Haem Flashcards
(254 cards)
1
Q
symptoms of anaemia?
A
fatigue
SOB
faintness
palpitations
headache
tinnitus
2
Q
signs of anaemia
A
pallor
hyperdynamic circulation: tachycardia, flow murmur (apical ESM), cardiac enlargement
ankle swelling w heart failure
3
Q
types of microcytic anaemia?
A
Haem defect:
IDA
Anaemia of chronic disease
Sideroblastic/ Lead poisoning
Globin defect:
thalassaemia
4
Q
causes of normocytic anaemia?
A
recent blood loss
bone marrow failure
renal failure
early anaemia of chronic disease
pregnancy (raised plasma volume)
5
Q
causes of macrocytic anaemia?
A
megaloblastic:
folate/ B12 deficiency
anti folate drugs: methotrexate, phenytoin
cytotoxics: hydroxycarbamide
non-megaloblastic:
reticulocytosis
alcohol or liver disease
hypothyroidism
myelodysplasia
6
Q
Causes of IDA?
A
increased loss:
GI bleeding, menorrhagia, hookworms
decreased intake:
poor diet
malabsorption: coeliac, crohns
7
Q
Ix of Iron deficiency anaemia?
A
haematinics: low ferritin, high TIBC, low transferrin saturation, low Fe
Blood film: anisocytosis, poikilocytosis, pencil cells
OGD + Colonoscopy
8
Q
Mx of Iron deficiency anaemia?
A
Ferrous Sulphate 200mg PO TDS
(se: GI upset)
9
Q
what is sideroblastic anaemia?
A
ineffective erythropoiesis
- increased iron absorption
- iron loading in bone marrow -> ringed sideroblasts
- haemosiderosis: endo, liver and cardiac damage
10
Q
causes of sideroblastic anaemia?
A
congenital
acquired: myelodysplasia/ myeloproliferative disease
drugs: chemo, anti-TB, lead
11
Q
Ix of sideroblastic anaemia?
A
microcytic anaemia and not responsive to iron
high ferritin, high serum Fe, normal TIBC
12
Q
mx of sideroblastic anaemia?
A
tx underlying cause
pyridoxine may help
13
Q
featuers of Beta thalassaemia trait?
A
mild anaemia - usually harmless
low MCV
high HbA2 (a2d2) and high HbF (a2y2)
14
Q
Features of Beta thal major?
A
features develop from 3-6mo
- severe anaemia, jaundice (haemolysis), FTT
extramedullary erythropoiesis: frontal bossing, maxillary overgrowth, hepatosplenomegaly
Hameochromatosis after 10 yrs (transfusions)
15
Q
Ix of Beta thal major?
A
low Hb, low MCV, high HbF, high HbA2
Blood film: target cells and nucleated RBCs
16
Q
Mx of Beta thal major?
A
lifelong transfusions
+ desferrioxamine for iron chelation
BM transplant may be curative
17
Q
features of alpha thal trait?
A
asymptomatic
hypochromic microcytes
18
Q
HbH disease?
A
type of alpha thal
moderate anaemia: may need transfusions
haemolysis: jaundice, hepatosplenomegaly
19
Q
Hb Barts?
A
Fatal
hydrops fetalis -> death in utero
20
Q
Blood film findings of B12/ Folate deficiency?
A
Hypersegmented PMN -> megaloblastic
oval macrocytes
21
Q
Mx of Folate deficiency?
A
assess for underlying cause
give B12 first! (unless B12 level known to be normal)
-> may precipitate or worsen SACD if folate prescribed when b12 is low
Folate 5mg/d PO
22
Q
Sources of Folate?
A
Diet: Green veg, nuts, liver
stores for 4mo in the body
absorption: proximal jejunum
23
Q
Causes of Folate deficiency anaemia?
A
low intake: poor intake
increased demand: pregnancy, haemolysis, malignancy
malabsorption: coeliac, crohns
Drugs: anti folates e.g. phenytoin, methotrexate, alcohol
24
Q
Bloods to Ix macrocytic anaemia?
