HAEMATOLOGY & ONCOLOGY Flashcards
what enzyme catalyses final step of coagulation cascade
thrombin
factor II, crosslinking occurs via factor XIII
t15;17
PML (AML)
t12;21
B-ALL
favourable prognosis
(t9;22 poor prognosis)
t8;14
Burkitt lymphoma
aggressive non-hogkins lymphoma
t14;18
follicular lymphoma
DLBCL
non-hogkin lymphoma (m/c)
t9;22
CML
AML
ALL* (poor prognosis)*
CD10+, CD19+, TdT
B-ALL
CD3+, CD7+, TdT
T-ALL
t9;22
BCR-ABL1
LAP negative
CML
CD13+, CD33+, CD117+
MPO
Auer rods
AML
CD5+, CD20+, CD23+
smudge cells
CLL
what cancers are more prone in Down Sydrome
ALL
AML - megakaryoblastic type
risk factors for AML
myeloproliferative
Down Syndrome
what cancers can result from radiotherapy
**leukaemias: **
AML, MDS (precursor to AML)
**solid: **
breast, lung, bladder
**Children: **
brain, osteosarcoma
what syndrome involves inneffective haematopoesis due to haemopoetic stem cell problem
myelodysplatic syndrome
what can myelodysplastic syndromes progress to
AML
AML > 20% blasts
MDS <20% blasts
causes of MDS
idiopathic 1’
radiation, benzene, chemotherapy 2’
CML can be classed as a
myeloproliferative syndrome
driven by BCR-ABL1 mutation, not JAK2 (like other MPS)
TKI treat CML
ruxolitinib treats JAK2
name 4 myeloproliferative conditions
polycythemia vera
essential thrombocytopenia
myelofibrosis
CML
proliferation/hyperplasia of megakaryocytes and functionally abnormal platelets
myeloproliferative disorder
essential thrombocythemia
(leukocyte count can be normal)
bleeding/clotting, thromboplebitis, thromboembolism, DVT, abortion, hyperviscosity - headache, paraesthesia, lightheaded
differentiate from antiphospholipid syndrome - DVT, abortions but no thrombocythemia (increased megakaryocytes)
in CKD, platelet function is disrupted by what
inappropriate upregulation of nitric oxide
NO downregulates vWF secretion, reduces ADP and TXA2 levels, inhibits GpIIa/IIIb receptor
(as urea levels rise, arginine and precursors shunted to different pathway guarnidinsuccinic (GSA), precursor to nitrix oxide - high NO inhibits primary haemostasis
what is the precursor amino acid of urea
arginine
sheets of lymphocytes with interspersed tingible body macrophages
burkitt lymphoma
EBV positive
C-MYC
endemic - jaw
sporadic - ileocecal
skin patches, plaques, itchy rash
atypical CD4 cells
cribiform nuceli
intraepidermal neoplastic cell aggregates
mycosis fungoides
cutaneous T cell lymphoma
can progress to Sezary syndrome (T-cell leukaemia)
Histology interpretation:
- epidermotropism (atypical T-cells within the epidermis)
- pagetoid or linear pattern
- Pautrier’s microabscesses (clusters of lymphocytes in the epidermis)
- atypical lymphocytes with cerebriform nuclei
B symptoms + painless lymphadenopathy can raise suspicion for …
lymphoma
aggressive B cell lymphoma
affecting adults
CD20+
DLBCL
t8;14 translocation result from ____________ of C-MYC gene
overexpression
proto-oncogene
hypercalcaemia in Hogkins lymphoma caused by
paraneoplastic:
IFN-Y –> 1a-hydroxylase –> 25D to 1,25D –> calcium reabsorption
suppresses PTH
activated T lymphocytes surrounding reed-sternberg cells secrete IFN-Y
Increased 1a-hydroxylase in macrophages and lymphocytes
Excessive convernsion 25D -> 1,25D
increases intestinal and renal reabsorption calcium
hypercalaemia
also seen in sarcoidosis, tuberculosis (granulomatous diseases)
name causes of inappropriate absolute polycythemia
increased EPO
hepatocellular carcinoma
renal cell carcinoma
polycystic kidney disease
pheochromocytoma
hemangioblastoma.
EPO doping / androgens
Increased erythropoietin (EPO) levels +
RBC mass (red cell volume) +
normal plasma volume & arterial oxygen saturation (SaO2) = **secondary polycythemia **
(due to autonomous EPO production or exogenous EPO intake)
EPO independant proliferation of myceloid cell lines
increased RBC mass
polycythemia vera
Increased RBC mass - suppresses EPO
Normal arterial O2 saturation (SaO2)
Increased or normal plasma volume
Normal SaO2 distinguish PV from types of secondary polycythemia caused by chronic hypoxia.
