Myeloproliferative Disorders Flashcards
Define the term Myeloproliferative Disorders
Describes a group of conditions arising from marrow stem cells and characterized by clonal proliferation of one or more haematopoietic components in the bone marrow and often liver and spleen
List three Myeloproliferative Disorders
Polycythemia rubra vera (PRV)
Essential thrombocytopenia (ET)
Myelofibrosis
What is the common aetiology of Polycythemia Rubra Vera (PRV), Essential thrombocytopenia (ET), Myelofibrosis
Acquired mutation of the cytoplasmic tyrosine kinase
JAK2 mutation
What is polycythemia (erythrocytosis)
Defined as an increase in the haemoglobin concentration above the upper limit of normal for the patient’s age and sex
What are the two classifications of Polycythemia
Absolute Polycythemia
Relative/Pseudopolycythemia
Describe Absolute Polycythemia
This is when the red cell mass (volume) is raised
Describe Relative/ Pseudopolycythemia
Red cell volume is normal but the plasma volume is reduced
What are two subdivisions of Absolute Polycythemia
Primary Polycythemia (PRV- Polycythemia rubra vera) Secondary Polycythemia
Is Polycythemia rubra vera primary or secondary
Primary
What is the cause of increased red cell volume in Polycythemia (rubra) vera (Primary Polycythemia)
Clonal malignancy of a marrow stem cell
Which somatic mutation is present in haemopoietic cells in almost 100% of patients
JAK2 mutation
What are two causes of Primary Polycythemia
Polycythemia (rubra) vera
Familial (congenital) Polycythemia
What are two main causes of Secondary Polycythemia
Caused by compensatory erythropoietin increase
Caused by inappropriate erythropoietin increase
Compensatory erythropoietin increase is a cause of Secondary Polycythemia
What factors lead to this increase
High altitude Pulmonary disease Cardiovascular disease Increased affinity haemoglobin Heavy cigarette smoking
Inappropriate erythropoietin increase is a cause of Secondary Polycythemia
What factors lead to this increase
Renal diseases
Tumours
What are four factors that cause Relative Polycythemia
Stress
Cigarette smoking
Plasma loss : burns
Dehydration
What are the criteria for diagnosis of Polycythemia (rubra) vera
(Include red cell mass, and arterial oxygen saturation)
Total red cell mass
Male: >35 mL/kg
Female: > 32mL/kg
Arterial Oxygen saturation >92%
Splenomegaly
JAK2 mutationPolycythemia rubra vera usually affects which age group
Older people
What is the sex incidence of Polycythemia (rubra) vera
Equal
Clinical features of Polycythemia are as a result of which three conditions caused by the Polycythemia
Hyperviscosity
Hypervolemia
Hypermetabolism
What are some clinical presentations of Polycythemia (Rubra) Vera
- Headaches
- Dyspnoea
- Blurred vision
- Night sweats
- Pruritus (itchy skin) after hot bath
- Plethoric appearance
- Splenomegaly
- Hemorrhage or Thrombosis
- Gout
- Peptic Ulceration
- Hypertension
Splenomegaly is found in what percentage of pts with Polycythemia (Rubra) Vera
75%
Laboratory Findings//
Describe haemoglobin, hematocrit, and red cell count in Polycythemia (Rubra) Vera
All increased
Laboratory Findings//
Describe Neutrophil levels in Polycythemia (Rubra) Vera
Neutrophils Leucocytosis
Laboratory Findings//
Neutrophil Leucocytosis is seen in what fraction of patients with Polycythemia (Rubra) Vera
Over half
Laboratory Findings//
A raised platelet count is seen in what percentage of Polycythemia (Rubra) Vera pts
Platelet count present in about half of pts
Laboratory Findings//
What mutation is present in the bone marrow and peripheral blood granulocytes in nearly 100% of Polycythemia (Rubra) Vera pts
JAK2 mutation
Laboratory Findings//
The JAK2 Mutation is present in which structures of pts with Polycythemia rubra vera
Bone marrow
Peripheral blood granulocytes
What is the score of Neutrophil alkaline phosphatase (NAP) in Polycythemia rubra vera
Usually increased
Laboratory Findings//
What is the change in the level of B12 seen in Polycythemia rubra vera
Increased
Why is B12 and B12 binding capacity increased in Polycythemia rubra vera
Because of an increase in haptocorrin
Laboratory Findings//
Describe serum erythropoietin in Polycythemia rubra vera
Low
What happens to blood viscosity in Polycythemia rubra vera
Increased
List five treatment methods for Polycythemia Rubra Vera
Venesection Cytotoxic Myelosuppression Phosphorus-32 Therapy Inerferon Aspirin
What is the aim of Polycythemia Rubra Vera Treatment
To maintain a normal blood count
Haematocrit -0.45
Platelet count below - 400 x 10^9/L
Does venesection Control platelet count
No
When is Cytotoxic Myelosuppression Treatment for Polycythemia Rubra Vera considered ?
