ET, PV, MPF Flashcards by Kyra Catedral

ESSENTIAL THROMBOCYTEMIA

aka (3)

known as primary thrombocytosis

idiopathic thrombocytosis

hemorrhagic thrombocythaemia

How well did you know this?

Not at all

Perfectly

platelet count:

greater than 600 × 10^9/L

sometimes 1000 × 10^9/L

How well did you know this?

Not at all

Perfectly

WHO: requires a sustained thrombocytosis (platelet count of_________)

450 × 10^9/L or greater

How well did you know this?

Not at all

Perfectly

Majority: between the ages of_____

50 and 60 years

How well did you know this?

Not at all

Perfectly

is a chronic myeloproliferative neoplasm (MPN) characterized by elevated platelet counts due to excessive proliferation of megakaryocytes in the bone marrow.

Essential thrombocythemia (ET)

How well did you know this?

Not at all

Perfectly

two MPL mutations results in:

cytokine-independent growth

constitutive downstream signaling pathways and favors the ET phenotype

How well did you know this?

Not at all

Perfectly

CALR

type 1 (quantitative) and two type 2 (qualitative) mutations

______type 1 mutations____ type 2 mutations.

45%

39%

How well did you know this?

Not at all

Perfectly

MPL meaning

Myeloproliferative Leukemia Virus Oncogene

How well did you know this?

Not at all

Perfectly

MPL encodes the_______, which is critical for regulating megakaryocyte development and platelet production.

thrombopoietin receptor

How well did you know this?

Not at all

Perfectly

There are two major types of CALR mutations:

•________ – Accounts for 45% of cases and leads to a complete loss of CALR function, causing increased cell proliferation.

•________ – Found in 39% of cases and results in an altered CALR protein with enhanced oncogenic potential.

Type 1 (quantitative mutation)

Type 2 (qualitative mutation)

How well did you know this?

Not at all

Perfectly

CLINICAL PRESENTATION OF ET
VRBAT

Vascular occlusions
Repeated splenic infarcts
Bleeding
Arterial thrombi
Thrombosis

How well did you know this?

Not at all

Perfectly

• Caused by microvascular thromboses in small blood vessels, especially in the digits (fingers and toes).

Vascular Occlusions

How well did you know this?

Not at all

Perfectly

Vascular occlusion

• Can also involve major arteries and veins, leading to_____ and _____

deep vein thrombosis (DVT) pulmonary embolism (PE)

How well did you know this?

Not at all

Perfectly

ET
• Recurrent______(blockage of blood supply to the spleen) lead to progressive_____(shrinkage of the spleen).

• This can contribute to hypersplenism (overactive spleen function) and increased platelet destruction.

splenic infarctions

splenic atrophy

How well did you know this?

Not at all

Perfectly

Thrombosis
• _______– Clot formation in the lungs, leading to shortness of breath and chest pain.

• Neurologic complications – Including________ and ______

Pulmonary embolism (PE)

transient ischemic attacks (TIAs) and strokes (cerebrovascular accidents, CVAs)

How well did you know this?

Not at all

Perfectly

Bleeding
- occurs most often from mucous membranes in the (4)

GIT
skin
urinary
URT

How well did you know this?

Not at all

Perfectly

Arterial Thrombosis
• Can cause severe cardiovascular events, including:
• ______– Heart attack due to blocked coronary arteries.
• ______– Temporary stroke-like symptoms caused by brief blockage of blood flow to the brain.
• ______– A full-blown stroke caused by prolonged blockage in the brain.

Myocardial infarction (MI)

Transient ischemic attack (TIA)

Cerebrovascular accident (CVA)

How well did you know this?

Not at all

Perfectly

DIAGNOSIS

may be secondary to chronic active blood loss, hemolytic anemia, chronic inflammation, infection, or nonhematologic neoplasia

Thrombocytosis

How well did you know this?

Not at all

Perfectly

Peripheral Blood Smear
• Platelets may appear normal, but some show giant, bizarre shapes, and platelet aggregates.
• Micromegakaryocytes (immature small megakaryocytes) may be found in clusters.
• Abnormal platelet function can be detected through specialized platelet aggregation tests.

How well did you know this?