RBC mass increased
O2 sat decreased
EPO increased
appropriate absolute polycythemia
lung diease, congenital heart disease, high altitude, OSA
hypoxia driven
decreased plasma volume
normal RBC mass
normal O2 sat
normal EPO
relative polycythemia
dehydration, burns
normal plasma volume
increased RBC mass
normal O2 sat
increased EPO
inappropriate absolute polycythemia
EPO exogenous, androgen supplements, malignancy - RCC, HCC
increased plasma volume
increased RBC mass
normal O2 sat
decreased EPO levels
polyythemia vera
negative feedback suppress EPO production
JAK2 mutation, ‘myeloproliferative neoplasm’
clonal proliferation of RBCs
increased RBC without increased EPO or hypoxia stimulation
blood in urine, but no RBC in urinalysis
haemoglobinuria
myoglobinuria
i.e. PNH
true hematuria - blood and RBC in urine
Red urine (no RBCs on dipstick)
fatigue
abdominal pain (NO depletion - vasoconstriction)
jaundice
pancytopenia
unconjugated hyperbilirubinemia (jaundice)
elevated LDH
negative Coombs test
venous thrombosis - Budd-Chiari
haemolytic anaemia (intravascular)
paroxysmal nocturnal hemoglobinuria (PNH)
defect PIGA gene -> CD55, CD59
Tx elicizumab -> targets C5
rheumatoid arthritis & reduced response to EPO
anaemia of chronic disease i.e. (autoimmune disease - inflammation)
high doses EPO can overcome this
EBV infection can be complicated by
IgM mediated (cold) autoimmune haemolytic anaemia
Cold is Miserable
pernicious anaemia is caused by a lack of intrinsic factor produced by what cells
parietal cells
intrinsic factor required for B12 production
exclusively breastfed infant can result in what deficiency
iron deficiency
breastmilk contain very little iron
vitamin D and K are also low in breast milk
iron overload due to 2’ haemochromatosis is a risk in what patients?
hyperpigmentation, fatigue
beta thalassemia patients with multiple transfusions
microcytic hypochromic anaemia,
target cells
minimal variation in RBC size/shape (normal RWD)
a-thalassemia
(mild-mod)
severe a-thalassemia - hydrops fetalis
microcytic hypochromic anaemia, target cells,
variable RBC size/shape (anisocytosis) = iron deficiency
decreased Hb
decreased MCV
decreased MCHC
decreased ferritin
iron deficiency anaemia
most common cause of iron deficiency anemia in the elderly - CRC
can look similar to thalassemia or anaemia of chronic disease - but this would have high ferritin
splenomegaly
jaundice
increased MCHC
recent URTI
hereditary spherocytosis
autosomal dominant
spherocytes
ankyin, spectrin, band defect
more prone to URTI - because of** splenic dysfunction** - lacks ability to effectively clear encapsulated bacteria **(Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis) - common causes of URTIs
complication of infection with E coli O157:H7 is
HUS
haemolytic uremic syndrome
shiga toxin (STEC)
inflammation, bloody diarrhoa, vascular damage
triad:
haemolytic anaemia
AKI
thrombocytopenia
**PT **& PTT normal (or slight increase)
**thrombocytopaenia and **elevated creatinine **caused by gram-negative, oxidase-negative bacteria that does not ferment sorbitol
haemolytic uremic syndrome
from E coli infection
indicating renal railure
normally between 5-13 days after diarrhoea
chest pain, dyspnea, splenomegaly, and mild normocytic anemia
vaso-occlusive crisis
(sickle cell disease)
jaundice, hepatosplenomegaly, and difficulty breathing
mixing mother blood & infants invitro causes agglutination
autoimmune hemolytic disease of the fetus and newborn (HDFN)
(erythroblastosis fetalis)
The Rh-negative mother had a prior pregnancy with an Rh-positive fetus
results in formation of maternal IgG antibodies that can affect future pregnancies.
