Haematology / Oncology Flashcards
Myeloma - ft / Inx
Neoplasm of BM plasma cells –> 60 - 70 yrs
Ft:
- Bone - pain, osteoporosis, pathological #. Osteolytic lesions
- Lethargy
- infection
- HYPERCA
- Renal Fx
- other ft: amyloidosis.
Ins:
- IgG or IgA !!!!
- Urine –> BENCE - JONES protein
- whole body MRI
- Skull xray –> RAIN DROP SKULL
Hyper Ca of myeloma:
- Primarily due to increased osteoblastic resorption due to local cytokines (IL-1/TNF) = released by myeloma cells:
- other causes = impaired renal fn/increased renal abs of Ca/ elevated PTH-rP
Myeloma diagnostic criteria
Major:
- > 30% plasma cells in BM
- Plasmacytoma - BM sample
- Elevate M protein
Minor:
- 10% - 30% plasma cells –> BM sample
- Minor elecation of M protein
- Osteolytic lesions
- low levels of Ab
Myeloma prognostic indicator?
B2 - macroglobulin
increased macroglobulin is worse survival.
MGUS
Ft:
- Asx
- no bone pain or inc risk of infection
- Demyelinating neuropathy
MGUS vs Myeloma:
- No beta-2 macroglobulin
- normal immune fn
- lowere paraporteinaemia (igG and IgA)
- Paraproteinaemia doesn’t increase.
- no lytic lesions or renal dx
Complications of. CHOP regimen
Used in NHL
Can get neutropaenic sepsis
High risk of tunour lysis - - “> give allopurinol
Causes of macrocytic anaemia
Low Vit B12:
- found in red meat/fish
0absorbed terminal ileum
- Bound to IF
- Pernicious anemia - Ab vs GAstric parietal cells, therefore get low IF –> do schillin test which is measure uriniary B12 w/ and w/o IF.
- No neuro signs –> IM HYDROXYCABAAMIN
- If foloic A deficient as well –> replace folic A first - avoid SCDC
Folic A:
- found in FOLIAGE and Liver
- absorbed in Jejenum
Drugs that affect nuceleic Acid synthesis:
- MTX
- Hydroxycarbamide
- Aza
Macrocytosis w/ normoblasic BM
Alcohol -->low folate Liver dx --> TARGET CELLS Reticulocytosis -- RETICULOCYTES - acute blood loss or HA - PRegnancy - hypothyroid - myelodysplasia -- > Cytopenias. BM = DYSPLASTIC - myeloprolif --> TEAR DROP i BM Myeloma
Microcytic anaemia
IDA:
- Pencil cells
- hypochromic
- Fe. TIBC. Ferritin
Thalassaemia:
- Meditarannean/asian patient
- beta thalassaemia minor - microcytosis = disproprotionate to anaemia
Anaemia of CD
Sideroblastic
Pb poisoning
Patient with previously normal Hb –> acute px of low MCV and not at risk of thalassaemia —- what is it?
polycythaemia vera
IDA secodary to bleeding
Thalassaemias
Alpha thalamssaemia:
- Chromsome 16
- required for HbA/HbA2/HBF
- Severity dependent # of allles affected:
- 1 or 2 allele –> Normal Hb
- 3 alleles –> low Hb and MCV
- > 4 alleles –> in utero death = hydrops fetalis/barts hydrops
Beta thal major:
- Chromosome 11
- Absence of bet chain production
- px = 1st yr of life with FX TO THRIVE + HEPATOSPLENOMEGALY
- ow MCV
- HbF/HbA2 = raised
- HbA = Normal
- Tx = RPT TRANSFUSIONS (Fe overload) / SC DESFERRIOXAMINE
Beta - Thal Trait:
- HbA2 - raised
- Hb minor drop - remains >90
- ASx
Sickle cell anaemia
AR - more common in african decent as provides protection vs Malaria
Polar glutamate is switched for non-polar valine –> increased susceptible to hypoxia –> Polymeruse –> Sickling
Sickle RBC –> HAemolyse –> block BV –> Infarction
HbAS = hetero = sickling at pO2 of 2 --> 4.5 HbSS = homo = sickling at pO2 of 5 --> 6
Inx: Hb electrophoresis
Mx:
- Hydroxyurea - inc HbF = PROPHYLAXIS vs sickle crisis
- pneumococcal vax
Sickle cell Crises
Thrombotic:
- painful vaso-occlusive crisis
- precipitants = low O2/ infeection/ dehydration
- infarction of bones/organs - AVN/gut/lungs.brain
Sequestration:
- Pooling of blood in lungs + spleen
- WORSENING ANAEMIA
Acute chest sydndrome:
- CHEST PAIN + SOB + LOW SATS + PULM INFILTRATES:
- most common cause of death in adults.
