haematology conditions Flashcards
1
Q
what is haemoglobin below in anaemia
A
haemoglobin below lower limit of normal
F= 110-147g/L
M=131-166g/L
2
Q
what does MCH mean
A
MCH= mean cell haemoglobin- amount of haemoglobin in each cell
hypochromic= less haemoglobin than normal
normochromic= normal amount of haemoglobin in each cell (27-33pg)
3
Q
what does MCV stand for and how is anaemia classified based on cell size
A
MCV= mean cell (corpuscular) volume
microcytic (smaller than norm)=iron deficiency, thalassemia, sideroblastic
normocytic (norm=80-98fl)= sickle cell, G6PDH deficiency, hereditary spherocytosis, autoimmune haemolytic, malaria, non-haemolytic
macrocytic (larger than norm)= folate deficiency, B12 deficiency, haemolysis, bone marrow disorders
4
Q
name four types of microcytic anaemia
A
iron deficiency
sideroblastic
alpha thalassaemia
beta thalassaemia
5
Q
name 6 types of normocytic anaemia
A
autoimmune haemolytic
G6PDH
hereditary spherocytosis
malaria
sickle cell
non-haemolytic anaemia
6
Q
name 2 types of macrocytic anaemia
A
B12 deficiency (pernicious anaemia)
Folate deficiency
7
Q
how much iron does an average adult require per day and where is it absorbed
A
15mg/day, approx 1mg/day absorbed- needed for haemoglobin synthesis
absorbed in duodenum + upper jejunum
8
Q
what kind of anaemia is iron deficiency
A
microcytic anaemia, size of RBCs= <80
-most common anaemia
9
Q
what is iron bound to when it is a. stored and b. transported in the blood to tissues
A
iron is stored as Fe 2+ bound to ferritin
-converted to Fe3+ and carried by transferritin in blood
10
Q
causes of iron deficiency anaemia
A
blood loss via: heavy periods, GI blood loss (H.pylori infection), hookworm
dietary insufficiency- children + vegetarians
poor iron absorption= coeliac disease/IBD, gastric surgery resulting in less HCl production
increased iron requirements, eg pregnancy, growth in children
11
Q
pathology of iron deficiency anaemia
A
iron molecule required for O2 binding in haemoglobin (check iron notes)
- therefore iron deficiency = impaired haemoglobin production
not enough haemoglobin 4 normal sized RBC> bone marrow pumps out microcytic, hypo chromic (pale) RBCs
microcytic RBCs can’t carry enough O2 to tissues= hypoxia > signals bone marrow 2 increase RBC production> bone marrow pumps out incomplete RBCs
12
Q
presentation of iron deficiency
A
kolionychia (spoon-shaped nails)
atrophic glossitis (enlarged tongue)
angular stomatitis (dry skin, ulceration @ mouth corners)
pica (eating things which aren’t food)
hair loss
restless leg syndrome
gastric stricture
general anaemia:
-fatigue
-pallor
-shortness of breath
-palpitations
-chest pain
-tachycardia
-exertional dyspnoea
13
Q
investigations for iron deficiency
A
FBC: low MCV + MCHC + Hb
blood film =microcytic hypochromic RBCs
Fe studies:
serum Fe-low
serum ferritin- low
TIBC= (high)- used as marker for how much transferrin Is in the blood
high transferritin
bone marrow biopsy- absent iron stores
endoscopy if 60 + (look at cause of GI bleeding)
14
Q
management of iron deficiency
A
treat underlying cause
oral iron supplements- ferrous sulphate
side effects= nausea, diarrhoea, constipation
IV iron if oral poorly tolerated (ferric gluconate)
blood transfusion if severe
15
Q
define sideroblastic anaemia
A
anaemia characterised by smaller than normal RBCs due to impaired haemoglobin production
16
Q
what kind of deficiency causes sideroblastic anaemia and what do the RBCs look like
A
X linked ALA synthase deficiency
-causes bone marrow to produce ringed sideroblasts
17
Q
investigations for sideroblastic anaemia
A
FBC + blood film= microcytic with ringed sideroblasts + basophilic stippling
Fe studies= increased serum Fe, high ferritin, high transferritin, low TIBC
18
Q
what is folate deficiency anaemia (include type)
A
anaemia caused by folate (vit B9) deficiency
macrocytic megaloblastic anaemia- <95
19
Q
causes of folate deficiency
A
malnutrition
malabsorption
increased demand (pregnancy)
drugs/toxins (methotrexate)
20
Q
risk factors for folate deficiency
A
elderly
poverty
alcoholic
pregnant
Crohn’s or coeliac disease
21
Q
how much folate is required per day and where is it absorbed
A
0.1-0.2 mg/day required
absorbed in proximal jejunum
22
Q
pathology of folate deficiency
A
folate= required for DNA/RNA synthesis
DNA impairment will have largest affect on bone marrow since it’s most active in cell division- leading to pancytopenia
-in response, bone marrow releases megaloblasts
