Myeloproliferative Disorders Flashcards by Iseoluwa Ojo

Myeloproliferative disorders

These are clonal neoplastic disorders of _____________ characterized by excessive proliferation of one or more of the ______ cell lineages ( granulocytic, erythroid ,megakaryocytic , and ____ cells)

pluripotent haematopoietic stem cell (HSC)

myeloid

masst

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Myeloproliferative disorders characteristics are:

Originates from ________
Usually _______ predominates in a given disorder.
Enlargements of _____ and ____ occur commonly.
Usually in (children or adults?) with a peak in the ___ to ____ decade

a single stem cell

one cell line

spleen and liver

adults; 5th to 7th

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INTRODUCTION to myeloproliferative disorders

Maturation of blood cells is relatively (normal or abnormal?) , so that (mature or immature ?) cells increase in number in the absence of ___________

Normal

mature

physiologic stimulus.

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INTRODUCTION to myeloproliferative disorders

There is a close relationship between different disorders with ________, overlapping ___________, and progression to __________ and ___________.

interconversions

manifestations

myelofibrosis and acute leukaemia

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INTRODUCTION to myeloproliferative disorders

Extramedullary hematopoiesis: blood cell production can also occur outside the bone marrow leading to ________________

enlargement of the liver and spleen.

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CLASSIFICATION is Based on nature of predominant proliferating cell line:

____________ (erythroid)

___________(megakaryocytic)

________________(granulocytes)

__________________ (fibrous tissue)

Primary polycythemia

Essential thrombocythemia

Chronic myeloid leukemia

Primary myelofibrosis

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CLASSIFICATION is Based on nature of predominant proliferating cell line:

_____________ leukaemia

Mastocytosis

_________________ (unclassifiable)

Chronic neutrophilic

Chronic eosinophilic

Myeloproliferative neoplasm

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PATHOGENESIS of Myeloproloferative diseases

The presence of mutated, constitutively activated _______ protein: ______.

Which results in the ______- (dependent or independent?) proliferation and survival of marrow progenitors

Proliferation of HSCs leads to a _______ marrow.

Proliferating cells undergo ( normal or abnormal?) differentiation, which results in increased blood counts of one or more mature blood elements.

tyrosine kinases ; JAK2

growth factor

independent; hypercellular

normal

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Tyrosine kinases activation normally occurs by the binding of __________ to ________ on the marrow progenitor cells.

hematopoietic growth factors

surface receptors

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POLYCYTHAEMIA

Polycythemia (Erythrocytosis) is defined as an increase in the ____________, usually with a corresponding increase in _________ level.

total red cell mass (RCM)

haemoglobin

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POLYCYTHAEMIA

The increase in RCM can be ______ or _______.

absolute or relative

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POLYCYTHAEMIA

can be classified into:

________ polycythemia (red cell mass is __________)

__________ or __________ polycythemia (red cell mass is _______________).

Absolute

raised

Relative or pseudo

normal but the plasma volume is reduced

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POLYCYTHAEMIA

Absolute polycythemia : which is subdivided into ____ and _______ polycythemia.

primary and secondary

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POLYCYTHAEMIA

In men, Hb > ____ g/dL or HCT >____

In women, Hb >____ g/dL or HCT >___

18.5; 0.52

16.5; 0.48

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Relative polycythemia

Characterized by ______ plasma volume with a _____ red cell mass.

reduced

normal

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Relative polycythemia

May result from ________: following ———-,———- , excessive use of _______

dehydration

vomiting, diarrhea,

diurectics

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Relative polycythemia

It can occur in ______ syndrome(______ spurious )

______ age
_____weight
Hypertensive
_____

Gaisbock

Middle

Over

anxiety

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POLYCYTHAEMIA

Secondary
Caused by physiologically appropriate increase in __________ in :

(Low or high?) altitudes
Pulmonary disease and alveolar hypoventilation (______)
Cardiovascular disease , especially ___________
Increased _____ of haemoglobin
Familial (congenital) polycythemia
Heavy cigarette smoking

erythropoietin

High; sleep apnea

cyanotic heart disease

affinity

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Causes of relative polycythemia

______________.

_________ syndrome

Haemoconcentration

Gaisbock

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POLYCYTHEMIA VERA(PCV)

Clonal, acquire disorder of the pluripotent haematopoietic stem cells causing excessive proliferation of the __________________________________ lineage

erythroids, myeloids, and megakaryocyte

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POLYCYTHEMIA VERA(PCV)

However, the major manifestation is seen in _______.
M

erythropoiesis

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POLYCYTHEMIA VERA(PCV)

Many cases of PCV also has an increase number of granulocytes or platelets

T/F

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POLYCYTHEMIA VERA

Two phases of PV can be recognized:

A _________ or _________ phase

A _____ or ___________ phase

proliferative or polycythemic

“spent”, or post-polycythemic

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POLYCYTHEMIA VERA

A proliferative or polycythemic phase: a ________ phase characterized by ________ leading to ____________

A “spent”, or post-polycythemic phase: this is characterized by _______ and ______

initial; proliferation of erythoid cells

increased red cell mass

cytopaenia and myelofibrosis

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_______ is the most common myeloproliferative disorder.

