haematology Flashcards
signs and symptoms of anaemia
tiredness pallor koilonychia dizziness angina/claudication if concomitant arterial disease breathlessness tachycardia
investigations into red blood cell disorders
FBC - HCT, MCV, Hb serum iron ferritin TIBC reticulocytes haematinics (b12/folate)
causes of anaemia with low MCV, normal MCV, high MCV
low mcv - iron def, thalassaemia, anaemia of inflammation
normal mcv - renal anaemia, multiple myeloma, anaemia of inflammation, mixed haematinic and iron def, bleeding, haemolytic anaemia
high mcv - b12/folate, pregnancy, hypothyroid, liver disease, bleeding with increased retics, alcohol
how is high or low ferritin interpreted?
low ferritin is almost always iron deficiency
high ferritin is non-specific
what is pernicious anaemia?
inability to make or use intrinsic factor, which binds B12 to be absorbed
what is TIBC?
total iron binding capacity, surrogate measurement of transferin. combined with serum iron, can determine % blood iron saturation.
what is haemochromatosis?
abnormally high iron in the body causing multisystem disease
signs/symptoms of haemochromatosis?
heart failure, palpitations liver failure joint pains diabetes bronzed skin hypogonadism
investigations into haemochromatosis?
iron studies
genetic test for HFE gene
liver biopsy
MRI
2 broad categories of causes of anaemia?
high destruction
decreased production
causes of decreased production in anaemia?
haematinics deficiency
bone marrow failure
anaemia of inflammation
renal anaemia
what kind of anaemia would you get with renal anaemia?
normocytic
examples of anaemia caused by high destruction
haemolysis
haemorrhage
what is multiple myeloma and when should it be suspected?
cancer of BM causing over production of antibodies which causes destruction of BM and anaemia.
suspect in normocytic anaemia
signs/symptoms of multiple myeloma
CRAB
high calcium
renal failure
anaemia
bone lytic lesions
diagnostic investigation of multiple myeloma?
serum/urine test for lightchains
what can cause haemolysis?
odd shaped RBCs e.g. spherocytosis
autoimmune haemolysis
what would haematinic levels be like in autoimmune haemolysis?
normal
how to investigate autoimmune haemolysis?
blood film
reticulocytes
direct agglutanin test (ab)
LFTs: bilirubin raised
what can cause changes in white cells?
high - infection, leukaemia
low - drugs, disease, sepsis
what is the risk in thrombocytosis
stroke, clotting events
what is the risk in low platelets?
bleeding
what can cause high platelet count?
reactive to infection
bone marrow dysfunction e.g. myeloproliferative neoplasm
how to investigate abnormal platelet counts?
redo the FBC
serial platelet monitoring
markers of inflammation
what can cause low platelets?
platelet clumping during testing haemtinic deficiency acute leukaemia sepsis DIC ITP
what is polycythaemia vera?
primary cause of polycythaemia, genetically linked
how to investigate polycythaemia?
rule out secondary causes
genetic test for primary cause
FBC, ferritin, EPO, blood film
what is the gene involved in polycythaemia vera?
JAK2
what are secondary causes of polycythaemia?
alcohol
smoking
exogenous testosterone/EPO/steroids
EPO secreting tumour
signs and symptoms of polycythemia?
itching
flushing
splenomegaly
clotting event
treatment for polycythaemia
aspirin
venesection
hydroxycarbamide
adverse effect of hydroxycarbamide?
leg ulcers
what is essential thrombocytosis?
primary cause of raised platelets
treat like polycythaemia
what is myelofibrosis?
cancer of bone marrow causing fibrosis and progressive damage
signs and symptoms of myelofibrosis?
sweats massive splenomegaly cachexia fatigue bone pain gout pancytopaenia
investigations into myelofibrosis?
blood film - poikilocytes
bone marrow biopsy
look for splenomegaly
what causes chronic myeloid leukaemia?
associated with philadelphia gene - 9:22 translocation causing combination of BCR/ABL genes - upregulate tyrosine kinase causing overproliferation of cells
features of CML?
high wcc and platelets
splenomegaly
investigations into CML
blood film
BM biopsy
genetic/chromosome test
treatment of CML
tyrosine kinase inhibitors
stem cell transplant
complication of tyrosine kinase inhibitors?
pleural effusion
what neurological symptoms do you get with b12/folate deficiency?
paraesthesia
what vaccinations must be given before splenectomy?
