Haematology (blood stuff) Flashcards
describe clots formed in arterial circulation
high pressure system = platelet rich
describe clots formed in venous circulation
low pressure system = fibrin rich
what are the risk factors for venous thrombus formation
surgery immobility leg fracture/cast oral contraceptive pregnancy HRT long haul flight
what is a DVT
clot within venous system, usually in area between knee and hip
what investigations are carried out to diagnose a DVT
D-dimer test
ultrasound compression test/doppler USS
what is a D dimer test
measure of levels of degrading fibrin which is present in clotting
if positive = may be DVT/PE but not specific
if negative you can exclude DVT/PE
when is d dimer raised
infection
malignancy
inflammation
how is DVT treated
immediate:
DOAC
LWMH in pregnancy
long term:
DOAC
warfarin in antiphospholipid (INR 2-3)
LWMH in pregnancy
compression stockings
treat/seek for underlying cause
what is a PE
clot breaks off in leg/pelvis
embolus breaks off travels through venous system to right side of heart = stuck in pulmonary circulation
what investigations for suspected PE
ECG = sinustachy + S1Q3T3
CXR = usually normal
ABG = T1 resp failure/decreased O2 and CO2
D dimer = raised
V/Q scan = shows mismatch
CT pulmonary angiogram = inject dye allows visualisation of major segmental thrombi
how is PE treated
Immeadiate:
DOAC or LWMH
Massive:
unfractionated heparin + thrombolysis (alteplase)
Long term = same as DVT
what is myeloma
malignant neoplastic proliferation of bone marrow plasma cells
what is monoclonal gammopathy of unknown significance
the process of abnormal myeloma protein being found in standard blood tests
can lead to formation of multiple myeloma but doesnt necessarily mean myeloma is present
what is amyloidosis
group of symptoms caused by amyloid protein build up
what are the symptoms of amyloidosis
raccoon eye enlarged tongue HF hepatosplenomegaly nephrotic syndrome AKI peripheral neuropathy carpal tunnel
what can cause a lump in the neck
- reactive lymph node - infection/inflammation
- malignant - lymphoma, metastases, head/neck cancer
- underlying structure - thyroid
what is leukemia
malignant neoplasm of blood or bone marrow
classified into lymphoid or myeloid
what is rituximab
drug that targets CD20 on surface of lymphoma/leukemia B cells = marks them out for killing
what are the usual symptoms of bone marrow failure
anaemia
infection
bleeding
what are auer rods
red staining, needle like bodies found in cytoplasm of myeloblasts in certain leukemias (acute myeloid leukemia)
how is leukemia diagnosed
- bone marrow sample = more than 20% increase in blast cells
- bloods = decreased Plts, low Hb, low neutrophil, myelofibrosis with circulating blasts
- lymph node biopsy
what are the complications of leukemia
death
infection
haemorrhage - pulmonary or intercranial
depression
what are the complications of chemotherapy
anaemia neutropenia thrombocytopenia bystander organ damage hair loss
what is chemotherapy
combination of drugs that cause damage to rapidly diving cells
what is anaemia
reduced RBC mass with or without decreased haemoglobin concentration
mmicrocytic, macrocytic, normocytic based on RBC size
what are the complications of lymphoma
increased risk infection recurrence and mets increased risk CVS disease complications of chemo neurological complications
what are the normal Hb concentrations
male = 130-180g/L female = 115-160 g/L
describe the pathological changes in anaemia
heart/liver fat change
skin/nail atrophy
ischaemia
CNS death
describe the physiological changes in anaemia
reduced O2 transport = hypoxia = compensatory mechanism
what are the symptoms of general anaemia
fatigue/lethargy/tiredness
dyspnoea
headaches
faintness
what are the signs of general anaemia
conjunctival pallor
hyperdynamic circulation
palpitations
what is microcytic anaemia
RBCs have a low mean cell volume MCV
what is macrocytic anaemia
RBCs have a high MCV
name some microcytic anaemias
iron deficient = most common thalassemia chronic disease (late phase)
name some normocytic anaemias
haemolytic anaemia = sickle cell
acute blood loss