PCV

Epidemiology of PCV The incidence is approximately ___ cases per _____ per year. Median age at diagnosis is ____ years

3; 100000 60

PCV occurs at all ages PCV is very common below 30 years

T F(but it is very rare below 30 years)

Pathophysiology of PCV An ____eased number of cases have been reported in survivors of the ___________ Cytogenetic abnormalities are found in only _____% of patients at diagnosis.

incr ; Hiroshima atomic bomb. 10-20

Pathophysiology of PCV ____________ mutation associated Growth factor- independent proliferation and progenitor survival

JAK2 V617F

A genetic predisposition has been reported in some families of patients that have PCV T/F

Pathophysiology of PCV Increased _______in PV results in an increased _______ and increased blood ______ which can lead to vascular _______ and/or _______.

red cell production red cell mass ; viscosity; thrombosis; bleeding

Pathophysiology of PCV The ______ is directly proportional to the number of thrombotic events.

hematocrit

Pathophysiology of PCV Studies have demonstrated a reduction in cerebral blood flow in patients with hematocrits above ____%. ___________ can also contribute to bleeding and thrombosis.

53 Thrombocytosis

Clinical features of PCV Patients are frequently (symptomatic or asymptomatic?) at diagnosis and are discovered ______ when an elevated hematocrit is noted on a FBC. Most patients will develop symptoms as the __________ and _______ ————

asymptomatic; incidentally hematocrit and/or platelet count increase.

PCV Clinical features Major symptoms can be listed as follows: •Symptoms of _______ associated with an elevated hematocrit include headache, _______, _______, weakness, ______ and _______

hyperviscosity blurred vision; dizziness priapism and paresthesias.

PCV Clinical features _________ typically following a (cold or hot?) shower may be the main complaint. The etiology is unclear but may be associated with cutaneous _________

Pruritus Hot mast cell degranulation.

PCV Clinical Features Venous or arterial _______, involving ________ vessels is common. Complications include _______, TIA, CVA, myocardial infarction, and ________

thrombosis small and large cyanosis deep vein thrombosis.

PCV Clinical Features ________ sites of thromboses are seen more frequently in PCV: splenic, hepatic, portal, and mesenteric veins Ten percent of patients with _________ syndrome (_______________) have coexisting PV.

Unusual Budd-Chiari hepatic/IVC thrombosis

PCV Clinical Features Abnormalities in __________ can lead to epistaxis, bruising, gastrointestinal and gingival bleeding. Hyper metabolism caused by __________ can lead to ________ and _______

platelet function increased blood cell turnover hyperuricemia and gout.

PCV Clinical Features Gastrointestinal complaints are (common or rare?) including __________ and ________. Physical findings include _____,________, and _________

Common epigastric discomfort and peptic ulcer disease splenomegaly, hepatomegaly and facial plethora.

Laboratory findings of PCV Full blood count: 1. The haemoglobin , haematocrit and red cell count are increased (In men, Hb >_____ g/dL or HCT >0.52 and in women, Hb >_____ g/dL or HCT >0.48). 2. A ______ leukocytosis, raised ______ and raised _______ count is present in about half of the patients.

18.5 16.5 neutrophil; platelets; basophil

Laboratory findings of PCV JAK2 mutation analysis: JAK2 mutation is present in the _______ and peripheral blood _______ in 95% of patients. ____________________ (NAP) score is usually increased.

bone marrow; granulocytes Neutrophil alkaline phosphatase

Laboratory findings of PCV Bone marrow examination: The bone marrow is _______ with prominent _______ , best assessed by a ______ biopsy. Serum erythropoietin assay: Serum erythropoietin usually low in __________ but high in _______________

hypercellular; megakaryocytes; trephine polycythemia vera secondary polycythemia.

Laboratory findings of PCV Arterial oxygen saturation T/F

Criteria for diagnosis of polycythaemia (rubra) vera Major: ________ or __________ Minor: _____,______, or ________

Elevated red cell mass JAK2-V617F mutation Hypercellular bone marrow Low erythropoietin (EPO) EEC growth in vitro

PCV treatment Treatment focuses on decreasing the _________ to reduce ________ and its attendant complications.

hematocrit plasma viscosity

PCV treatment The goal of therapy is a hematocrit <___% and a platelet count <______.

