Macrocytic Anemias
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Transcript 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
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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:
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Pernicious Anemia
Gastrectomy/Gastric Bypass
Ileal disorders
Inadequate intake
Additional Symptoms:
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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
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
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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
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
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
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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)
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
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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
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