proteins CD55 and CD59 use ? to attach to extracellular surface of cells
GPI anchors
proteins act to inhibit complement and prevent host cells from being lysed by nonspecific activation of the complement pathway
jaundice
hepatosplenomegaly
oedema
coombs test (+)
anaemia
nucleated RBCs
extramedullary haeamtopoesis
haemolytic disease of the newborn (erythroblastosis foetalis)
oedema (hydrops foetalis)
destruction of foetal RBC by material antibodies
antibodies cross placenta –> opsonise foetal erythrocytes –> haemolysis
directed against foetal RBC antigens
IgG ABs
most often Rh incompatability (**Rh- mother **against Rh+ foetus)
fever
chills
dyspnoea
hypotension
back/chest pain
haemoglobinuira (red/brown urine)
transfusion
acute haemolytic transfusion reaction
symptom of ‘shock’
vasodilation
can experience DIC or **renal failur
ocurs minutes-hours
T2HS
often ABO incompatability
i.e. MVA –> transfusion –> reaction seen early
poikilocytosis
abnormally shaped RBCs
seen in - i.e. iron deficiency
schistocytosis
fragments of RBCs
‘helmet cells’
seen in i.e. mechanical destruction
Iron in hemoglobin is in ferric (Fe3+) state instead of the normal ferrous (Fe2+) state
Methemoglobinemia
can be congenital or aquired
Methaemoglobin cannot bind O2
CO poisoning will show what values of:
carboxyhaemoglobin
PaO2
methaemoglobin
Carboxyhaemoglobin: increased (40%)
PaO2: normal (95mmHg)
Methaemoglobin: normal (1%)
what does CRAB stand for
hypercalaemia
renal insufficiency
anaemia
bone lytic lesions
multiple myeloma
punched out bone lesions
bence jones proteins
IgG
increased cytokines - IL-1, TNF-a, RANK-L
increased osteoclast activity
intracytoplasmic inclusions (IgG)
clock faced chromatin
increased platelets & megakaryocytes
bleeding and thombosis
erythema, warmth, and recurrent burning pain of extremities
essential thryombocythemia
myeloproliferative disease
Erythromelalgia - triad of erythema, warmth, and recurrent burning pain of extremities
vitamin K is a cofactor for y-glutamyl carboxylase that activates coagulation factors (1972) via…
post-translational y-carboxylation
translational
vit k deficiency: mucosal bleeding, bruising, prolonged PT, PTT, intestinal diseases assoc with malabsorption ie. IBD
migratory thrombophlebitis should raise suspicion for
cancer
= trosseau syndrome
(hypercoagulability = paraneoplastic condition of visceral adenocarcinomas - pancreas, colon, lung)
mature erythrocytes loose their ability to synthesise heme (and thus Hb) when they loose what organelle
mitochondria
(not present in mature erythrocytes)
mature rbc have no nucleus, ER, golgi, mitochondria
mitochondria are present in erythroid precursor cells (neede for stage 1 and 3 of heme synthesis)
the paraneoplastic condition polycythemia (increased RBC) is associated with what neoplasms
RCC
HCC
pheochromocytoma
hemangioblastoma
leiomyoma
due to increased EPO (often tumour secreted)
EPO
Seen in
Hb 18.5g/dL.
secondary polycythemia
(COPD)
increased EPO from hypoxia**
**increased Hb
plasma volume normal
increased density of normocytic normochromic erythrocytes
no blasts (may indicate myeloproliferative)
Stem cell disorders involving ineffective
hematopoiesis
myelodysplatic syndrome
<20 blasts present
Pseudo-Pelger-Huët anomaly - biloped nuclei neutr
de novo mutations
drugs - radiation, chemo, benzene
define hypersplenism
one or more cytopenias in the setting of splenomegaly
cirrhosis
portal HTN
common complication of;
overactive spleen
destroys blood cells too quickly
leads to low blood cell counts and
enlarged spleen
othe causes:
lymphoma, sickle cell, malaria, mononucleosis, CT disorders
cirrhosis
portal HTN
pancytopenia
normal/increased Rtc
normal PT, PTT, fibrinogen
hypersplenism
overactive spleen
destroys blood cells too quickly
leads to low blood cell counts and
enlarged spleen
othe causes:
lymphoma, sickle cell, malaria, mononucleosis, CT disorders
What Rtc would be expected in Wernicke-Korsakoff
decreased reticulocyte index
sevre pancytopenia - decreased production of BM cells
polycythemia is determined by haematocrit level of:
___ in men
___ in women
> 52%
48%
increased haematocrit
normal red blood cell mass
relative polycythemia
plasma volume contraction
i.e. dehydration
diuresis
hypoxia induced polycythemia = increased RBC mass (by EPO)
polychtmeia vera = increased RBC mass (overproduction)
red blood cell mass distinguishes
absolute from relative polycythemia
most common bacteiral infections in sickle cell patients
encapsulated:
s. pneumoniae
n. meningiditis
h. influenzae
encapsulated - functional asplenia
fulminant bacterial infection
also bacteremia: salmonella osteomyelitis
what is the key diagnostic feature needed to Dx thrombotic thrombocytopenic purpura (TTP)?
MAHA - haemolytic anaemia - schistocytes
ADAMTS13
pentad
DIC is a common side effect of
gram negative sepsis
i.e. following n. meningiditis infection
consumptive coagulopathy
schistocytes
thrombocytopenia
decreased fibrinogen
prolonged PT, PTT
heavy mensturation
intermitten nose bleeds
bloor in urine/stool
ecchymoses, petichiae LL
circulating antiplatelet AB +
what is the pathogenesis
immune throbocytopenic purpura (ITP)
caused by platelet dysfunction
anti-platelet AB (GpIIb/IIIa) - opsonises the platelets
LOW platelet count
absense of other causes of thrombocytopenia
Bone marrow biopsY:
increased megakaryocytes - adequate platelet production but increased peripheral destruction
acute ITP can follow infection
Tx steroids, splenectomy
