erythropoietin level


› Low in Polycythemia Vera
› High in Secondary Polycythemia

Oxygen saturation
› Low levels can suggest secondary causes

JAK-2 Mutation Status
› JAK2 V617F mutation is identified in >90% PV

Complete evaluation for secondary causes

Hypoxemia leading to EPO overproduction
› Lung disease, high altitude, smoking, right-to-left
heart shunts, sleep apnea, obesity
hypoventilation

EPO overproduction
› Tumors – renal, hepatoma, fibroids,
pheochromocytoma
Androgen Therapy
 Relative Erythrocytosis (decreased plasma
volume)

› Diuretics, blood doping

Most common myeloproliferative disease
Major Criteria
Hemoglobin >18.5/16.5g/dL
Presence of JAK2 mutation
Minor Criteria
Bone Marrow Biopsy: Hypercellularity for Age with
prominent erythroid proliferation
Low EPO level
Endogenous erythroid colony formation in vitro

Diagnosis requires either Both Major and
1 Minor or 1st Major and 2 Minor Criteria
Goal: reduce blood volume to normal
and prevent complications (thrombosis)
 Phlebotomy to a goal Hematocrit of
<45% for men; <42% for women
 Aspirin Therapy
 If refractory to Phlebotomy: hydroxyurea
 Can progress to myelofibrosis and/or
acute leukemia

Immune system cells involved in
protecting the body from infectious
disease and foreign invaders
 Derived from a mulitpotent stem cell in
bone marrow (hematopoietic stem cell)
 Several types of leukocytes with different
primary functions
 When evaluating abnormalities in WBC
number must also consider which subtype of WBC is involved

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Neutrophil – mature WBC of the
Granulocyte series; part of the innate
immune system
Lymphocyte – facilitate humoral and
cellular immunity against foreign proteins
and pathogens.
Monocyte – Large phagocytic WBC; serves
as part of the innate immune system
Eosinophil – WBC implicated in
inflammatory/allergic response
Basophil – WBC that is active in the
inflammatory response

Red Cell Disorders
› Anemia
› Polycythemia

White Cell Disorders
› Leukocytosis
 Neutrophilia
 Lymphocytosis
 Monocytosis
 Eosinophilia
› Leukopenia

Platelet Disorders
› Thrombocytosis
› Thrombocytopenia

Primary
› Myeloproliferative
Disorders (CML, PV,
ET)
› Chronic Idiopathic
Neutrophilia
› Down’s Syndrome

Secondary
› Infection
› Stress (physical or
emotional)
› Drugs – steroids,
lithium, G-CSF
› Non-hematologic
malignancy
› Asplenia
Uncontrolled proliferation of mature and
maturing granulocytes
 Associated with the fusion of two genes:

› BCR on chromosome 9
› ABL1 on chromosome 22

Reciprocal translocation creates the
fusion protein BCR-ABL

Up to 50% can be asymptomatic
Malaise/Fatigue
 Weight Loss
 Night sweats
 Splenomegaly/Andominal discomfort


Leukostasis – Headache, neurologic
deficits (usually with WBC>300,000)
High leukocyte count
 Hypercellular marrow
 Basophilia
 PCR/Chromosome analysis for BCR-ABL


Peripheral smear: Left shifted WBC
(myeloblasts, myelocytes,
metamyelocytes and band forms) and
Basophilia
Phase
Symptoms/Signs
Chronic
Gradual rise in WBC, splenomegaly, hyperleukocytosis
<15%/20% blasts PB/BM
<20% Basophils
Accelerated
Escape of blood counts from treatment control
Myelofibrosis
>15-30%/>20-50% blasts PB/BM
>20% basophils
Blastic
Weight loss, B symptoms, bone pain, increased blasts
Marrow Failure : thrombocytopenia and anemia
>30%/>50% blasts PB/BM



Drugs targeting BCR-ABL tyrosine kinase
Can provide long term disease control
Supplanted previous standard therapies
such as bone marrow transplant
Imatinib mesylate (Gleevec) was the initial
targeted therapy developed for this
indication
 Several additional second and third
generation TKI drugs are available and can
be used in firs or subsequent lines of therapy


Reactive
› Viral infections: EBV,
CMV, VZV, influenza
› Other infections:
pertussis, toxo.
› Stress: trauma,
smoking
› Autoimmune: LGL,
RA