Aplastic:
- Follows infection with PARVOVIRUS
- Sudden drop in Hb
HAemolytic crisis:
- Rare
- Fall in Hb due to haemoysis
Mx: IVI O2 Analhesia consider Abx Bloods transfusion if NEURO SIGNS ---> EXCHANGE TRAINSFUSION!!!!!
Aplastic anaemia
Causes:
- IDiopathic
Drugs - Gold/phhenylbutazone/chloramohenme
- post hepatitis supervening post infection
- Chemo/RT –> Low TPMT when starting Aza/matacopurine
MX:
- blood productions + infection prevention
- Anti0-thymocyte globulin and anti - ymphocyte globulin
- stem cell transplant
Tumour lysis syndrome
Triggered by chemo
BReak down of tumour cells
URic acid hgh
K+ high
PO4- High
Ca Low
IF high risk:
- IV allopurinol or IV rasburicase immed prior to Chemo 1st dose
If lower risk:
- PO Allopurinol
Waldenstroms macroglobulinaemia
Older en
Anaemia monoconcal IgM production Hyperviscosity syndrome hepatosplenomegaly LN
TTP - PENTAD
1) Fever
2) NEuro signs
3) Thrombocytopaenia
4) Haemolysis
5) Renal Fx
HEreditaru angioedema
Think in a young patient with signs of andioedema but not anaphylactoid
AD - Low C1 inhibitor levels
Mx:
- IV C1 inhibitor or FFP if not avail
- prophylaxis - anabolic steroid = Danzol
Fe Metabolism
icnreased by
- Vitamin C
- Gastric H+
Decreased by : PPI Tetracyclin Gastric anchlorydia Tannin
Sideroblastic anaeia
RBC fx to completely form haem
therefore get Fe depositis in mitochndria –> Sideroblasts
Can be congenital or acquired
Acquired:
- Myelodysplasia - pimary aquired
- AtOH, Anti-TB or LEad = secodnry acquired
Inx:
- Low MCV/MCH
- BM –> Sideroblasts + high Fe Stores
Mx:
- Supportive + tx underlying +/- Pyridoxine
Myeloma - prognosis marker
B2-microglobulin
Haemolytic anaemias by site - intravasc.
Mismatched blood transfusion:
- chest pain, fever , agitation, low BP
- HBO mismatchin –> within misn
- Mx: STOP TRANFUSION + IVI
G6PD:
- Low glutathione –> susceptible to Oxidative stress
- HEINZ BODIES
- neonatal jaundice
- precipitants: SPESIS/BROAD BEANS/CIPRO/PRIMAQUINE
- Inx - G6PD activity
Red cell frgamentation:
- HEart Valves
- TTP/DIC/HUS
Paroxysmal nocturnal haemoglobinuria:
- increase sensitivity to complement
- CD 59 and CD55 activity low
- get haemoglobinuria in early am DARK URINE IN A.M.
Cold AIHA:
- Raynauds
- Acrocyanosis
- IgM!!!!!!
