84 Essential Thrombocythemia Flashcards
TRUE OR FALSE
The annual incidence of ET is approximately 2 per 100,000 population and appears slightly more common in females.
TRUE
The annual incidence of ET is approximately 2 per 100,000 population and appears slightly more common in females.
Mutation present in the majority of JAK2/MPL–wild-type patients
Calreticulin gene (CALR)
A JAK2V617F mutation is found in approximately _____ of patients with ET.
50%
Acquired mutations in C-MPL are found in 4% of ET patients
A key endoplasmic reticulum protein with calcium-buffering and protein chaperone activity
Calreticulin
Approximately ____% of ET patients have a mild degree of palpable splenomegaly at diagnosis
10%
Major source of morbidity and mortality in ET
Thrombosis
A distinct clinicopathologic syndrome caused by occlusion of small blood vessels, manifests as discomfort and burning sensations in the fingers or toes, sometimes accompanied by mottling or discoloration of the skin.
Erythromelalgia
The strongest predictive factors for thrombotic complications
Age greater than 60 years
A history of previous thrombosis
Poor predictors of thrombotic risk
Platelet count and leucocyte count
The presence of this mutation is associated with a lesser risk of thrombosis or disease progression.
CALR
TRUE OR FALSE
Serious bleeding is less common than thrombosis and mainly affects the nasal and buccal mucosa and the gastrointestinal tract, although central nervous system hemorrhage may occur.
TRUE
Serious bleeding is less common than thrombosis and mainly affects the nasal and buccal mucosa and the gastrointestinal tract, although central nervous system hemorrhage may occur.
Laboratory investigation of thrombocytosis
two tests taken at least 3 months apart
- Medical History
- CRP/ESR
- MCV/Ferritin
Diagnostic Criteria for Essential
Thrombocythemia
- A1 Sustained platelet count >450 × 109/L
- A2 Presence of an acquired pathogenic mutation (eg, in JAK2,CALR, or MPL)
- A3 No other myeloid malignancy, especially polycythemia vera, primary myelofibrosis, chronic myeloid leukemia, or myelodysplastic syndrome
- A4 No reactive cause for thrombocytosis and normal iron stores
- A5 Marrow studies showing increased megakaryocytes displaying a spectrum of morphology with prominent large hyperlobulated forms; reticulin is generally not increased
Diagnosis requires A1 to A3 or A1 + A3 to A5
Causes of Spurious Thrombocytosis
- Cryoglobulinemia
- Cytoplasmic fragmentation in acute leukemia
- Red cell fragmentation
- Bacteremia
TRUE OR FALSE
The neutrophil count may be slightly to mildly elevated but is usually not above 20 × 109/L.
TRUE
The neutrophil count may be slightly to mildly elevated but is usually not above 20 × 109/L.
Levels of thrombopoietin are (decrease, normal or elevated) in ET and have no diagnostic utility.
Normal or slightly elevated
In the absence of marrow cytogenetic analysis, molecular testing for the ___________ is also recommended
BCR-ABL1 fusion gene
to exclude CML
The marrow aspirate in ET often shows
Large, hyperlobulated megakaryocytes
Mutation that shows hypocellular marrow in BMA
C-MPL
A secondary increase in platelet count, initiated by cytokines such as _________
Interleukin-6
Familial thrombocytosis is a rare disorder caused by mutations in ____________, _____________ or other unknown genes.
THPO (thrombopoietin gene)
C-MPL
Characteristics of patients with CML present with an isolated thrombocytosis
- Often female
- With absent or minimal splenomegaly
- A normal or marginally elevated white cell count
- Usually without basophilia or circulating myeloid progenitors.
- Small hypolobulated megakaryocytes typical of CML
TRUE OR FALSE
Suspected cases of ET that are negative for a relevant somatic mutation undergo molecular analysis of blood for the BCR-ABL1 fusion gene.
TRUE
Suspected cases of ET that are negative for a relevant somatic mutation undergo molecular analysis of blood for the BCR-ABL1 fusion gene.
MDS with associated thrombocytosis
Isolated deletion of chromosome 5q (“5q-minus syndrome”)
Refractory anemia, with ringed sideroblasts and thrombocytosis (MDS/MPN-RS-T)
Approximately half of patients with MDS/MPN-RS-T harbor a JAK2V617F mutation or, rarely, a mutation in C-MPL.