Malignant
› ALL
› CLL
› Follicular
Lymphoma
› Marginal Zone
Lymphoma
› Hairy cell
› Other Lymphomas
Evaluation: Blood Lymphocyte Morphology
Peripheral Blood Flow Cytometry
Neoplasm of small mature lymphocytes
 Can involve peripheral blood, bone
marrow, organs or lymph nodes (SLL)
 Most common leukemia in United States
 Diagnosed by the demonstration of an
absolute lymphocytosis and a clonal
population of lymphocytes expressing
CD5, CD19, CD20 and CD23 along with
low levels of surface immunoglobulins

Lymphocytosis on screening blood test
 Asymptomatic lymphadenopathy

Abdominal fullness
 Fatigue/decreased exercise tolerance
 Other constitutional symptoms

Most patients with early CLL are
asymptomatic and have a relatively good
long term prognosis
 Historically several trials of early
chemotherapy did not demonstrate survival
benefit
 Deferral of treatment/Watch and Wait is the
standard of care for early stage disease
with monitoring every 3-6 months
 Treatment is reserved for symptomatic or
rapidly progressive disease

Usually <10% of total WBC
 Relatively non-specific finding

Asplenia
 Inflammation (sarcoid, IBD)
 Autoimmune Disorders
 Steroids
 Infections (VZV, TB, malaria)
 Malignancy (Hodgkins, CMML)


Numerous allergic, infectious and
neoplastic disorders
Allergic – Atopic, Medications (NSIDS, ASA,
allopurinol, PCN, cephalosporins)
 Infectious – parasitic, fungal
 Specific organ disease – eosinophilic
esophagitis, asthma, skin disease,
renal/vascular disease
 Hematologic Neoplasm – Hypereosinophilic
syndrome, tumor associated, mastocytosis


Red Cell Disorders
› Anemia
› Polycythemia

White Cell Disorders
› Leukocytosis
› Leukopenia –
 Neutropenia: ANC <1500
 Lymphopenia: ALC <1000

Platelet Disorders
› Thrombocytosis
› Thrombocytopenia


Widely variable implications; life-threatening to
benign
Benign (familial) Neutropenia
› African, W Indian, Sephardic Jews, Yemenites, Arab
Jordans

Acquired Neutropenia
›
›
›
›

Post infectious (bacterial, viral, paracytic)
Drug-induced – within 3 months
Autoimmune/Collagen Vascular Disorders
Immune Mediated
Hospitalized Patient
› Drugs, Toxins, Sepsis, Virus
› Bone marrow failure (rarely isolated neutropenia)
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Infections: TB, HIV, hepatitis, malaria
Congenital Immune Deficiencies
Immunosuppressive therapy: Rituxan, steroids
Chemotherapy/Radiation
Autoimmune disorders
Lymphoma
Sarcoid
Alcohol Abuse
Malnutrition

Red Cell Disorders
› Anemia
› Polycythemia

White Cell Disorders
› Leukocytosis
› Leukopenia

Platelet Disorders
› Thrombocytosis
› Thrombocytopenia

Laboratory finding of elevated platelets
>450,000/microL

Can be primary (essential thrombocytosis)
or secondary
Is the thrombocytosis reactive or a result of
bone marrow overproduction?
 Is there any immediate risk to the patient?

Asymptomatic Laboratory Finding
 Vasomotor symptoms: Visual
disturbance, Lightheadedness,
Headaches, Palpitations, Atypical Chest
Pain, Erythromlealgia, Paresthesias
 Thrombosis (15% at presentation)
 Major Hemorrhage (5-10% of patients
over disease course)
 Splenomegaly (less than 50%)

Iron Deficiency
 Severe Trauma/Burns
 Post-Splenectomy or CABG
 Metastatic Malignancy
 Acute Pancreatitis
 Chronic Infections (TB)
 Rheumatologic Disorders/Vasculitis
 IBD/Celiac Disease

Careful patient history to exclude
reactive causes of thrombocytosis
 Iron Studies, CRP/ESR, Peripheral Smear
 JAK-2 Mutation (present in 55-60% of
essential thrombocytosis cases)
 Bone Marrow Biopsy (increased
Megakaryocytes)


One of the myeloproliferative disorders
WHO Criteria for Diagnosis of ET
Sustained Platelet Count >450,000
Bone Marrow showing proliferation of Megakaryocytes
Does not meet the criteria for the diagnosis of another MPD
JAK2 mutation positive or, if JAK2 negative, an unrevealing
evaluation for secondary causes of thrombocytosis

