Heam week 3 Flashcards
what increases lymphocytes
viral illness: glandular fever (inc mononucleosis - EBV), CMV, toxoplasmosis, rubella, pertussis, mumps, HIV (seroconversion)
chronic infections: TB, brucellosis, syphillis
thyrotoxicosis
what can increase neutrophils
bacterial infection
inflammatory disorders
metabolic (uraemia, gout)
acute haemorrhage
what can decrease neutrophils
some viral infections (hepatitis, infuenza, HIV
SLE
what is the lifecycle and role of eosinophils
circulate for 24 hours then enter tissues
functional role= mediation of allergic response through release of leukotrienes and IgE/ direct parasitic killing
what can increase eosinophils
allergic disease
parasitic infections
drug sensitivity
skin diseases (psoriasis), hodgkins, hypereosinophilic syndromes
what is the lifecycle and role of monocytes
20-40 hours in blood before entering tissues to become macrophages
phagocytic/ antigen presenting function
what increases monocytes
chronic bacterial infections (TB, bacterial endocarditis, brucellosis)
protozoan infections
hodgkins disease
what is the role of basophils
infrequent in peripheral blood
transit the blood en route to tissue to become mast cells (histamine release)
what increases basophils
hypothryoidism
UC
chicken pox
what can happen to clones during expansion of malignancy
sub clones may appear containing other genetic damage
why do you need to assess clonality
to help diagnosis:
- lymphoproliferative disoders: need to teel reactive increase lymphocytes from malignant causes in lymph node biopsies
- myelodysplastic syndrome: distinguish from other marrow pathology
what malignancy presents with features in predominantly one cell lineage
acute myeloid leukaemia
name a malignancy that presents with features in mature cells
polycythaemia rubra vera
what are the two subgroups of lymphcytes
T cells- cell immunity
B cells- humoral immunity
what are the primary lymphoid organs
bone marrow
thymus
what are the secondary lymphoid organs
lymph nodes
spleen
lymphoid tissue of the alimentary & resp tracts + circulating lymphocytes in the blood and tissue space
what lymphocytes go to the paracortex in the lymph node
T cells
what are the types of B cell lymphomas
lymphocytic lymphoma intermediate differentiation (mantle zone) lymphoma CLL well differentiated lymphomcytic lymphoma (WDLLL WDLL with plasmacytic differentiation walderstoms macroglobulinaemia nodular lymphoma large cell lymphomas burkitts lymphoma
what are malignant lymphoma
malignant lymphoproliferative diseases in which there is replacement of normal lymphoid structure by collections of abnormal cells
what are the two types of malignant lymphoma
hodgkins and NHL
what age does malignant lymphoma usually present
HL- younger
NHL- elderly
what are the common symptoms of lymphoma
painless lymphadenopathy
splenomegaly and hepatomegaly
constitutional symptoms: fever, night sweats, weight loss
anaemia
what are common sites of involvement n lymphoma
mediastinum (more in HL) bone marrow skin brain testis thyroid CNS
how is lymphoma diagnosed and classified
diagnosis by excision biopsy of lymph node/ appropriate tissue
if red sternberg cells= hodgkins disease
how is HL classified
4 types: mixed cellularity lymphocytic predominant nodular sclerosing lymphocyte depleted
how is NHL classified
follicular or diffuse architecture:
- low grade= follicular or nodular involvement
- high grade= diffuse involvement
(diverse group of diseases)
what is the origin of NHL
can be B lymphocyte (more common) or T lymphocyte (less common)
what staging system for lymphoma
ann arbor system:
Stage I One lymph node area involved
Stage II Two or more lymph node areas on one side of the diaphragm
Stage III Involvement of nodes above and below the
diaphragm
Stage IV Involvement outside the lymph node areas
The Stage number is followed by the letter A or B indicating the absence (A) or presence (B) of constitutional symptoms.