Haemophilus influenza
meningococcal
pneumococcal
what kind of anaemia would also present with jaundice?
haemolytic anaemia
what will reticulocyte % be like in haemolytic anaemia?
raised %
what haematological condition do you give hydroxycarbamide?
polycythaemia, essential thrombocytosis
describing the classical description of the coagulation pathway and which tests it corresponds to
Tissue factor activates F7, F7a activates F10, F10a converts prothrombin into thrombin. Thrombin converts fibrinogen into fibrin which key ingredient in forming stable clots
F7 is extrinsic pathway (PT), F8, F9, F11 and (F12) is intrinsic pathway (APTT).
some examples of inherited bleeding disorders
haemophilia A and B
VW disease
other factor disorders
examples of acquired bleeding disorders
DIC liver failure renal failure - platelets anticoagulant and antiplatelet drugs vitamin K deficiency
questions to ask in history taking of bleeding d/o
history of abnormal bleeding
menstrual bleeds
family history of bleeding
bruises
investigations used in bleeding disorders?
coagulation screen - PT and APTT
specific factor levels
VWF levels
genetic testing
what is haemophilia A?
deficiency in F8. X linked recessive disease
how does haemophilia A usually present
childhood, boys, around age start to be mobile
abnormal bleeding, bruising, haemarthrosis
what is the function of F8 in clotting?
key factor in forming thrombin.
what will coagulation screen look like in haemophilia A
prolonged APTT. low or none F8 levels
if APTT comes back prolonged, what can be done to correct it to investigate further?
addition of individual Factors to find deficient factor
treatment of haemophilia A
lifelong F8 replacement
what is haemophilia B
less severe version of haemophilia A. deficiency in F9. usually present in adulthood
what is von willebrand disease
deficiency in VWF
what is the function of VWF?
binds platelets to endothelium
binds platelets to platelets
binds to F8 and brings it to site of coagulation
what is the most common inherited bleeding disorder?
von willebrand disease
what is the inheritance pattern of von willebrand disease?
autosomal dominant
what will coagulation screen look like in von willebrand disease?
mildly prolonged APTT
reduced F8 and VWF
what is disseminated intravascular coagulation
state where body depletes all procoagulant and anticoagulant factors
what is the process and clinical progression of DIC?
stage 1 starts of covertly with increased coagulation times, increased fibrin degredation products
stage 2 shows signs of haemostatic imbalance and decreased fibrinogen
stage 3 is full on clinical symptoms with raised FDPs, haemostatic failure
what are symptoms of DIC
bruising, petechiae, ecchymosis, purpura
blood clots symptoms - PE, DVT, stroke
abnormal bleeding
what are some causes of DIC
sepsis - gram -ve septicaemia, malaria, viral
malignancy
trauma - burns, crush injury
obstetric emergencies - placental abruption, bleeding
liver disease
major haemorrhage
how to diagnose DIC?
clinical signs
lab signs - low platelets, prolonged PT and APTT, low fibrinogen, high D dimers
management of DIC
resuscitation
blood products - RBC, FFP, platelets
what do mixed myeloid progenitor cells differentiate into?
colony forming unit -> RBC or platelets or neutrophils among others
what is the normal range for reticulocytes
0.5-2.5
what can cause iron def anaemia
bleeding - GI or menstrual
coeliacs disease
what is serum Fe, TIBC, and transferrin saturation like in iron def anaemia
low serum FE, high TIBC, low transferrin saturation
what is serum Fe, TIBC, and transferrin saturation like in anaemia of chronic disease?
low serum iron, low TIBC, normal transferrin saturation
what is the most common cause of B12 def in adults in western countries?
achlorhydria
symptoms of B12 deficiency anaemia
glossitis, angular stomatitis, mild jaundice. neurological symptoms e.e. peripheral paraesthesia
what specialised investigations to do in B12 deficiency anaemia?
autoantibodies, LFTs: bilirubin, intrinsic factor
what will bone marrow biopsy show in aplastic anaemia?
hypocellularity - empty BM
what will retics look like in aplastic anaemia?
