Blood Cancers/Disorders Flashcards
Breakdown of chronic and acute leukaemias?
Acute = rapid increase in immature blood cells which crowd out the marrow. Abnormal differentiation and excessive proliferation
Chronic = excessive build-up of abnormal but relatively mature. Normal(ish) differentiation proliferation. Mainly in older people
Features of acute myeloid leukaemia?
Rapid proliferation of myeloblasts -> neutropenia, anaemia and thrombocytopaenia
Rfs and presentation of AML?
RFs: incidence increases with age, Downs, irradiation and anti-cancer drugs
Bone marrow failure: infection, bleeding, pallor
Tissue infiltration: mild splenomegaly and swollen gums
Ix for AML?
Sudan black to show Auer rods
What is acute promyelocytic leukaemia?
Hyper aggressive subtype of AML
Genetic translocation 15:17 fuses PML with RAR-alpha
Faggot cells on cytology with lots of AUer rods
RFs and presentation of ALL?
Most common childhood. Genetics (Downs/NF), radiation, influenza.
Thrombocytopaenia, neutropaenia and anaemia so bone marrow failure = pallor, bleeding, infections
Tissue infiltration = lymphadenopathy, hepatosplenomegaly, swollen testes and tender bones
B symptoms = fever, night sweats and weight loss
Ix for ALL?
> 20% lymphoblasts on bone marrow biopsy
CML features?
Hyperproliferation of granulocyte precursosrs = bone marrow failure, hypermetabolism and hyperviscosity.
Has chronic phase, accelerated phase and blast phase.
Rfs and presentation of CML?
Rfs: M1.4:1F
Philadelphia Chr 9:22 BRC-ABL1 fusion gene
50% asymptomatic
90% massive splenomegaly
Hypermetabolic syndrome: weight loss, malaise, sweating
Bone marrow failure: anaeia, bleeding, infections
Hyperviscosity syndrome: thrombotic events, headaches
CLL features?
Progressive accumulation of functionally incompetent lymphocytes =-> occasional features of bone marrow failure and hypermetabolism
Caused by a failure of apoptosis
Rfs and presentation of CLL?
M:F 2:1
Genetic risk factors
50% asymptomatic, occasaionaly non-tender lymphadenopathy, occasional bone marrow failure
Usually diagnosed by routine bloods = lymphocytosis and smear/smudge cell on blood films
What are the general investigations for leukaemia?
FBC, LDH, blood smear
Bone marrow aspirate for biopsy
Immunophenotyping or CXR
LDH is often elevated in cancer
What is Lymphoma?
A group of blood cancers which develop from lymphocytes and the tumours are mainly found on lymph ndes
Often present with a lump/systemic B symptoms
Hodgkins, non hodgkins -> Burkits
Rfs and presentation of Hodgkins?
Bimodal age 20-30 and >50
50% EBV associated
Painless enlarging neck mass, which can be painful after alcohol
Neutrophilia
B symptoms
Non-tender, firm and rubber lymphadenopathy with splenomegaly +- hepatomegaly
Ix for Hodgkins?
Reed-sternberg cells on lymph node biopsy = bi-nucleate lymphocytes
Rfs and presentation of NHL?
More common that hodgkins (85% b cell, 15% T cell or NK)
RFs: EBV, HIV, sjogrens. Incidence increases with age
Painles enlarging mass in neck, axilla or groin
B symptoms (less common than HL)
Neutropaenia
Skin rashese.g. mycosis fungoides, headache, hepatosplenomegaly (more common than HL)
NO REED STERNBERG CELLS
Features of Burkitts lymphoma?
Strong EBV association, chronic malaria reduces resistance to EBV infection ( Papua new guinea, Equatorial africa and brazil), HIV
Rapidly enlarging lymph node in the jaw
Ix for Burkitts?
Starry sky appearance under microscopy
How to stage lymphoma>
Ann Arbour stagings
What is tumour lysis syndrome?