Not at all

Perfectly

ET PBS

Red Blood Cells (Erythrocytes)

• Typically_____
• If bleeding occurs,_____ (increased immature red cells) may be seen as a compensatory response.

normocytic and normochromic (normal size and hemoglobin content).

reticulocytosis

How well did you know this?

Not at all

Perfectly

PBS

Leukocytosis
- ranges from______
-______ neutrophils may be increased

22 to 40 × 10^9/L

Segmented

How well did you know this?

Not at all

Perfectly

TREATMENT

When is Treatment Needed?
• Patients with thrombocytosis but no history of______ may not require immediate treatment.
• However, if platelet counts are extremely high or if the patient has a history of thrombosis, intervention is necessary.

thrombosis

How well did you know this?

Not at all

Perfectly

TREATMENT

production of platelets must be reduced - by suppressing marrow megakaryocyte production with_____ and _____

hydroxyurea
anagrelide

How well did you know this?

Not at all

Perfectly

TREATMENT

• A procedure that removes excess platelets from the blood in severe cases

Plateletpheresis

How well did you know this?

Not at all

Perfectly

ET PROGNOSIS Median survival is______, even in younger patients.

~20 years

ET PROGNOSIS Most common causes of death:

• Thrombosis (clotting complications). • Bleeding (due to dysfunctional platelets).

ET PROGNOSIS Patients with______ abnormalities have a poorer prognosis, indicating more aggressive disease progression

chromosomal

***Splenomegaly is common*** disease arises in an HSC and is clonal in nature

- associated risk of ***hemorrhage*** and ***venous and arterial thrombosis***

> neoplastic clonal MPN producing erythrocytosis, often accompanied by ***increased granulocytes and platelets*** in the peripheral blood

• Most common MPN: It is the ***most frequently diagnosed myeloproliferative disorder.*** • Varies by country: Incidence rates differ based on geographic and ethnic factors. • Rare in children: It is almost never seen in children and primarily affects adults.

PV Most commonly diagnosed between ages_____ and _____ > peak incidence after the age of___ > Peak incidence for women is ____

40 and 60 years 60 years (men) < 40 years of age

> occurs more often in men than women and is > more common in people of Jewish descent.

PV > more common in people of_____ descent

Jewish

PATHOGENIC MECHANISM > neoplastic clonal stem cells are hypersensitive to, or function independently of, EPO for cell growth. > increasing allele burden for JAK2 mutations correlates with disease progression in ___ patients,

PATHOGENIC MECHANISM OF PV • Hypersensitive to_____– Meaning that even low levels of it will trigger excessive RBC production. • Independent of ____ signaling – Some mutated cells do not require ___ at all to continue proliferating.

erythropoietin (EPO)

is a key signaling molecule in the JAK-STAT pathway, which ***controls blood cell production in response to cytokines like EPO.***

JAK2 (Janus Kinase 2)

The ________ mutation is found in over 95% of PV cases and results in constant activation of this pathway, leading to uncontrolled red cell production.

JAK2 V617F mutation

PATHOGENIC MECHANISM OF PV The allele burden (the percentage of blood cells carrying the____ mutation) correlates with disease severity and progression. • Higher allele burden → Increased risk of progression to myelofibrosis (MF) or acute myeloid leukemia (AML).

JAK2

CLINICAL PRESENTATION PV In the early stages of PV, the excessive RBC production leads to markedly increased_______, which thickens the blood and causes______-related symptoms such as: • _______– Present in ~50% of PV patients, due to increased blood volume and resistance.

hematocrit (>60%) hyperviscosity Hypertension (high blood pressure)

CLINICAL PRESENTATION PV Patients, especially those over____ years old or with a history of thrombosis, are at high risk for thrombotic or hemorrhagic events

60 yrs old

TREATMENT AND PROGNOSIS OF PV (3) types of therapies TMT

Therapeutic phlebotomy Myelosuppressive therapy Targeted molecular therapy

TREATMENT AND PROGNOSIS OF PV • First-line treatment for ***low-risk PV patients*** (______, no history of thrombosis).