Decision to treat is based on risk
stratification
Low Risk
Age <60
No CV Risk Factors
PLT <1,500,000
No prior thrombosis
Consider ASA
Intermediate
Risk
Not High or Low Risk
Consider ASA
High Risk
Age >60
Prior thrombosis
Consider ASA and
Cytoreductive
therapy
Patients >60 years, Aspirin should not be
used if platelets >1,500,000 because of
increased risk of bleeding
 Low and Intermediate Risk patients
should be observed and cytoreductive
therapy initiated when platelets are
>1,500,000

Myelosuppressive Agents – Hydroxyurea
(usually the first agent of choice)
 Maturation Modulators – Anagrelide
 Antiplatelet Agents
 Plateletpheresis – in extreme, acute
situations


Goal of cytoreductive treatment should
be a sustained platelet count <400,000

Red Cell Disorders
› Anemia
› Polycythemia

White Cell Disorders
› Leukocytosis
› Leukopenia

Platelet Disorders
› Thrombocytosis
› Thrombocytopenia

Platelet count less than the lower level of
normal (130-150,000/microL)

Surgical Bleeding (solely due to low
platelets) starts with <50,000/microL

Spontaneous Bleeding <10-20,000/microL

Decreased Platelet Production
›
›
›
›

Infection: HIV, hepatitis C, parvovirus
Chemotherapy/Radiation
Alcohol
Congenital/Acquired Bone Marrow Failure
Increased Platelet Destruction
› Drugs: heparin, Valproic Acid, quinine, Bactrim,
Digoxin, Amiodarone, H2-blockers
› Autoimmune Platelet Destruction: ITP, TTP/HUS
› DIC

Pseudothrombocytopenia
› Platelet Clumping
Inadequately anti-coagulated or
incompletely mixed samples can form a
clot that traps platelets
 Exposure of blood to the anti-coagulant
EDTA may induce platelet clumping;
platelet clumps are counted as
leukocytes instead of platelets

› 0.1% of people have EDTA dependent
agglutinins
If observed platelet count should be
repeated using heparin (green top tube)
or sodium citrate (blue top tube) as the
anticoagulant
 If citrate is used as the anticoagulant the
platelet count should be adjusted based
on a correction factor to account for
dilution

Acquired thrombocytopenia caused by
autoimmune destruction of platelets
 Typical presentations:

› Markedly reduced platelet counts and
mucocutaneous bleeding
› Asymptomatically with mildly decreased
platelets found incidentally

Generally idiopathic but can be
associated with disorders of immune
dysregulation or lymphoproliferation
No single test is diagnostic of ITP; primarily
a diagnosis of exclusion
 New onset isolated thrombocytopenia
with no other readily identifiable cause
 Requires careful review of patient’s
medications, peripheral smear review
and screen for viral causes


Initial Management: Corticosteroids
› 60-75% initial response rate

Additional Treatments:
› IVIG 1gm/kg x2 days
› Anti-D 75 mcg/kg/day (Rh+, non-anemic
patients only)
› Rituxan 375mg/m2 IV weekly x4 doses
› TPO Agonists
 Romiplostim (N-plate)
 Eltrombopag (Promacta)
Aplasia
 Acute leukemia, myelodysplasia,
myeloma
 Infiltration with lymphoma, solid tumours,
tuberculosis
 Megaloblastic anemia
 Paroxysmal nocturnal hemoglobinuria
 Myelofibrosis


Group of disorders characterized by
uncontrolled proliferation of myeloid or
lymphoid progenitor cells that gradually
replace normal hematopoiesis in the
bone marrow
› Acute Myeloid Leukemia (AML)
› Acute Lymphoblastic Leukemia (ALL)

Several subtypes exist based upon the
specific cell type which has become
malignant
Usually present with bone marrow failure
and pancytopenia
 Tissue infiltration by leukemic blasts
 Fatigue, dyspnea, fever, infection,
bleeding, bone pain
 Anemia, thrombocytopenia,
neutropenia, DIC, hyperuricemia,
elevated LDH
 Elevated peripheral blood WBC with
increased blast population


Therapy is individualized based on
patient factors (age, co-morbidities) and
disease factors (sub-type, molecular
mutations, cytogenetics)
High dose chemotherapy
 Bone Marrow Transplant
 Palliative chemotherapy
 Primary palliative care


Lichtman, M. et.al. Williams Hematology, seventh
edition. McGraw-Hill Medical. 2006
 Rodgers, G. and Young, N. The Bethesda
Handbook of Clinical Hematology, second edition.
Lippincott, Williams and Wilkins. 2010.
 Images from UptoDateOnLine as sited.