Metabolic abnormalities from cancer treatment = especially leukaemias and lymphomas
Phosphate -> forms calcium phosphate crystals = kidney failure and hypocalcaemia
Hyperkalaemia = arrhythia
Uric acid = gout and uric acid renal stones
WHat is multiple myeloma?
Proliferation of plasma cells so production of monoclonal immunoglobulin (IgG or IgA)
features of MM?
Rfs: >70, afrocarribean
Ionising radiation, agricultural work, HIV
CRAB
Hypercalcaemia
Renal impairments: 20%, worse prognosis
Anaemia = due to crowding, frequent infections
Bone lesions = increased osteoclast = back/rib pain
Ix for MM?
Bloods = raised ESR/CRP, irea, Cr, Ca, normal ALP
Rouleaux on blood film
Bence jones proteins in serum/urine electrophoresis
Bone marrow aspirate shows increased plasma cells >10%
WHat is MGUS?
Monoclonal Gammopathy of unknown significance:
Pre-malignant condition with accumulation of some monoclonal plasma cells
1% acquire additional mutations -> MM
Absent CRAB features
What is myelodysplasia?
Def: group of syndromes where the immature blood cells do not mature normally
Primary = intrinsic bone marrow problem Secondary = previous chemo/radiotherapy
Causes chronic pancytopaenia
Breakdown = refractory anaemia. refractory anaemia with ringed sideroblasts, refractory anaemia with excess blasts, refractory anaemia with excess blasts in transformation, chronic myelomonocytic leukaemia
Ix for myelodysplasia?
Bone marrow apsirate is hypercellular due to ineffective erythropoeisis
Breakdown of normal wound healing?
Primary haemostasis = platelet aggregation and plug formation depednign on patelets and vWF. Disorders are superficial bleeding
Secondary haemostsis = fibrin formation to stabilise the platelet plug. Depends on clotting gfactors and disroders are deep bleeding and bruising
What is haemophilia?
Inherited disorder of clotting factor deficiency/
secondary and xling recessive
a = 8 and b = 9
Presentation and Ix for haemophilia?
Haemarthrosis, haematoma and excessive bleeding and haematuria
Prolnged APTT and factor assay to confirm diagnosis
What are the roles of vWF?
Platelet adhesion between endothelium and platelets (GP1b)
Platelet aggregation
factor 8 stabilisation
Breakdown of vWF syndrome?
1 = reduced level of normal vWF and autosomnal dominant
2 = adequte levels of defective vWF = autosomnal dominant
3= complete lack of vWF and high reduced factor 8
Autosomnal recessive
presentation of vWF syndrome?
Superficial bleeding, bruising, epistaxis, menorrhagia, prolonged gum bleeding after dental procesures, prologned bleeding from minor wounds
Type 3 = deep bleeding into joints and soft tissue due to factor 8
Diagnosis of vWF syndrome?
Prolonged bleeding time
Prolonged APTT and normal PT
Reduced vWF
Normal platelets
Breakdown of DIC?
Acute overt = emergency and life threatening. lots of bleeding
Chronic non-overt = slower rate with time for compensatory response and hypercoagulable but less bleeding
DIC MOA?
Endothelial damage causes increased TF -> coagulation cascade activation = depleation of clotting factors and platelets. Concomitant activation of fibrinolysis causes bleeding into subcut tissues, mucous membraes and skin
Fibrin deposits in microcirculation -> MAHA and ischaemic organ damage
DIC presentation?
Signs of underlying pathology e.g. sepsis
ACUTE = bleeding issues, petechiae, ecchymosises, purpura, epistaxix, resp distress
CHRONIC = clotting issues = signs of DVT or arterial thombosid
Diagnoss of DIC?
FBC = low platelets adn Hb
Clotting = low fibrinogen, high fibrin degradation products, prolonged OT + APTT
Blood film = shistocytes