45 400,000

PCV treatment _________ ___________ agents A small daily dose of ______ is recommended for its anti-platelet effect. ___________ to prevent urate nephropathy

Phlebotomy Myelosuppressive aspirin Allopurinol

Prognosis of PCV Without therapy, median survival of patients with PV is only __________, but is more than ______ with treatment. Major causes of death are _______ and _______ Up to 20% of patients develop __________ or __________ which are fatal.

6-18 months; 10 years thrombosis and hemorrhage. acute myelogeneous leukemia or myelodysplastic syndrome

Prognosis of PCV PCV patients can develop a “spent phase” late in their courses that resembles chronic idiopathic _______ with _____ and marrow _____ and ____ – referred to as post polycythemic myelofibrosis or _________ Post polycythemic myelofibrosis frequently transforms to _________

myelofibrosis; cytopenia hypoplasia and fibrosis; secondary myelofibrosis. acute leukemia

ESSENTIAL THROMBOCYTHEMIA Clonal myeloproliferative disorder that involves primarily the _____ cell line. It leads to the dysregulated production of large numbers of _________ in the marrow resulting in marked rise in platelet counts. ________ mutation are found in approximately 50% of patients with ET.

megakaryocyte mature megakaryocytes JAK2

ET Epidemiology The incidence of the disease is ______/100,000 individuals annually. Usually occurs at the age of _______ years. A second peak occurs at approximately ____ years of age, typically in (men or women?) .

2-3 50-60 30 Women

ET Clinical features Many patients are (symptomatic or asymptomatic?) and discovered when a routine blood count is performed. ______ manifestation and a predisposition to _______ events are the main clinical findings

asymptomatic Bleeding thrombotic

ET Clinical features _________ is classic of ET and is believed to be due to microvascular thrombosis of the digital vessel of fingers and toes. Spontaneous ______ due to placental thrombosis.

Erythromelalgia abortion

ET Clinical features Bleeding occurs most commonly from mucosal surfaces especially the __________ There may be mild ________ and less often _______________.

gastrointestinal tract. splenomegaly hepatomegaly

ET clinical features Transformation of ET to ________ or a _________ occurs in fewer than ___% of patients. There can also be delayed disease transformation into a fibrotic state called ______________ or _________

acute myeloid leukemia; myelodysplastic syndrome 5 post thrombocythemia myeloid metaplasia or myelofibrosis

ET Lab features Peripheral blood film shows marked ________. The platelets often display _______ (range from tiny forms to Giant platelets)

thrombocytosis anisocytosis

ET Lab features The bone marrow biopsy is usually ______. The most striking abnormality is marked proliferation of ___________________, usually occurring in loose clusters

hypercellular large and giant megakaryocytes

ET Lab features The white blood cell count and differential are usually (normal or abnormal?) . The red blood cells are ____cytic and _____chromic. _______________________.

Normal normo normo Leukoerythroblastosis

Diagnostic Criteria for ET 1. Persistent elevation of the _____ count ≥ _____ x 109/L. 2. Megakaryocyte proliferation with _______ and ———- morphology: _______ or _______ granulocyte or erythroid proliferation.

Platelet; 450 large and mature little or no

Diagnostic Criteria for ET 3. Not meeting ______ criteria for CML, PV, PMF, MDS, or other myeloid neoplasm. 4. Demonstration of ________ or other clonal marker or in the absence of a clonal marker, no evidence of reactive thrombocytosis.

WHO JAK2-V617F

ET Treatment and Prognosis ET is (an indolent or aggressive?) disorder, characterised by long symptom free intervals, interrupted by occasional life- threatening _________ or _______ episodes. Most patients enjoy a normal life expectancy.

indolent thromboembolic or hemorrhagic

ET Treatment and Prognosis Risk stratification in ET is primarily based upon factors that influence the occurrence of _______ complications. Patients are considered to be at high risk if they are >____ years of age and/or have a __________

thrombotic 60 prior history of thrombosis.

PRIMARY MYELOFIBROSIS (PMF) Clonal disorder of pluripotent stem cell characterised by the proliferation of mainly _________ and _______ elements in the bone marrow associated with reactive _______________________

megakaryocytic and granulocytic deposition of bone marrow connective tissue.

