Myelofibrpsos Flashcards
What is myelofibrosis
Bone marrow is replaced with collagedn and become fibrosed
Aetiolofy of myelpfibrosis
Disease typically manifests >50, can occur in children
Familial relationship, preponderance in ashkenazi jews
Pathology myelofribrosis
Haematopoietic cell progenitor mutation in megakaryocute line -< proliferation of fibroblasts and collagen deposition reactive to cytokine production incl TGF-B
EPO impaired -> anaemia
Extramedullary haemtopoiesis
TGF-beta effects
Fibrosis
Osteoclast proliferation-> osteosclerosis
Clinical features of myelofibrosis
20% asymptomatic
Severe fatigue
Hepatosplenomegaly
Can get massive splenomegaly
B symptoms - weight loss, fever, night sweats
Anaemia
VTE secondary to thrombocytosis
unexplained bleeding -> TP
Sev bony pain - periosteal infalmmation and osteosclorosis
Extramedaullry haematopoiesis causing?
Seizures, paralysis, ascite, pericardial, abdominal, pleural effusions, raised ICP, lymphadenopathy
liver and spleen most common sites
Initial investigation myelofirbsosi
FBC, U+Es, LFTs, coag studies
Blood smear
LDH
Bone marrow exam
Gentic testing
Bloods in myelofibrosis
Pancytopenia
Decreased RBC
WCC and platelet - VARY
PT + APTT prolonged, raised ALP - hepatic involevemnt
LDH raised - RCC lysis
Blood film in myelofibrosis shows
Teardrop RBC - dacrocytes
How can examine bone marrow
Need a biopsy
Can do aspirate/MRI also
MRI monitor progression
Myelofibrosis - bone marrow aspirate what see
May yield dry tap
Success - entire myeloid lineage abnormal
Bone marrow biopsy what see in myelofibrss
Fibrosis and abnormal megakaryocyte appearance
MRI myelofibrosis what see
Decreased signal from bone marrow as fat replaced w fibrosis
Genetic ass w myelofibrosis
JAK2 -60%
CALR - 25%
MPL - 5%
Triple negative variant - 10%
Major criteria for myelofibrosis
Proliferation and atypia of megakaryocytes acc by fibrosis
Doesnt mathch other myeloid neoplasms
JAK2, CALR, MPL mutation
If absent mutations - clonal arker or absence of reactive myelofibrosis
Minor criteria for Myelofirbsois
Anaemia UEO
Leukocytosis >11 x10
Palpable splenomegaly
Raised LDH
LEUKOERYTHRoblastosis
Non haematological causes of myelofibrosis
hyperparathyroidsim
SLE
vit D deficiency
Systemic sclerosis
Treatment for asymptomatic patients myelofibrosis
none - routine follow up
Curative treatment for myelofibrosis
ONly cure is haemtopoietic stem cell transplant
Symptomatic/palleative treatment for myelofibrosis
Ruxolitinib - JAK2 inhibitor
Splenectomy, splenic irradiation if causing pain
Blood transfusions for anaemia or EPO injections
Extrameduallyr Haematpoiesis - foci irradiates
Aspirin - VTE
Hyperuricaemia - allopurinol
How treat anaemia in myelofibrosis
Blood transusions - thalidomide and prednisone as adjuncts
Iron, B9, B12 deficiencies investigated and managed
EPO not shown to benefit
Ruxolitibinib how works in myelofibrosis
Improves splenomegaly and constitutional symptoms
Works irrelevant of whether have JAK2 mutation
Effective regardless of whether splenomegaly present
Doesnt prolong survival
Alternatives to ruxolitibin
Hydroxyurea , interferon alpha
Most deadly complication of myelofibrosis
Progression to acute myeloid leukaemia
Complications of myelofibrosis
Haemorrhage - thrombocytopenia
Infections - low WCC
Portal HPTN - hepatomegaly
Splenic infarctions
Sequelae raised urea eg gout, kidney stones
Neurologic manifestations - EMHS - seizures, cord compression, raised ICP
VTE earlier phases
Osteosclerosis
Prognosis myelofibrosis
mean - 6 years
Massive variation
Most common cause death - AML
Others - infection, haemorrhage, thrombosis, cachexia
What can turn into myelofibrosis
essentiall thrombocytopenia
What need to review in essential thrombocytopenia
Cardiovacular risk factors - cholesterol, BP etc
Aspirin for all
When do you ive cytoreduction in essential thrombocytoprnia
High risk eg
Over 60
Platelets >1500x 10^9/L
Prev thrombotic event
Other CVS risk factors
cytoreduction treatment
Hydroxycarbamide - reduce throbotic events
Interferon, anagrelide
Busulfan
What is cytoreduction treatment
Reducing platelets
Presentation of essential thrombocytosis
Migraine
Erythromyalgia - burning pain
Itch
arterial and venous thrombosis
bleeding
how confirm essential thromboytopenia
bone marrow biopsy
Myelofibrosis vs essential thrombocytopenia
More agressive
Is teh proliferation of mutliple cell lineages vs just platelets
Progressive marrow fibrosis
Myelofibrosis - low OR high WCC and platelets depending on disease stage