-megaloblast= not good at carrying O2, can get stuck in BM, destroyed early
other rapidly dividing cells affected, eg epithelial cells in tongue, prevents healing (glossitis)
can cause neural tube defects- spina bifida
23
Q
presentation of folate deficiency
A
angular stomatitis
glossitis
symptoms of ischaemic heart disease or stroke
general anaemia:
pallor
fatigue
chest pain
shortness of breath
palpitations
24
Q
investigations for folate deficiency
A
FBC- high MCV
blood film- macrocytic, megaloblastic RBC, HYPERSEGMENTED NEUTROPHILS
vit B12 levels = normal
serum + RBC folate levels= low
GI investigations
25
management of folate deficiency
| which foods contain folate
treat underlying cause
folic acid supplements- always give alongside B12, folic acid supplements + B12 deficiency can cause neurological disease
fortifying foods= grains, cereals, green veg
26
what are normal B12 levels and where is it found + absorbed
normal B12= 197-771ng/L
exclusively found in animal derived products: meat,, fish, eggs dairy
absorbed in ileum- must bind 2 intrinsic factor produced by gastric parietal cells
27
what kind of anaemia is B12 deficiency
macrocytic megaloblastic anaemia
28
causes of vit B12 deficiency
lack of B12 in diet (veganism)
pernicious anaemia
malabsorption eg Crohn's
inadequate release of B12 from food eg gastritis, alcohol abuse
zollinger-ellison syndrome
29
pathology of vit B12 deficiency
vit B12 (cobalamin)= essential 4 DNA synthesis in cells undergoing rapid proliferation
-therefore bone marrow is affected- pancytopenia >bone marrow compensates by producing macrocytic megabalstic RBCs
B12 keeps levels of methylamonic acid low (can cause neurological damage):
-peripheral neuropathy
-subactue degeneration of the cord
-focal demyelination
30
describe pernicious anaemia
vit B12 deficiency as a result of autoimmune destruction of the gastric epithelium- due to antibodies against parietal cells or intrinsic factor which prevent absorption of B12
overtime patients with PA develop gastric inflammation, which may lead to gastric atrophy
31
presentation of vit B12 deficiency
general anaemia=
pallor
fatigue
palpitations
shortness of breath
tachycardia
chest pain
glossitis
lemon-yellow skin
CNS involvement:
personality change
depression
memory loss
visual disturbances
paraesthesia
ataxia
loss of vibration or sense of proprioception
bladder/bowel dysfunction
32
investigations for vit B12 deficiency
| what is positive in pernicious anaemia
FBC=
raised MCV
blood film- megaloblastic anaemia + hyper segmented polymorphonuclear cells
gold=
serum B12- decreased
pernicious anaemia: both intrinsic factor antibody + gastric parietal cell antibody positive
33
management of vit B12 deficiency
| and pernicious anaemia
for dietary deficiency- oral B12 (cyanocobalamin)
for pernicious anaemia- oral = inadequate because problem is absorption- B12 injections, 1mg IM hydroxocobalamin 3x weekly for 2 weeks
34
define alpha thalassemia
autosomal recessive defect causing a deficiency in the production of alpha globin chains of haemoglobin
microcytic anaemia (MCV<80)
35
risk factors for alpha thalassemia
FHx
Middle Eastern, south asian, African decent
36
causes of alpha thalassemia
AT= autosmal recessive therefore needs 2 genes to cause disease
-either partial or complete deficiency on alpha globin chains due to mutations in 4 alpha genes on chromosome 16
-usually deletion
37
pathology of alpha thalassemia with 1 and 2 defective alpha genes
1 defective alpha gene= silent carrier
2 defective alpha genes= alpha thalassemia minor (can be either cis or trans mutation) - mild symptoms
38
pathology of alpha thalassemia with 3 defective genes
3 defective genes= Haemoglobin H disease (HbH)
-unable to form alpha chains- excess of beta chains
beta chains clump together 2 form tetramers (HbH)
HbH= causes hypoxia through haemolysis + have a high affinity for O2 so don't release it to tissues
39
pathology of alpha thalassemia with 4 defective genes
4 defective genes= Hb Barts
-people with 4 gene deletions die in utero because gamma chains form tetramers>v high affinity with O2>tissues get no O2 therefore severe hypoxia> high output cardiac failure + massive hepatosplenomegaly >oedema all over body- hydros fetalis
40
investigations for alpha thalassemia
| 1st + GOLD
1st= FBC
-low Hb
-low MCV
blood film= microcytic, hypo chromic RBCs, TARGET CELLS look like BULLSEYES, golf-ball like RBCs, RBC count increased
gold=
