Myeloproliferative Flashcards
What are myeloproliferative neoplasms?
Group of disorders characterised by clonal expansion of a stem cell population
Increased production of myeloid cells with relatively preserved maturation
What will a blood film be like in myeloproliferative neoplasms?
Polymorphic - wide variety of cells at different stages of maturation
Hypercellular
What is proliferation of red cells?
Polycythaemia vera
What is proliferation of white cells?
Chronic myeloid leukaemia
What is proliferation of platelets?
Essential thrombocythaemia
What is proliferation fo fibroblasts?
Primary myelofibrosis
Which myeloproliferative neoplasm is BCR-ABL1 positive?
CML
What is the Philadelphia chromosome associated with?
CML
When should you consider myeloproliferative neoplasms?
Splenomegaly Thrombosis in an unusual place High granulocyte count (eosinophilia, basophilia, neutrophilia) High red cell count/Hb High platelet count No reactive cause
What is the mean age of diagnosis of myeloproliferative neoplasms?
65 (but can be much younger)
What are the general features of myeloproliferative neoplasms?
Can be asymptomatic Increased cellular turnover Splenomegaly Marrow failure Thrombosis
What are the clinical features of increased cellular turnover?
Gout
Fatigue
Weight loss
Sweats
What are the clinical features of splenomegaly?
Early satiety
LUQ pain
What are the clinical features of thrombosis in myeloproliferative neoplasms?
Arterial or venous (TIA, MI, abdominal vessel thrombosis, claudication)
Erythromelelgia - paint nd redness in hands and feet
What is polycythaemia?
Increase in red cells
What is the pathophysiology of polycythaemia vera?
Increased red cell mass due to increased production
What should polycythaemia vera be distinguished from?
Secondary polycythaemia (reactive) Pseudopolycythaemia
What are causes of secondary (reactive) polycythaemia?
Chronic hypoxia (COPD, smoking) Increased erythropoietin production (renal or hepatic carcinoma)
What is pseudo-polycythaemia?
Relative increase in Hb due to plasma cell depletion
What are causes of pseudo-polycythawmia?
Alcohol
Obesity
Dehydration
Diuretic therapy
What mutation causes polycythaemia vera, and how?
JAK2
A tyrosine kinase that controls erythropoiesis by auto-inhibition
Mutation causes loss of auto-inhibition and stimulation of red cell production in the absence of stimuli?
How common are JAK2 mutations in polycythaemia vera?
Present in over 95% of patients with polycythaemia vera
What is the presentation of polycythaemia vera?
Hyperviscocity - lethargy - confusion - headache - dizziness - visual disturbance Splenomegaly - abdo pain and distension - gout Aquagenic pruritus (itch after warm shower/bath) Erythromelelgia Facial plethora
What do investigations show in polycythaemia vera?
JAK2 mutation positive
Bloods - high Hb, high reticulocytes, high platelets
Erythroid hyperplasia on marrow biopsy
Neutrophil alkaline phosphatase score increased
What investigations can be done in polycythaemia to check for secondary/pseudo causes?
CXR
O2 saturation
Arterial blood gases
Drug history
What is the aim of management of polycythaemia vera?
Reduce risk of thrombosis
What is the management of polycythaemia vera?
Low risk - venesection, aspirin
High risk - hydroxycarbamide, aspirin
What does high risk mean in polycythaemia vera?
> 60
Previous thrombosis
What is essential thrombocythaemia?
Uncontrolled increase in platelets
What is the pathophysiology of essential thrombocythaemia?
Uncontrolled proliferation of megakaryocytes causing increased production of abnormal platelets
Causes thrombosis tendance
At high levels can cause bleeding due to acquired von Willebrand disease as vWF is absorbed into abnormal platelets, reducing circulating vWF levels
What mutations can cause essential thrombocythaemia?
JAK2 (not as common as PV)
CALR
What are other causes of thrombocythaemia?
Bleeding Infection Malignancy Trauma/surgery Splenectomy nad hyposplenism
What is the presentation of essential thrombocythaemia?
MPN common clinical features (thrombosis, marrow failure, high cellular turnover, splenomegaly)
Vaso-occlusive complications
Bleeding
What can thrombosis commonly cause in essential thrombocythaemia?
Stroke, DVT/PE
Recurrent miscarriages
Digital ischaemia (gangrene fingers and toes)
Erythromelalgia (erythema and shooting pain in limbs)
Microembolisms
What do investigations show in essential thrombocythaemia?
Thrombocytosis
Marrow biopsy - hypercellular, megakaryocytes
Genetics - JAK2, CALR
What is the management of essential thrombocythaemia?
Lifestyle factors to reduce thrombosis risk
Aspirin
Hydroxycarbamide if high risk for thrombosis
What is hydroxycarbamide, how does it work and what are other similar options?
Cytoreductive therapy to control proliferation
Other options: anagrelide, interferon alpha
What is idiopathic myelofibrosis?
Megakaryocyte proliferation causing stimulation of fibroblasts
What is the pathophysiology of idiopathic myelofibrosis?
Increase in megakaryocytes is associated with increased release of platelet derived growth factor, causing stimulation of fibroblasts and bone marrow fibrosis
Fibrosis causes marrow failure, compensated for by extra medullary haematopoiesis in the liver and spleen
What are the key blood film features of idiopathic myelofibrosis?
Leucoerythroblastic film appearance - both myeloid and erythroid precursors in the blood
Teardrop shaped RBCs
What is the presentation of idiopathic myelofibrosis?
Non-specific Fever, night sweats Abdominal pain in LUQ Symptoms of marrow failure (bleeding, infections, anaemia) Massive splenomegaly
What do investigations show in idiopathic myelofibrosis?
Bloods - low Hb, high WCC, high platelets
Bone marrow biopsy - marrow fibrosis
Genetics - JAK2, CALR, MPL
What are the possible mutations in idiopathic myelofibrosis in order of most to least common?
JAK2 > CALR > MPL
How many people with idiopathic myelofibrosis have no mutation?
10% are triple negative
What is the management of idiopathic myelofibrosis?
Supportive care as required for marrow suppression (blood transfusion, platelets, antibiotics, allopurinol if hyperuricaemia)
Active treatment
- bone marrow transplant
- ruxolitinib (JAK2 inhibitor)
