geeky medics Flashcards
thalassaemias is a group of genetic disorders that lead to
reduced haemoglobin in red blood cells
alpha genes located on chromosome
16
beta chains located on chromosome
11
alpha thalassaemias will cause an excess of
unpaired beta globin chains and vice versa
when 4 alpha globin genes are affected in thalassaemia it can lead to
hydrops fetalis
blood film of the thalassaemia show what
hypochromic, microcytic
hair on end appearance can be seen on xray in
thalassaemia
what is differentiates thalassaemias from iron deficiency anaemia
thalassaemia has normal ferritin
what is LFTs are raised in thalassaemias
isolated hyperbilirubinemia
what stippling can be seen in thalassaemias
basophil
mx for thalassaemias
regular red cell transfusions to maintain haemoglobin levels
what supplements can be given for thalassaemis
folic acid
thalassaemias inheritance pattern
autosomal recessive
are there the same amount of alpha and beta genes
no there is twice as many alpha genes
hypsplenism increases the risk from infection of what
pneumococcal
leading cause of death in thalassaemias
heart failure secondary to iron induced cardiomyopathy
Vitamin B12 is called
cobalamin
folate is vitamin …
B9
pica and restless leg syndrome can be seen in
iron deficiency
there is a direct correlation between serum ferritin and
overall iron stores in health however serum ferritin is also an acute phase protein
in suspected iron deficiency anaemia. initial screening investigations should include
FBC, CRP and seum ferritin
if iron deficiency the body will produce more what
transferrin
what can predict iron response in patients with CKD
Mean reticulocyte haemoglobin
serum iron is useless. it only measures iron in what state
ferric - FE3
what is a negative acute phase protein and so decreases in inflammatory states
transferrin
what can help distinguish anaemia of chronic disease from iron deficiency anaemia
soluble transferrin receptors
what can also present with glossitis
vit b12 deficiency
drugs that can decrease levels of vitamin B12
Metformin, anti-convulsants, proton pump inhibitors/H2 antagonists, hormone replacement therapy/combined oral contraceptive pill, colchicine and certain antibiotics
patients who have undergone what surgery can often develop vitamin B12 deficiency
gastric or bariatric
what is the primary investigation for vitamin B12 deficiency
serum cobalamin
blood film may show macrocytosis, hyperhsegmented neutrophils and oval macrocytes in
vit B12 defieicny
if vit B12 deficiency ans has FH of — or personal history of autoimmune condition investigate for
pernicious anaemia
once treatment of IM bit B12 injections what should increase in the first 7-10 days
reticulocyte count
where is folate absorbed
terminal ileum
half of the bodies folate is found where
liver
what is important in DNA synthesis
folate
class of medications that can cause folate deficiency
anti epileptics
average human has how many litres of blood
5
what is the majority of blood
plasma
the Buffy coat consist of
leukocytes and platlets
what are the most numerous of the leukocytes
neutrophils
what are the most common agranular leukocyte
lymphocytes
what cells eradicate virus infected cells
NK
kupffer cells of the liver or microglia of the CNS are what kind of cells
macrophages
triad of hyperviscocity syndrome
visual changes, mucosal bleeding and neurological symptoms
plasma mostly consists of
water
ABO gene is on chromosome
9
if not given anti d infections in negative mother and positive baby the next baby could get
haemolytic disease of the newborn
what invasive procedure might mean you need to give anti D
amniocentesis
what is the only antibody that can cross the placenta
IgG
ABO antibodies are typically
IgM
an ideal blood transition would have
identical ABO and Rh group
what is emergency blood that can be given to everyone
O negative blod
what are not being transfused in plasma exchange
antigens
what is the universal donor for plasma
AB
factor II is usually referred to as
thrombin
what mediates the extrinsic pathway
tissue factor
in the extrinsic pathway, tissue factor combines with factor 7 to form a complex that activates factor
10
factor 10a combines with factor 5 and some other stuff to convert prothrombin into
thrombin (common pathway )
common pathway activates what factor
10
things that inhibit the coagualtion cascade
Protein C, S, antithrombin
