Haematology pathology Flashcards
what determines each blood group ? two main types of grouping ?
depending on surface antigens on RBCs
- ABO grouping
- rhesus grouping
name the RBC antigens and antibodies someone in blood group A would have ?
- A antigen (on RBC)
- anti B (antibodies in plasma)
name the RBC antigens and antibodies someone in blood group B would have ?
- B antigen (on RBC)
- anti A (antibodies in plasma)
name the RBC antigens and antibodies someone in blood group AB would have ?
- A and B antigens on RBC
- no antibodies in plasma
name the RBC antigens and antibodies someone in blood group O would have ?
- no surface antigens
- Anti A and Anti B (in plamsa)
what blood group is the urinersal donor ?
O-
what blood group is universal recipient ?
AB+
what does Rhesus +ve mean ? what blood can they recieve ?
have the Rh D antigen and can receive both Rh +ve and -ve blood
what does Rhesus -ve mean ? what blood can they recieve ?
lack Rh antigen so should only receive Rh -ve blood
what are the 2 pathways of the coagulation process ? what links them ?
- extrinsic pathway (triggered by external trauma which causes blood to escape circulation)
- intrinsic (triggered by internal damage to vessels)
- united to form common pathway
activation of which factor signals the start of the common pathway of coagulation ?
X
where does Fe absorption occur ? by what transporter ?
occurs in duodenum and upper jejunum by DMT1 transporter
what is the main regulatory hormone of fe ?
hepcidin
what is erythropoiesis ? occurs where ?
it is the process by which RBCs are made (erythrocytes)
- in adults this occurs in the box marrow of some bones
what are normoblasts ? where are they present ? what do they become ?
normoblasts (present in bone marrow only) => los their nucleus as they mature to reticulocytes (immature RBC) => los remaining organelles as mature to erythrocytes
what stimulates increase in erythropoiesis ?
driven by erythropoietin (EPO) - secreted by kidney
- when interstitial peritubular cells detect decrease PaO2 => increase EPO => act on bone marrow
what does high reticulate count indicate ?
increased RBC turnover (increase erythopoesis)
- haemolytic, haemorrhage
what is thrombin also known as ?
factor II
what is the action of clopidogrel ?
prevents ADP binding to its platelet receptor
what does blasts on peripheral blood film indicate ?
indicate myelofibrosis + leukaemia
what pathway does Prothrombin time test ? what factors ?
tests extrinsic system
- test for abnormailites in I, II, V, VII, X
what could cause a prolonged PT ? (4)
- warfarin
- Vit K deficiency
- liver disease
- DIC
what pathway does active partial thromboplastin time test ? what factors ?
APPT test intrinsic system
- test for abnormailites with I, II, V, VIII, IX, X, XI, XII
what could cause a prolonged APTT ? (4)
- heparin treatment
- haemophilia
- DIC
- liver disease
what do you give in unfractioned heparin overdose ?
protamine sulphate counteracts UFH
what is the cut off for aneamia in men and women ?
<135 g/l in men
<115 g/l in women
what is anaemia ?
low level of haemoglobin as a result of underlying disease
- if low Hb found on FBC then check for MCV
what are the categories of causes of anaemia ? (pathophys)
- increase RBC loss (bleeding)
- increased RBC destruction (haemolytic)
- reduced RBC production (iron, folate or B12 deficiency, bone marrow failure)
causes of microcytic anaemia ? most common ?
TAILS
- thalassaemia
- Anaemia of chronic disease
- IDA (most common)
- Lead poisoning
- sideroblastic anaemia
causes of normocytic anaemia ?
AAAHH
- Acute blood loss
- Anaemia of chronic disease
- Aplastic anaemia
- Haemolytic anaemia
- Hypothyroidism
(pregnancy)
causes of macrocytic anaemia ? (6)
- B12 deficiency
- folate deficiency
- alcohol
- reticulocytosis
- hypothyroidism
- liver disease
anaemia sx ? some specific to IDA ?
