Ch 20: WBCs

Question 1

Neutrophil count that defines neutropenia? (List ranges for mild, moderate, and severe)

Answer 1

Mild: 1000-1500/ µL Moderate: 500-1000/ µL Severe: <500/ µL

Question 2

What are the general principles that lead to neutropenia?

Answer 2

Decreased production, ineffective production, or increased destruction

Question 3

List some causes of decreased production of neutrophils

Answer 3

Irradiation, drug induced, viral infection, congenital (Kostmann syndrome or infantile genetic agranulocytosis), cyclic

Question 4

List causes of ineffective production of neutrophils

Answer 4

Megaloblastic anemia, myelodysplastic syndromes

Question 5

List causes of increased destruction of neutrophils

Answer 5

isoimmune neonatal, autoimmune, idiopathic, drug induced, Felty syndrome, SLE, dialysis, splenic sequestration, increased margination **BIG PICTURE: 1) too much consumption, like in infection 2) too much sequestration, like in hypersplenism 3) too much Ab destruction

Question 6

Neutrophil count that defines neutrophilia?

Answer 6

Above 7000/ µL

Question 7

Causes of neutrophilia?

Answer 7

1) increased mobilization from bone marrow 2) enhanced release from marginal pool 3) stimulation of granulopoiesis

Question 8

Huge elevation of WBCs, usually in response to acute infections or severe hemorrhage. May be mistaken for leukemia, esp CML. Distinguished by segmented neutrophils, high leukocyte alkaline phosphatase activity, and blue cytoplasmic inclusions (Dohle bodies).

Answer 8

LEUKEMOID REACTION

Question 9

Seen in response to allergic reactions, parasitic infections, or persistent Ag-Ab complexes. Leads to necrosis, especially of myocardium and nervous system.

Answer 9

Eosinophilia - remember major basic protein causes the cell injury!

Question 10

Commonly observed in immediate-type hypersensitivity reactions and chronic myeloproliferative neoplasms. Think histamine, chondroitin sulfate, leukotrienes.

Answer 10

Basophilia

Question 11

Often occurs in neutropenic states as a compensatory mechanism

Answer 11

Monocytosis

Question 12

Myeloproliferative neoplasm, derived from abnormal pluripotent stem cell, strong association with Philadelphia chromosome, BCR/ABL, t(9;22)

Answer 12

Chronic Myelogenous Leukemia

Question 13

Phase of CML associated with lower blasts, normal platelets, hypercellularity in BM, and clusters of megakaryocytes.

Answer 13

Chronic phase

Question 14

Phase of CML associated with increasing WBC count, increasing splenomegaly, persistent thrombocytopenia, and 10-20% blasts

Answer 14

Accelerated phase

Question 15

Phase of CML associated with at least 20% blasts, extramedullary proliferation of blasts, clusters of blasts (hint: ___ from the past)

Answer 15

Blast phase

Question 16

Myeloproliferative neoplasm from clonal hematopoietic stem cell that leads to autonomous production of RBCs not regulated by EPO. Associated with JAK2 mutation. Hyperplasia of all hematopoietic elements.

Answer 16

Polycythemia Vera

Question 17

List the 3 stages of PV, and the erythropoietic pattern for each

Answer 17

1) Prepolycythemic - erythroid precursors abundant, maturation of cells normal 2) Polycythemic - erythroid precursors abundant, maturation of cells normal 3) Postpolycythemic - erythropoiesis ceases and there is an increase in extramedullary hematopoiesis (spleen!). Despite this EMH, stage characterized by anemia.

Question 18

So PV is an unregulated increase of RBC production. How high can the lab values actually go?

Answer 18

Hemoglobin can exceed 20 g/dL. Hematocrit surpasses 60%. Whoa. This implies all kinds of circulation difficulties including angina pectoris, claudication, GI ulcers, thrombosis (stroke, MI)

Question 19

Myeloproliferative neoplasm characterized by megakaryopoiesis, granulopoiesis, and marrow fibrosis

Answer 19

Primary myelofibrosis

Question 20

Stage of primary myelofibrosis presenting with thrombocytosis, hypercellular bone marrow, and megakaryocytes with atypical “cloud-like” nuclei

Answer 20

Prefibrotic (early stage)

Question 21

Stage of primary myelofibrosis presenting with tear drop RBCs, a characteristic reticulin or collagen fibrosis in the marrow, and extramedullary hematopoiesis

Answer 21

Fibrotic (late stage)

Question 22

Myeloproliferative neoplasm associated with JAK2 mutation or MPL mutation. Peak incidence ~70yo. In rare cases, can transform to AML.