when warfarin treatment is initiated what must also be prescribed alongside until the INR is in target range
LMWH
prothrombin time for what pathway
extrinsic
causes of prolonged PT
DIC, vit K deficiency and chronic liver disease
what is the vitamin K dependent clotting factor with the shortest half life
7
prothrombin time forms the basis of what ratio
INR
INR monitors the levels of
anticoagulation
causes of a prolonged APTT
DIC, haemophilia, lupus anticoagulant, von willebrands disease
activation of what clotting factor leads to the conversion of prothrombin into thrombin
10
what is the % of blood that is made up by red cells
haematocrit
3 key causes of secondary polycythaemia to remember
COPD, OSA, cushings syndrome, alcohol
relative polycythameias can be caused by
low fluid intake or burns (states of excess fluid loss)
other cause of macrocytic anaemia
myeloma
raised what can lead to hyper viscosity syndrome
haematocrit
what is anisocytosis
red cells of varying sizes
what reticulocyte count implies a problem with the bone marrow
low
other causes of leukocytosis
steroids, acute leukemias
what white cells account for the majority of them in the blood
neutrophils and lymphocytes
a cause of lymphopenia
HIV
when basophilia is present alongside elevated neutrophil and eosinophil counts or if the elevation is significantly above the normal range, this should raise the suspicion of
myeloproliferative disorder
blasts are usually only found in the bone marrow and high numbers in circulating blood could be caused by a
leukaemia
platelets are what shaped
disc
pregnancy causes of acute thrombocytopenia
pre eclampsia
cause of chronic thrombocytopenia
HIV
what haemolysis is more common
extravascular
extravascular haemolytic occurs primarily in the
spleen
if intravascular haemolytic predominates the patient may complain of what … due to haemoglobinuria
back pain and dark urine
in haemolytic anaemia, urinalysis will show
increased urinary urobilinogen, but conjugated bilirubin will be negative
The presence of blood on a dipstick urine sample but the absence of red cells on microscopy suggests haemoglobinuria, which is seen in
intravascular haemolysis
what is a non specific marker of cell turnover and is significantly raised in haemolytic
serum lactate dehydrogenase
what lab features may show in intravascular haemolysis
decresed plasma haptoglobin and urine dipstick may show haemoglobinuria
is a protein that ‘mops up’ free circulating haemoglobin so that it can be removed by the liver. It will therefore be reduced in intravascular haemolysis as a large amount of free haemoglobin is present in the circulation.
haptoglobin
what may occur after several weeks of intravascular haemolysis
haemosiderinuria
what can be detetected in the urine at least one week after onset of haemosideruria
Prussian blue staining
what is when haptoglobin capacity is depleted and free haemoglobin accumulates in the renal tubules
haemosiderinuria
what test is an important part of the haemolysis screen
Direct Coombs test
The Direct Coombs test identifies red cells coated with… , which suggests an immune cause for the haemolysis
antibody or complement components
what can a hypo chromic microcytic indicate
thalassaemia
what are schistocytes
fragments of red blood cells
schistocytes are seen in the microangiopathic haemolytic anaemia eg
(TTP, HUS, HELLP, and DIC).
what is the other that spherocytes might be seen in
autoimmune haemolysis
heinz bodies and bite cells may be seen in
G6PD deficiency
what is an important cause of autoimmune haemolytic anaemia
CLL
in sickle cell disease what agent reduces haemolysis and crises
Hydroxycarbamide
… is also given as standard in chronic haemolysis even if levels are normal
folate
mutation in what gene in primary polycythaemia
JAK2
2 rf for polycythaemia
advancing age or Budd chairi syndrome
itch particularly after a hot bath
polycythaemia
Erythromelalgia: burning pain, warmth and redness in the hands and feet
polycythaemia vera
in pts with polycythaemia are most thromboses venous or arterial
arterial
what on blood are commonly seen in patients with polycythaemia vera
neutrophilia and thrombocytosis
management that is given for polycythaemia vera
phlebotomy, aspirin, hydroxycarbamide
…It is usually diagnosed by the presence of a raised haematocrit OR red cell mass plus the presence of the JAK2 mutation.