Hb electrophoresis (diagnostic)- looks for presence of HbH and Hb Bart
DNA testing for genetic abnormality
41
management of alpha thalassemia
1st= blood transfusions
iron chelation 2 prevent iron overload
folate supplementation
splenectomy
stem cell transplant
42
complications of alpha thalassemia
iron overload- due 2 regular transfusions
pregnancy comps
osteopenia
hypersplenism
43
define beta thalassemia
autosomal recessive defect leading to a deficiency in the production of B-globin chains of haemoglobin
microcytic anaemia (MCV <80)
44
risk factors for beta thalassemia
mediterranean, africa and south East Asian
FHx
45
mutations causing beta thalassemia
| describe minor, intermedia and major B thalassemia
BT caused by either partial or complete beta-haemoglobin chain deficiency due to point mutation in beta-globin gene on chromosome 11
autosomal recessive= 2 mutations needed to develop disease
1 gene mutation codes for reduced/absent beta-globin production= beta thalassemia minor (carrier)
2 genes that code for reduced beta-globin chains= beta thalassemia intermedia (marked anaemia)
2 genes that code for absent beta-globin chains= beta thalassemia major (severe anaemia)
46
pathology of beta thalassemia
beta globin chain deficiency causes accumulation of free alpha-globing chains in RBCs > damages RBC cell membrane > causes haemolysis in bone marrow or destruction of RBCs in spleen
haemolysis leads 2 hypoxia as there are fewer RBCs to carry oxygen- signals bone marrow + liver + spleen to increase RBC production> causes enlargement of these organs
47
presentation of beta thalassemia
minor=asymptomatic
major= symptoms appear in 1st year of life bc foetal haemoglobin is still used in early months
hepatosplenomegaly
jaundice
chipmunk facies
swollen abdomen
bone abnormalities
low weight + height
general anaemia symptoms
48
investigations for beta thalassemia
| including gold
1st=
FBC- low Hb, low MCV
blood film- microcytic hypochromic RBCs
-target cells= small RBCs that look like bullseyes
reticulocytosis
gold=
Hb electrophoresis- low HbA, high HbF + HbA2
x-ray- 'hair on end'
49
management of beta thalassemia
1st= recurrent blood transfusions for major and intermedia with worse symptoms
iron chelation (deferoxamine) 2 prevent iron overload
splenectomy
ascorbic acid- increases iron excretion
consider stem cell transplant
50
complications of beta thalassemia
iron overload
leg ulcers
gallstones
51
define sickle cell anaemia
autosomal recessive mutation in the beta chain of haemoglobin resulting in sickle shaped RBCs and haemolysis
52
what type of anaemia is sickle cell anaemia
normocytic haemolytic anaemia
MCV= 85-95, RBCs are destroyed faster than they are made
53
epidemiology of sickle cell anaemia
most common in sub-saharan Africa due 2 its advantage against p. falciparum (i.e protective against malaria)
54
risk factor for sickle cell anaemia
| 4 triggers of sickling
family history- autosomal recessive
triggers of sickling=
dehydration
acidosis
infection
hypoxia
55
cause of sickle cell anaemia
single point mutation in the beta-globin gene causing amino acid replacement at the 6th codon from glutamic acid to valine- changes the structure of the beta chain
1 mutation= sickle trait (carrier)- no health problems unless exposed 2 extreme conditons eg altitude or dehydration
56
pathology of sickle cell anaemia
sickle cell disease patients have abnormal HbS isoform consisting of 2 alpha + 2 abnormal beta chains
under physiological stress, eg hypoxia, sickled HbS polymerises, distorting RBC into sickle shape > deformed RBCs can cause vast-occlusion or slow blood flow
57
what are stressors inducing sickling in sickle cell disease patients
hypoxia
acidosis
infection
cold temps
dehydration
58
what does repeated sickling of RBCs do
damages the RBC membrane + promotes premature haemolysis- causing anaemia
bone marrow + liver compensate for haemolysis by producing more RBCs >causes bone deformities and hepatomegaly
59
presentation of sickle cell anaemia
chronic symptoms:
pain
general anaemia symptoms
related to haemolysis: jaundice and gallstones
symptoms due 2 crisis-
splenic sequestration crisis
vaso-occlusive crisis
acute chest crisis
60
describe a splenic sequestration crisis
splenic sequestration crisis= RBCs sickle `= block blood flow out of spleen- blood remains in spleen causing- splenomegaly (enlarged and painful spleen)
61
describe vaso-occlusive crisis