how is lymphoma staging done
via: clinical exam, CXR, CT scan, bone marrow trephine
what is the treatment for HL
early stage: radiotherapy
late stage: combination chemo
what is the treatment for NHL
low grade- palliative radio and/or chemo
high grade- combo chemo
what is the prognosis for lymphoma
HL- 60-70% cured (prognosis dependent on stage)
NHL- low grade: incurable (except early stage), indolent course, 7-10 year survival, 60-80 progress to high grade
high grade rapidly progressing, 30-40% cured
(prognosis dependent on histology: follicular or diffuse)
what are the functions of the spleen
filtration (pitting- removal of cell debris and culling- removal of old or abnormal red cells)
storage (platelet, granulocytes and red cells, iron)
haematopoiesis
immunological
does the spleen usually do haematopoiesis
pathological sign
what can cause hyposplenism
congenital absence
developmental: neonatal, old age
surgical: trauma
infarction: sickle cell disease, essential thrombocytopenia
infiltration: lymphoma, amyloid
drugs: methyl dopa, irradiation/ chemo
- immune: SLE, RA, coeliac disease
what is seen on blood film in hyposplenism
peripheral blood red cells show distortion, acanthocytes (spikes on RBCs), and target cells, together with inclusion of nuclear remnants (Howell-Jolly bodies) reflecting the absence of splenic “pitting” function
what organisms become high risk in hyposplenism
strep pneumonia and haemophilis influenzae
blood borne polysaccharide encapsulated bacteria
what infection prophylaxis is given in hyposplenism
pneumococcal immunisation
haemophilus influenza B vaccine (before splenectomy)
long term oral antibiotic prophylaxis
what is hypersplenism
enhanced cellular filtration, pathological pooling and increased plasma volume
modest shortening of blood cell lifespan
what are the effects seen in hypersplenism
enlarged spleen
deficit in one/ more blood cell lines
normal/ increased cellularity of bone
what can cause splenomegaly
work hypertrophy: haemolytic disease, acute infections, subacute bacterial endocarditis, chronic infections (TB, brucellosis, syphilis), parasitic infections
immune relates: RA, SLE
portal hypertension: congestive splenomegaly
infiltrative
what are the infiltrative causes of splenomegaly
extramedullary haematopoiesis:
- myeloproliferative diseases (CGL, myelofibrosis, polycythaemia)
- acute leukaemia
- haemoglobinopathies (thalassaemia)
lymphoproliferative:
- chronic lymphocytic leukaemia (lymphoma)
amyloidosis
gauchers disease
iron overload
what are the indications for a splenectomy
pain: due to enlargement/ infarction
hypersplenism: severe cytopenias
autoimmune cytopenias: immune thrombocytopenias, autoimmune haemolysis
intrinsic red cell abnormalities: cell membrane (HS, elliptocytosis), enzyme defects (pyruvate deficiency), haemoglobinopathies (thalassaemia, sickle cell)
diagnosis
traumatic rupture
what sites can be used for bone marrow examination
posterior iliac crest
sternum
anterior iliac crest
what does a bone marrow aspirate allow
cellular morphology
flow cytometry/ immunostaining (cellular antigenic profile)
cytogenetics
what does trephine allow
analysis of bone marrow architecture
immunohistochemistry (B cell markers in lymphoma)
how is bone marrow processed for morphological diagnosis
aspirate (liquid): smeared onto microscopy slide, stained with haematoxylin/ eosin stains
specific stains for acute leukaemia (peri-iodoc acid schiff/ sudan black) and iron status (perls stain)
trephine (core of bone): formalin fixed and parafin embedded, stained with haematoxylin/ eosin (silver stain for reticulin fibrosis)
what is pancytopenia
rediced Hb, white cell and platelets
what are the clinical complications of pancytopenia
anaemia: fatigue, cadiovascular compromise, pallor
thrombocytopenia: increased risk of bleeding, skin purpura, epistaxis, oral, GI, internal (fundus, cerebral)
neutropenia: sepsis, infections: soft tissue/ skin, oral/ perianal, indwelling central line (hickman)
what are myeloproliferative disorders
clonal malignant disorders characterised by overgrowth of one or more haematopoietic lineages
myeloproliferative disorder of red cells=?
