MedED blood cancers and disorders Flashcards
What do all RBCs originate from?
Haematopoeitic stem cells
What are the 2 types of haematopoeitic stem cells?
Myeloid stem cells
Lymphoid stem cells
What do myeloid stem cells give rise to?
Platelets RBCs Basophil Neutrophil Eosinophil Monocyte
What do lymphoid stem cells give rise to?
Natural killer cells
T lymphocytes
B lymphocytes
What are the 3 main categories of blood cancers?
Leukaemia
Lymphomas
Others
What are the types of leukaemia?
Myeloid
Lymphoid
What are the types of lymphoma?
Hodgkin
Non hodgkins
What type of cell is there an increase of leukaemia?
WBC
What is the key difference between lymphoma and leukaemia?
The location of WBCs- were they arise and end up
Leukaemia- originates in the bone marrow
Lymphoma- originates from the lymphocytes themselves (in lymph nodes and lymphatic tissue)
Where are cancer cells in leukaemia likely to be found?
In bones and blood
Where are cancer cells in lymphoma likely to be found?
Lymph nodes and other lymphatic tissues
How can leukaemia be classified?
By onset: chronic or acute
By lineage: myeloid or lymphoid
Why is leukaemia disruptive?
The extra cells produced are not useful and crowd out the bone marrow so other useful cells cannot be produced
What are the 4 main types of leukaemia?
Acute lymphoid
Acute myeloid
Chronic lymphoid
Chronic myeloid
Out of acute and chronic leukaemia which is more severe?
Acute
What type of blood cells arise in acute vc chronic leukaemia?
Acute= immature blood cells Chronic= mature white blood cells
What leukaemia is more common in children?
Acute lymphoblastic
What leukaemia is more common in adults?
Chronic myeloid
How is differentiation of cells in acute vs chronic leukaemia different?
Acute= abnormal differentiation Chronic= normal (ish) differentiation
What cells proliferate in acute myeloid leukaemia?
Myeloblasts
What are the features of acute myeloid leukaemia?
Neutropenia
Anaemia
Thrombocytopenia
What happens to the pathway of blood cell differentiation once there is a mutation in one cell?
The cells downstream are not produced
What are the risk factors for acute myeloid leukaemia?
Increasing age
Downs syndrome
Irradiation
Anti cancer drugs
What are the 2 categories of signs and symptoms of acute myeloid leukaemia?
Bone marrow failure
Tissue infiltration
What are the signs and symptoms of acute myeloid leukaemia?
Bone marrow failure= pallor, bleeding, infections
Tissue infiltration= swollen gums, mild splenomegaly
What symptom is characteristic of acute myeloid leukaemia and helps differentiate it from other blood cancers?
Bleeding gums
What is the buzz word for acute myeloid leukaemia?
Auer rods- seen on cytology
What are auer rods?
They are seen on cytology in acute myeloid leukaemia
What is acute promyelocytic leukaemia?
A hyper agressive AML
What is the genetic translocation for acute promyelocytic leukaemia?
t(15;17) fuses the PML gene with the RAR- alpha gene
What is seen on cytology in acute promyelocytic leukaemia?
Faggot cells- lots of auer rods
What cell proliferates in acute lymphoid leukaemia?
Lymphoblasts
What are risk factors for ALL?
More common in children
People who are genetically prone and then they get influenza
What are the 2 catagories of signs and symptoms of ALL?
bone marrow failure
tissue infiltration
What are the signs and symptoms of ALL?
Bone marrow failure= pallor, bleeding, infections
Tissue infiltration= lymphadenopathy, hepatosplenomegaly, swollen testes, tender bones
In ALL what % lymphoblasts will be seen on bone marrow biopsy?
20%
What proliferates in CML?
Granulocyte precursors (which also mature into granulocytes)
What are features of CML?
Bone marrow failure
Hypermetabolism
Hyperviscosity
What is the difference in cells in AML vs CML?
In CML there are mature cells produced too- differentiation continues
What are the 3 phases in CML?
Chronic phase, accelerated phase and blast crisis
Out of males and females who is more likely to get CML?
Males
What chromosome is involves in CML?
Philadelphia chromosome
What fusion gene is made in CML?
t(9:22) BCR-ABL1 fusion gene
What is the hallmark of CML and why?
Massive splenomegaly- there is time for the cells to accumulate in the spleen
What are signs and symptoms of CML?
Massive splenomegaly
Hypermetabolic symptoms= weight loss, malaise, sweating
Bone marrow failure= pallor, bleeding and infections
Hyperviscosity= thrombotic events, headaches
What cells are accumulate in CLL?
Incompetent lymphocytes
What is there a failure of in CLL?
Failure of apoptosis of CLL
What is the least concerning type of leukaemia?
CLL
Out of men and women who is more likely ot get CLL?
Men
What are signs and symptoms of CLL?