low
what kind of haematological condition would someone be predisposed to if he/she had a metallic heart valve?
haemolytic anaemia
what will LDH be in haemolytic anaemia?
raised
uncontrolled clonal proliferation of one or more cell lines is the definition of what kind of haematological disorder?
myeloproliferative disorder
which disorder would you be more likely to find splenomegaly? primary or secondary polycythaemia
primary
of the three cell types which ones would you find raised in primary and secondary polycythaemia?
all 3 in primary, only Hb in secondary
how to differentiate myelofibrosis VS Chronic myeloid leukaemia?
philadelphia gene - chromsomal study
what will Hb, WCC and PTs be in myelofibrosis?
low Hb, raised WCC and PTs at first then low in late stage
what some causes of pancytopenia?
increased destruction - immune mediated e.g. SLE, sepsis,splenomegaly
decreased production - bone marrow failure, aplastic anaemia
features of pancytopaenia?
anaemia, neutropenia, thrombocytopenia
risks of pancytopenia?
infection, bleeding
how to investigate pancytopenia?
FBC, retics, haematinics, autoantibodies, bone marrow biopsy, blood film. drug history
what are 2 functions of neutrophils and consequently the biggest risk in neutropenia?
stopping infections from getting in and localising infections by inducing inflammation. without neutrophils, many pathogens can get in and without the process of inflammation, the pathogens can enter the blood very easily and quickly, causing distant infections within hours
how does a neutropenic infection defer from a normal infection?
less inflammatory signs, no redness or swelling. very quick spread contiguously and haematogenically. patients are also prone to other types of infections that healthy people dont usually get e.g. candidiasis
what causes ITP?
antibody mediated platelet destruction
signs and symptoms of ITP?
bruising, bleeding.
how to diagnose ITP?
by exclusion of every other possible causes e.g. haematinic def, bone marrow failure, leukaemia, SLE
what is the common presentation of ITP
young, easy bruising, previous infection.
how to treat ITP?
steroids, IV IG, monoclonal AB in chronic cases
2 broad causes of bone marrow failure
haematological cancer
non-haematological cancer (mets)
what are 6 common cancers that metastasise to the bone marrow
breast prostate lung renal thyroid melanoma
5 haematological malignancy that causes bone marrow failure
acute leukaemia myeloma myelofibrosis infiltration with lymphoma myelodysplastic syndromes
signs of bone marrow failure?
pancytopenia
neutropenic sepsis
renal failure
deranged coagulation
presence of blast cells is the differentiator between what two types of leukaemia?
acute vs chronic leukaemia
what are the possible complications of leukaemia
bone marrow failure
neutropenic sepsis
DIC
tmour lysis syndrome
how does acute leukaemia present?
bone marrow failure
general symptoms - sweats, malaise, anorexia, weight loss
tissue infiltration
causes of acute leukaemia
genetic predisposition, trisomy 21,
haematological disease
irradiation
chemicals - chemotherapy
how to investigate acute leukaemia
FBC - pancytopenia, raised WCC due to blasts
blood film - blast cells
BM biopsy - hypercellularity
a patient on chemotherapy treatment starts to become confused and dehydrated, what should be checked and what are the possible causes? how to manage?
hypercalcaemia, tymour lysis syndrome. rehydration, allopurinol
complications of leukaemia treatment?
hair loss, nausea, vomiting, tiredness, short stature, loss of intellect, depression, infertility, cardiac risks
blasts cells can be found on BM biopsy in chronic lekaemia - T or F
F, blast cells are found in acute leukaemia
what is a dermatological symptom of lymphoma?
itch without rash
why are women less likely to present with haemochromatosis?
due to more frequent loss of blood through out life e.g. menstrual cycle, pregnancy
what endocrine symptoms can occur in haemochromatsosi?
pituitary dysfunction, bronzed skin, hypogonadism
what is ferritin like in haemochromatosis?
very very very high, hundred even thousands
what can cause macrocytic anaemia with normal blood counts?
chronic alcohol use
why should you not transfuse someone with macrocytic anaemia due to b12 def?
normal circulating volume, fluid overload will cause heart failure
what are possible complications of blood transfusion during haemorrhage?
hypothermia due to cold blood
depletion of other blood components e.g. platelets,
what is the cause of RUQ pain in haemolytic anaemia?