polycythaemia rubra vera
myeloproliferative disorder of platelets=?
essential thrombocythaemia
myeloproliferative disorder of white cells=?
chronic myeloid leukaemia
myeloproliferative disorder of reactive fibroblasts=?
myelofibrosis
what is the age of presentation and survival of CML
40-50
18 months untreated, 5 years treated
what is the age of presentation and survival of polycythaemia rubra vera
55-60
8-15 years treated
what is the age of presentation and survival of myelofibrosis
60-70
1.4-5 years (treated)
what is the age of presentation and survival of essential thrombocythaemia
females 30-40
both sexes 50-70
>10 years treated
what precursor is affected in CML
granulocyte precursor
what is an overlapping myeloproliferative syndrome
overproduction predominating in one lineage, often accompanied by an increase in cell numbers (to a lesser degree) in others e.g. chronic myeloid leukaemia often accompanied by a high platelet count
what is a myeloproliferative transformation
when a MP disorder transforms either into another MP state (PRV -> myelofibrosis) or to acute leukaemia (common in CML)
what is the clinical presentation of myeloproliferative disorders
all have: gout (increased nucleoprotein turnover) and (hypermetabolism) fatigue, weight loss, night sweats
myelofibrosis: splenomegaly, bone marrow failure (infections, anaemia, bleeding)
CML: splenomegaly, hepatomegaly
PRV: hyperviscosity: HAs, dizziness, tinnitus, visual disturbance, itching after hot bath, burning sensation in fingers and toes, facial plethora, splenomehagly
ET: bleeding (abnormal platelet function) or arterial venous thrombosis: HAs, atypical chest pain, light headedness, erythromelalgia
how are myeloproliferative disorders diagnosed
Polycythaemia rubra vera
- Red cell mass increased
- Bone marrow trephine
Chronic myeloid leukaemia
- Morphology
- Philadelphia chromosome
Essential thrombocythaemia
- Persistent raised platelet count >600 x 109/l with no other explanation
- Bone marrow trephine shows clumps of megakaryocytes
Myelofibrosis
-Bone marrow fibrosis ++ (trephine biopsy)
what is the treatment for ET
No treatment if no previous thrombosis and platelets <1500 x 109/l
Oral cytotoxics to control myelo-proliferation e.g. Hydroxyurea
what is the treatment for CML
Cytotoxics e.g. Hydroxyurea or α-Interferon
Allogenic bone marrow transplant (may be curative)
what is the treatment for myelofibrosis
supportive: blood product transfusion
what is polycythaemia
high Hb concentration, red cell count and haemtocrit
in polycythaemia why must you measure red cell mass and plasma volume
to distinguish between:
low plasma volume Polycythaemia (low plasma volume and normal red cell mass) (aka reactive polycythaemia)
true polycythaemia (normal plasma volume, increased red cell mass)
what can cause reactive polycythaemia
acute: dehydration, diuretics, burns
chronic: obesity, HPTx, high alcohol and tobacco intake
what can cause true polycythaemia
primary: polycythaemia rubra vera
secondary: hypoxia (high altitudes, chronic lung disease, cyanotic congenital heart disease, heavy smoking) or inappropriately high erythropoietin secretion (renal or hepatocellular carcinoma)
what test for polcythaemia
primary: platelet and white cell counts high
bone marrow aspirate/ trephine
spleen USS/ electrophoresis
secondary: arterial O2 sats
CXR
renal USS
Hb/ erythropoietin assay
what can cause excess erythropoietin production with tissue hypoxia
chronic lung disease
congenital heart disease
altitude
high affinity Hb variant
what can cause excess erythropoietin production with no tissue hypoxia
tumour (e,g, renal)
what can cause autonomous bone marrow proliferation causing polycythaemia
myeloproliferative polycythaemia
haemopoietic (stem cell disorder)
what are the possible complications of polcythaemia
thrombosis (risk greatest in PRV)
transformation into acute leukaemia
gout
how do you stop malignant overproliferation and its consequences in polycythaemia
(to reduce thrombotic risk)
- venesection
- cytoxic chemo (oral hydroxyurea)
what chromosome in CML
philadelphia chromosome: t(9:22)
what results from monosomy 7
myelodysplasia
