MLAB 1415- Hematology Keri Brophy-Martinez

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MLAB 1415- HematologyKeri Brophy-Martinez

• Chapter 22
• MYELOPROLIFERATIVE DISORDERS (MPD)

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CHRONIC MYELOPROLIFERATIVE DISORDERS (MPD)

• Neoplastic clonal proliferation of hematopoietic
  precursors
• Defect found in pluripotential hematopoietic stem
  cell
• Bone marrow and peripheral blood show increases
  in RBCs, WBCs and/or platelets
• Characterized by a hypercellular bone marrow with
  increased quantities of one or more cellular
  lineages in the peripheral blood.

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MPDs

• Most common diseases included in the WHO
  classification of MPDs
• Chronic myelogenous leukemia (CML) Ph positive
• Polycythemia rubra vera (PRV or PV)
• Essential thrombocythemia (ET)
• Idiopathic myelofibrosis
• Clinically, patients with MPD present in a
  clinically stable phase that may transform to an
  aggressive cellular growth phase such as acute
  leukemia or just a more aggressive form of MPD

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General Features of MPD

• Affect middle-aged and older adults, peaks in the
  fifth to seventh decade of life
• Onset is gradual

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Clinical Features of MPD

• Hemorrhage
• Thrombosis
• Infection
• Pallor
• Weakness
• Hepatosplenomegaly, splenomegaly
• Night sweats
• Weight loss

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Lab Findings of MPD

• Anemia or polycythemia
• Leukoerythroblastosis
• Leukocytosis
• Thrombocytosis, bizarre platelets
• Decreased bone marrow iron

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Chronic Myelocytic Leukemia
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CML

• Also known as Chronic Granulocytic Leukemia (CGL)
• A clonal myeloproliferative disorder of
  hematopoietic pluripotent cell transformation
  characterized by marked leukocytosis and
  excessive production of granulocytes at all
  stages of maturation
• Etiology unknown (95 of cases)
• Associated with acquired chromosomal abnormality
  called Philadelphia Chromosome
• 90-95 of patients with CML carry Philadelphia
  Chromosome
• Translocation of chromosomes 9 and 22 t(922)

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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
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Three Phases of CML

• 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
• Unresponsive to treatment
• Prognosis less than 6 months
• gt 20 blasts in bm

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Laboratory Findings in CML

• Extreme leukocytosis (WBC gt 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)
• NRBCs
• Bone marrow ME ratio is 101
• Low LAP score (leukemoid reaction has high LAP)

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Blasts in accelerated phase
CML with left shift
Blasts in blast crisis
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Chronic myelogenous leukemia (CML)

• Treatment
• Chemotherapy to reduce the myeloid mass
• Bone marrow transplant
• Interferon (myelosuppressive drug)
• Gleevec (molecular targeted therapy)

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Polycythemias

• Classified into three Groups
• Polycythemia vera
• Normal or decreased EPO levels
• Autonomous cell proliferation
• Secondary polycythemia
• High altitude
• Chronic pulmonary disease
• Inappropriate EPO production
• Hemoglobins with a high O2 affinity
• Relative polycythemia
• Dehydration
• Stress polycythemia
• Pseudopolycythemia

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Polycythemia Vera

• Stem cell disorder characterized by a remarkable
  increase in red blood cell mass and total blood
  volume. There is also an increase in myeloid and
  megakaryocytic elements in the bone marrow.
• The clonal neoplastic transformation arises in a
  pluripotential hematopoietic stem cell
• Onset is usually around 60 years of age.
• Increased incidence in white males

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Polycythemia Vera

• Causes
• Hypersensitivity of erythroid progenitor cells to
  erythropoietin
• Hypersensitivity of erythroid progenitor cells to
  growth factors other than erythropoietin
• Inhibition of cell death, leaves alters cells

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Polycythemia vera

• Clinical features
• Patients have a ruddy cyanotic complexion due to
  congestion of blood vessels.
• Itching(pruritus)
• Headache
• Weakness
• Fever and night sweats
• Splenomegaly
• Brain circulatory disorders
• Myocardial infarction

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Lab Features of PV

• Absolute erythrocytosis of 6-10 x 10 12/L
• Hemoglobin Concentrations
• Male gt18.5 g/dL
• Female gt16.5 g/dL
• Hct Concentrations
• Male 52
• Female 48
• Increased WBC, plts
• Bone marrow
• Hypercellular

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Polycythemia vera

• Treatment
• Therapeutic phlebotomy for rapid reduction of RBC
  mass.
• Radioactive phosphorous for myelosuppression.
• Prognosis
• Survival time from diagnosis is 8-15 years
• 10-15 of patients convert to acute
  nonlymphocytic leukemia.

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Secondary polycythemias

• There are many causes that all result in
  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

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Relative polycythemia

• Stress polycythemia
• Hypertension
• Dehydration causes decreased plasma volume

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Essential thrombocythemia

• Rare chronic MPD in which platelets are increased
  and function is abnormal.
• Synonyms include primary thrombocythemia,
  idiopathic thrombocytosis, primary thrombocytosis

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ET

• Platelet count is
• gt 600 x 109/L
• Giant Bizarre platelets
• Platelet aggregates

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Idiopathic myelofibrosis

• Characteristics
• Marrow fibrosis
• 90 of attempts result in dry tap.
• Fibroblasts and increased collagen production
  lock in the marrow contents.
• Extramedullary hematopoiesis or myeloid
  metaplasia of spleen and liver
• NRBCs and immature WBCs in the peripheral
  blood, teardrop red cells, abnormal platelets

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Idiopathic myelofibrosis

• Treatment
• Transfusion for anemia
• Iron, folate and B12
• Steroids
• Splenectomy
• BM transplant
• Prognosis
• Median survival time is about 5 years from time
  of diagnosis.

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References

• McKenzie, Shirlyn B., and J. Lynne. Williams.
  "Chapter 21." Introduction. Clinical Laboratory
  Hematology. Boston Pearson, 2010. Print