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MLAB 1415- HematologyKeri Brophy-Martinez
MYELOPROLIFERATIVE DISORDERS (MPDs)
CHRONIC MYELOPROLIFERATIVE DISORDERS (MPDs)
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
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) Primary myelofibrosis (PMF)
MPDs present in a clinically stable phase that may transform to an aggressive cellular growth phase
General Features of MPDs
Occurs in persons over the age of 50 Peak incidence over age 60
Onset is gradual
Clinical Features of MPDs
Hemorrhage Thrombosis Infection Pallor Weakness Hepatosplenomegaly, splenomegaly Night sweats Weight loss
Chronic Myelocytic Leukemia
-CML-
6
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CML Also known as Chronic Granulocytic Leukemia (CGL) A clonal myeloproliferative disorder Observe marked leukocytosis and excessive production of
granulocytes at all stages of maturation
Etiology unknown (95% of cases) Seen more commonly in males
Associated with acquired chromosomal abnormality called Philadelphia Chromosome 90-95% of patients with CML carry Philadelphia Chromosome Translocation of chromosomes 9 and 22 t(9:22)
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 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 Unresponsive to treatment Prognosis less than 6 months > 20% blasts in bm
CML with left shift
Blasts in accelerated phase
Blasts in blast crisis
Laboratory Findings in CML
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)
Treatment Chemotherapy to reduce the myeloid mass Bone marrow/stem cell transplant Imatinib mesylate to inhibit tyrosine kinase
Polycythemia
Erythrocytosis with increased hgb concentration and red cell mass (hct)
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)
Stem cell disorder characterized by an increase in red blood cell mass and total blood volume. 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
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
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
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.
Secondary polycythemias
EPO levels increased
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
Red cell mass normal Decreased plasma volume Normal EPO Mild polycythemia
Essential thrombocythemia
Defect in megakaryocytic line 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
Primary myelofibrosis
Characteristics Marrow fibrosis
90% of attempts result in dry tap. Fibroblasts and increased collagen production lock in
the marrow contents. Extramedullary hematopoiesis occurs in spleen
and liver Splenomegaly, hepatomegaly
Left shift, thrombocytosis with bizarre platelets, teardrops, elliptocytes, ovalocytes
Primary 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.
References
McKenzie, Shirlyn B., and J. Lynne. Williams. "Chapter 21." Introduction. Clinical Laboratory Hematology. Boston: Pearson, 2010. Print