- tiredness, sob, headaches, dizziness, palpitations
- IDA: pica, hair loss
what is haemltocrit ?
measurement of the proportion of blood which is made up of cells
describe the transferrin in IDA ?
if iron deficient => increase transferring (less iron so not enough to occupy)
patient has low folate, what do you check ?
do no replace folate (B9) without checking B12
- because folate can mask B12 deficiency sx)
causes of anaemia of chronic disease ?
many: chronic infection, vasculitis, RA, malignancy, renal failure
patient has microcytic anaemia not responding to iron. what should you be thinking ?
sideroblastic anaemia
- ineffective erythropoiesis => increase iron absorption + iron loading in marrow => iron deposition in organs
what are some of the causes of IDA ? (4)
- reduced iron intake
- increased iron loss (bleeding, blood donation, menorrhagia)
- increase iron requirement (growth)
- impaired iron absorption (coeliac)
IDA signs ?
- koilonycia (spoon shpaed nails)
- atrophic flossitis
- angular cheilosis
IDA: describe these levels
- Serum iron
- TIBC
- transferrin
- serum ferritin
- low Serum iron
- high TIBC
- low transferrin
- low serum ferritin
IDA Mx ? for how long ?
diagnosis of IDA requires investigation of the underlying cause (coeliac serology)
- oral or IV iron replacement (ferrous sulphate)
- continue for at least 3 months after Hb normalises
what is aplastic anaemia ? describe a bit
(low RBC, WBC + platelets)
- condition where body stop producing enough new blood cells which leaves patient fatigued and prone to infections + uncontrolled bleeding
- (pancytopenia with hypo cellular marrow + no abornla cells or evidence of dysplasia)
aplastic anaemia aetiology ? (2)
- usually idiopathic
- occasionally drug exposure
aplastic anaemia Px ?
- often presents with infections (due to leukopenia)
- fatigue, dyspnoea, pallor, tachy (anaemia)
- bleeding or bruising (thrombocytopenia)
aplastic anaemia Ix ?
- FBC shows 2 or more cytopenias
- low reticulocyte count (low shows hypoproductive anaemia)
- bone marrow biopsy: hypo cellular marrow without abnormal cells
aplastic anaemia Mx ? (2)
- immunosuppressive therapy
- haematopoetic stem cell transplant
what is pernicious anaemia ? cause of what type of anaemia ?
it is a cause of vit B12 anaemia (macrocytic)
what can cause b12 deficiency anaemia ? (2)
- insufficient dietary intake
- pernicious anaemia
pernicious anaemia pathosphsy ?
autoimmune condition where antibodies form against parietal cells or intrinsic factor => lack of intrinsic factor => B12 remains unbound => proven B12 absorption in intestine => vit B12 deficient
what is vit B12 needed for ?
to form RBC and DNC
- severe deficiency => severe neurological damage
-
what does a deficient in B12 cause ? (4)
- peripheral neuropathy with paraestxesia
- loss of proprioception
- visual changes
- mood and cognitive changes
what is intrinsic factor ? released from where ?
protein released by stomach
- binds to vit B12 so that it can be absorbed in intestine (terminal ileum)
pernicious anaemia Ix ?
test for autoantibodies (intrinsic factor antibody)
pernicious anaemia Mx ?
hydroxycobalamin
what is haemolytic anaemia ?
a blood disorder that occurs when red blood cells are destroyed faster than the body can replace them
name some hereditary haemolytic aneamia ?
- RBC defect
- enzyme deficieny
- abrnomal Hb production
name a RBC defect that causes haemolytic anaemia ?
hereditary spherocytosis
name an enzyme deficient that causes anaemia ? what kind of anaemia ?
glucose-6-phsophate deficiency causes haemolytic anaemia
name a condition where abnormal Hb production causes haemolytic anaemia ? (2)
- sickle cell anaemia
- thalssaemia
what is hereditary spherocytosis ? what inheritance
(memebranopathy)
- it is where RBC are sphere speed => fragile + easily destroyed when passing through spleen
- autosomal dominant genetic condition
hereditary spherocytosis px ?