polycythaemia vera
in severe — there is paradoxically simultaneous thrombosis and spontaneous bleeding
DIC
an other cause of DIC
acute pancreatitis
typical symptoms of DIC
- bleeding from unusual sites
(bleeding from 3 unrelated sites is highly suggestive of DIC) - widespread or unexpected bruising with no history of trauma
- new confusion or disorientation (a sign of microvascular thrombosis affecting cerebral perfusion)
sign of DIC
- bleeding from cannula/venepuncture sites
lived reticualris
IN FBC of DIC there is typically
thrombocytopenia
what prolongs both PT and APTT
DIC
what kind of fibrinogen is decreased in DIC
clauss
how to distinguish DIC from acute hepatic failure
acute hepatic failure may have mild increased d -dimer but would be markedly so in DIC.
platelets may be low in both but in DIC will fall over time whereas more likely to be stable in acute liver failure
d - dimers is markedly elevated in
DIC
key features of help Syndrome
hypertension, deranged LFTs and thrombocytopenia
what is fibrinogen like in DIC
low
an other cause that can have prolonged Pt and APTT and low fibrinogen
post thrombolysis (treatment with alteplase)
transfusion of what may be given if fibrinogen is low
cryoprecipitate
Any patient over — with iron deficiency anaemia requires an upper and lower gastrointestinal endoscopy.
40
what is the only investigation finding that is high in iron deficiency anaemia
total iron binding capacity
sideroblastic anaemia is characterised by defective – synthesis
protoporphyrin
classic clinical features of chipmunk facies and a crew cut appearance on xray
thalassaemias
what is normal in thalassaemias but low in iron deficient anaemia
ferritin
ferritin in high in anaemia of chronic disease due to build up of stores from
hepcidin
what allows for the differentiation between the causes of haemolysis or underproduction in normocytic anaemia
reticulocyte count
what acute phase protein is produced in anaemia of chronic disease
hepcidin
the only thing that is high in anaemia of chronic disease
ferritin
what is is due to a defect of RBC cytoskeleton membrane proteins such as ankyrin or spectrin
Hereditary spherocytosis
what is often performed to treat hereditary spherocytosis
splenectomy
what 2 things are increased in hereditary spherocytosis and in sickle cell disease and in G6PD deficiency and immune haemolytic anaemia
reticulocyte count and serum uric acid
sickle cell anaemia occurs due to an autosomal recessive mutation in the beta-globin chain of haemoglobin, causing – to replace glutamic acid.
valine
target cells and Howell jolly bodies may be seen in
sickle cell anaemia
investigations findings in paroxysmal nocturnal haemoglobinuria
reticulocyte count is normal but serum uric acid is increased
normally G6PD creates —- which in turn creates reduced glutathione to protect the cell from oxidative stress
NADPH
IgM mediated haemolysis is usually — and igG mediated haemolysis is usually —
intravascular, extravascular
microangiopathic haemolytic anaemia can occur due to
microthrombi, prosthetic heart valves and aortic stenosis
which type of macrocytic anaemia is due to impaired DNA synthesis
megaloblastic
what can be used to differentiate megaloblastic and non megaloblastic macrocytic anaemias
serum homocysteine and methylmalonic acid
what is the most common cause of vitb12 deficiency
pernicious anaemia
The main difference in clinical manifestation between folate and vitamin B12 deficiency are the neurological symptoms that occur in B12 deficiency, due to elevated levels of — acid.
