Haematology Flashcards
What is hodgkins lymphoma?
malignant tumour of lymphatic system - characterised histologically by Reed Sternburg Cells
Describe the histology of Hodgkin’s lymphoma
Reed Sterburg cells (multinucleated giant cells)
abnormal and smaller mononuclear cells originating from B lymphocytes
Risk factors for Hodgkins lymphoma
EBV
previous mononucleosis
HIV
immunosuppression
Presentation of Hodgkins lymphoma
- enlarged but asymptomatic lymph node in lower neck or supraclavicular region (pain with alcohol)
- cyclical fever
- chest discomfort - cough dyspnoe (mediastinal lymph node involvement)
- B symptoms - night sweats, fever, weight loss
Staging of Hodgkins lymphoma
Ann Arbor
- one lymph node region or structure (spleen, thymus, waldeyers ring)
- >1 lymph node region on same side
- involvement both sides
- splenic, hilar, coeliac or portal
- para-aortic iliac or mesenteric
- extranodal
Modifying features of Hodgkins lymphoma
A: no symptoms
B: night sweats, fever, weight loss
X: > 1/3rd mediastium widening or >10cm diameter of mass
E: extranodal site
Potential examination findings of Hodgkins lymphoma
Lymphadenopathy
Hepatomegaly
Splenomegaly
Superior VC syndrome (facial swelling associated with SOB)
Hodgkins lymphoma investigations
FBC (leukamia, mono)
ESR (>70 bad prog)
LFT (low albumin bad prog)
HIV
CXR (lymphadenopathy and mediastinal expansion)
Lymph node and bone marrow biopsy (staging)
CT thorax and abdo (staging)
ABVD chemo
Doxorubicin
Bleomycin
Vinblastine
Dacarbazine
BEACOPP chemo
Bleomycin
Etoposide
Doxorubicin
Cyclophosphamide
Vincristine
Procarbazine
Prednisolone
What can additional things can you give with chemo
- Abx to any pt with severe neutropenia
- Recombinant human granulocyte colony - stimulating factor stimulates neutrophil production so could reduce duration of chemo induced neutropenia reducing incidence of associated sepsis
Management of Hodgkins lymphoma
Early: ABVD then radio (preceeded by BEACOPP in unfavourable prog)
Advanced: ABDV/BEACOPP
ASCT= autologous stem cell transplant
follow up for Hodgkins lymphoma
OPD 2-5 years
TFT if radio to neck and upper mediastinum
made aware theyre increased risk of secondary mags, CVD, pulmonary disease and infertility
Prognosis of Hodgkins lymphoma
80-90% patients achieve permanent remission
poor prognostic indicators
- increasing age
- male
- B symptoms
*
Patho behind non-hodgkins lymphoma
Genetic mutation causes B/T cells to divide uncontrollably producing a neoplastic cell.
This can be
1) nodal lymphoma
2) extranodal lymphoma
- GI tract
- Bone Marrow
- Spinal cord
What types of B cell lymphoma are there?
Indolent : follicular lymphoma
aggressive e.g. Diffuse large B cell lymphoma
mantle cell lymphoma
highly aggressive e.g. Burkitts lymphoma (chromosomal translocation 8->14) associated with EBV
Types of T cell lymphoma
adult T cell lymphoma
mycosis fungoides
Non-Hodgkins lymphoma symptoms
gastric MALT: GORD + constitutional symptoms
Burkitts: abdo swelling, nausea and diarrhoea
small bowel T cell: associated with coeliac
NHL investigations
Lymph node biopsy
Burkitts starry sky on hisology
CT - staging
NHL Management
localised - Radiotherapy
High grade - R-CHOP
Rituximab
Cyclophosphamide
Hydroxydaunomycin
Vincristine
Prednisolone
Which cancer is associated with coeliac disease?
small bowel T cell lymphoma
What is bacteria is assoicated with Burkitts lymphoma?
H. pylori
how do you treat h.pylori?
PPI
clarithromycin
metronidazole or amoxicillin
What are the possible causes of a mediastial tumour?
Terrible lymphoma (Hodgkins)
Teratoma
Thymoma
Thyroid Mass
Which groups of patients have a higher risk of acute lymphoblastic leukaemia?
Children
Downs Syndrome
Which cell line is affected in ALL?