- jaundice
- anaemia
- gallstones
- splenomegaly (spheres get trapped in spleen)
- episodes of haemolytic crisis
hereditary spherocytosis Ix ?
- family history
- clinical features
- blood film (spherocytes)
- high reticulocyte count
hereditary spherocytosis mx ?
folate supplementation + penectomy
- transfusion during acute crisis
what is hereditary elliptocytosis ? what inheritance ?
autosomal dominant causes elliptical RBC
- similar presentation as hereditary spherocytosis
what is G6PD deficiency ? what inheritance ? where is G6PD found ?
it is where there is a defect in G6PD enzyme that normally found in all cells of body
- x linked recessive inheritance (usually affects males)
G6PD complicaitons ? triggers ? (3)
causes crisis (rapid anaemia and jaundice)
- triggered by infections, medications, fava beans
what is the role of G6PD in the body ?
it is responsible for protecting from damage form reactive oxygen species (ROS)
- particularly important in RBC
- so without G6PD => more vulnerable to ROS => RBC haemolysis
G6PD deficiency presentation ?
- anaemia
- intermittent jaundice
- gallstones
- splenomegaly
G6PD deficiency Dx ?
G6PD enzyme assay
G6PD deficiency Mx ?
avoid triggers of acute haemolytic
- transfuse if severe
what is the genotype for sickle cell anaemia ?
HbSS
what is the genotyped for sickle cell trait ?
HbAS
what is sickle cell anaemia ? what inheritance ?
caused by an autosomal recessive single gene defect in beta chain of haemoglobin leading to sickle cell haemoglobin (HbS) => rigid crescent RBC => vast occlusive crisis
how do sickle cells cause complications ? how does it causes anaemia ?
sickle cells obstruct blood flow + adhere to vascular endothelium + small capillaries => pain, damage to major organs and increased vulnerability to infections
- the sickled cells re more prone to haemolytis => anaemia
when is faetal haemoglobin usually replaced by adult ?
it is usually replaced by adult (at 6 weeks) but sickle cell aneamia patients have haemoglobin S => sickle shape
what is the relation of SCA to malaria ?
one copy of gene (sickle cell trait) => reduce severity of malaria => selective advantage
SCA px ?
parent with SCA
- persistent pain on skeleton/chest/abdomen
- dactylitit
- high temp
- visual flutes
- pallor
jaundice
SCA Ix ? when usually present ?
- usually detected in infant screening (unlikely to get to adulthood without diagnosis)
- DNA based assays will show replace of both beta Hb subunits with HbS
SCA general Mx ? what is curative ? what drug ?
- avoid dehydration
- ensure up to date vaccination
- Abx prophylaxis
- blood transfusion (if severe anaemia)
- bone marrow transplant (curative)
- hydroxycarbamide (if frequent crisis)
sickle cell crisis Mx ?
can be mild to life threatening
- treat any infection
- keep patient warm
- hydration
- ANALGESIA
- penile aspiration (if priapsim)
what is is acute chest syndrome and what is it associated with ? how does it present ?
medical emergency associated with SCA
- fever, pain, tachypnoea, wheeze and cough
acute chest syndrome Mx ? (4)
- Abx
- blood transfusion (anaemia)
- incentive spirometry
- artificial ventilation
complicaitons of SCA ?
- anaemia
- increases infection risk
- stroke
- avascular necrosis
- pulmonary HTN
- priapsim
- sickle cell crisis
- acute chest syndrome
what infection can cause a particular bad outcome in SCA ?
aplastic crisis
- due to parvovirus B19 infection
What is thalassaemia ?
it is a genetic condition that causes defects in the protein chain that make up haemoglobin
- overall effect is varying degrees of anaemia
describe the different types of thalassaemia ? what inheritance ?
directs in alpha robin chains => alpha thalassaemia (same for beta)
- both autosomal recessive
describe he RBC in thalassaemia ?