A
LFTs: mild raised Br in folate/ B12 deficiency
TFT
Serum B12
Red cell folate: reflects body stores over 2-3 mo
25
Source of Vit B12?
meat fish and dairy (vegans likely deficient)
stores for 4 yrs
absorbed in terminal ileum bound to intrinsic factor (released from gastric parietal cells)
role: DNA and myelin synthesis
26
Causes of B12 deficiency?
low intake: vegans
low intrinsic factor: post gastrectomy, pernicious anaemia
terminal ileum: crohns, ileal resection, bacterial overgrowth
27
features of B12 deficiency?
general: symptoms of anaemia
lemon tinge- pallor + mild jaundice
glossitis (beefy, red tongue)
Neuro:
parasthesia
peripheral neuropathy
SACD
optic atrophy
28
what is subacute combined degeneration of the cord?
usually only caused by pernicious anaemia
combined symmetrical dorsal column loss and corticospinal tract loss
- \> distal sensory loss: esp joint position and vibration
- \> ataxia w wide gait and Rombergs +ve
Mixed UMN and LMN signs
- spastic paraparesis
- brisk knee jerks, absent ankle jerks
upgoing plantars
pain and temp remain intact
29
Ix of Vit B12 deficiency?
low Hb, high MCV
low WCC and platelets if severe
intrinsic factor Abs: specific
Parietal cell Abs: sensitive
30
Mx of Vit B12 deficiency?
Malabsorption: Parenteral B12 (hydroxycobalamin)
Dietary -\> oral B12 (cyanocobalamin)
Parenteral B12 reverses neuropathy but not SACD
31
What is pernicious anaemia?
autoimmune atrophic gastritis caused by autoabs vs parietal cells or IF
-\> low IF and low H+
assoc w other AI disease and Ca: 3x risk of gastric adenoca
32
myositis
interstitial lung disease
thickened and cracked skin of the hands (mechanic's hands)
Raynaud's phenomenon
Antisynthetase syndrome
subtype of dermatomyositis
anti Jo1 +ve
33
Causes of cold AIHA?
Mycoplasma/ EBV, CLL
idiopathic
34
Mx of cold AIHA?
avoid cold
Rituximab (anti-CD20) to deplete B cells
35
Ix of Cold AIHA?
Direct antiglobulin test +ve
36
Features of cold AIHA?
igM-mediated, bind @\<4 degrees
often fix complement -\> intravascular haemolysis
may cause agglutination -\> acrocynanosis or Raynauds
37
Features of warm AIHA?
IgG mediated, bind @37 degrees
extravasc haemolysis and spherocytes
38
Ix of warm AIHA?
Direct antiglobulin test +ve
39
Causes of warm AIHA?
idiopathic
SLE
RA
CLL
Medications: NSAIDs
40
Mx of Warm AIHA?
immunosuppression
splenectomy
41
IgG Donath-Landsteiner Abs
Paroxysmal Cold Haemoglobinuria
rare
assoc w measles, mumps, chicken pox
IgG Donath-Landsteiner Abs bind RBCs in the cold and
-\> complement mediated lysis on rewarming
42
Paroxysmal Cold Haemoglobinuria
?
assoc w measles, mumps, chicken pox
IgG Donath-Landsteiner Abs bind RBCs in the cold and
-\> complement mediated lysis on rewarming
43
Features of Paroxysmal nocturnal haemoglobinuria?
Visceral viscous thrombosis (hepatic, mesenteric, CNS)
haemolysis and haemoglobinuria
44
Visceral viscous thrombosis (hepatic, mesenteric, CNS)
haemolysis and haemoglobinuria
absence of RBC anchor molecule -\> lysis of RBCs
may also cause low Platelets + PMN
Paroxysmal nocturnal haemoglobinuria
45
Ix of Paroxysmal nocturnal haemoglobinuria?
Anaemia +/- thrombocytopenia +/- neutropenia
FACS: low CD55 and CD59
46
Mx of Paroxysmal nocturnal haemoglobinuria
Chronic disorder -\> long term anticoagulation
Eculizumab (prevents complement MAC formation)
47
what organism is most assoc w HUS?
E coli O157:H7
48
features of Haemolytic Uraemic Syndrome?
Bloody diarrhoea and abdo pain precedes:
- MAHA
- Thrombocytopenia
- Renal failure
49
Ix of HUS?
schistocytes (MAHA)
low Platelets
normal clotting
U+E, Ur/Cr deranged (renal impairment)
50
Mx of HUS?
usually resolves spontaneously
Exchange transfusion and dialysis may be needed
51
Deficiency of what causes TTP?