Small lymphocyte
How does ALL present?
Bone marrow failure
RBC: anaemia, dyspnoea, fatigure, dizziness
WBC: more infections
Platelets: bleeding
Which investigations would you do in suspected ALL?
FBC: anaemia, neutropenia, thrombocytopenia
Blood film: Blast cells >=20%
Increase LDH (lactic dehydrogenase) due to increased cell turnover
LP- CNS involvement
Imaging to assess mass
What are poor prognostic indicators in ALL
Philadelphia Chromosome
adult
male
CNS signs
What is the management of ALL?
- chemo
- SCT if poor prog
How does AML present?
Bone marrow failure
RBC: anaemia, dyspnoea, fatigue dizziness, palps
WBC: infections
Platelets: Bleeding Gum hypertrophy and bleeding
AML investigations
FBC: anaemia, neutropenia, thrombocytopenia
Blood film: blast cells Auer Rods
increased LDH
BM aspiration/biopsy: >=20 blast cells
Management of patient with AML
Induction: cytarabin and daunoribicine
SCT
What is the cell line affected in acute myeloid leukaemia
myeloblasts
Chronic myeloid leukaemia cell line affected
Basophils, neutrophils, eosinophils
What chromosome is assoicated with CML and what does it do?
Philadelphia t(9;22)
Activates tyrosine kinase
How does CML present?
1) chronic stage: constititional symptoms
2) accelerated: anaemia, thrombocytopenia, neutropenia
3) Blast cell crisis (AML): no mature cells left, terminal
How do you manage CML?
Tyrosine kinase inhibators - imatinib
SCT
Which cell line is affected in chronic lymphocytic leukaemia?
B-lymphocytes
CLL pathology
gradual build up of B lymphocytes that evade immune system - dont die
Build up in blood/bone marrow, lymph nodes and spleen
How does CLL present?
Often asymptomatic
Bone marrow failure
Which infection is associated with CLL?
SHingles
What investigations would you do in suspected CLL?
Blood film: Smudge cells
FBC: anaemia, neutropenia, thrombocytopenia
How would you manage a patient with CLL
watch and wait
chemo
rituximab
Bone marrow transplant
Which other cancer can develop in patients with CLL?
Richter’s syndrome - NHL, high grade
what is the patho of myeloma?
Basically increase in plasma cells which:
1) Accumulation in BM -> failure
2) produce IgG and IgA and paraproteins (bence jones) -> renal failure
3) | increase osteoclast and inhib osteoblasts -> hypercalcaemia, bone destruction
How does myeloma present?
CRABI
- *C**alcium high
- *R**enal impairment
- *A**naemia
- *B**oney lesions - pepper pot skull
Infections +
what oncology emergency could be caused by myeloma?
Spinal cord compression
hyperviscosity of blood -> soft tissue swelling
How would you investigate suspected myeloma
FBC: bone marrow failure
hypercalaemia
serum protein electrophoresis: monoclonal plasma cells
urine protein electrophoresis: monoclonal antibodies - Bence Jones proteins
X-ray: pepper pot skull
What are the diagonstic criteria for myeloma?
1) monoclonal plasma cells in bone marrow
2) monoclonal antibodies in urine (bence jones protein)
2) symptom from CRAB - end organ failure
How would you manage a patient with myeloma?
- chemo: bortezomib, thalidomide, dexomethasone
- SCT
- other: radio, bisphosphonates, infection prophylaxis
68 yo male pt with enlarged lymp nodes neck, axillae, groin.
low Hb, high WBC
Blood film: 60% white cells are small mature lymphocytes
diagnosis
CLL
What is the most commonly inherited thrombophilia?
Activated protein C resistance (Factor V Leiden)
What is Thromobotic thrombocytopenic purpura?
lack of enzyme that cleaves vWF so you have more vWF
Mini thrombi form which use up platelets/clotting factors -> clotting
What are the symptoms of TTP?
The Terrible Pentad
- Anaemia
- Thrombocytopenia
- Fever
- Renal problems
- CNS involvement
What investigation findings would confirm TTP?