vaso-occlusive crisis= sickled RBCs block capillaries blood flow to bones, dactylitis- swelling and pain of hands + feet, pain crisis, avascular necrosis of bones
62
describe acute chest crisis
acute chest crisis= pulmonary vaso-occlusion causing fever, cough, dyspnoea, hypoxia, respiratory distress
63
investigations for sickle cell anaemia
primary=
screening- Guthrie heel prick test @ 5 days
FBC-anaemia
blood film: reticulocytosis,Hb 60-80g/L, increased RBCs, sickled cells, Howell-Jolly bodies, sickle cell solubility test (positive)
gold=
haemoglobin electrophoresis- sickle cell= presence of HbS,
no HbA
sickle trait= HbA + HbS
64
acute management of sickle cell anaemia
IV fluids and O2
antibiotics (chest crisis or infection)
NSAIDs for bone pain
65
long term management of sickle cell anaemia
avoid precipitating factors
pain management
hydroxycarbamide- increases levels of HbF- protective against sickling
lifelong phenoxymethylpenicillin due 2 risk of infection due 2 hyposplenism + autosplenectomy
blood transfusion + iron chelation to prevent iron overload
stem cell transplant
66
define autoimmune haemolytic anaemia
| including type of anaemia
normocytic haemolytic
autoantibodies target + cause haemolysis of RBCs
67
what are warm and cold autoimmune haemolytic anaemia each mediated by
WARM weather= Great, IgG
COLD weather= miserable, IgM
68
what test is positive in autoimmune haemolytic anaemia
Coombs test= positive
69
management of warm + cold autoimmune haemolytic anaemia
warm=
prednisolone
immunosuppressants
blood transfusions if severe
cold=
supportive tx
warm blood transfusion
rituximab (in resistant cases)
70
define G6PD deficiency (including type of anaemia)
normocytic anaemia
x linked recessive condition- G6PD enzyme protects RBCs from reactive oxygen species from damaging them + causing haemolysis
anaemia occurs because nothing is stopping ROS from haemolysing RBCs
71
what is produced when free radicals attack haem molecules in G6PD deficiency
Heinz bodies
72
name 4 precipitating factors for G6PD deficiency
fava beans
pesticides
antimalarials
aspirin
73
investigations for G6PD deficiency
FBC=
norm btwn attacks
attack- normocytic, normochromic, w. increased reticulocytes
presence of HEINZ BODIES + BITE CELLS
74
management of G6PD deficiency
avoid precipitating factors
severe attack= blood transfusions
75
define hereditary spherocytosis (including type of anaemia)
normocytic anaemia
autodom condition
- deficiency in structural membrane proteins spectrin or ankyrin> causes RBCs to become spherical shaped and will be more easily destroyed by spleen
76
signs of hereditary spherocytosis
gen anaemia
neonatal jaundice
splenomegaly
gallstones
77
investigations and management for hereditary spherocytosis
FBC + blood film= normocytic, normochromic, high reticulocytes + SPHEROCYTES
coombs= negative
Tx=
splenectomy- wait until at least 6 y/o (spleen fights off encapsulated bacteria
78
name 2 types of non haemolytic normocytic anaemias
CKD- anaemia of chronic disease
aplastic anaemia- pancytopenia where bone marrow fails
FBC for both= normocytic w. decreased reticulocytes
79
what type of anaemia is malaria
normocytic
80
what kind of mosquito causes malaria and what are the four types of parasites they can carry
female anopheles mosquito carries:
plasmodium falciparum
plasmodium ovale
plasmodium vivax
plasmodium malariae
81
describe the pathology of malaria
1. infected blood from mozzy injected as sporozoites when person bitten
2. sporozites travel to liver + mature 2 merozites
3. merozites enter blood + infect RBCs
4. merozites mature into > trophozoites > schizonts > new merozites
5. RBCs rupture causing systemic infection + haemolytic anaemia
82
presentation of malaria
* fever w sweats and rigors + exotic travel
* n+v
* myalagia (musc aches)
* headaches
(black water fever esp)
* anaemia Sxs
* jaundice
* hepatosplenomegaly
83
investigations for malaria (including what is needed to exclude malaria)
FBC, U&E, LFT= normocytic, normochromic, thrombocytopenia, elevated LDH
malaria blood film- shows type of parasite + concentration
to exclude malaria:
x3 negative samples over 3 consecutive days
84
management of malaria (uncomplicated & complicated)
1. uncomplicated= Artemether with lumefantrine (Riamet) is the usual first choice
2. Quinine plus doxycycline
3. Quinine plus clindamycin
Primaquine (can cause severe haemolysis in patients with G6PD deficiency)
complicated (severe)= IV artesunate
85
define HIV
