MLAB 1415- Hematology
Keri Brophy-Martinez
MYELOPROLIFERATIVE
DISORDERS (MPDs)
CHRONIC MYELOPROLIFERATIVE
DISORDERS (MPDs)
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Defect found in pluripotential hematopoietic stem cell
due to a genetic mutation
 Production of a pathogenic clone
Bone marrow and peripheral blood show increases in
RBCs, WBCs and/or platelets
 Clonal expansion
Characterized by a hypercellular bone marrow with
increased quantities of one or more cellular lineages in
the peripheral blood.
MPDs
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Most common diseases included in the WHO
classification of MPDs:
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Chronic myelogenous leukemia (CML) Ph positive
Polycythemia rubra vera (PRV or PV)
Essential thrombocythemia (ET)
Primary myelofibrosis (PMF)
MPDs present in a clinically stable phase that
may transform to an aggressive cellular growth
phase
General Features of MPDs
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Occurs in persons over the age of 50
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Peak incidence over age 60
Onset is gradual
Clinical Features of MPDs
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Hemorrhage
Thrombosis
Infection
Pallor
Weakness
Hepatosplenomegaly, splenomegaly
Night sweats
Weight loss
Chronic
Myelocytic Leukemia
-CML-
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CML
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Also known as Chronic Granulocytic Leukemia (CGL)
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A clonal myeloproliferative disorder
Observe marked leukocytosis and excessive production of
granulocytes at all stages of maturation
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Etiology unknown (95% of cases)
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Seen more commonly in males
Associated with acquired chromosomal abnormality called
Philadelphia Chromosome
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90-95% of patients with CML carry Philadelphia Chromosome
Translocation of chromosomes 9 and 22 t(9:22)
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Philadelphia Chromosome
Main portion of the long arm of chromosome 22 is
deleted and translocated to distal end of long arm of
chromosome 9, and a small part of chromosome 9
reciprocally translocates to the broken end of
chromosome 22
Three Phases of CML
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Chronic
 Controllable with chemotherapy
 Lasts 2-5 years
Accelerated
 Lasts 6-18 months
 10-19% blasts in PB and BM
 Low Platelet counts
 Increasing WBC counts
Blast crisis
 Involves the PB, BM, extramedullary tissue
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Unresponsive to treatment
Prognosis less than 6 months
> 20% blasts in bm
Blasts in accelerated
phase
CML with left shift
Blasts in blast crisis
Laboratory Findings in CML
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Extreme leukocytosis (WBC > 100,000 x 109/L)
Marked left shift
 Predominance of segs and myelocytes
Thrombocytosis (can exceed 1000 x 109/L)
 Variant platelet shapes
 Function can be abnormal
Normochromic-normocytic anemia (Hgb 9-13 g/dL)
NRBC’s rare
Bone marrow M:E ratio is 10:1(Hypercellular)
Low LAP score (leukemoid reaction has high LAP)
Uric acid elevated- due to cell turnover
Chronic myelogenous leukemia
(CML)
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Treatment
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Chemotherapy to reduce the myeloid mass
Bone marrow/stem cell transplant
Imatinib mesylate to inhibit tyrosine kinase
Polycythemia
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Erythrocytosis with increased hgb concentration and
red cell mass (hct)
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Classified into two types
 Absolute- Result from increased red cell mass
 Polycythemia vera (PV)
 Secondary polycythemia
 Relative- Due to a decrease in plasma volume
Polycythemia Vera (PV)
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Stem cell disorder characterized by an increase in
red blood cell mass and total blood volume.
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Mutation in JAK2 gene- activated erythrocyte
production
EPO levels are decreased to normal
Cell death is inhibited
There can also be an increase in myeloid and
megakaryocytic elements in the bone marrow.
Peak incidence in white males, around age 60
Clinical Features:
Polycythemia vera
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Patients have a ruddy cyanotic complexion due to congestion of
blood vessels. “Plethora”
Itching(pruritus)
Headache
Weakness
Fever and night sweats
Splenomegaly
Brain circulatory disorders
Myocardial infarction
Lab Features of PV
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Absolute erythrocytosis of 6-10 x 10 12/L
Hemoglobin Concentrations
 Male: >18.5 g/dL
 Female: >16.5 g/dL
Hct Concentrations
 Male: 52%
 Female: 48%
Increased WBC, plts
Bone marrow
 Hypercellular
Polycythemia vera
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Treatment
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Therapeutic phlebotomy for rapid reduction of
RBC mass.
Radioactive phosphorous for myelosuppression.
Prognosis
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Survival time from diagnosis is 8-15 years
10-15% of patients convert to acute
nonlymphocytic leukemia.
Secondary polycythemias
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EPO levels increased
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Causes of increased secretion of erythropoietin
 Increase in erythropoietin in response to tissue hypoxia
 High altitude
 Chronic pulmonary disease
 Obesity/sleep apnea
 Smoking
 Familial hemoglobin variants
 High oxygen affinity hemoglobinopathies
 Inappropriate increase in erythropoietin
 Renal cysts or renal transplants due to tissue hypoxia of the
juxtaglomerular apparatus that generates EPO
 Neoplasms
 Endocrine disorders
Relative polycythemia
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Red cell mass normal
Decreased plasma volume
Normal EPO
Mild polycythemia
Essential thrombocythemia
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Defect in megakaryocytic line
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Results in increase in megakaryocytes in the BM
Increase in platelets in PB
Platelet abnormalities in diameter, shape,
granularity, function
Synonyms include primary thrombocythemia,
idiopathic thrombocytosis, primary
thrombocytosis
ET
Platelet count is
> 600 x 109/L
 Giant Bizarre platelets
 Platelet aggregates
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Primary myelofibrosis
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Characteristics
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Marrow fibrosis
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Extramedullary hematopoiesis occurs in spleen
and liver
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90% of attempts result in dry tap.
Fibroblasts and increased collagen production lock in
the marrow contents.
Splenomegaly, hepatomegaly
Left shift, thrombocytosis with bizarre platelets,
teardrops, elliptocytes, ovalocytes
Primary myelofibrosis
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Treatment
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Transfusion for anemia
Iron, folate and B12
Steroids
Splenectomy
BM transplant
Prognosis
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Median survival time is about 5 years from time of
diagnosis.
References
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McKenzie, Shirlyn B., and J. Lynne. Williams.
"Chapter 21." Introduction. Clinical
Laboratory Hematology. Boston: Pearson,
2010. Print