RBC are more fragile => breakdown more easily => spleen collects all destroyed RBC => splenomegaly
what happens to the bone marrow in thalassaemia ?
boen marrow expand to produce extra RBC (compensate chronic anaemia) => susceptible to fractures + pronounced forehead
thalassaemia signs and symptoms ? what MCV type of anaemia ?
- microcytic anemia
- fatigue
- pallor
- jaundice
- gallstones
- splenomegaly
- poor growth and development
- pronounced forehead (bossing due to extra medullary haematopoesis)
thalassaemia Dx ?
- FBC (microcytic anaemia)
- haemoglobin electrophoresis (diagnose globin abnormalites)
- DNA testing (genetic abnormality)
alpha thalassaemia Mx ?
- monitor FBC
- monitor for complications
- blood transfusions (to keep Hb > 90, may need life-long)
- bone marrow transplant (curative)
common complication of thalassaemia ?
iron overload: has similar effects as haemochromatosis
- consider iron chelators (deferiprone)
- avoid unnecessary iron supplementation
beta thalassaemia sub types ?
- thalassaemia minor: one abnormal + one normal gene (carrier state + usually asymptomatic)
- thalassaemia intermedia: two abnormal copies (either 2 defective of 1 defective, 1 deletion)
- thalassaemia major: homozygous for deletion gene (no function beta goblin genes)
What is thrombocytopenia? caused by problems with what ?
it is low platelet count that can be caused by problems with production or destruction
- production (issue with bone marrow or megakaryoctyes): sepsis, B12 or folic acid deficiency, liver failure
- destruction: medications, alcohol, ITP, TTP
thrombocytopenia px ? (9)
- asymptomatic
- easy or spontaneous bruising
- prolonged bleeding times
- GI bleeds
- nosebleeds
- bleeding gums
- heavy periods
- blood in the urine
- petechiae
what is ITP ?
thrombocytopenia
- autoimmune, antibodies attack platelets
ITP mx ?
- steroids (prednisolone)
- IV immunoglobulins
- rituximab
- splenectomy (reduce destruction of platelets)
- platelet transfusion
what is TTP ? what does it cause
(thrombotic thrombocytopenia purpura)
- tiny blood clots develop throughout the small vessels of the body => uses up platelets => thrombocytopenia + bleeding under skin (purpura)
TTP pathophys ? what causes it ?
what kind of anaemia does it cause ?
blood clots form due to problem with protein (ADAMTS13) which normally inactivates vwf and reduces platelet adhesion
- the blood clots also form a mesh which breaks up RBC => haemolytic anaemia
TTP what seen on peripheral smear ?
microangiopathic haemolytic anaemia with fragmented RBC + thrombocytopenia
TTP Mx ? prognosis without treatment ?
- plasma exchange
- steroids (prednisolone)
- rituximab
95% of cases are fatal if left untreated
haemophilia A and B. state what factor each is a deficiency in ? and what inheritance each is
- A (deficiency in factor VIII)
- B (deficiency in factor IX)
both are x linked recessive
haemophilia C. what factor affected ? what inheritance ?
factor XI
autosomal recessive
signs and symptoms of haemophilia a,b
severe bleeding disorders (bleed excessively in response to minor trauma or spontaneous haemorrhage)
- abnormal bleeding in: gums, GI tract, urinary tract (haematruia), intracranial
how is haemophilia diagnosed ? Ix ?
- based on bleed scores
- coagulation factor assays
- raised APTT
- low factor VIII assay (for A)
haemophilia Mx ? during acute bleeding ?