chronic kidney disease
chronic disease (early phase)
name some macrocytic anaemias
B12 deficiency (pernicious anaemia) = most common folate deficiency anaemia excess alcohol = liver disease hypothyroidism chemotherapy BM failure
what is epidemiologically significant about sickle cell disease
highly prevalent in malarial countries as carriers = increased protection to falciparum malaria
what are the chains of normal Hb
2 x alpha, 2 x beta
each chain has haem group which binds to O2
what are the chains of foetal Hb
2 x alpha, 2 x gamma (y)
how many genes control alpha and beta Hb
4 genes control alpha
2 genes control beta
what is alpha thalassemia
caused by depletion of alpha chains
number of faulty genes = severity of disease
highly prevalent in african/asian populations
what is beta thalassemia
caused by depletion of beta chains
number of faulty genes = NOT associated with severity
highly prevalent in european communities
what is hydrops fatalis
fatal condition not compatible with life
what are membranopathies
condition that causes destabilised RBC membrane
what is hereditary sperocytosis
autosomal dominant condition
caused by structural protein loss within RBC membrane
= RBCs abnormally shaped and spherical
what are the 2 types of hereditary spherocytosis
MILD = compensated haemolysis = haemolytic anaemia = asymptomatic MODERATE = severe anaemia = splenomegaly during childhood due to RBC lysis = gallstones often occur due to increased bilirubin levels
how is hereditary spherocytosis treated
splenectomy in cases of severe anaemia
no spleen? = needs vaccinating
what are enzymopathies
RBCs have nucleus = Enbden-Meyerhof pathway created
enzymopathies = deficiency in enzymes controlling this pathway which results in abnormal RBCs = spleen acts to lysis these
what is pyruvate kinase deficiency
autosomal recessive condition
clinical features of chronic haemolysis
late life presentation
those with disease = prone to aplastic crisis, no RBC production, lysis
define haemolysis
rupture or destruction of RBC
define reticulocytopenia
abnormal decrease of reticulocytes in the body
define aplastic crises
decrease in Hb
with reticulocytopenia
without evidence of haemolysis
how are enzymopathies treated
folic acid
transfusion in severe crises
consider splenectomy if recurrent crises to prevent lysis
what is polycythaemia
increase in RBC mass/haemocrit
what is relative polycythaemia
an apparent rise in RBC mass, however underlying cause is reduced plasma levels
e.g. dehydration
what is erythropoietin
hormone released from kidneys
stimulates stem cells in bone marrow to produce RBCs
how are platelets produced
fragments of megakaryocytes
process regulated by thrombopoietin = produced in the liver
what are the normal features of platelets
anucleate cells
life span 7-10 days
normal count of 15 to 400x10^9/L
have surface glycoproteins
what are platelets activated by
adhesion to collagen via GP1a
OR
adhesion to vWF via GP1b and IIb/IIIa
what does platelet activation lead to
- release of alpha granules containing fibrinogen, PDGF, vWF, PF4
- release of dense granules containing nucleotides, calcium ions, seratonin
- membrane bound phospholipids activating clotting factors 2,5,10
describe the process of clotting
- patelets adhere to vascular endothelium via colagen and vWF
- stimulates cytoskeleton shape change w/n platelets
- increases SA = platelet activation = release granules to facilitate clotting cascade
- platelets aggregate due to cross linking by fibrin
- activated Plts provide neg charge phospholipid surface = allows coagulation factors to bind and enhance clotting cascade
how is platelet function assessed
FBC = number
blood film = appearance
flow cytometry = surface proteins
platelet function analyser PFA = can see response to aggregating agents like collagen/ADP to be seen
bleeding times = small cut in forearm to see how long clotting takes - dont often do this anymore
what causes bleeding disorders (4)
- vascular disorders
- low platelet count
- abnormal platelet function
- defective coagulation
what are the clinical features of bleeding disorders