what results from trisomy 12
CLL
what is immunoglobulin light chain restriction
κ or λ light chain ratio on surface of B-lymphocytes skewed if clonal population of B- cells expressing only one of these e.g. in lymphoma/ chronic lymphocytic leukaemia
how many immunolgobulin gene arrangements are seen in malignant lymphoid cells
one = clonality
what crisis would require increased white cell production
Infection, inflammatory diseases, malignancy, injury or trauma (including surgery)
what are the functions of each type of white cell
Neutrophils: phagocytosis (non-specific) – release lysozyme
Lymphocytes: B – antibody production; T – cell-mediated
Monocytes: big – differentiate into macrophages – phagocytose
Eosinophils: secrete granules to attack parasites
Basophils: release histamine in inflammatory response
what kind of leucocytosis should you worry about
non reactive: malignancy- clonal, intrinsic
give some examples of leucocytosis that is not reactive?
Acute leukaemias – immature cells in blood AML if myeloid precursor (and different types), B or T ALL – maturation defect
Chronic leukaemia – mature cells in the blood, but too many – overproduction CML, CLL
what is clonality
A single precursor cell multiplying rapidly and becoming the predominant cell
are reactive disorder and leukaemias poly or monoclonal
reactive disorders= polyclonal
leukaemias= monoclonal
what is pancytopenia
global reduction in all cells in the blood - reduced red and white cell and platelets
what is aplastic anaemia
pancytopenia with hypocellular bone marrow but no infiltration/ marrow fibrosis
most idiopathic but can also be:
-congenital (fanconi anaemia)
-acquired (idiopathic, infection, EBV, HIV, parovirus, toxic exposure, drugs, pregnancy, transfusional graft vs host disease, sickle cell anaemia (aplastic crisis with parovirus))
environmental factors (damage induced by chemicals, drugs, viruses) that alter the antigen profile of haemopoietic stem/progenitor cells. This could lead to lymphocyte activation and an autoimmune reaction against haemopoietic stem/progenitor cells. Consequently, there is bone marrow failure affecting production of red cells, neutrophils and platelets.
what can cause pancytopenia
increased destruction: hypersplenism
marrow infiltration: cancer, sarcoidosis
ineffective erythropoiesis: megaloblastic anaemia (B12/folate def)
myelodysplasia
aplastic anaemia
what is MCH
mean corpuscular Hb
what is MCHC
mean corpuscular Hb concentration
what is RDW
recticulocyte count
what can high haematocrit count mean
increased red cells
reduced plasma- alcohol, sudden stress, siuretics
what happens to plasma volume in pregnancy
increases
what can cause polycythaemia
-1st true polycythaemia – related to bone marrow defect- myeloproliferative polycytheamia (clonal abnormality)
-2nd polycythaemia – physiological response to hypoxia etc
- smoking can produce polycythaemia because carbon monoxide combines with haemoglobin
Lung disease, cardiac disease i.e low oxygen stimulation→ ↑ erythropoietin →↑ rbc production, can see similar effect with some epo secreting tumours – renal Ca
Iatrogenic epo use, testosterone supplements (compare male and female hb/rbc/hct indices)
how does myeloproliferative polycythaemia present clincally
Global symptoms: fatigue, poor concentration(sluggish blood flow); headache; itching; redness; enlarged liver and /or spleen; or asymptomatic
hypermetabolic consequences sweats wt loss gout
thrombotic consequences eg portal vein thrombosis
what is the risk in polycythaemia
- increased viscosity of blood → stroke
- increased risk of thrombosis esp in 1o true polycythaemia because all cells can be increased including platelets
- gout – due to increased uric acid due to increased cell turnover
what two mechanisms cause high platelets
Reactive response to infection, inflammation, malignancy
Primary clonal marrow disorder
Two years later she returns complaining of blurred vision and painful finger tips. One of her toes has turned ‘blue’ overnight and she is concerned. This time blood count demonstrates a normal haemoglobin and white cell count, but her platelet count is 900 x 109/l.