Iv infusion of missing clotting factor
- during acute bleeding: IV clotting factor infusion, antifibrinolytics
what is leukaemia ? classified how ?
leukaemia is cancer of particular line of stem cells in the bone marrow => unregulated production of some type of bleed cells
- classified on how rapidly they progress (chronic is slow and acute fast
- myelogenous of lymphocytic according to predominate cell type
what are the sx of leukaemia a result of ?
sx are result of
- bone marrow failure (pancytopenia)
- organ infiltration (hepatosplenomelgay)
- hyperviscosity
describe leukaemia pathophys ? what happens in the bone marrow
leukaemia is a form of cancer of the cells in the bone marrow => excessive producitonof single type of abnormal WBC => suppression + underproduction => pancytopenia
acronym for leukaemia ages distribution ?
ALL CeLLmates have CoMmon Ambition
- ALL: <5
- CLL: >55
- CML: >65
- AML: >75
leukaemia presentation ?
- non-specific (pancytopenia)
- fatigue
- fever
- failure to thrive
- palor
- petichae
, abnormal bruising and bleeding - lypphadenopathy
leukaemia Ix ? (4)
- FBC first thing
- bone marrow biopsy (definitive diagnosis)
- lymph node biopsy (investigate fo lymphoma)
- CT/MRI staging
What is ALL ?
malignant change in one of lymphocyte precursor cells => acute proliferation of single type of lymphocyte (usually B) => replace bone marrow cells => pancytopenia
- lymphoid precursor cells replace haematopoeitc cells of bone marrow and infiltrate carious body organs
who is ALL associated with ? (2)
- most common leukaemia in children
- associated with downs syndrome
- old white man
ALL Ix ? what seen on blood film ? definite diagnosis ?
- FBC (anaemia, cytopenia)
- blood smear (leukaemia lymphoblasts present)
- definitive diagnosis: bone marrow aspiration + biopsy (>20 lymphoblasts)
what is used to present tumour lysis syndrome in ALL ?
allopurinol
ALL prognosis ?
overall good prognosis in kids, bad in adults
which two leukaemias are clinically indistinguishable ? how to distinguish ?
AML + ALL
- so confirm cell origin with peripheral blood smell or bone marrow biopsy
auer rods indicate what leukaemia ?
AML
(on bone marrow biopsy)
what is AML ?
life threatening haematological malignancy caused by clonal expansion of myeloid blasts in the bone marrow
=> bone marrow failure
AML RF ?
->75
- male
- chemo
- prev haematological disorders (aplastic anaemia)
AML Ix ?
what are the phases to CML ? how many phases ? describe a bit
has 3 phases including a 5 yr (asymptomatic chronic phase)
- chronic phase
- accelerated phase
- blast phase (higher proportion of blast cells in blood)
what is CML ? which cells ?
chronic myelogenous leukaemia
- malignant clonal disorder of haemotopoetic stem cells (affecting neutro, eosino and basophils) => bone marrow hyperplasia
which what genetic abnormality is CML associated with ?
Philadelphia chromosome
CML RF ? (3)
- > 65 years
- male
- ionising radiation
CML Px ?
(detection usually follows incidental FBC finding)
- 1/3 assymtomattic
- if presents: malaise, fever, weight loss, abdominal discomfort, night sweats
-
CML Mx ?
tyrosine kinase inhibitor (TKI): imatinib
what is the most common leukaemia in western world ?
CLL
CLL Px ?
slow growing
- absolute lymphocytosis (often picked up on routine FBC)
- asymptomattic lymphadenopathy
smudge cells found on blood smear, what leukaemia ?
CLL
CLL mx ?