- Causes: lymphoma/mycoplasma/EBV
Haemolytic anaemias - intravasc
TTP / DIC / HUS
TTP:
- Pentad =
- Causes
- Mx
H.U.S: - - Triad: - Secondary to - Blood film --> Mx:
Haemolytic anaemias - intravasc
TTP / DIC / HUS
TTP:
- ADAMST2
- Pentad = FEVER + NEURO + PLT LOW + LOW Hb + RENAL FX
- Causes - GU/GI Infection/ PReg/Ciclosporin + Penicillin + OCP/tumour / SLE/ HIV
- Mx: PLASMA EXHNAGE
H.U.S: - YOUG cchild - Triad: Microangiopathic haemolytic anaemia + low platelets + AKI - Secondary to E.COLI - Blood film --> FRAGMENTED RBC Mx: - Supportive - if Sev w/o diarrhoea --> Plasma exhange
DIC:
- Stress –> TF release –> aExtrinsic + intrinsic pathways.
- Inc PT/APTT/bleeding time
- low plt
- Schistocytes
- FIBRIN DEGRADATION PRODCCTS
- Mx = supportive.
Multiple myeloma mx
Watchful wait
AMjor criteria:
- Plasmacytoma
- 30% plasma cells in BM samle
- Elevated M protein
Haematological malignancies: infections
Virus:
- EBV –> Hodgkins/burkitts/naspharyngeal Ca
- HTLV-1 - Adult T cell leukaemia/lymhoma
- HIV-1 - high grade B-cell lymohoma
BActeria:
- H.pylori - gastric MALT
Protozoa:
- Malaria –> Burkitts lymohoma
Waldenstroms macroglobulinaemia
IgM Paraproteinaemia !!!
MONOCLONAL
Most likely get –> HYPERVISCOSITY SYNDROME
AML
most common leaukaemia - ADULTS
Can be primary or secondary transformation of myeloprolif.
Px –> BM Fx
Poor prognostic:
- > 60 yrs
- > 20% blasts
- Detection of Chromosome 5 or 7
Classification = French - american - british (FAB)
ALL
most common leukaemia in CHILDREN
PRolif of B + T cells
Poor prognostics:
- MAle
- non-caucasian
- <2yr or >10 yrs
- CNS involvement
- philidelphaia translocation
- initial high WCC
- B + T cell surface marker
- FAB L3
Acute promyelocytic leukaemia M3
Assox with t(15,17)
Younger onset
Fusion of PMR + RAR
AUER RODS
DIC + Thrombocytopaenia
CML
BCR - ABL = philideplphia chromosome + 9 and 22
BCR- ABL –> increase in TK ACTIVITY
Ft:
- Splenomegaly –> ABDO PAIN
- granulocyte formatio
MX:
- imatinib –> inhibit TK
CML
BCR - ABL = philideplphia chromosome + 9 and 22
BCR- ABL –> increase in TK ACTIVITY
Ft:
- Splenomegaly –> ABDO PAIN
- granulocyte formatio
- LOW LEUKOCYTE ALANINE
MX:
- imatinib –> inhibit TK
CLL indications for Mx
- progressive BM Fx
- Lymphocyte inc >50% in 2 years
- LN >10cm
- Splenomegaly >6cm
- Lymphocyte dboubling time <2 months
- Systemic Sx - WL >10% in 6 months / T >38 for 2 weeks
FCR = Mx
if no indications –> observe
Hairy cell leukaemia
male
malignant prolif of B cells
- VASCULITIS
- DRY TAP
Hodkins Lymphoma
assoc with REED STERNBERG CELL
Px in 30s / 70s
LN
ETOH INDUCED LN PAIN
Types:
- Nodular sclerosing - most common - good prognosis
- Mixed cellularity - lots of REED STERNBERG cells - good prognosis
- Lymphocyte predominant - BEST PROGNOISIS
- Lymphocyte deplete - WORST PROGNOSIS
Staging: 1 - 1 LN 2 - >=2 LN on SAME SIDE of diaphragm 3 - >=2 LN on DIFF SIDE of diaphragm 4 - Spread beyond LN
Poor prognostic factorS: - B symptoms - Stage 4 dx - Male - >45 yrs - Lymhocyte < 600 WCC >15,000 Hb <105 Alb <40
Non - hodgkins lymphoma
MORE COMMON THAN HL
Px later - 75yrs
Extranodal sx:
- Gastric - dyspepsia/dysphagia/WL
- BM –> supression/bone pain
- lungs/skin
- Neuro palsies
Assoc w/ EBV
B Sx present later
Inc:
- Excisional node biopsy –> BURKITTS = STARRY SKY!!!