Blood film examination reveals numerous giant platelets. All inflammatory markers are normal and she is otherwise well.
How do you explain Mrs Matthews blood results ?
primary marrow overproduction – clonal myeloproliferative disorder
(no positive inflammatory markers)
what treatment to prevent thrombotic complications in thrombocytosis
antiplatelets- aspirin
what happens in autoimmune pancytopenia e.g. SLE
autoimmune destruction of cell lineages through the recognition of multiple antigens on MATURE cells
what causes lymphcytosis
infections acute and chronic
leukaemias and lymphomas (esp CLL)
what causes atypical lymphocytes
(clear cytoplasm with blue rim)
EBV
CMV, HIV, parovirus, denguev
what are risk factors for hodgkins lymphoma
EBV, affected sibling, SLE, post transplantation
what is the peak age for HL
young adults (15-24) elderly
what are the symptoms of HL
rubbery non tender nodes
systemc symptoms: sweats, weight loss, itch, fever, lethargy
alcohol induce node pain
how is HL staged
Ann arbour system
which has quicker onset heparin injections or warfarin tablets
heparin
what does prothrombin time depend on
thromboplastin
name a drig that impaired warfarin metabolism
alcohol
what is lymphoplasmacytic lymphoma
aka waldenstroms macroglobulinaemia= slow growing low grade NHL
what can cause hyperiscosity syndrome
polycythaemia (PV) leukocytosis (leukaemia) myeloma wladenstroms drugs: COCP, diuretics, chemo
what increases plasma viscosity
any inflammation, anaemia or macrocytosis
what paraproteins are made in waldenstroms
IgM paraprotein
ciculating blasts/ lymphoblasts suggests what
lymphoblastic leukaemia
which type of leukaemia commonly has CNS involvement
acute lymphblastic (cranial nerve palsies, meningism)
pain where is common in myeloma
back pain- osteolytic bone lesions
what electrolyte abnormality is common in myeloma
hypercalcaemia
how does HUS present in biochem and blood tests
microangiopathic haemolytic anaemia low Hb increased LDH decreased haptoglobin fragments on film decreased platelets AKI (thrombosis of glomerular capillaries)
what is the diagnostic traid for HUS
Microangiopathic haemolytic anaemia (Coombs’ test negative).
Thrombocytopenia.
Acute kidney injury (acute renal failure)
what are neurological complications of HUS
altered mental state
CVA
seizures
what happens to neutrophils post chemo
drop 7-14 days after
go back to normal in 3-4 weeks
20year old student complains of one week of severe sore throat, malaise, and lethargy and sweats. He is also complaining of painful and swollen neck glands. On examination: looks unwell and has significantly enlarged Cervical and tonsillar glands. Hb 158g/dL WBC 20.0x109/L (raised) Platelets 100x109/L (slightly low) slightly low neutrophils high lymphocytes numerous aytpical lymphocytes
diagnosis?
EBV
what are atypical lymphocytes
activated forms- are responding to something
are bigger, cytoplasm scallops around red cells, blue in colour (active proteins: T cells= enzymes, B cells= immunoglobulins)
what activates lymphocytes
viral infections:
EBV (glandular fever)
HIV (always do HIV test where activated lymphocytes)
URTI (RSV, influenza, parainfluenza)
what does infective mononucleosis cause (EBV)
infects throat epithelial and B lymphocytes
activates T cells in response
results in glandular fever= tonsilar exudate and lymphadenopathy
how is EBV diagnosed
EBV serology (IgM)
what might you get if you give amoxicillin in EBV
amoxycillin induced rash
what can cause lymphadenopathy
regional:
- bacterial abscess
- mets
generalised:
- viral
- CTD/RA/sarcoidosis
- vasculitis
- lymphoid malignancy (lymphoma)
- metastatic cancer
what nodes are commonly affected in sarcoidosis
hilar
cervical
axillary
what are nodes like in viral infection
Painful/tender
Hard
Regular
Not associated with overlying inflammation.