(mab)
- rituximab
What is tumour lysis syndrome ? release of what ?
oncological emergency
- it is caused by release of urin acid form cells destroys in chemo
- uric acid forms crystals in renal interstitial tissue => AKI
tumours lysis syndrome Px ?
haematological malignancy
- seizures
- vomiting
- muscle weakness
tumours lysis syndrome Ix ?
serum uric acid (raised)
tumour lysis syndrome Mx ?
allopurinol (reduce the high uric acid levels)
- fluid resus
what is lymphoma ?
group of cancers that affect the lymphocytes inside the lymphatic system
- proliferate within lymph bodes => become abnormally large (lymphadenopathy)
- affects anywhere where lymphocytes are (nodes, spleen, thymus, bone marrow)
lymphoma px ? (3)
- painless lymphadenopathy
- compression syndromes
- B sx
how is lymphoma diagnosed ?
lymph node biopsy
- presence of reed Sternberg cells
difference between Hodgkin and non-hodgkin lymphoma
classified by presence of reed Sternberg cells
non-hodgkin lymphoma low grade vs high grade ?
low grade: slower usually incurable
high grade: aggressive, curable
what is stage 1lymphoma staging ?
1 nodal area
what is stage 2 lymphoma staging ?
2 nodal areas on same side of diaphragm
what is stage 3 lymphoma staging ?
2 nodal areas on other side of diaphragm
what is stage 4 lymphoma staging ?
presence of extra nodal disease )liver, spleen, bone marrow)
from what cells does NHL originate ? (3) most common
- B cells (90%)
- T cells
- NK cells
NHL Px ? how compare to Hodgkins lymphoma ?
heterogeneity so vary alot
- b symptoms
- lymphadenopathy
- sob
(similar to HL but b sx less common and there may be GI and skin involvement)
what are myeloproliferative disorders ?
these occur due to uncontrolled proliferation of single type of stem cell (bone marrow cancer)
Myeloproliferative neoplasms are a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow
what is polycythaemia vera ?
is result of proliferation of erythroid cell line
why are the increased risks associated with polycythaemia vera ?
- thrombus
- haemorrhage
- progression to myelofibrosis
- translations to acute (AML)
what is primary and secondary polycythaemia ?
- primary: polycythaemia vera
- secondary: due to underlying ill health
name some causes for secondary polycythaemia ?
- due to hypoxia (high altitude, congenital heart disease, heavy smoking)
- abnormally high EPO (renal cell carcinoma, HCC)
polycythaemia presentaiton ?
- asymptomatic
- portal htn (ascites, varices, abdo pain)
- low platelets
- thrombosis
- high RBC
- low WBC
with what genetic mutation is polycythaemia vera strongly associated ?
JAK 2
how is polycythaemia vera diagnosed ?
bone marrow biopsy checking for the genes (JAK 2)
how is polycythaemia vera managed ?
- phlebotomy
- aspirin (reduce risk of blood clots)
what haematological cell does multiple myeloma affect ?
plasma cells
(b lymphocyte that produce Ab)
what does spikey old crab mean ? what condition ?
multiple myeloma
- spike: Immunoglobulin spike on electrophoresis
- old: age of incidence is >70
- C: hypercalcaemia
- R: renal impairment
- A: anaemia
- B: bone osteolysic lesions (osteoporosis)
what is myeloma protein ?
abnormal antibody (IG light chain) produced by abnormal proliferation of plasma cells (causes spike)
what is MGUS ?
monoclonal fammopathy of undetermined significance
- overproduction of IG in benign conditions
what causes the renal impairment in multiple myeloma ?
the excess light chains get filtered out though kidneys => renal damage
multiple myeloma px ?
- bone pain
- anaemia
- fatigue
- high calcium
- renal impairment
multiple myeloma dx ?
- serum + urine protein electrophoresis (para protein spike)
- whole body CT (osteolytic lesions)
- serum free light chain assay (raised)
- bone marrow biopsy (monoclonal plasma cells infiltration in the bone marrow)
- Serum calcium (high)
with what cancer are bench jones proteins associated ?
multiple myeloma
rouleux seen on blood film - what does this indicate ?
multiple myeloma
what can be given to help myeloma bone disease ?
bisphosphonates