50% of patients are asymptomatic
Occasional non tender lymphadenopathy
Occasional bone marrow failure symptoms
What is the hallmark of CLL?
Smudge/ smear cells on blood film
How is CLL diagnosed?
Usually on routine blood test when there is lymphocytosis
What are some investigations for leukaemia?
First line blood test: FBC, LDH (tumor marker for lots of cancers), blood smear
Biopsy: bone marrow aspirate
Other tests include immunophenotyping (to see what type of specific cancer is it) or CXR
What buzz word should you remember for AML?
Auer rods
What buzz word should you remember for ALL?
Child under 6
What buzz word should you remember for CML?
Philadelphia chromosome
What buzz word should you remember for CLL?
Smudge/ smear cells
How is leukaemia managed?
First line chemotherapy
Second line bone marrow transplant
How do patients with lymphoma classically present?
With a lump Systemic symptoms (or B symptoms) too like fever, weight loss, night sweats
What is a main subtype of non hodgkin’s lymphoma?
Burkitt’s lymphoma
What virus is HL commonly associated with?
EBV
What are signs and symptoms of hodgkin’s lymphoma?
Painless enlarging neck mass which may become painful after drinking alcohol
B symptoms
Non tender, firm, rubbery lymphadenopathy with splenomegaly and they may not have hepatomegaly
What will be seen on lymph node biopsy in HL?
Reed-sternberg cells (bi nucleate lymphocytes)
What type of lymphoma is more common?
Non hodgkins
What type of cell is NHL?
85% b cell
15% t cell or NK cell
What are some risk factors for NHL?
EBV, HIV, SLE, Sjogren’s syndrome
Increasing age
What are signs and symptoms of NHL?
Painless enlarging mass in neck, axilla or groin
B symptoms (less common than in HL)
Organ involvement- skin rash, headache, hepatosplenomegaly (more common than in HL)
What is the best way to differentiate NHL and HL?
In NHL there will be no Reed-Sternberg cells on lymph node biopsy
What are some ways to differentiate NHL and HL?
In NHL there will be no reed sternberg cells on blood film
B symptoms are less common than in HL
Organ involvement is more common eg skin rashes, headache, hepatosplenomegaly
What are risk factors for burkitt lymphoma?
EBV infection
Chronic malaria- this reduces resistance to EBV
HIV
How does burkitt lymphoma classically present?
A rapidly enalrging lymph node in the jaw
What will burkitt lymphoma look like under microscopy?
Starry sky appearance
What is the buzz word for burkitt lymphoma?
Starry sky appearance under microscopy
What system is used to stage lymphoma?
Ann Arbor staging system
How is lymphoma managed?
First line chemotherapy
What is a common complication of treating blood cancer?
Tumor lysis syndrome
What is tumor lysis syndrome?
Metabolic abnormalities that arise due to cancer treatment, especially leukaemia and lymphoma
What is commonly released in tumor lysis syndrome from cancer cells?
Phosphate, uric acid and potassium
What does the release of phosphate in tumor lysis syndrome lead to?
Calcium phosphate crystals are formed
This causes kidney failure and hypocalcaemia
What does the release of uric acid in tumor lysis syndrome lead to?
Urate crystals causing gout
What does the release of potassium in tumor lysis syndrome lead to?
Hyperkalemia which causes arrhythmia
What is there proliferation of in multiple myeloma?
Plasma cells
What is produced in multiple myeloma and why?
Monoclonal immunoglobulin (IgG and IgA) There is proliferation of plasma cells and these produce antibodies
What are risk factors for multiple myeloma?
Increasing age
Argicultural workers exposed to herbicides/ pesticides
What acronym is used to remember signs and symptoms of multiple myeloma?
CRAB
What are signs and symptoms of multiple myeloma? Explain why they arise
C- high calcium= bones, stones, abdominal groans
R- renal impairment
A- anaemia= due to bone marrow crowding (there is also less production of polyclonal IgG which leads to more infections)
B- bone lesions= there is signalling which increases osteoclast activation causing back and rib pain
What are investigations for multiple myeloma?
First line bloods= DO ALP (will be normal in multiple myeloma so you know its not a bone cancer), raised ESR, CRP, Cr, CA
Blood film= will show rouleaux formation
Serum/ urine electrophoresis= shows bence jones proteins
Bone marrow aspirate= plasma cells will be raised more than 10%
What is the buzz word for multiple myeloma?
Bence jones proteins
How diagnostic are bence jones proteins for multiple myeloma?
They are not sensitive or specific but when present alongside hypercalcaemia, kidney failure, anaemia and bone pain are highly diagnostic
What is MGUS?
Monoclonal gammopathy of unknown significance
It is a pre malignant condition where there is accumulation of some monoclonal plasma cells and it may lead to multiple myeloma
CRAB features will be absent
What is myelodysplasia?
