Chapter 19: Myeloproliferative disorders Flashcards
What are myeloproliferative disorders?
Disorders arising in marrow stem cells that are characterized by clonal proliferation of hematopoietic elements
What are the three disorders that are considered myeloproliferative disorders?
(1) Polycythemia rubra vera
(2) Essential thrombocytopenia
(3) Myelofibrosis
What mutation is common to PRV, ET, and myelofibrosis?
A mutation in JAK2 is found in almost all patients with PRV, and over 50% of patients with ET and myelofibrosis.
What is polycythemia?
Polycythemia also known as erythrocytosis is an increase in hemaglobin concentration above the upper limit of what is normal for the patients age and sex.
How are polycythemias classified?
Polycythemia can be absolute in which red cell mass is increased, or relative in which decreased plasma volume artificially alters the Hgb concentration. Absolute polycythemia can be classified as primary or secondary.
What is the cause of polycythemia rubra vera?
Polycythemia rubra vera is caused by clonal malignancy of a marrow stem cell.
What genetic abnormalities are found in most incidences of PRV?
(1) JAK2 mutation is found in almost 100% of patients
(2) Deletions of 9p or 20q are found in most patients.
What are the criteria for the diagnosis of PRV?
(1) total red cell mass >32-35mL/kg
(2) Oxygen saturation >92%
(3) splenomegaly
(4) JAK2 mutation
(5) increased NAP score
(6) Increased serum B12.
The clinical features of PRV are due to what pathological changes?
(1) hyperviscosity
(2) Hypervolemia
(3) Hypermetabolism
What are the symptoms of PRV?
(1) Headache
(2) dyspnea
(3) blurred vision
(4) night sweats
(5) pruritus especially after a hot bath
What are the signs of PRV?
(1) plethoric appearance
(2) Splenomegaly (75%)
(3) Hemorrhage and thrombosis
(4) Hypertension (33%)
(5) gout
(6) peptic ulceration (5-10%)
What are the laboratory features of polycythemia rubra vera?
(1) RBCs, neutrophils, and platelets are all increased
(2) Hgb and Hct are increased
(3) JAK2 mutation
(4) NAP score increased
(5) Increased B12
(6) Low erythropoietin
(7) Increase blood viscosity and urate
(8) Increased erythroid progenitors in the peripheral blood. prominent megakaryocytes in the BM.
What is the goal of PRV treatment?
(1) Maintaining the Hct at 45%
(2) keeping the platelet count below 400 x 10^9
Why is venesection used to treat PRV?
venesection reduces the Hct, and reduced iron stores may limit erythrpoiesis. Does not control platelet counts.
What treatments for PRV may be considered if there is poor tolerance of venesection with persistence of other symptoms?
Myelosuppression
(1) hydroxyurea
(2) Busulfan
There may be a small risk of inducing malignant transformation.
Why is Phosphorous-32 used to treat PRV?
P-32 is used for older patients. It is concentrated in the bone marrow and releases beta radiation. It is very effective at myelosuppression.
What is the first line PRV drug for patients under 40 years old?
Alpha-interferon is used for patients under 40 years old. It is given subcutaneously and suppresses excess BM proliferation.
Why is aspirin given for PRV?
Aspirin helps limit thrombosis without significantly increasing the risk for hemorrhage.
To what diseases does PRV sometimes progress into?
PRV can progress to myelofibrosis (30%) and acute leukemia in 5% of patients.
What mutation is associated with Primary familial polycythemia?
Mutation of the von hippel-lindau protein.
What are the causes of secondary Polycythemia (generally speaking)?
(1) hypoxia
(2) abnormally high EPO production
What is the differential diagnosis for Polycythemia?
(1) PRV
(2) Cardiac disease
(3) Lung disease
(4) Erythropoietin secreting tumors
What is essential thrombocytopenia?
Essential thrombocytopenia is the overproduction of platelets because of megakaryocyte over proliferation. Characterized by a platelet count over 400 x 10^9
What are the clinical findings associate with ET?
Thrombosis, hemorrhage, and less frequently splenomegaly or splenic atrophy. Megakarycyte fragments may be seen on the blood film.
What risk factors guide treatment for ET?
(1) platelets greater than 1000 x 10^9
(2) smoking
(3) hypertension.
How is ET treated?
(1) hydroxyurea
(2) Alpha-interferon
(3) Anagrelide
(4) aspirin (if patient is lower risk)
What is myelofibrosis?
Myelofibrosis is clonal stem cell disease characterized by generalized reactive fibrosis of the bone marrow with hemopoiesis in the spleen and liver.
What causes the fibrosis of the bone marrow?
Hyperplasia of abnormal megakarycytes leads to secretion of growth factors and other substances that stimulate the activity of fibroblasts.
What are the clinical findings of myelofibrosis?
(1) massive splenomegaly
(2) Hypermetabolic symptoms
(3) bleeding problems
(4) gout.
What are the laboratory findings of myelofibrosis?
(1) Anemia (but Hgb can be increased)
(2) High WBC and platelets early in disease
(3) Leukopenia and thrombocytopenia later in disease
(4) Trephine biopsy shows fibrotic marrow
(5) teardrop poikilocytes on blood film
(6) high NAP score
(7) High urate and LDH.
How is the anemia of myelofibrosis treated?
Blood transfusion and regular folic acid is used to treat anemia.
How is the massive splenomegaly of myelofibrosis treated?
(1) hydroxyurea
(2) Splenectomy
(3) Splenic irradiation.
Why is allopurinol given for myelofibrosis?
Allopurinol is given to treat the hyperuricemia.
What is the prognosis for myelofibrosis?
Median survival is 3.5 years. Causes of death are usually heart failure, infection, and leukemic transformation.
What is systemic mastocytosis?
A defect of bone marrow stem cells that leads to proliferation of mast cells.
What mutation is commonly associated with mastocytosis?
the somatic c-kit mutation is detected in the majority of mastocytosis cases.
What are the symptoms of systemic mastocytosis?
Symptoms are related to the release of histamine and prostaglandins.
(1) flushing
(2) pruritus
(3) pain
(4) bronchospasm