TRUE OR FALSE
Karyotypic abnormalities are present in up to 50% of ET patients compared with only approximately 5% of patients with PMF, indicating a greater degree of genetic instability.
FALSE
Karyotypic abnormalities are present in up to 50% of myelofibrosis patients compared with only approximately 5% of patients with ET, indicating a greater degree of genetic instability.
TRUE OR FALSE
In contrast to de novo AML, balanced chromosomal translocations are rare in post-MPN AML.
TRUE
In contrast to de novo AML, balanced chromosomal translocations are rare in post-MPN AML.
Drug that is recommended for nearly all ET patients unless contraindicated and is possibly not needed in patients with the lowest risk profile (eg, patients with CALR mutations and no other risk factors)
Aspirin
Risk Stratification for Patients with Essential Thrombocythemia
High Risk:
* Age >60 years
* Prior thrombosis
* Platelets >1500 × 109/L
Intermediate Risk:
* Age 40–60 years
Low Risk:
* Age <40 years
Drug used as first-line therapy for patients requiring treatment, and is the only cytoreductive agent proven to reduce thrombotic events
Hydroxyurea
Major complications of Hydroxyurea
Reversible myelosuppression
Ulceration of the buccal mucosa or lower leg
Drugs only recommended in patients older than 75 years of age
Pipobroman
Busulfan
Radioactive Phosphorus
A quinazoline derivative, reduces the platelet count by inhibition of megakaryocyte differentiation
Anagrelide
Side effects of Anagrelide
- palpitations
- fluid retention
- heart failure
- headaches
- Associated with an increase in marrow reticulin over time
- Result from its vasodilatory and positive inotropic actions
- Caution in older adult patients or those with preexisting cardiac disease.
Clinical trial showing nonsuperiority of Anagrelide to HU
ANAHYDRET Trial
Because this agent is free from leukemogenic or teratogenic effects, it is often used for younger patients or during conception and pregnancy.
Recombinant interferon-α
Pegylated interferon-α, for which less frequent administration is required, may be more convenient but the side effect profile appears similar to the native compound.
Drugs thar are effective at controlling the platelet count but are associated with an increased risk of progression to acute leukemia, particularly when used sequentially with hydroxyurea
Radioactive (32P) phosphorus
Alkylating agents such as busulfan
Both 32P and busulfan can be given intermittently, with long intervals between doses, and may be useful in treating older patients who are unable to visit the clinic on a regular basis.
Treatment for each type of ET
Very-low-risk:
Low-risk:
Intermediate-risk:
High-risk:
Very-low-risk: observation alone or, at most, Low-dose:aspirin therapy
Low-risk: once- or twice-per-day aspirin
Intermediate-risk: aspirin and hydroxyurea
High-risk: hydroxyurea and either twice-daily aspirin (arterial thrombosis) or hydroxyurea and systemic anticoagulation (eg, low-dose heparin or a direct thrombin inhibitor)
The three risk factors for classification of ET
History of thrombosis
Age greater than 60 years
Presence of either a JAK2 or C-MPL mutation
Thromboprophylaxis appears to be safe during pregnancy (eg, with low doses of low-molecular-weight heparin) and may be considered for patients with a history of thrombosis or pregnancy loss; in those with prior thrombosis, treatment should be continued for _______________postpartum
6 weeks
Factors independently associated with decreased overall survival in ET
History of prior thrombosis
Anemia
Leukocytosis
Additional factors with an increased risk of thrombosis:
* Predisposition to atherosclerotic diseases (diabetes, hypertension, hypercholesterolemia, or tobacco use)
* Presence of a JAK2V617F or C-MPL mutation or increased marrow fibrosis at diagnosis
Obstetric complications in ET are more prominent in those with_______________disease
JAK2V617F-positive
The agent of choice for patients with high-risk disease should cytoreductive therapy be required during pregnancy
Interferon-α
TRUE OR FALSE
Incidental (eg, traumatic) or elective splenectomy in ET patients generally results in an increase in the platelet count and also an increase in thrombotic and hemorrhagic complications, so should be avoided if at all possible.
TRUE
Incidental (eg, traumatic) or elective splenectomy in ET patients generally results in an increase in the platelet count and also an increase in thrombotic and hemorrhagic complications, so should be avoided if at all possible.
Considered to mandate cytoreductive therapy in ET patients
Age older than 60 years or
History of previous thrombosis