Not tethered.- not invading surrounding tissues
what happens to neutrophils when there is infection/ tissue damage
toxic granulation and vacuolation (response to tissue damage: fight bacterial infection, granules release enzymes that fight bacterial/ repair tissues)
what is the differential cell count
breaks it down into constituent cell
what can cause a neutrophilia
bacterial infection inflammation e.g. RA trauma/ post op corticosteroids (decrease neutrophil margination in circulation) myeloproliferative diseases (rare)
what is the most common cause of leukocytosis
neutrophilia
what causes a lymphcytosis
viral infection esp pertussis (often associated with a mild neutropenia/ thrombocytopenia)
childhood response to infection (immune system not fully formed)
chronic lymphocytic leukaemia (smear cells)
what is the main role of lymphocytes
fight infection- viral
what constitutes a pancytopenia
low Hb
low WBC
low platelets
when should you suspect HL over NHL
if young female
disease more common ABOVE the diaphragm
if B symptoms and itch, alcohol induce pain present
how do you differentiate HL from NHL and the other causes of lymphadenopathy
node biopsy
what is the histology of HL
nodular sclerosing
reed sternberg cells
what is the histology of high grade NHL
immature lymphoid cells (blasts- big prominent nucleoli)
what is the histology of low grade NHL
mature lymphcytes are the malignant clone (normal size mature lymphocytes)
what does leucoerthroblastic mean
immature red (nucleated) and white cells (myelo blast)
what can cause a leucoerythroblast blood picture
marrow infiltration
- lymphoma
- non haem mets
- fibrosis (myelofibrosis- when scar tissue forms in bone marrow)- these push out immature cells
marrow stress: -sepsis -bleeding -shock (hypercellular marrow needed to make more blood)
what does survival of HL depend on
stage (1= 90%, 4= 50%)
how is HL staged
CT and PET scans
what cell type are you most worried about dropping in pancytopenia
neutrophils- sepsis
is marroe stroma derived from haemopoietic stem cell
no
what are the immediate effects of cytotoxic drugs
Bone marrow suppression
Gut mucosal damage (mucositis)
Hair loss (alopecia)
what are the consequences of bone marrow failure
anaemia
neutropenia (infections: gram _ve sepsis, hickman line cellulitis, viral herpes simplex, fungal - chronic neutropenia, spergilloma (ball of fungus due to aspergillus)
bleeding
what bugs are you most worried about in neutropenia
gram -ve (esp from bowel in chemo- get mucositis- gut leaky, bug from here get into bloodstream)
what is the treatment for neutropenic fever
immediate Abx (esp against gram -ves) tamozin and gentamicin
if worried its a resp infection add in clarithromycin
what is given to prevent fungal infections in neutropenic patients
prophylatic anti fungal (spirgilloma can be fatal- forms cysts which has bleed as comp)
what can cause pancytopenia
increased destruction:
- immune
- sepsis (commonest cause)
sequestration:
- hypersplenism (liver disease)
decreased production:
- infiltration
- B12 def
- aplastic anaemia
- drugs (chemo, immunosuppressants)
- viruses (EBV)
- radiation
how do you find the cause of pancytopenia
Hx
exam- enlarged spleen, sepsis
Ix- reticulocyte count (shows if marrow working), B12/folate
abdo USS (spleen)
bone marrow exam:
- hypocellular
- hypercellular (normal cells increased + increased destruction/ replacement of normal cells with malignancy)
what causes hypocellular bone marroe
drug induced aplasia
some viruses
aplastic anaemia
what causes a hypercellular marrow
infiltration peripheral destruction (hypersplenism)
what supportive treatment for people on chemo with pancytopenia
prompt ABx if fever
red cell and platelet transfusions
what is the role of the spleen
immune response
removal of effete (old) red cells
mediator of autoimmune disease (reticuloendothelial system- v vascular, senses antigens on cells as they circulate)
needed for immunity against encapsulated organisms
what can splenectomy treat
ITP and AIHA
what do you need to vaccinate against if doing a splenectomy
meningococcus, pneumococcus and haemophilus influenzae type b
what does left shift mean on a blood film
when immature neutrophils are released e.g. in infection
what causes malaria
P. falciparum parasite (seen inside RBCs)
what can happen to the spleen in coeliac disease
hyposplenism
what do monocytes look like
horse-shaped nucleus and steel-grey cytoplasm with vacuoles
A 28 year old woman attending the antenatal clinic has a blood count performed with the results as follows: Haemoglobin low, MCV low, MCH low, white cell count normal, neutrophil count normal and platelet count normal. The serum ferritin is within the normal range.