human immunodeficiency virus= a retrovirus that primarily affects CD4+ T helper lymphocytes resulting in the progressive destruction of the immune system and the onset of acquired immunodeficiency syndrome (AIDS)
86
epidemiology of HIV
2 strains of HIV exist: HIV-1 & HIV-2
HIV-1 predominant in UK
HIV-2 predominant in west africa
uk successfully reached 90-90-90 target
87
causes of HIV
virus transmission:
sexual- bodily fluids during intercourse
parenteral- via needle stick or needle stick sharing
vertical- via breastfeeding or vaginal delivery
88
which cells have CD4 molecules
macrophages, t-helper cells, dendritic cells= all involved in immune response + have CD4 molecules so can be targeted by HIV
89
pathology of HIV
HIV attaches to CD4 via gp120 on its envelope and uses gp120 to attach to another co-receptor (either CXCR4 or CCR5)
-endocytosis of HIV RNA + reverse transcriptase + other viral proteins into cell
-reverse transcriptase converts HIV RNA to DNA
-viral DNA transported across nucleus + integrates into host DNA
-new viral DNA used as a genomic RNA for viral protein synthesis
-new HIV proteins & HIV RNA move to cell membrane and assemble a new, immature HIV
-new HIV virion exits the cell and viral protease forms mature, infectious HIV
90
what are the 4 phases of infection of HIV
1. acute infection- rapid viral reproduction, symptoms in 60-80% of patients, antibodies become detectable
2. chronic (latency phase)- symptoms from acute phase resolve and viral load reduces, no Sxs just enlarged lymph nodes
3. long-standing HIV, patient may develop opportunistic infections + non-AIDS defining Sxs
4. late stage HIV- AIDS- CD4 count drops <200/mm^3 , dramatic increase in viral load + development of AIDS- defining illnesses
91
presentation of acute HIV (seroconversion)
asymptomatic or flu-like illnesses:
mouth ulcers
lymphadenopathy
fever
maculopapular rash
malaise
diarrhoea
sore throat
92
presentation of clinical latency + long standing HIV
Clinical latency= asymptomatic + enlarged lymph nodes
Long-standing HIV=
opportunistic infections-
eg thrush, shingles, oral hairy leukoplakia, molluscum contagiosum
+
non-AIDS defining Sxs eg fever, night sweats, diarrhoea, wt. loss, cough
93
presentation of AIDS
CD4 <200:
cytomegalovirus (CMV)
pneumocystis pneumonia (PCP)
kaposi's sarcoma
candidiasis
TB
lymphoma
cryptosporidium fungal infection
weight loss
fever
diarrhoea
cough
nigh sweats
94
investigations for HIV
take venous blood sample: ELISA (4th gen test) to detect antibodies against HIV-1 & HIV-2 and to detect p24 antigen
to confirm initial diagnostic positive:
repeat combined HIV antibody and p24 test
OR
western blot= detects p24 antigen, gp120 and gp41 antibodies
(only positive tests 45 days after exposure= relaible for diagnosis)
@home point of care testing kits
monitoring=
CD4 T-cell count- indicates immune status with CD4 <200/MM^3 defining AIDS
viral load - can be used for diagnosis
95
initial management of HIV
all patients should start with antiretroviral therapy (ART)- aims to achieve normal CD4 count + undetectable viral load
initial management=
2 NRTIs (e.g., tenofovir plus emtricitabine) plus a 3rd agent (e.g., bictegravir).
96
what are the five classes of ARTs
-Protease inhibitors (PI)
-Integrase inhibitors (II)
-Nucleoside reverse transcriptase inhibitors (NRTI)
-Non-nucleoside reverse transcriptase inhibitors (NNRTI)
-Entry inhibitors (EI)
97
additional management of HIV
prophylactic co-trimoxazole: given 2 patients with CD4 <200/mm^3 to protect against pneumocystis jirovecii pneumonia
post exposure prophylaxis
close monitoring and management of cardiovascular risk
yearly cervical smears
vaccinations
advise use of condoms
98
what is a normal CD4 range and what is the CD4 count in AIDS
normal CD4 range= 500-1200 cells/mm3
CD4 <200= AIDS
the lower the CD4 count- the higher the risk of opportunistic infection
99
complications of HIV
opportunistic infections eg AIDS-defining illness
drugs side effects
immune reconstitution inflammatory syndrome (IRIS)
100
what is leukaemia
neoplastic proliferation of WBC line (cancer of WBCs -myeloblast/lymphoblast)
- results in decreased production of other haematopoetic cells= functional pancytopenia
101
what are general presentations of leukaemia
bone marrow failure= bone pain + bleeding (thrombocytopenia)
infections (leukopenia) + anaemia symptoms
* gum infections
* recurrent infections
* hepatosplenomegaly
* petechiae (pinpoint round spots)
* ecchymosis (bruise caused by blood leaking from broken vessels)
* anaemia
102