mucosal bleeding gum bleeding epistaxis (nose bleed) menorrhoea easy bruising petechiae/purpura (dotty rash) traumatic haematomas
name 3 congenital causes of impaired platelet function
von Willebrand disease
Bernard soulier
Glanzmann’s thrombasthenia
name 2 acquired causes of impaired platelet function
uraemia
drugs = clopidogrel, aspirin
what is Bernard-Soulier syndrome
autosomal recessive disease leads to deficiency in glycoprotein Ib =
prolonged bleeding time
low (or norma) platelet count
treat with desmopressin to decrease bleeding time and recombinant activated factor VII
what is Glanzmann’s thrombasthenia
autosomal recessive or acquired autoimmune condition = platelets are deficient of GPIIb/IIIa
bleeding time is prolonged
treat with desmopressin + recombinant activated factor VII
what is von Willebrand disease
caused by defect in vWF causes: increase activated partial thromboplastin time increased bleeding time normal prothrombin time (PT) decreased vWF decreased factor VIIIc
what is haemophilia
inherited condition that causes lack of factor VIII (type A) or lack of factor IX (type B)
PT time normal
increased partial thromboplastin time
X LINKED RECESSIVE
how do you treat haemophilia
replace missing clotting factors with regular transfusions
define thrombocytopenia
low platelet count (due to increased platelet usage or decreased platelet formation)
what causes SIRS
systemic inflammatory response syndrome trauma(inluding surgery) sepsis septic shock pancreatitis malignancy
what is bone marrow failure
reduction in number of pluripotential stem cells together with a fault in those remaining/immune reaction against them
= unable to repopulate
can occur in only 1 cell line = isolated deficiencies
what are the investigations in BM failure
FBC = pancytopenia with low reticulocytes
BM biopsy = hypocellular marrow with increased fat spaces
how would you treat bone marrow failure
removal of causative agent
cautious blood/platelet transfusion
if worse = BMT or immunosuppressive therapy
which age group is characteristically affected by hodgkins lymphoma
children and YA
what type of drug is ondansetron
anti-emetic
what is the mechanism of action of ondansetron
5HT3 antagonist = for chemo induced nausea
where are RBCs removed
spleen
liver
BM
blood loss
what types of infection see raised lymphocytes
viral
what types of infection see raised neutrophils
bacterial
what is febrile neutropenia
haematologic emergency
ABC
perform cultures
broad spec IV Ab within 1r e.g. tazosin and gentamicin
what does malignant spinal cord compression present with
back pain
spastic paresis and sensory level
how to manage malignant spinal cord compression
emergency urgent MRI bed rest + pressure care area steroids analgesia chemo/radiotherapy
how does aspirin exert antiplatelet effect
cyclooxygenase inhibitor
how does clopidogrel exert antipplatelet effect
P2Y12 inhibitor
how does tirofiban exert antiplatelet effect
GPIIb/IIIa inhibitor
what is the reticulocyte count expected to be in sickle cell anaemia
raised
what is alendronic acid and what is it usually taken with
bisphosphonate drug reduces rate of bone turnover to prevent osteoporosis
taken with vitamin D/calcium supplement
what advice is given to people taking alendronic acid and why
regular dental checkups because can cause osteonecrosis of jaw
what is letrazole
aromatase inhibitor that stops androgens conversion to oestrogen = lower oestrogen levels to prevent cancer growth
what group of women is letrazole used in
ONLY works in post-menopausal women
what is the difference between acute and chronic leukemias
acute leukemia = cells dont mature at all, rapid progression with no treatment
chronic leukemia = cells partially mature
describe the pathophysiology of chronic myeloid leukemia
- chromosomal translocation = philadelphia chromosome (BCR-ABL protein)
- myeloid leucocytes (granulocytes/monocytes)
- stop maturing and divide too fast
- buildup and cause hepatosplenomegaly (MASSIVE SPLENOMEGALY)
describe the pathophysiology of chronic lymphoid leukemia
- chromosomal abnormality = interfere with B receptor
- lymphoid leucocytes (B cells)
- stop maturing and die too slowly
