Myelofibrpsos

Question 1

What is myelofibrosis

Answer 1

Bone marrow is replaced with collagedn and become fibrosed

Question 2

Aetiolofy of myelpfibrosis

Answer 2

Disease typically manifests >50, can occur in children
Familial relationship, preponderance in ashkenazi jews

Question 3

Pathology myelofribrosis

Answer 3

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

Question 4

TGF-beta effects

Answer 4

Fibrosis
Osteoclast proliferation-> osteosclerosis

Question 5

Clinical features of myelofibrosis

Answer 5

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

Question 6

Extramedaullry haematopoiesis causing?

Answer 6

Seizures, paralysis, ascite, pericardial, abdominal, pleural effusions, raised ICP, lymphadenopathy
liver and spleen most common sites

Question 7

Initial investigation myelofirbsosi

Answer 7

FBC, U+Es, LFTs, coag studies
Blood smear
LDH
Bone marrow exam
Gentic testing

Question 8

Bloods in myelofibrosis

Answer 8

Pancytopenia
Decreased RBC
WCC and platelet - VARY
PT + APTT prolonged, raised ALP - hepatic involevemnt
LDH raised - RCC lysis

Question 9

Blood film in myelofibrosis shows

Answer 9

Teardrop RBC - dacrocytes

Question 10

How can examine bone marrow

Answer 10

Need a biopsy
Can do aspirate/MRI also
MRI monitor progression

Question 11

Myelofibrosis - bone marrow aspirate what see

Answer 11

May yield dry tap
Success - entire myeloid lineage abnormal

Question 12

Bone marrow biopsy what see in myelofibrss

Answer 12

Fibrosis and abnormal megakaryocyte appearance

Question 13

MRI myelofibrosis what see

Answer 13

Decreased signal from bone marrow as fat replaced w fibrosis

Question 14

Genetic ass w myelofibrosis

Answer 14

JAK2 -60%
CALR - 25%
MPL - 5%
Triple negative variant - 10%

Question 15

Major criteria for myelofibrosis

Answer 15

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

Question 16

Minor criteria for Myelofirbsois

Answer 16

Anaemia UEO
Leukocytosis >11 x10
Palpable splenomegaly
Raised LDH
LEUKOERYTHRoblastosis

Question 17

Non haematological causes of myelofibrosis

Answer 17

hyperparathyroidsim
SLE
vit D deficiency
Systemic sclerosis

Question 18

Treatment for asymptomatic patients myelofibrosis

Answer 18

none - routine follow up

Question 19

Curative treatment for myelofibrosis

Answer 19

ONly cure is haemtopoietic stem cell transplant

Question 20

Symptomatic/palleative treatment for myelofibrosis

Answer 20

Ruxolitinib - JAK2 inhibitor
Splenectomy, splenic irradiation if causing pain
Blood transfusions for anaemia or EPO injections
Extrameduallyr Haematpoiesis - foci irradiates
Aspirin - VTE
Hyperuricaemia - allopurinol

Question 21

How treat anaemia in myelofibrosis

Answer 21

Blood transusions - thalidomide and prednisone as adjuncts
Iron, B9, B12 deficiencies investigated and managed
EPO not shown to benefit

Question 22

Ruxolitibinib how works in myelofibrosis

Answer 22

Improves splenomegaly and constitutional symptoms
Works irrelevant of whether have JAK2 mutation
Effective regardless of whether splenomegaly present
Doesnt prolong survival

Question 23

Alternatives to ruxolitibin

Answer 23

Hydroxyurea , interferon alpha

Question 24

Most deadly complication of myelofibrosis

Answer 24

Progression to acute myeloid leukaemia

Question 25

Complications of myelofibrosis

Answer 25

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

Question 26

Prognosis myelofibrosis

Answer 26

mean - 6 years Massive variation Most common cause death - AML Others - infection, haemorrhage, thrombosis, cachexia

Question 27

What can turn into myelofibrosis

Answer 27

essentiall thrombocytopenia

Question 28

What need to review in essential thrombocytopenia

Answer 28

Cardiovacular risk factors - cholesterol, BP etc Aspirin for all

Question 29

When do you ive cytoreduction in essential thrombocytoprnia

Answer 29

High risk eg Over 60 Platelets >1500x 10^9/L Prev thrombotic event Other CVS risk factors

Question 30

cytoreduction treatment

Answer 30

Hydroxycarbamide - reduce throbotic events Interferon, anagrelide Busulfan

Question 31

What is cytoreduction treatment

Answer 31

Reducing platelets

Question 32

Presentation of essential thrombocytosis

Answer 32

Migraine Erythromyalgia - burning pain Itch arterial and venous thrombosis bleeding

Question 33

how confirm essential thromboytopenia

Answer 33

bone marrow biopsy

Question 34

Myelofibrosis vs essential thrombocytopenia

Answer 34

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