Therapeutic Phlebotomy (Blood Removal) Low dose aspirin <60 years old

TREATMENT AND PROGNOSIS OF PV Therapeutic phlebotomy • Involves removing blood periodically to maintain: • Hematocrit_____ in men • Hematocrit_____ in women • Effectively reduces blood viscosity and lowers the risk of thrombotic events. • Not a disease-modifying treatment – Does not eliminate the malignant clone but helps manage symptoms.

<45% <42%

TREATMENT AND PROGNOSIS OF PV > treatment of choice for PV in low-risk patients (<60 years old and no thrombosis history) (2) (maintain the hct at less than 45% for men and 42% for women)

low-dose aspirin therapeutic phlebotomy

TREATMENT AND PROGNOSIS OF PV ______ is a common clinical feature of PV - avoid (3)

Pruritus hot baths to towel dry gently to reduce skin irritation antihistamine

TREATMENT AND PROGNOSIS OF PV high-risk patients with PV (_____)

>60 years old with thrombosis history

TREATMENT AND PROGNOSIS OF PV high-risk patients with PV (>60 years old with thrombosis history) - first-line therapy:______ - in conjunction with_____ and _____

alkylating agent and hydroxyurea phlebotomy and low-dose aspirin

Suppresses bone marrow overproduction of RBCs, WBCs, and platelets.

Hydroxyurea (alkylating agent)

PMF It was previously known as

chronic idiopathic myelofibrosis

considered the least common but most aggressive form of MPNs.

PMF

is a clonal hematopoietic stem cell (HSC) disorder classified under myeloproliferative neoplasms (MPNs).

Primary myelofibrosis (PMF)

bone marrow ineffective hematopoiesis associated with areas of marrow hypercellularity, extramedullary hematopoiesis, fibrosis, and increased megakaryocytes

PMF

> least common but most aggressive form of MPN.

PMF

PBS • peripheral blood film immature • granulocytes and normoblasts, • Dacryocytes (teardrop-shaped RBCs) • Vother bizarre RBC shapes.

PMF

PMF is further subdivided:

prefibrotic/early stage PMF overt fibrotic stage PMF

PMF Extramedullary hematopoiesis (EMH) – Because the bone marrow cannot produce enough blood cells, blood cell production shifts to secondary sites, such as the____ and ______, leading to_____ and ______

spleen and liver splenomegaly and hepatomegaly

PMF Characterized by ***increased megakaryocytes and hypercellular marrow before fibrosis sets in.***

Prefibrotic/Early Stage PMF –

PMF – Progressive bone marrow fibrosis ***leads to pancytopenia*** (low counts of RBCs, WBCs, and platelets) and increased extramedullary hematopoiesis.

Overt Fibrotic Stage PMF

> reactive process causes ***overproduction of collagen***

MYELOFIBROSIS

- disrupts the normal architecture of the bone marrow - replaces hematopoietic tissue resulting in pancytopenia

MYELOFIBROSIS

***the abnormal release or leakage of Platelet-derived growth factor (PDGF) from the platelet*** - results in reduced platelet concentrations of PDGF and increased levels of serum PDGF that are characteristic of PMF

Myelofibrosis

________ is a protein that helps cells grow and divide, and is released from platelets. _____ is important for wound healing, blood vessel repair, and normal development

Platelet-derived growth factor (PDGF)

- recognized as hepatomegaly or splenomegaly (caused by the release of clonal stem cells into the circulation)

Extramedullary hematopoiesis

INCIDENCE AND CLINICAL MANIFESTATION PMF • patients older than age_____ and equally among men and women

INCIDENCE AND CLINICAL MANIFESTATION > may be asymptomatic - progresses as a slow, chronic condition. > Symptoms result from anemia, myeloproliferation, or splenomegaly

PMF

INCIDENCE AND CLINICAL MANIFESTATION PMF most common constitutional symptoms FB NPF

fatigue (84%) bone pain (47%) night sweats (56%) pruritus (50%) fever (18%)

INCIDENCE AND CLINICAL MANIFESTATION PMF ______- 90% of patients with PMF ______- 50%

Splenomegaly Hepatomegaly

PERIPHERAL BLOOD AND BONE MARROW PMF early stages / anemia,

• leukocytosis with a left shift, and • thrombocytosis

PERIPHERAL BLOOD AND BONE MARROW PMF - common in the later stages.

thrombocytopenia