- buildup and cause lymphadenopathy (rubbery lymph nodes)
how does a chromosomal mutation cause AML/ALL
cells lose ability to differentiate = dont function properly
cells undergo uncontrollable division = crowd out other cells in BM and cause cytopenias e.g. anaemia/thrombocytopenia/leucopenia = symptoms
what cells are characteristic of hodgkins lymphoma
reed-sternberg cells
which lymphoma is more common
nonhodgkins is more common
what type of cancer does epstein-barre virus most commonly cause
non hodgkin lymphoma
describe reed-sternberg cells
large lymphoid cell of B cell origin 2 nuclei eosinophilic nucleolus = owl eye appearance FOUND IN HODGKINS LYMPHOMA
describe ABVD chemo
adriamycin
bleomycin
vinblastine
dacarbazine
describe the mneumonic for presentation of myeloma
CRAB
- Calcium = increased due to increased osteoclast activity = dehydration, constipation, confusion
- Renal impairment = increased Ca and dehydration
- Anaemia = low BM RBC production = anaemia symptoms
- Bone lesions = high osteoclast activity = pepper pot skill, bone pain, hypercalcaemia
what is antiwarfarin
phytomenadione (vitamin K)
what is antiheparin
protamine sulphate
what is glucose-6-phosphate dehydrogenase deficiency
X linked recessive disorder G6PD = enzyme protects against oxidant injury in RBC deficiency = increased haemolysis = haemolytic anaemia precipitated by fava beans!!!!!!
what is immune thrombocytopenia purpura ITP
AI platelet destruction = antibodies form against platelets and destroy
caused by virus in children/SLE in adults
cause increased bleeding symptoms
prednisalone to treat
what is thrombotic thrombocytopenic purpura TTP
can be congenital/AI
ADAMTS13 = degrade vWF
lack of ADAMTS13 = no vWF degradation = widespread aggregation of platelets = microvascular thrombosis in heart/lungs/brain
cause increased bleeding symptoms + cerebral dysfunction + renal failure
bloods = raised lactate dehydrogenase
requires plasma exchange
what is disseminated intravascular coagulation DIC
cytokine response to SIRS = systemic activation of clotting cascade = excess diffuse clotting which then depletes platelets/clotting factors = uncontrolled bleeding
cause bleeding at unrelated sights
positive D dimer
platelet transfusion needed
what age group does non-hodgkins lymphoma usually present in
rare before 40 = disease of older age
describe ann arbour staging of hodgkins lymphoma AND non-hodgkins
1 = only 1 lymph node affected 2 = 1+ lymph node on same side of diaphragm 3 = lymph nodes on both sides of diaphragm 4 = spread to organs - liver/BM A = absence of B symptoms B = B symptoms
what are B symptoms in the presentation of hodgkins lymphoma
= systemic fever weight loss night sweats lethargy
what is the difference between hodgkins and non-hodgkins lymphoma
hodgkins: = B + T cell involved = Ann arbour staging = Reed-Sternberg cells = more treatable/survivable = NO rituximab given (CD20 NOT present) non-hodgkins: = 70% B cell 30% T cell involvement = extranodal involvement more common (MALT cells) = worse prognosis = rituximab Tx
which anaemia should you NOT treat with folic acid
B12 deficiency/pernicious anaemia
what is the most common cancer in children
acute lymphoblastic leukemia
what cancer shows smudge cells on a blood film
chronic lymphoblastic leukemia
what drugs are used to treat AML
chemo - cytarabine + anthracycline
what drugs are used to treat ALL
chemo = vincristine
with prednisolone
intrathecal methotrexate
what drugs are used to treat CML
imatinib sibling SCT (not v reliable) can transform to acute leukemia = bad prognosis
what drugs are used to treat CLL
fludarabine = lowers blood count and decreases lymphadenopathy /organmegaly
cyclophophamide
prednisolone
possible monoclonal Ab
what is a burkitts lymphoma
very high grade non-hodgkins lymphoma
what does the presence of bence jones proteins in the urine suggest the diagnosis is
multiple myeloma
what is a rare but classic complication of polycythaemia
can progress to acute myeloid leukemia
what blood cancer shows blast cells on blood film
ALL
which blood cancer is most likely to present with gum hypertrophy
acute myeloid leukemia