Answer 22

Primary myelofibrosis

Question 23

What do the megakaryocytes distinctly look like in essential thrombocytopenia?

Answer 23

Stag-horn-shaped

Question 24

Uncontrolled proliferation of megakaryocytes, accompanied by recurrent episodes of thrombosis and hemorrhage?

Answer 24

Essential thrombocytopenia

Question 25

Abnormal accumulation of mast cells in tissues

Answer 25

Mastocytosis

Question 26

Form of mastocytosis associated with nodules on skin, usually occurring in kids that can spontaneously resolve

Answer 26

Cutaneous - most common is urticaria pigmentosusm

Question 27

Form of mastocytosis associated with infiltration of mast cells to various organs. Can be indolent, aggressive, or leukemic. Often due to c-kit mutation, and compact aggregates of mast cells usually form

Answer 27

Systemic

Question 28

Group of syndromes characterized by peripheral blood cytopenia, marrow failure, and dysplastic morphology in one or more blood cell lineage

Answer 28

Myelodysplastic syndromes (up to 40% of these patients progress to have AML)

Question 29

All subtypes of myelodysplastic syndromes manifest these

Answer 29

Refractory anemia and/or cytopenia.

No erythrocytosis, leukocytosis, or thrombocytosis.

Question 30

Risk factors for developing a myelodysplastic syndrome

Answer 30

Hx of tx with alkylating agent or topo II inhibitor, radiation, benzene exposure, cigarette smoking, some congenital disorders

Question 31

Clonal proliferation of myeloblasts in the marrow, MPO+, may have presence of Auer rods in cytoplasm?

Answer 31

Acute Myeloid Leukemia

Question 32

What are the various classifications of AML?

Answer 32

1) Recurrent genetic abnormalities, 2) myelo-dysplasia related changes, 3) therapy related, 4) not otherwise categorized, 5) myeloid sarcoma, 6) related to Down Syndrome

Question 33

Type of AML with genetic abnormality t(15;17) that results in PML/RAR-alpha fusion gene. Patients frequently present with DIC.

Answer 33

Acute promyelocytic leukemia

Question 34

Extramedullary solid tumor of myeloblasts or monoblasts (called chloroma, granulocytic sarcoma, or monoblastic sarcome)

Answer 34

Myeloid sarcoma

Question 35

Pt presents with headache, itching, and splenomegaly. High Hgb (19.8), high WBCs (12,800), high platelets (550,000). Bone marrow displays hypercellularity. What kind of myeloproliferative disorder do they most likely have?

Answer 35

Polycythemia vera- uncontrolled upregulation of RBCs. Look for symptoms of hyperviscosity of blood (headache, blurry vision, itching, thrombosis/cerebrovascular accident)

Question 36

An older pt presents with increasing fatigue and pancytopenia. BM shows hypercellularity and ringed sideroblasts. What is the likely diagnosis? What is the best explanation of pathogenesis?

Answer 36

Myelodysplastic syndrome - changes in more than one cell lineage, can display ringed sideroblasts.

Usually occurs due to a clonal stem cell defect.

Question 37

60 yo pt presents with night sweats, weight loss, fatigability, discomfort in abdominal ULQ. Labs show marked leukocytosis, with a lot of mature granulocytes, myelocytes, and basophils. BM is hypercellular with mostly WBC precursors. What is your best diagnosis?

Answer 37

Chronic myelogenous leukemia. Forgot to mention that they found a t(9;22), with abl at the chromosomal breakpoint.

Question 38

60 yo pt presents with weakness, hematuria, hepatosplenomegaly, and numerous ecchymoses. Normochromic normocytic anemia, thrombocytopenia, neutropenia, and marked leukocytosis with myeloblasts in the peripheral blood are present. What is going on?

Answer 38

Pt has AML, which suppresses normal hematopoiesis

Question 39

48 yo pt presents with productive cough and fever. Leukocytosis and elevated leukocyte alkaline phosphatase are seen in labs. Is this CML, or a leukemoid reaction? How did you differentiate?

Answer 39

Leukemoid reaction! 1) LAP is elevated

Other things to look for are comparison of maturity of cells in peripheral blood vs marrow, blue cytoplasmic inclusions called Dohle bodies, and comparison of basophils