methymalonic
Causes of non megaloblastic macrocytic anaemia include alcoholism, hypothyroidism, reticulocytosis, and drugs such as
fluorouracil
serum homocysteine is normal in
non megaloblastic macrocytic anaemia
The – is useful for determining whether normocytic anaemia is resulting from increased destruction of RBCs or decreased production.
reticulocyte count
Serum methylmalonic acid and homocysteine levels are useful to distinguish between subtypes of – anaemia.
macrocytic
what is the most common rf for AML
myelodysplastic syndrome however in the majority of cases it appears as a de novo malignancy
Auer rods in AML are
pink/red rod-like granular structures in the cytoplasm
In AML, the bone marrow is usually
hypercellular
method that can identify circulating myeloblasts by characteristic patterns of surface antigen expression
Flow cytometry
mainstay of treatment in AML is
chemotherapy
3 most common chemotherapeutic agents used in AML
-cytarabine
-Daunorubicin
- all trans retinoic acid
what is antibiotic prophylaxis against pneumocystis pneumonia
co- trimoxazole
when cancer cells break down quickly in the body, levels of uric acid, potassium, and phosphorus rise faster than the kidneys can remove them
tumour lysis syndrome
when proteins that control blood clotting become overactive. This can cause blood clots in small vessels and hypo-perfusion of organs. It can also cause clotting proteins to be consumed, leading to an elevated risk of serious bleeding.
DIC
chemo agent used in lymphoma and leukaemia
Cytarabine
2 chemo agents used in ALL
6 mercaptopurien and azathioprine- measure thiopurine methyltransferase before prescibing either of these
methotrexate is a
folate antagonist
hydroxyurea is used in
CML
Chlorambucil is used in hodgkins lymphoma and CLL. side effect is
pulmonary fibrosis
chemo agent used in multiple myeloma
Melphalan
when is warfarin the anticoagulant of choice
mechnanical heart valves
valvualr atrial fib
end stage renal failure
DOACs inhibit how many clotting factos
one
dabigatran is a DOAC than inhibtis
thrombin
Rivaroxaban, apixaban and edoxaban are DOACs that inhibit what single blood clotting factor
Xa
what is a contraindication for warfarin
malignancy
INR is a standardised version of the
prothrombin time
The INR targets is slightl higher for
mechanical heart valves
how many days should heparin also be prescribed when initiating warfarin
5 days
3 drugs that can increase potency of warfarin
amiodarone, metronidazole and clarithromycin
2 drugs that can decrease the efficacy of warfarin
phenytoin and carbamazepine
what fruit can increase the potency of warfarin
cranberreis
what system in the liver metabolsies warfarin
Cytochrome P450
what condition is autosomal recessive and there is a switch from glutamic acid to valine
sickle
when does sickle cell anaemia features begin
between 3-6 months
what are the msot common reason for hospital admission in Sickle cell anaemia
vaso oclusive crises
aplastic crisis usually precipitated by parovirus and what happens
temporary cessation of erythropoiesis
sequestration crisis is defined as
sudden enlargement of the spleeen due to haemorrhage
how to differentiate thalassaemias from sickle cell anaemia
haemoglobin electrophoresis
in sickle cell anaemia there is no what type of haemoglobin
adult
target ceclls and howell jolly bodies can often be seen in
sickle
what antibiotic prophylaxis in sickle
oral penicillin
what supplementation is given in sickle to prevent severe anaemia
folic acid
what is a once daily medication which increases HbF production and thus reduces the proportion of HbS in sickle
hydroxycarbamide
sickle cell anaemia is diagnosed by
haemoglobin electrophoresis
Hodgkins lymphoma arises from what cells
B lymphocytes
difference between Reed Sternberg cell and malignant hodgkins cells
R- multi nucleated
hodgkins - mon nucleated
most common Hodgkins lymphoma
nodular sclerosis
what is common in Nodular sclerosis HL
mediastinal mass
estimated around 40% of HL are related to what infection
EBV
what are B symptoms in HL