Genetic/ acquired deficiency of ADAMTS13
52
Pentad of Thrombotic Thrombocytopenic Purpura?
Fever
CNS signs: confusion, seizures
MAHA
thrombocytopenia
renal failure
53
Ix of TTP?
schistocytes
low PL
normal clotting
U+E/ UR/Cr deranged: renal impairment
54
Mx of Thrombotic Thrombocytopenic Purpura?
Plasmapheresis
Immunosuppression
Splenectomy
55
What is Pyruvate Kinase deficiency?
autosomal recessive defect in ATP synthesis
- \> rigid red cells phagocytosed in spleen
features: splenomegaly, anaemia +/- jaundice
56
Ix of pyruvate kinase deficiency?
Pyruvate kinase enzyme assay
57
Mx of Pyruvate Kinase deficiency?
not needed
or transfusion +/- splenectomy
58
Pathology of G6PD deficiency?
X linked disorder
g6PD in pentose phosphate pathway -\> low NADPH production -\> low glutathione which is used to mop up free radicals that cause oxidative damage
-\> increased RBC oxidative damage
59
Triggers of haemolysis in G6PD deficiency?
Fava beans
Mothballs (naphthalene)
infection
Drugs: antimalarials, henna, dapsone, sulphonamides
60
ix of G6Pd deficiency?
blood film: irregularly contracted cells, bite cells, **Heinz bodies**
G6PD assay after 8 wks of acute haemolysis
61
mx of G6PD deficiency?
treat underlying infection
stop and avoid precipitants
transfusion may be needed
62
mx of hereditary elliptocytosis?
most pts asymptomatic
auto dom defect-\> elliptical RBCs
Folate (increased utilisation), rarely splenectomy
63
pathophysiology of hereditary spherocytosis?
auto dom defect in RBC membrane
spherocytes trapped in spleen -\> extravasc haemolysis
64
features of hereditary spherocytosis?
Splenomegaly
Pigment gallstones
Jaundice
65
complications of hereditary spherocytosis?
aplastic crisis
megaloblastic crisis
66
Ix of hereditary spherocytosis?
Blood film: spherocytes
DAT -ve
increased osmotic fragility
67
Mx of hereditary spherocytosis?
folate
rarely -\> splenectomy
68
pathogenesis of sickle cell?
point mutation in B globin gene: glu -\> val
SCA: HbSS
Trait: HbAS
HbSS insoluble when deoxygenated -\> sickling
sickle cells have lower life span -\> haemolysis
sickle cells get trapped in microvasc -\> thrombosis
69
Ix of sickle cell?
Hb 6-9, high reticulocytes/ Br
Blood film: sickle cells and target cells
Hb electrophoresis
Neonatal screening at birth: Guthrie Heel prick
70
presentation of sickle cell anaemia?
clinical features manifest 3-6 mo due to drop in HbF
triggers: infection, cold, hypoxia, dehydration
Splenomegaly -\> may get sequestration crisis
Infarction: Stroke, spleen
Crises: pain, pulmonary
Kidney, Liver, Lung disease
Erection
Dactylitis
71
Complications of Sickle Cell Disease?
Sequestration crisis:
splenic pooling -\> shock + severe anaemia
Splenic infarction: atrophy and hyposplenism
increased risk of infection: e.g. osteomyelitis
Aplastic crisis: parvovirus B19
Gallstones
72
Mx of chronic Sickle cell disease?
Folate
Pen V + immunisations if no spleen (pneumococcal, meningococcus, Hib)
hydroxycarbamide if freq crises
73
Mx of Acute Sickle cell crises?
A-\>E, call for senior help
Analgesia: Opioids IV
Good hydration
Give O2
keep warm
Ix for cause: e.g infection
Abx if suspect infection
Transfusion: exchange if severe
74
Features of DIC?
thrombosis and bleeding
increased APTT/PT/TT
low Platelets/ fibrinogen
high fibrin degradation products
75
Causes of DIC?
sepsis
malignancy esp APML
trauma
obstetric complications
76
Mx of DIC?
FFP
Platelets
Heparin
77
Haemophilia A vs B?
A: fVIII
B: fIX deficiency
78
Haemophilia features?