what is acute myeloid leukaemia (AML)
malignant neoplastic disease of WBCs, causing proliferation of myeloblast cells
103
risk factors for acute myeloid leukaemia
cause= unknown
myelodysplastic syndrome
pre-existing haematological disorders
Down's syndrome
gene mutation
radiation
most common in **over 75s**
benzene i.e painters, rubber manufacturers
104
pathology of acute myeloid leukaemia
uncontrolled growth of the myeloid cell line in bone marrow- cause proliferation of immature, non-functional WBCs called blasts
blasts disrupt normal haematopoiesis, causes pancytopenia= reduction in RBCs (anaemia), WBCs (infection) and platelets (bleeding)
105
presentation of acute myeloid leukaemia
gen anaemia Sxs
lymphadenopathy
fatigue
fever
failure to thrive
pallor
weight loss
dizziness
106
investigations for acute myeloid leukaemia
FBC (pancytopenia)
blood film- **high no. of myeloblasts and aurer rods**
lactate dehydrogenase= raised
gold=bone marrow aspirate + biopsy
2 confirm diagnosis- >**20% myeloid blasts** in bone marrow or detecting myelobalsts w aurer rods
other= immunophenotyping/flow cytometry (presence of myeloid antigens on blasts)
107
management of acute myeloid leukaemia
1st=
chemo using **combo of cytarabine & daunorubicin**
all-trans retinoic acid (**ATRA**)- used in acute promyelocytic leukaemia
supportive therapy= transfusions, antimicrobial prophylaxis, **allopurinol 2 prevent tumour lysis** syndrome (chemo releases uric acid from cells)
bone marrow transplant
108
complications of acute myeloid leukaemia
secondary to chemo= tumour lysis syndrome, sepsis
AML= disseminated intravascular coagulation
109
age mnemonic for leukaemias
ALL CeLL mates have CoMmon AMbitions
under 5 and over 45-
Acute Lymphoblastic Leukaemia (ALL)
over 55-
Chronic Lymphocytic Leukaemia (CeLLmates)
over 65-
chronic myeloid leukaemia (CoMmon)
over 75-
acute myeloid leukaemia (AMbitions)
110
what happens in chronic myeloid leukaemia
uncontrolled growth of myeloid cells causing increased granulocyte production (neutrophils, eosinophils, basophils)
111
what causes uncontrolled growth of myeloid cells in chronic myeloid leukaemia
chromosomal abnormality causes formation of Philadelphia chromosome-translocation 9:22
BCR-ABL gene fusion causes tyrosine kinase to be irreversibly switched on- increasing cell proliferation
112
presentation of chronic myeloid leukaemia
gen leukaemia Sxs
MASSIVE HEPATOSPLENOMEGALY
anaemia
petechiae
gout
113
investigations for chronic myeloid leukaemia
FBC= pancytopenia BUT granulocytosis
blood blast cell % shows severity
<10%- chronic, 1.
10-19% - accelerated, 2.
>20%- blast crisis 3.
114
management of chronic myeloid leukaemia
1st= tyrosine kinase inhibitors- imatinib
blast phase= imatinib + chemo
BM transplant if not responding 2 drugs
115
what happens in acute lymphoblastic leukaemia
malignant change in 1 of the lymphocyte precursor cells causes uncontrolled proliferation of lymphoblasts
-mostly B cell lineage
excessive proliferation + accumulation of lymphoblasts in BM + peripheral blood- replaces other cell types (pancytopenia)
116
who is mostly commonly affected by acute lymphoblastic leukaemia
children 2-4 yrs
associated w. Down's + radiation
117
presentation of acute lymphoblastic leukaemia
gen leukaemia (except in down's)
CNS involvement
lymphadenopathy
118
investigations for acute lymphoblastic leukaemia
FBC= pancytopenia
blood film= increased lymphoblasts
BM biopsy= >20% lymphoblasts (diagnostic)
immunofluorescence= TdT positive lymphoblasts
lumbar puncture= lymphoblasts in CSF
119
management of acute lymphoblastic leukaemia
chemo (consider adding allopurinol to prevent tumour lysis)
support w. CNS prophylaxis
last resort= stem cell transplant
120
what is chronic lymphocytic leukaemia
chronic proliferation of a single type of well differentiated lymphocyte
-usually B lymphocytes
causes uncontrolled proliferation of mature B-lymphocytes which have escaped apoptosis
-lymphocytes accumulate in bone then spread 2 lymphoid tissues
121
presentation of chronic lymphocytic leukaemia
gen leukaemia Sxs
hepatosplenomegaly
lymphadenopathy
petechaie
anaemia Sxs
122
investigations for chronic lymphocytic leukaemia
FBC= pancytopenia, anaemia, increased WBCs
blood film= SMUDGE CELLS + increased lymphocytes
antibody levels= hypogammaglobulinemia- B cells proliferate but don't differentiate into plasma cells (plasma cells produced antibodies)
123
management of chronic lymphocytic leukaemia
chemo + allopurinol