what test next
Haemoglobin analysis by high performance liquid chromatography (HPLC)
The mild anaemia in the presence of a normal serum ferritin reflects the dilutional (physiological) anaemia of pregnancy. The normal serum ferritin makes iron deficiency unlikely. The disproportionate reduction in MCV and MCH compared to the haemoglobin indicates the possibility of a haemoglobinopathy trait (heterozygous) which is best investigated by haemoglobin analysis.
what does a high Hb suggest
myeloproliferative polcythaemia vera
what test for polycythaemia vera
JAK2 gene
cytopenias and excess blasts suggest what
acute leukaemias
what test for leukaemia
immunophenotyping (will clarify myeloid or lymphoid lineages)
A 58 year old lady with a family history of hypothyroidism and atrophic gastritis presents with fatigue, macrocytosis and pancytopenia.
most likely diagnosis?
pernicious anaemia
B12 deficiency in patients with pernicious anaemia (autoimmune destruction of gastric parietal cells) can present with pancytopenia and not just an isolated macrocytic anaemia. It is not uncommon to elicit a personal or family history of other autoimmune disorders
A 25 year old male has recurrent admissions to hospitals with pain in his legs and chest wall. On one occasion, he became extremely breathless and required a red cell exchange transfusion.
most likely diagnosis
sickle cell anaemia
Patients with sickle cell disease can have uncomplicated vaso-occlusive crisis in their musculoskeletal system. Sickle cell crisis in the pulomonary vasculature is a life-threatening emergency that required prompt therapy with exchange transfusion
A 21 year old girl has a history of heavy periods and investigations indicate a defect in primary haemostasis. Her blood count is normal.
most likely diagnosis
von willebrands disease
disorder of primary haemostasis due to deficiency of von Willebrand factor which bridges platelets to sub-endothelial collagen following endothelial injury. This affects platelet adhesion at the site of injury.
how does rituximab work
humanised monoclonal antibody directed against CD20, expressed on B cells and B cell lymphomas
how does imatinibwork
tyrosine kinase inhibitor that is inhibits BCR-ABL-1 protein unique to chronic myeloid leukaemia
how does aspirin work
irreversible inactivator of cyclooxygenase that is required for the production of prostaglandins and thromboxanes for platelet aggregation
which drug:
It is an ADP antagonist
clopidogrel
how does clopidogrel work
selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. This action is irreversible.
which drug:
It irreversibly inactivates cyclooxygenase 1
aspirin
which drug:
It is a highly selective direct inhibitor of activated factor X
Riveroxiban
how does riveroxiban work
competitively inhibits factor Xa. Factor Xa along with factor Va for the prothrombinase complex which converts prothrombin to thrombin
most likely cause:
Normal prothrombin time, prolonged partial thromboplastin time, normal platelet count, normal fibrinogen.