- CT TAP - staging
Look for assoc:
- HIV
AI dx
- ESR - prognostics
Staging - same as HL
Chemo related nausea
Try metoclopramide/domperidone first
IF Fx or high risk
try a 5HT3 antag - ONDANSETRON
Polycthaemia
Relative - Normal Red cell mass:
- Dehydration
- Shock - Gaisbock syndrome.
Primary - Plycythaemia vera
Secondary:
- COPD
- High alt
- OSA
- Xs EPO :
- cerebellar hemangioma
- hypernephroma
- hepatoma
- uterine Fibroid
Polycythaemia Vera
Myeloprolif disorder
Clonal prolig of BM Stem Cells !!
Mutatuion - JAK-2
Hyperciscosity
- pruritus on hot bath
- splenomegaly
- haemorrhage - low plt.
Inx: FBC/blood film JAK-2 Ferritin RFT/LFT
JAK-2 criteria:
- High haematocrit/Red cell
- JAK 2 +
Mx:
- Venessection
- Aspirin
- Hydroxyurea
High Rate of transformation into
MYELOFIBROSIS
AML
Thombocytosis
Plt>400
Causes:
- Reactive - plt = acute phase response
- MAlignancy
- Hyposplenism
- Essential/primary
Primary thrombocytosis
Myeloprolif disorder –> megakaryocyte prolif
Ft:
- Thrombosis AND haemorrhage
- Burning sensation in hands and feet.
- JAK2 + in 50% of patient (CALR in 20% of JAK neg Pt)
Mx:
- Hydroxyurea
IFN alpha
- Low dose Aspirin
Myelodysplasia
Elderly patient
cytopenias
Dysplastic changes:
- Hypergranular neutrophils
- neutrophil nuclear lobulation
- megoblastic changes
monocytosis
PRE-LEUKAEMIC
tx:
- Transfusions/EPO/Abx
Stem cell Transplant
leukophoreiss post G-CSF
Stem cell Transplant
leukophoreiss post G-CSF
Pre transplant - High dose cyclophosphamde
Total body irradiation
Peripheral blood stem cells = further down maturtion pathway –> therefore quicker haem response
Coagulation cascade
Intrinsc factors:
- F 8,9, 11,12,
- Ca
- plt phospholipid
- APTT measure
Extrinsice:
- F7
- Tissue thromboplastin
- PT measure
Common pathway: - F 5,10a Ca thrombin fibrin
Porphyrias
produced when their are abnormalities in the enzymes for production of haem.
Acute intermittent porphyria:
- ABDO PAIN & NEUROPSYCH
- porphobilinogen deaminase
- urine = deep red on standing
Porphyria cutanea tarda - Think SKin
- hepatic porphyria
- Urine
- uroporphyrinogen decarboxylase - PINK fluroescens under WOOD LAMP
- photosensitive rash with bullae
- fragile skin on face + dorsal hands
- Mx - chloroquinw.
Drug induced pancytopenia
- Cytotoxics
- abx - trimthoprim/chloramphenicol
- Anti-RA - Gold/penicillamine
- Carbimazole
- Carbamazepine
- Tolbutamide
HAemophillia
X linked
HAemophillia A = F8 deficiency
HAemophilla B = F9#
HAEMARTHROSES AND HAEMATOMA (vs vWD)
INX:
- APTT increased
- PT/TT/Bleeding time = normal
Von Willebrand dx
MOST COMMON inherited bleeding disorder.