IV immunoglobulins (antibodies) - IVIG + rituximub for hypogammaglobulinemia
124
what is a complication of chronic lymphocytic leukaemia
Richter Transformation
-B massively accumulate in lymph nodes> massive lymphadenopathy + transformation from CLL to aggressive lymphoma
125
what is a lymphoma (and how does lymphadenopathy occur in lymphoma)
cancer affecting lymphocytes inside the lymphatic system
-cancerous cells proliferate inside the lymph nodes causing them to become abnormally large = lymphadenopathy
126
describe Hodgkin's lymphoma (what cells are present)
mutation in DNA of lymphocytes
= leads to presence of - REED STERNBERG CELLS (large, multi-nucleated, malignant Hodgkins cells)
127
list 5 risk factors for Hodgkins lymphoma
EBV
HIV
FHx
autoimmune conditions
teens + elderly (bimodal age distribution)
128
presentation of Hodgkins lymphoma
non-tender, rubbery lymphadenopathy (painful after drinking alcohol
fever, wt. loss, night sweats
abdo pain
recurrent infections
fatigue, itching, cough, shortness of breath
129
investigations for Hodgkins lymphoma
lymph node biopsy- reed Sternberg cells positive
increased LDH
FBC= decreased Hb, increased ESR
CT/MRI for lymphoma staging
130
what is used to stage Hodgkins lymphoma
ANN ARBOUR STAGING
1. only @ 1 region of lymph nodes
2. 2 or more lymph nodes on same diaphragm side
3. @ lymph nodes on both sides of the diaphragm
4. widespread involvement of non-lymphoid organs (liver, lungs)
## Footnote
Lugano classification- 4 stages
1. only @ 1 region of lymph nodes
2. 2 or more lymph nodes on same diaphragm side
3. @ lymph nodes on both sides of the diaphragm
4. widespread involvement of non-lymphoid organs (liver, lungs)
(Add Clarifier)
Add Footnote
131
management of Hodgkin's lymphoma + a comp
ABVD chemo: adriamycin, bleomycin, vinblastine, dacarbazine
+ radiotherapy
comp= febrile neutropenia (tx w amoxicillin)
132
name 3 sub-types of non-hodgkin's lymphoma
diffuse large B cell lymphoma- mc.
Burkitt lymphoma (caused by EBV)
MALT lymphoma (caused by H. pylori)
133
list 5 risk factors for non-hodgkins lymphoma
EBV
H. pylori
HIV
hep B/C
FHx
134
presentation of non-hodgkins lymphoma
painless rubbery lymphadenopathy
+
malaise
abdo pain
recurrent infections
fatigue
shortness of breath
cough
headache
135
management of non-hodgkins lymphoma
lymph node biopsy= diagnostic
- NO reed-sternberg cells
- confirms subtype eg burkitt= starry sky biopsy
LDH= raised
ESR= raised
CT/MRI of chest, abdo pelvis for ANN ARBOR STAGING
136
management of non-hodgkins lymphoma
R-CHOP chemo- rituximab, cyclophosphamide,, hydroxydaunorubin, vincristine, prednisolone
- monoclonal antibodies target CD20 B cells
137
what is polycythaemia
proliferation of erythrocyte (RBC) cell line
-increase in RBC count + haemocrit
138
what are primary and secondary polycythaemia each caused by
primary= polycythaemia vera- caused by JAK2 mutation
secondary= caused by hypoxia, increase in erythropoietin, dehydration (alcohol induced)
139
what does JAK2 mutation cause in polycythaemia vera
mutation= JAK2 gene always activated- always produces RBCs without erythropoeitis
140
presentation of polcythaemia vera
itchy after bath
redness of conjuctiva
blurred vision
splenomegaly
'ruddy' complexion
erythromelagalia- burning in fingers + toes
prone 2 clotting
141
investigations for polcythaemia vera
FBC= raised WCC, platelets, Hb
GS= genetic test 4 JAK2 mutation
142
management of polycythaemia vera
no cure- aim is to maintain norm blood count
venesection- removes blood to keep Hb in norm range
myelosuppressive meds- hydroxycarbomide/hydroxyurea OR JAK2 inhibitor
aspirin- prevents clotting
143
what are the two types of thrombocytopenia
immune thrombocytic purpura
thrombotic thrombocytic purpura
144
what happens in immune thrombocytic purpura + who do the different types affect
autoimmune platelet destruction (IgG)
Type 1- children 2-6 yrs, post viral infection
Type 2- adult women w. malignancy, HIV, other autoimmune conditions
145
presentation of immune thrombocytic purpura
PURPURIC RASH
easy bleeds
menorrhagia
146
investigations + management of immune thrombocytic purpura
Dx= thrombocytopenia + increased BM megakaryoblasts
Tx= prednisolone + IV IgG- decreased splenic platelet destruction (then splenectomy)
147
what deficiency causes thrombotic thrombocytic purpura and what does this cause
ADAMTS13 deficiency - VWF cleaving enzyme
VWF normally cleaved into fragments- here remain as multimers + aggregate @ endothelial injury sites