PRIMARY MYELOFIBROSIS (PMF) As the bone marrow becomes ____ and normal hematopoiesis can no longer occur, ______________ (EMH) occurs in the _________ - which worsens throughout the disease course. •

fibrotic extramedullary hematopoiesis liver and spleen

PRIMARY MYELOFIBROSIS (PMF) The EMH seems to be (effective or ineffective?) and the patients become _________. A leukoerythroblastic blood smear with ________ shaped red cells ( _______ ) is a characteristic finding in the fibrotic stage.

ineffective; pancytopenic tear drop; dacrocytes

PRIMARY MYELOFIBROSIS (PMF) Bone marrow fibrosis results from stimulation of _______ proliferation and ________ synthesis by _____________ and transforming growth factor

fibroblastic; collagen platelet derived growth factor

PMF Epidemiology Is a (common or rare?) disease The incidence MF is ___ per 100,000 populations per year. . Occurs predominantly in in persons over the age of ____ year.

Rare; 1.5 60

PMF Epidemiology Exposure to ______ and ______ has been documented in some cases. Up to 50% of patients have clonal ______ abnormalities at diagnosis.

benzene and ionizing radiation karyotypic

PMF Clinical Features About _____ of patients are asymptomatic at the time of diagnosis n. The symptoms of this disease are often non-specific. The majority are due to the ________ and ______.

one third anemia and splenomegaly

PMF Clinical Features The anemia can lead to weakness, fatigue and dyspnea. The enlarged spleen and liver can lead to abdominal discomfort and early _____. Progressive ______ is common because of early satiety _________ is present in at least 50% of the patients.

satiety weight loss Hepatomegaly

PMF Clinical Features Other constitutional symptoms include fever, anorexia, night sweats and bone pain. As the disease progresses, _______ occurs due to both ____________ and decreased ______________

pancytopenia splenic sequestration effective hematopoiesis.

PMF Clinical Features Rarely, extramedullary hematopoiesis can occur at other sites such as the skin, lung, bladder, lymph nodes, genitourinary tract, gastrointestinal tract and the central nervous system. T/F

PMF Clinical Features Bleeding is typically due to _______ or related to ______ from portal vein thrombosis. The proliferation of cells leads to chronic overproduction of _____ which can cause attacks of gouty arthritis.

thrombocytopenia; varices uric acid

PMF Diagnosis gold standard” for the diagnosis of PMF is ???

There is no “gold standard” for the diagnosis of PMF.

PMF Diagnosis Full blood count; RBC Haemoglobin usually ____(because of _________ and _______) _____chromic ____cytic indices

low ineffective erythropoiesis and hypersplenism Normo; normo

PMF Diagnosis Full blood count; WBC ____________ but it can be markedly _____. Platelet; usuall ____________,but ____eases as diseases progress

normal or reduced normal or elevated decr

PMF Diagnosis Blood film: •________ shaped red cell •____________ •Bone marrow aspirate: usually _____(____) •Bone marrow biopsy: shows _____,increase in the number of __________. It is essential for the diagnosis

Tear drops Leucoerythroblastosis unsucessfull (dry tap) fibrosis; abnormal megakaryocytes

Leucoerythroblastosis (________ red cells and ________ white blood cell)

nucleated immature

PMF stages _________ (_______) stage: _______ stage:

Prefibrotic(cellular) Fibrotic

PMF stages Prefibrotic(cellular) stage: _________ marrow due to _______ proliferation  Minimal or absent reticulin fibrosis Increased and abnormal ________

Hypercellular; granolocytes megakaryocytes

PMF stages Fibrotic stage: Presence of _______ fibrosis _____________ features

marrow Leucoerythroblastic

PMF Treatment and Prognosis ____________ treatments to reverse the process of idiopathic myelofibrosis. Treatment is mainly ________ Most care is directed toward ___________

There are no available supportive symptomatic management

PMF Treatment and Prognosis The anemia usually requires _____________ but may also respond to __________, ( low or high?) dose steroid or erythropoietin. Patients younger than ______ years old should be considered for allogeneic bone marrow transplantation.

red blood cell transfusions androgens ; Low 55

PMF Treatment and Prognosis The most common causes of death include infection, hemorrhage, thrombosis, cardiovascular disease, cerebrovascular disease and transformation to acute leukemia which occurs in 10-20% of patients in the first 10 years.

PMF Treatment and Prognosis _______ splenomegaly can be treated with chemotherapy (Hydroxyurea), splenectomy, splenic radiation or alpha Interferon.

Painful

PMF Treatment and Prognosis Average life expectancy is the worst among the CMPDs at ______years, but may approach _____ years in young patients with good prognostic factors.

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Myeloproliferative Disorders Flashcards

(87 cards)