vWF = causes massive sticky multimers –> platelet adhesion. It carres FVIII
Ft:
- Epistaxis
- Mennorhagia
Tyes:
1) PArtial loss of vWF (80% of cases)
2) Abnormal fn
3) Total loss
Inx:
- INCREASED BLEEEDUNG TIME
- Low F8
Mx:
- DESMOPRESSIN –> Inc vWF release from Endothelial cells
- TXA
- F8 concentrate
ITP
Ab vs glycoprotein 2b/3a
Acute ITP:
- Children following VIRAL illness
- Self limiting
Chronic ITP:
- Young –> Mid age woman
- Relapsing and remitting
Evans syndrome:
- ITP + AIHA
ITP Assoc:
- Viral infection
- AI hepatitis
- SLE
- Anti-phospholipud
Indications for tx:
- Plt <20
- Sig bleeding
Mx:
- STEROIDS
- Splenectomy
- High dos IV Ig
- IV Anti -D
- Rituximab
Thrombophillias - Gain of Fn mutations
Factor V Leiden:
- Most common
- Factor V = inactivated
- Heterozgous: 2-5x inc risk
- Homozygous: 10x increase risk
Prothrombin Gene mutation
Thrombophillia - deficiency in anticoag
Antithrombin 3 deficiency:
- Normally inhibits F9 + F10
- Px = VENOUS THROBOSES
- Mx - Lifelong warafrin/hep in preg
- if udnergoign surgeru/childbirth –> Antithrombin 3 concentrate.
Protein C deficiency:
- Venous thromboembolism
- Most give initial Warfarin with heparin, otherwise –> pro-coag state –> NEcrosis.
LMWH
Anti-Factor 10a!!!!!!!!
Antiphospholipid syndrome
Either primery or secondary to SLE !!!!
paradoxical rise in APTT
Ft:
- Recurrent A/V thrombus
- Recurrent fetal loss
- liverdo reticularis
- Thrombocytopaenia
- pre eclampsiai/pulm HTN
Mx:
- Intial VTE –> WARFARIN –> target 2-3 –> for 6 months
- Recurrent - target 3-4 –> life long
- Arterial thromboses - target 2-3 –> LIFELONG
Antiphospholipid in preg - Mx
If Positive on urine test –> ASpirin
If +ve sca –> ASA + LMWH —> Discontinue at 34 weeks
Blood products
FFP:
- used in clin sig bleeding (not maj haemrrhage) with APTT or PT >1.5
- 150-220 ml
- Prophylaxis: Pt undegroign invasive surgery and risk of sig bleed
- Universal donor = AB blood - no Ab to A or B
Cryoprecipitate:
- contains: F8, F13, Fibrinogen , vWF
- most commonly used to replace FIBRINOGEN
- used if clin sig haemorrhage with fibrnogen conc <1.5
- prophylactic use those ndegroing surgery with fibrinogen <1.0
PTCC:
- used for rapid reversal fo anticoag patient with maj haemorrhage
- Can be used prophylactically
Cytotoxic - drugs
3 As keep runing after a single C, miss it and end up on MTV
Alkylating agents - Think Cs
- Cyclophosphamide
- Chlorambucil
- Carmustine
- Cisplatin /oxaliplatin/carboplatin
- Melphalan/busulfan
Abx (-mycin and -bicin)
- Dactinomycin
- bleomycin
- mitomycin
- Doxuribicin
- Mitoxantrone
Antimetabolites (ate/-purine/-bine)
- Folate antag - MTX
- purine atage - 6-mertacopurine/fludabarine/cladribine
- Pyrimidine antag - 5 - FU/Cytarabine/Capecitabine/Gemcitabine
Campothecin analogues
- Topotecan
- irinotecan
Miscelaneous
- Procarbazine
- Hydroxurea
- Imatinib/Nilotinib/Sorafenib/bortezomib - TK inhibitor
- L-Asparagine
Taxanes - Microtubule inhiitor !
- End in “-taxel”
- Docetaxel
- PAclitaxel
Vinca alkaloids - Microtubule inhibitor!
- Start with “Vin-“
- Vincristine
- Vinblastine
- Vinorelbine
Brukitts lymphoma - Gene
C-myc translocation
Cryoglobulinaemia
Igs that rpecipitate out at 4 degrees and then dissolve at 37 degrees.