An isolated prolonged partial thromboplastin time reflects deficiency of factors involved in the ‘intrinsic’ pathway of coagulation (Factor VIII/IX) or the presence of an anti-phospholipid antibody (lupus anticoagulant) that is not associated with a bleeding phenotype
most likely cause:
Prolonged prothrombin time, normal partial thromboplastin time, normal platelet count, normal fibrinogen
An isolated prolonged prothrombin time reflects deficiency of factors involved in the ‘extrinsic’ (but not ‘common’) pathway of coagulation and the only coagulation factor involved is therefore Factor VII. Deficiencies of common pathway factors (II,V and X) will cause prolongation of both the prothrombin and activated partial thromboplastin time
Prolonged prothrombin time, prolonged partial thromboplastin time, low platelet count, low fibrinogen
most likely cause?
Disseminated intravascular coagulation
what is the treatmen for AIHA
steroid (prednisolone) and folic acid
which of these is false: vit k is: -bsorbed in upper intestine -responsible for bile salt absorption -carboxylates specific preformed clotting factors -is antagonised by warfarin -is water soluble
vit k is fat soluble
what usually causes febrile non haemolytic transfusion reactions
antibodies against donor leukocytes and HLA antigens
who is most at risk of TACO
those with chronic anaemia and a compensatory high cardiac output
what causes transfusion related acute lung disease
anti- leucocyte antibodies present in the donation that bind to the patients white cells and cause acute lung injury by degranulation of the affected neutrophils in the lungs. Pulmonary infiltrates are seen on CXR.
A 68 year old woman with fatigue has a blood count performed and the results are as follows: Haemoglobin 87g/L (low), MCV 110 fl (high), white cell count 2.4 x 109/l (low), neutrophil count 1 x 109/l (low) and platelet count 100 x 109/l (low). The blood film shows macroovalocytes and hypersegmented neutrophils
Pernicious anaemia that causes B12 deficiency will result in impaired nuclear maturation affecting the development of all three haemopoietic lineages, so pancytopenia with macrocytic red cell development can occur in deficiency states. The blood film features are strikingly sensitive for B12/folate deficiency
low Hb, high WBC, low neutrophils, low platelets
excess blasts and auer rods on film
58y/o man with fatigue
acute myeloid leukaemia
Marrow failure (resulting in the low Hb, Neutrophil and Platelet count) in acute myeloid leukaemia is caused due to the excessive proliferation of primitive cells (myeloblasts). Abnormalities of granulation in these blasts can be visualised in the form of Auer rods.
A 52 year old man with a stroke has a blood count performed and the results are as follows: platelet count 930 x 109/l (v high) . The blood film shows an excess of platelets with some giant forms.
Essential thrombocythaemia
what is essential thrombocythaemia
chronic myeloproliferative disorder characterised by excess production of platelets in the bone marrow and an increased risk of thrombosis.
what is thrombocytopenia
reduced platelets
does thrombophilia mean high platelets
NO it means increased thrombotic tendency
what is HbS
glutamic acid to valine substitution in the beta chain of haemoglobin
indicates sickle cell anaemia (homozygous)
red cells with loss of central pallor =?
spherocytes
what causes sickle cell disease
a point mutation in the beta chain and this predisposes the haemoglobin to polymerisation resulting in sickled cells and reduced red cell survival
what causes myelodysplasia
Acquired DNA mutations in haematopoietic stem cells= ineffective haematopoeisis
what causes hereditary spherocytosis
Congenital mutation in structural red cell proteins= reduced cell deformity= membrane removed in spleen = spherocytes + reduced cell survival
77 year old asymptomatic man is found to have a lymphocytosis.
chonic lymphocytic leukaemia
67 year old man admitted to hospital with back pain, hypercalcemia and renal failure is found to have significant Bence Jones proteinuria
multiple myeloma
what does bence jones protein in urine mean
the excretion of (clonal ie kappa or lambda only)immunoglobulin light chains- seen in myeloma
which of these is not a cause of hereditary thrombophilia: antithrombin deficiency protein C deficiency protein S deficiency Factor V Leiden antiphospholipid syndrome
antiphospholipid syndrome