fever, drenching night sweats and unintentional weight loss of greater than 10% in the last 6 months
alcohol induced pain at nodal sites is a textbook symptom of what
HL
what is the gold standard for staging in HL
PET -CT
what is required for diagnosis and classification of HL type
lymph node excision biopsy
what antigens are expressed on Reed Sternberg cells
CD15 and 30
why does irradiated blood need to be used for HL patietns
reduces the risk of transfusion associated graft versus host disease
drug that reduce absoption of iron
tetracyclines/quinolones and PPIs
less common symptoms of iron deficiency anaemia
restless leg syndrome , pica
Plummer vinson syndrome has a triad of
atrophic glossitis, oesophageal strictures, iron deficiency anaemia
other than iron deficiency anaemia what other conditions can cause microcytic, hypochromic
thalassaemia, sideroblastic anaemia
hyperchromic microcytic anaemia is rare and caused by
hereditary spherocytosis
reduced what indicates hypochromia
MCH - mean corpuscular haemoglobin
other findings from blood film in iron deficiency anaemia
anisocytosis (cells differ in size) and shape (poikilocytosi s)
when do you do further GI investigations for GI malignancy if iron deficient and worries about malignancy
60 years or over
Premenopausal women with bowel symptoms
Family history of gastrointestinal cancer
Persistent anaemia despite treatment
what to do if over 60 with iron deficiency anaemia
urgent 2 week referral
how long should you take iron supplements after the deficiency is corrected
for 3 months (to replenish stores)
what can help reduce the side effects of iron supplemements
taking them with food
key features that distinguishes most lymphomas from leukemia
lymphomas - mature lymphcytes that arise within sites outside of the bone marrow
leukemia- develop from immature blasts from within the bone marrow
exception to this rule are the lymphoblatic lymphomas which develop from immartuer percursor lymphoblasts similarly to leukemia
what is the type of non classic NHL
nodular lymphocyte predominant HL
NHL is more common in what gender
boys
B cell NH usually affects lymph nodes where
abdomen
T cell NHL usually affects lymph nodes where
chest
examples of high grade lymphomas
burkitts, large B cell, anaplastic large cell
examples of low grade lymphomas
follicular, marginal zone
what is the most common cause of lymphadenopathy in children
infection
what lymphoma has more rapidly growing bulky lymphadenopathy
non hodgkins
hodgkins lymphoma typically affects
cervical, supraclavicular and axillary
what classification is used for NHL
St Jude classification
what HL is slow growing but has a high risk of transforming to high grade NHL
nodular lymphocyte predominant HL
what is the mainstay of treatment for both kinds of lymphoma and leukemia
chemo
lymphoblastic lymphoma howevere is treated with chemo that is used for
ALL
rituximab can be used in what kind of lymphoma
NHL
what is the only thing that is low in tumour lysis syndrome
calcium
what can be given prior to chemo to reduce chances of tumour lysis syndrome
hydration, allopurinol, rasburicase
what should be excluded before giving rasburicase
G6PD deficiency
what is the most common type of cancer in children, accounting for 31% of all childhood cancer
leukemia
does acute or chronic leukemia involve more immature cells
acute
what leukemia can have chronic phase, accelerated phase and blast crisis phase
CML
if a child presents with either of these 2 symptoms should get an urgent specialist for leukemia
unexplained petechiae, unexplained hepatosplenomegaly
blast cells should not be seen where
peripheral blood
what lab investigations are needed before starting chemo in leukemia pts
baseline kidney and liver function
why is a CXR really important to do in lymohoma/ leukemia
to see if there is a mediastinal mass is present
cytogenetics detects what
chromosomal abnormilites
lumbar puncture with what aims to prevent spread of leukemia to CNS
methotrexate
what antibiotic is givent to prevent infection with pneumocystis jirovecii in ALL