If there is poor tolerance of venesection
List two Cytotoxic drugs used In Myelosuppression of Polycythemia Rubra Vera
Hydroxycarbamide (hydroxyurea)
Busulfan
List three side effects of Hydroxyurea
Nausea
Skin toxicity
Myelosuppression
Which group of patients with Polycythemia Rubra Vera is given Phosphorus-32 therapy
This is only used for older patients with severe disease
Even though P-32 is the most effective myelosuppressive agent, why isn’t it popularly administered as Polycythemia Rubra Vera Treatment
Concern about late development of leukemia limits its use
What is the first line of drug for patients with Polycythemia Rubra Vera less than 40yrs
Alpha Interferon
How does Interferon work in treatment for Polycythemia Rubra Vera
Subcutaneously suppresses excess proliferation in the marrow and has produced good haematological responses
What is the effect of Aspirin on Polycythemia Rubra Vera
Reduces thrombotic complications , without an increased risk of major haemorrhage
What is the prognosis and median survival of pts with Polycythemia Rubra Vera
Good prognosis
Survival 10-16 yrs
What percentage of pts with Polycythemia Rubra Vera PRV experience a transition from PRV to myelofibrosis
30% of pts
What causes Primary Familial (congenital) Polycythemia
Mutation of von Hipp- Lindau gene which creates abnormal oxygen sensing with increased erythropoietin production
Which test is done to confirm Polycythemia
PCR (polymerase chain reaction) test for the JAK2 mutation
What is Essential Thrombocythaemia
In this condition there is a sustained increase in platelet count, because of megakaryocyte proliferation and overproduction of platelets
What is the central diagnostic feature for Essential thrombocythaemia
A persisting platelet count of >400 x 10^9/L
Other diagnostic causes of a raised platelet count need to be fully excluded before the diagnosis can be made
What are two types of causes of a raised platelet count
Reactive
Endogenous
What are 6 Reactive causes of a raised platelet count
Haemorrhage, trauma, postoperative Chronic iron deficiency Malignancy Chronic infections Connective tissue disease Post- splenectomy
What are four endogenous causes of a raised platelet count
Essential thrombocythaemia
Sometimes- Polycythemia vera, myelofibrosis, chronic myeloid leukemia
What are the dominant clinical features of Essential thrombocythaemia
Thrombosis and
Haemorrhage
What is a characteristic symptom of Essential thrombocythaemia
Erythromelalgia (burning sensation felt in the hands or feet and promptly relieved by aspirin)
What percentage of pts with Essential thrombocythaemia have palpable Splenomegaly
40%
Others have splenic atrophy because of infarction
Which group of pts with Thrombocythaemia is most at risk
Those over 60yrs , with a platelet count >1000 x 10^9/L
What is the aim of treatment of pts at high risk with Thrombocythaemia
Keep the platelet count as low as 600 x 10^9/ L
What is the most widely used treatment for Thrombocythaemia
Hydroxyurea
Alpha Interferon used in younger pts
What is the course of Essential thrombocythaemia
Usually stationary for 10-20 yes and progresses to myelofibrosis
What is the predominant feature of myelofibrosis
Progressive generalized reactive fibrosis of the bone marrow in association with the development of haemopoiesis in the spleen and liver
List four Clinical Features of Myelofibrosis
- insidious onset in older people with symptoms of anaemia
- Symptoms resulting from massive Splenomegaly (Abdominal discomfort , pain or indigestion)
- Hypermetabolic symptoms (such as weight loss, anorexia, fever and night sweats)
- Bleeding problems, bone pain or gout
What is the haemoglobin level in Myelofibrosis
Normal or high
What type of blood film is seen in Myelofibrosis
Leucoerythroblastic blood film
Red cells show characteristic ‘tear-drop’ poikilocytes
Which test is done to observe Myelofibrosis
Trephine biopsy