Schistocyes on blood film
low platelets
How would you manage a patient with TTP?
plasmapheresis
+rituximab
+corticosteroids
What is disseminated intravascular coagulation?
systemic activation of blood coag, initally form clots but then no more platelets -> bleeding
how does DIC present?
bleeding
petechiae
purpura
What causes DIC
systemic: infection, trauma, leukaemia
How would you investigate ?DIC
D dimer high (fibrin degradation)
High PT/APTT
Low platelets
How would you manage a pt with DIC
bleeding: platelet transfusion, FFP, fibrinogen conc
Not bleeding: heparin
what is idiopathic thrombocytopenic purpura?
antibodies that bind to platelets and destoy them, diagnosis of exlusion
How would a patient with ITP present?
Bruising, petechiae
Bleeding: gums, GI, nose, menorrhagia
How would you investigate a pt with ?ITP
Low platelets
serology: Antibodies
How would you manage a patient with ITP?
1st: pred + IVIG
2nd: splenectomy
What is haemolytic uraemic syndrome
Infection with E.Coli causing platelet destruction
- haemolytic anaemi
- thrombocytopenia
- AKI
How does HUS present?
Bloody diarrhoea
abdo pain, fever, vomiting
How would you investigate a pt with ?HUS
Stool sample: E.coli
Increased: Cr, LDH, WCC
Decreased: platelets
how would you manage a pt with HUS?
supportive
fluids and electrolytes
*notifiable disease*
what is von willebrands disease
Low vWF leads to defective platelet plug formation and decreased factor VIII
How does vWD present?
bruising
bleeding: post surgery, mucosal, GI epistaxis
What would bloods show in a person with vWD?
High APTT
Low: vWF, VIII
How would you manage a patient with vWD?
avoid: NSAIDS, aspirin, IM injections
- tranexamic acid + desmopressin - increase VIII and vWF from endothelial stores
- Type 3: vWF concentrates
- screening
What is haemophilia A/B
X linked recessive condition resulting in deficiency in factor VIII (A) or IX (B)
How would a patient with haemophilia present?
- bruising
- bleeding: after small trauma, into small joints
What woudl bloods show in haemophilia?
Increased APTT
decreased VIII or IX
how would you manage haemophilia?
recombinant VIII or IX
Which factors are vitamin K dependent?
2, 7, 9, 10
What is coombs test?
antibody added to blood sample
+Ve = immune system causing RBC destruction
What is MCV and MCH
Mean corpuscular volume: Size of RBC
Mean corpuscular hb: Hb content of average RBC
What are causes of normocytic anaemia?
Haemolytic
aplastic
What are causes of microcytic anaemia?
Iron def
thalassaemia
What are causes of macrocytic anaemia?
Pernicious
Folate def
How does haemolytic anaemia present?
Asymptomatic unless severe
- weakness
- angina
- jaundice
- tachy
- dyspnoea
What would investigations show in haemolytic anaemia
Hb: low
MCV: normal
Reticulocytes: high (increased production)
UCB/LDH: high (break down of RBC)
+ve coombs if immune mediated
Blood film: spherocytes
How do you manage haemolytic anaemia?
Corticosteroids
folic acid
transfusion if necessary
What causes haemolytic anaemia?
Genetic: SCA, thalassaemia, G6PD def
Aquired: Haemolytic disease of the newborn, SLE, CLL, trauma
What is aplastic anaemia?
Pancytopenia with hypocellular BM
How would a patient with aplastic anaemia present?
General: pallor, fatigue, oedema, palps, headache
Post hep: 2-3 months jaundice
Congential: short stature, cafe au lait spots, skeletal abnorms
What would you see on investigations for aplastic anaemia?
Hb: low
Platelets: low
Neutrophils: low
Reticulocytes: low
Viral studies
How would you manage a pt with aplastic anaemia?
non severe: immunosups - ATG + ciclosporine or alemtuzumab
severe: haematopoietic SCT
Blood/platelet transfusion
What causes Aplastic anaemia?
Idiopathic
Infection: post hepatitis
Viral: EBV, HIV
congenital/inherited
Causes of Iron def anaemia
Blood loss: GI, menorrhagia, NSAID use
Dietary inadequacy: growing children and elderly
Malabsorption: tetracyclines, PPIS, coeliac, H. Pylori
Increased need: growth, preg
How does iron def anaemia present
Fatigue, SOB, palps, headache
OE: pallor, koilnychia (spoons shaped)
angular chelitis, atropic glossitis
What would you expect to see on investigations of pt with Iron def anaemia ?