co-trimoxazole
allopurinol can be given in leukemia to prevent
tumour lysis syndrome
haemophilia gene mutation are on what chromosome
X and are recesive
can haemophilia be acquried
yes ocassioanly in malignnacy
what happens in haemostasis before primary haemstasis
blood vessel vasoconstriction
what 2 chemicals do platelets release to activate other platelets in a postive feedback mechanism
ADP and thromboxane A2
what turns prothrombin into thrombin
activated factor X
factors 8 and 9 in terms of haemophilia relate to what pathway
intrinsic
drugs that can precipitate bleeding in mild haemophilia
NSAIDs or aspirin
deficiencies in haemophilia can affect what clotting screen
APTT - as it relates to the intrinsic pathway
analgesia is given for pain in haematomas and haemarthroses in haemophilia but what should be avoided as they increase the risk of GI bleeding
NSAIDs
can treat acute haemophilia bleeds with what
desmopressin
what would a son and daughter of a haemophilia patient have
daughter would be a carrier and the son would be unaffected as they inherit their fathers normal Y chromosome
risk of children getting haemophilia of a female carrier
50% chance the daughter will be a carrier and 50% chance the son will be affected
chorionic villus sampling can be done when and what about for amniocentesis
CV- 11-14 weeks
amniocentesis - 15-20 weeks
neutropenic sepsis most commonly occurs how many days after chemo
7-10
emperical antibiotic treatment should be startedd within how long in cases of neutropenic sepsis
1 hr
platelets look like what
disc shaped cell fragments
average lifespan of a platelet
5 days
ADAMTS13 relates to
TTP
pts with thromboctyopenia should avoid what medications
NSAIDs
what can increase clot stability and reduce the risk of bleeding
Tranexamic acid
what is the first factor in the intrinsic pathway
12
what is the first factor in the extrinsic pathway
7
what breaks down clots
plasmin
APTT can indicate issues with what clotting factors
8,9 and 11
how do all anticoagualnts affect the PT/INR and APTT
increase them
how do platelets affect PT or APTT
wont affect them
paraproteins are what
abnormal light chains which can cause damage to the kidneys
what condition produces paraprotein
multiple myeloma
most myelomas produce what type of immunoglobulin
igG
common areas to get bone pain are
spine and ribs
lytic lesions have what appearance on a xray
punched out lesions ( the skullk can appear to have a pepper pot appearnace)
what is the anaemia normally like in multiple myeloma
normocitic and normochromic
increase of what in multiple myeloma
phosphate - can cause itch or muscle cramping
hyperviscocity that can happen in multiple myeloma can have what symptoms
headaches and visual disturbances
blood film in multiple myeloma can show rouleaux formation. What is this
red cells stacked on top of each other
what levels are good in multiple myeloma for assessing response to treatment and can identify relapse of disease before the onset of clinical symptoms
free light chain
smouldering myeloma does not have
end organ damage
how to treat smouldering myeloma
nothing at first just watch and wait
difference in multiple myeloma mx based on if you are under or over 65
under 65- chemo +stem cell transplant
over 65- chemo
in CML there is uncontrolled growth of myeloid cells and these can spill into the peripheral blood showing abnornmally riased levels of mature granulocytes such as
neutrophils, basophils and eosinophils
gene that is formed in CML
BCR- ABL
in peripheral blood film: all stages of granulocyte maturation noted
CML
in CML what is necessary to stage the disease and what enables confirmation of the diagnosis
stage - bone marrow aspiration and
confirm - cytogenic sampling (philidelphia chromosome)
methods of identfying the Philidelphia chromsome
FISH and then PCR for the BCR-ABL gene
order of stages in CML
chronic then accelerated then blast
what % of blasts in accelerated vs blast phase in CML
a- 10-19
b- >20
what targets BCR-ABL in CML
tyrosine kinase inhibitor eg Imatinib