gall stones -> cholecystisis/biliary colic
low Hb, high ESR, normal MCV is indicative of?
anaemia of chronic inflammation
when should someone with polycythaemia be investigated for renal tumour?
if no signs of chronic hypoxic disease
WCC of over 50 is until proven otherwise?
leukaemia
how to differentiate acute and chronic lekaemia?
chronic will have mature cells
acute will have blast cells
someone presenting with normocytic anaemia with raised calcium and renal failure, what is one possible haematological disease that can cause this
multiple myeloma
what can cause raised PT? with normal APTT?
vitamin k deficiency, liver disease causing fat malabsorption, factor 7 def,
old man with normocytic anaemia and difficulty voiding urine and numbness, what is a very important emergency not to miss out?
cord compression - urgent MRI
causes of prolonged APTT?
lupus anticoagulant (more common than you think) heparin factor deficiency
common cause of lymphadenopathy in teens?
EBV
what is lymphoma
neoplastic changes in B/T cells in lymphoid tissue
describe hodgkins lymphoma
aggressive, high grade, peaks 20s and 70s. but treatable
describe 3 non-hodgkin’s lymphomas
burkitts - HIV associated, aggressive
diffused large B cell lymphoma - aggressive
follicular lymphoma - low grade, slow growing
what are some red flags in persistent lymphadenopathy
painless, persistent, multiple, rapid change
on immunosuppresion, or HIV, B symptoms, supraclavicular node
when to refer to specialist in someone with persistent lymphadenopathy
longer than 6 weeks, OR with B symptoms. 2 or more non-contiguous enlarged nodes,
presentation of lymphoma
persistent lymphadenopathy, systemic symptoms (fever, weight loss, anorexia, fatigue, night sweats), signs of metastasis e.g. BM failure, cord compression, TLS
how to investigate suspected lymphoma?
FBC - raised lymphocytes LFTs - deranged LDH -raised (but not diagnostic) do monospot check viral screen blood film immunoglobulins CT/PET CXR
how to diagnose lymphoma?
lymph node tissue sample biopsy
what is the characteristic cell seen in hodgkin’s lymphoma?
reed sternberg - owl eyes
describe the staging used in lympoma
ann arbour
stage 1 - 1 node
stage 2 - 2 nodes
stage 3 - cross diaphragm nodal involvement
stage 4 - extranodal mets
B - b symptoms
S - spleen involvement
E - extranodal
X - large mass >10cm
complications of lymphoma?
cord compression
tumour lysis syndrome
hypercalcaemia
compression of other organs
what can cause thromboebolisms
AF metallic heart valves ventricular assist devices antiphospholipid syndrome haemolytic disorders
what can thromboembolisms cause
DVT PE budd chiari syndrome cerebral infarct mesenteric vein thrombosis
what are some unmodifiable risk factors for thromboembolisms
age pregnancy cancer inherited thrombophilic disorders antiphospholipid antbodies
what are some modifiable risk factors for thromboembolisms
air travel
immbobilisation
oral contraception
HRT
what are 3 natural anticoagulants in your body
protein C
protein S
antithrombin
what is factor V leiden
a point mutation in the FV gene corresponding to the cleavage site of protein C, causing inefficiency of protein C and accumulation of FV, leading to prothrombotic environment
what is the utility of D dimer in suspected blood clot
it has a high NPV, i.e. if it’s negative, very unlikely to be a clot. but if it’s high, it doesn’t mean it’s a clot
how to investigate suspected DVT?
wells score and ddimer. if suggestive, do leg ultrasound, and treat with lmwh. otherwise, look for alternate diagnosis
what are some anticoagulation drugs
heparin lmwh warfarin dabigatran factor Xa inhibitors
pros and cons of warfarin
cons: takes 3-4 days to achieve steady dose, narrow therapeutic index, requires monitoring
pros: can be reversed in bleeds
pros and cons of DOACs
quick action, no need monitoring
cannot be reversed, can’t use in renal impairment
what are some options in warfarin reversal, depending on situation
omit warfarin dose
oral vitamin K
IV vitamin K
prothrombin complex concentrate
complications of anticoagulation therapy?
too high INR can cause spontaenous bleeding, esp worse if intracerebral