3 Types:
1) Monoclonal
2) mixes
3) polyclonal#
Type 1:
- monoclonal = IgG otr IgM
- RAYNAUDS
- assoc with multipele myeloma and waldenstroms macroglobulinaemia
Type2:
- Mixed mono & polyclonal
- Hep C, RA, Sjrogrens
Type 3:
- polyclonal
- Assoc Ra/Sjrogrens
Sx:
- Raynauds - type 1
- Pupura and distal ulceration
- arthralgia
- Diffuse glomerulonephrtis
Inx:
- low C4
- High ESR
Tx
- Immunosupress
= plasma exhange
PRegnancy and DVT/PE
PReg = hypercoaguable state
Majority = last trimester
Pathophysiology:
- Increase Factor 7,8,10 + fibrinogen
- Decrease protein S
- IVC copresison
Mx:
- LMWH
- Warfarin = CI
What is Factor V leiden
Thrombophllia disorder
Activated PROTEIN C RESISTANCE !!!!!!
Myelofibrosis
Myeloprolif disorder
Ft:
- Elderly person with sx of anaemia
- MAssive splenomegaly
Hypermetabolic sx
LAb findifns: - Anaemia High WBC/platelets - Tear drop cells - Dry Tap - High urate and LDG
Autoimmune haemolytic anaemias
+ Coombs test
Warm:
- IgG - Ganesh is always warm
- assoc with SLE
- Lymphoma, CLL
- Methyldopa
Cold AIHA:
- IgM - Malika is always cold
- causes: Lymphoma, mycoplasma, EBV
Sode effevt of. Dapsone
Depsone is. Used in methaemoglobinaemia
It is an oxidiaknf agent
Therefpre Fe2+ that is normally bound to Hb - - > Fe3+.
High prevelance of G6PD in west africa
Which blood product most commonly causes bacterial transfusion reaction ???
PATELETS
TRALI vs TRACO
transfusion related acute lung inury vs transfusion associated circulatory overload
TRALI = HYPOTENSION
TRACO = HYPERTENSION
Industrial carcinogens
Nitrosamines - OEsophageal + gastric Ca
Arsenic = Lung Ca + liver haemaniomas
Alfatoxin = hepatocellular Ca
Alanine = TCC
Benzene = leaukaemia
Most common type of organism isolated in neutropaenixc sepsis
G + Cocci
Multiple myeloma - investgations
1) Diagnosis ?
2) Prognosis ?
1) Serum electrophoresis
2) Beta-2 microglobulin
Translocations - haem malignancies
1) (9,22)
2 - (15,17)
3 - (8,14)
4 - (11,14)
5 - (14,18)
1 - Philidelphia - CML
2) 15 - 17 year old almost an adult - AML
3) 8 = looks like B - burkitts lymphoma
4) 11 - 14 yr old - start to get awards on the mantle = mantle cell
5) 4 in the first number - F = Folicular lymphoms
Cause of Immunofeficiency in CLL ?
CLL is a B cell disorder –> hypogammaglobulinaemia
LEaukamoid rxn
infiltration of BM –> Pushing out of immature blood cells
Causes:
- Sev infection
- Sev haemolysis
- haemorrhage
- Metastatic Ca with BM Involvement
looks like CML On bloods
CML vs leukamoid rxn
CML:
- Low ALP
LEukamoid:
- High ALP
- Dohl bodies in white cells
- LEft shift of neutrophils
Heparin induced thrombocytopaenia
Ab vs PLATEKET FACTOR 4
Low platelets yet STILL PROTHROMBOTIC
Tx:
- Lepirudin
- Danaparoid
Most common organisms for neutropaenic sepsis
G+ Cocci
Neutropaenia - when to start G-CSF
If High risk of Febrile neutropaenia:
- Elderly
- NHL/ALL
- Prev neutropaenia
- On chemo/RT
AML poor prognistics
Age >60
>20% Blasts
Chromosme 5 or 7 deletion
Unprovoked DVT >40yrs
Malignancy screen and anti-phspholipids
CLL investigation
Blood film - smudge cells
Immunophenotyping
Factor V leiden mutation MX
LT warfarin