148
presentation of thrombotic thrombocytic purpura
PURPURIC RASH
menorrhagia
AKI
haemolytic anaemia
neuro Sxs
149
investigations and management of thrombotic thrombocytic purpura
Dx= thrombocytopenia + SCHISTOCYTES
- low levels of ADAMTS13
Tx=
1. plasmaphoresis
2. prednisolone + rituximab
150
Epstein-Barr virus: who does it affect and how is it spread
glandular fever= infection caused by EBV
affects 15-24 y/o
spread via sharing saliva/ bodily fluids
151
describe an arterial thrombus and give 3 examples
arterial=
ischaemia to organs/tissue
cyanotic, cold
Cardiovascular disease (CVD)= IHD induced, MI, angina
cerebrovasc= ischaemic stroke + TIA
Peripheral vascular disease (PVD)
152
describe a venous thrombus and give 2 examples
venous (Virchow's triad)
-red + warm
DVT
PE
153
name 3 causes of bleeding dysfunction and give examples
overanticoagulation:
heparin, aspirin, clopidogrel, thrombolytics eg alteplase
DIC (disseminated intravascular coagulation)
inherited Conditions:
Haemophilia A (F8)
Haemophilia B (F9)
von willebrand disease
154
what is haemophilia and which clotting factors are affecting in types A and B
x-linked factor deficiency
A= factor 8 (mc)
B= factor 9
155
what does a lack of factor 8/9 cause win haemophilia
lack of factors= delayed thrombin formation + unstable clot that is easily dislodged causing excessive bleeding
156
presentation of haemophilia
spontaneous bleeding
haemarthrosis (bleeding into joint spaces)
easy bruising
nose bleeds
157
investigations for haemophilia (including GOLD)
norm prothrombin time BUT prolonged activated partial prothrombin time
GOLD= decreased F8 or F9 assay
158
management of A or B haemophilia
A= IV F8 + desmopressin (stimulates VWF, boosting F8 activity)
B= IV F9
159
describe von willebrand's disease (VWF)
autodom mutation of VWF gene on chromosome 12
VWF= responsible for base of platelet plug- absence= more spontaneous. bleeds + bruising
160
investigations for VWF
norm PT
increased activated partial prothrombin time
norm F8/F9
decreased VWF (GS)
161
management of VWF
non-curable
Tx= desmopressin- releases VWF from endothelial weibelpalade bodies
162
what is disseminated intravascular coagulation (DIC)
trauma/sepsis/malignancy causes massive activation of coagulation cascade (crisis)
platelets= unnecessarily consumed
lack of platelets = increased bleeding risk
163
investigations and management of DIC
Dx=
decreased fibrinogen + platelets
increased D .dimer (released when blood clots are broken down)
Tx=
platelet transfusion + RBC transfusion if bleeding
replace clotting factors
replace fibrinogen (cryoprecipitate)
164
what is tumour lysis syndrome and what happens
complication of cancer therapy
- rapid breakdown of large numbers of cancer cells + subsequent release of their intracellular content (K+, phosphate, nucleic acids) into bloodstream overwhelms normal homeostatic mechanisms
165
presentations of tumour lysis syndrome
arrythmias
seizures
syncope
chest pain
dyspnoea
n+v
diarrhoea
musc. weakness + cramps
parathesia
166
investigations for tumour lysis syndrome
increased:
serum uric acid
phosphate
creatinine
FBC= increased WBCs
serum Ca= decreased
LDH= increased
167
management of tumour lysis syndrome
treat arrythmias or seizures
fluid resuscitation + diuretic
rasburicase (prevention)
phosphate binder
hyperkalaemia= Ca gluconate
168
neutropenia vs neutrophilia
neutropenia= decreased no. of neutrophils
per micrometer of blood
mild= 1000-1500
severe= <500
neutrophilia= increased no. of neutrophils
>7500 neutrophils per micrometer of blood
169
lymphopenia vs lymphophilia (lymphocytosis)
lymphopenia= decrease in no. of lymphocytes
<1000 lymphocytes per micrometer of blood
lympophilia (lymphocytosis)= increase in no. of lymphocytes
>4000 lymphocytes per microliter of blood
(often due 2 viral infections eg EBV)
170
what is thrombocytopenia (levels and causes)
bone marrow not producing enough platelets
mild= 101000- 140000 per microliter of blood
severe= 51000-21000 per microliter of blood
causes= blood cancers: leukaemia, lymphoma
171
what is thrombophilia and what is the mc acquired thrombophilia
blood is hyper coagulable
mc. = anti-phospholipid syndrome
172
what is PT/INR
PT= prothrombin time- Time it takes for clot to form (tests extrinsic pathway)
INR= international normalised ratio- type of calc based on PT test results
173
what is aPTT
aPTT= activated partial thromboplastin time
-tests clotting factors in intrinsic pathway