A group of syndromes where immature blood cells do not mature normally
What are the 2 causes of myelodysplasia?
Primary= intrinsic bone marrow problem Secondary= previous chemo/radiotherapy
What does myelodysplasia cause?
Bone marrow failure= chronic pancytopenia (anaemia, neutropenia and thrombocytopenia)
What are the features of bone marrow failure?
Anaemia
Thrombocytopenia
Neutropenia
What is the buzz word for myelodysplasia?
anaemia with RINGED SIDEROBLASTS
What are bence jones proteins?
Monoclonal Ig light chain antibodies (can be found in the urine)
What are the 2 stages of wound healing?
Primary haemostasis
Secondary haemostasis
What is primary haemostasis?
Platelet aggregation and plug formation
What is secondary haemostasis?
Fibrin formation to stabilise the platelet plug
What does primary haemostasis depend on?
VWF
What does secondary haemostasis depend on?
Clotting factors
What type of disorder does disruption of primary haemostasis cause?
Superficial bleeding
What type of disorder does disruption of secondary haemostasis cause?
Deep bleeding and bruising
What test measures the intrinsic pathway?
APTT
What test measures the extrinsic pathway?
PT
What clotting factors are involved in the intrinsic pathway?
XII, XIIa
XI, XIa
IX, IXa
VIII
What clotting factors are involved in the extrinsic pathway?
VIIa
What is haemophilia?
A bleeding disorder caused by the inherited deficiency of a clotting factor
What stage of haemostasis is involved in haemophilia?
Secondary- it involves deficiencies in clotting factors
What type of bleeding is present in haemophilia?
Deep bleeding and bruising
What gender does haemophilia mainly affect and why?
Males- it is X linked recessive
What are the 2 types of haemophilia?
A and B
What type of haemophilia is more common?
A
What is deficient in haemophilia A?
Factor 8
What is deficient in haemophilia B?
Factor 9
At what age does haemophilia usually present?
Early or after surgery
What is the buzz word for haemophilia?
Haemarthosis
How does haemophilia present?
Haemarthrosis= bleeding into joints which are swollen and painful
Haematoma= painful bleeding into muscles
Excessive bruising and haematuria
What investigations are done to diagnose haemophilia?
Factor assay is done to diagnose it
APTT will be pronged
What clotting pathway does haemophilia affect?
Intrinsic
What are some roles of VWF?
Platelet adhesion- forms bridges between damaged subendothelium and platelets via GP1b receptor
Platelet aggregation- facilitates platelets binding to each other
Factor 8 stabilisation- binds to factor 8 and prevent degredation
What is type 1 von willebrand syndrome?
Reduced levels of normal VWF
What is type 2 von willebrand syndrome?
Adequate levels of defective VWF
What is type 3 von willebrand syndrome?
Complete lack of VWF and reduced factor 8
How are type 1, 2 and 3 von willebrand syndrome inherited?
1 and 2= autosomal dominant
3= autosomal recessive
How does VWD classically present?
Superficial bleeding eg bruising, nosebleeds, heavy periods, prolonged gum bleeding, prolonged bleeding from minor wounds
In type 3 it is more severe and reduced factor 8 causes deep bleeding into joints and soft tissues
How is VWD diagnosed?
Depends on type of syndrome
type 1= prolonged bleeding time, reduced VWF, normal platelets
type 2= prolonged bleeding time, normal VWF, normal platelets
type 3= prolonged bleeding time, reduced VWF, normal PT but prolonged APPT due to lack of factor 8, normal platelets
What DIC?
When an underlying condition causes up regulation of the clotting cascade
What happens in DIC?
There are blood clots in parts of the body where they are not needed
You are also prone to bleeding because platelets and clotting factors are being used up where they aren’t needed
What is deposited in DIC?
Fibrin
What are the 3 main issues in DIC?
Blood clots in the body where you dont need them
Being prone to bleeding as platelets and clotting factors are used up
Deposition of fibrin cutting up RBCs causing anaemia
How is DIC classified?
By onset
Acute overt= emergency and life threatening, significant platelet and clotting factor depletion presenting with bleeding
Chronic non overt= slower rate, with time for compensatory responses, present more with clotting less with bleeding
What is the difference between presentation of acute overt and chronic non overt DIC?
acute overt= presents with bleeding and is an emergency
chronic non overt= presents with clotting
How does DIC classically present?
Signs of underlying pathology eg cancer, sepsis, pregnancy
Acute DIC= bleeding issues (petechiae, purpura, epistaxis etc), respiratory distress
Chronic DIC= DVT or arterial thrombosis
How is DIC diagnosed?
FBC= low platelets and HB
Clotting= low fibrinogen, high fibrin degredation products, prolonged PT and APTT
Blood film= schistocytes
What is a buzz word for DIC?
Shistocytes
How is DIC managed?
Treat underlying cause
Give platelets, fresh frozen plasma and fibrinogen