Hb: low
MCV: low, microcytic
MCH: low, hypochromic
Ferritin: low
Film: varying size and abnormal shaped RBC
males/post meno fems : endoscopy
coeliac screening
How do you manage Fe def anaemia>
Ferrous sulphate tablets
what are the side effects of ferrous sulphate tablets?
Constipation, nausea, black stools
What is thalassemia?
Autosomal recessive condition where either ɑ or β chains on haemoglobin are absent or decreased resulting in reduced hemoglobin in RBC
How does thalassaemia present?
Normally asympotmatic
Severe: pallor jaundice, HF
What would you expect to see on investigations for ?thalassaemia?
Hb: low
MCH/MCV: low
iron: high
ferritin: high
Haemoglobin electrophoresis is diagnostic
How do you manage a pt with thalassaemia?
Asx: monitor
intermediate: ?blood transfusion
major: regular hypertransfusions to mainly enough Hb
Desferrioxamine, oral chelating agents (deferasirox)
SCT: better outcome when younger
what is pernicious anaemia?
An autoimmune coniditon which involves gastritis and loss of parietal cells.
For B12 to be absorbed in terminal ileum parietal cells which produce intrinsic factor are required
Causes of Pernicious anaemia
intake: lack of animal producs
Gastric: H.pylori infection, gastritis
Intestinal: malabsorption, crohns, HIV
Drugs: neomycin, colchicine
how would a pt with pernicious anaemia present?
Fatigue, lethary
palps and headaches
B12 def: neuro (loss of vibration postion, reflexes) , paraesthesia, numbess, visual changes
OE: pallor, glottis, oral ulceration
Investigation findings in pernicious anaemia?
Hb: low
MCV: high
Autoab screen: Parietal cell antibodies
Blood film: hypersegmented neutrophils, oval macrocytes and megaloblasts
Management of pernicious anaemia?
IM hydroxocobalamin
What are the causes of folate def?
Diet: goats milk, alcohol XS
Malabsorption: coeliac, IBD
Excretion: CHF
Antifolate drugs: nitrofurantoin, anti-c, methotrexate
Increased need: preg
Genetic Disorder
What is sickle cell trait and anaemia?
Autosomal recessive condition with abnormal HbS
Homozygous= sickle cell anamia
heterozygous (HbA HbS) = sickle cell trait, asx, malaria protec
How does sickle cell anaemia present
3-6 months old bc decrease in HbF
symptoms triggered by infection
- anaemia: pallor, lethargy
- growth restriction
- jaundice
When does a SC patient need hopsital referal?
Symptoms: severe pain, haematuria
OE
- temp >38.5 or <36 in adults
- temp>38 in kids
- hypotensive
- dehydrated
- low Hb
How do you diagnose SCA?
Hb electrophoresis
Decreased Hb
Blood film: sickled erythrocytes
What are the sickle cell crises?
- Vasco-occlusive: obstruction of micro-circ by sickled RBC -> anaemia
- Aplastic: erythopoiesis cessation due to parvovius B19
- Sequestration: sickling in spleen causing pooling of blood
What can trigger a vaso-occulsive SC crisis?
DICE
Dehydration
Infection/Ischaemia
Cold
Exertion
How does a vaso-occulsive SC crisis present?
- Pain
- dactylitis
- stroke
- retinal occulsion
- tachy
- abdo distension
how you you manage aplastic SC crisis?
Transfusion
How does a sequestration SC crisis present and how do you u manage?
Px: hypovolaemia, splenomegaly
Ix: low Hb, high reticulocytes
Mx: splenectomy if recurrent
What is polycythaemia?
increased RBC associated with JAK2 mutation which means haematopoietic stem cells keep producing RBC regardless of EPO
How does polycythaemia present?
1) plethoric stage
- fatigue
- dizziness
- itching (worse when hot)
- facial plethora
2) spent stage
scar tissue formation means BM cant produce RBC - anaemia, thrombocytopenia, leukopenia
How would you investigate polycythamia?
FBC: high Hb, WCC and platelets,
Genetic: JAK2
Bm: fibrosis, teardrop cells in spent phase
How do you manage polycythaemia
Venesection
hydroxycarbamide:
CVD prophylaxis: Aspirin