X-linked
affects males
present w haemarthroses, bleeding after surgery/ extraction
79
Ix of Haemophilia?
low fVIII: A, fIX: B assay
prolonged APTT, normal PT
80
Mx of Haemophilia A?
avoid IM Injections and NSAIDs
minor bleeds: desmopressin + tranexamic acid
Major bleeds: fVIII
81
von willebrands disorder features?
vWF: stabilises fVIII
binds platelets via Gp1b to damaged epithelium
if mild, APTT and bleeding time normal
if not: high APTT, bleeding time, normal Pl and decreased vWF
82
Mx of Von Willebrands Disease?
Desmopressin: raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
tranexamic acid for mild bleeding
fVIII concentrates
83
Causes of thrombocytopenia?
decreased production:
BM failure: aplastic, infiltration, drugs
Megaloblastic anaemia
increased destruction:
immune - ITP, SLE, CLL, Heparin, viruses
non immune: DIC, TTP, HUS, PNH, anti-phospholipid
Splenic pooling:
portal HTN, sickle cell
84
features of idiopathic thrombocytopenic purpura?
children commonly post URTI
self limiting
in adults: F\>M, long term
Anti-platelet abs present
85
mx of ITP?
conservative
steroids
IVIg
splenectomy
86
Causes of Functional platelet defects?
drugs: aspirin, clopidogrel
secondary to: uraemia, paraproteinaemias
Hereditary: bernard-soulier (Gp1b deficiency), Glanzmanns (GpIIb/IIIa deficiency)
87
features of coagulation disorders e.g. haemophilia/ VWD?
deep bleeding: muscles, joints, tissues
delayed but severe bleeding after injury
88
features of vascular or platelet disorder?
Bleeding into skin: purpura, petechiae, ecchymoses
Bleeding into mucous membranes: epistaxis, menorrhagia, gums
Immediate, prolonged bleeding from cuts
89
Thrombin time tests?
Fibrinogen function
Increased w Heparin, DIC
90
What does bleeding time test?
platelet function
increased if decreased pl number/ function, VWD, aspirin, DIC
91
What does APTT test?
intrinsic pathway: 12, 11, 9, 8
+ common: 10, 5, 2, 1
Increased:
haemophilia, VWD, unfractionated heparin, DIC, hepatic failure, antiphospholipid
92
What does PT test?
extrinsic pathway: 7
+ common: 10, 5, 2, 1
increased:
warfarin/ Vit K deficiency, hepatic failure, DIC
93
Types of thrombophilia?
- predisposing to thrombosis
Inherited:
Factor V Leiden
Prothrombin Gene mutation
Protein C and S deficiency
Antithrombin III deficiency
Acquired:
Antiphospholipid syndrome
OCP
94
Pathophysiology of Factor V Leiden -\> thrombosis?
Factor V Leiden is resistant to protein C
Protein C normally deactivates fV and fVIII w protein S and thrombomodulin cofactors
-\> increased risk of VTE
95
indications for thrombophilia screen?
arterial thrombosis \< 50
venous thrombosis \< 40 w no RFs
familial VTE
unexplained recurrent VTE
unusual site: portal, mesenteric
recurrent foetal loss
neonatal
96
Ix of thrombophilia?
FBC, clotting, [fibrinogen]
Factor V Leiden/ APC resistance
Lupus anticoagulant and anti-cardiolipin Abs
Assays for ATIII, Protein C and S
PCR for prothrombin gene mutation
97
Mx of thrombophilias?
tx acute thrombosis as normal
anticoagulate to INR 2-3
consider lifelong warfarin
if recurrence occurs on warfarin -\> INR 3-4
98
prevention of thrombosis in pts w thrombophilia?
lifelong anticoagulation may be needed
avoid OCP/HRT
prophylaxis in high risk situations e.g. surgery, pregnancy
99
ix of Aplastic Anaemia?
Bone marrow biopsy: Hypocellular marrow
100
Mx of aplastic anaemia?
supportive; transfusion
immunosuppression: anti-thymocyte globulin
Allogeneic Bone marrow transplant: may be curative
101
Causes of pancytopenia?
congenital: fanconis anaemia
acquired:
idiopathic
BM infiltration
Haemotological: Leukaemia, Lymphoma, Myelofibrosis, Myelodysplasia, Megaloblastic anaemia
infection: HIV
Radiation
Drugs: e.g. cyclophosphamide cytotoxics, chloramphenicol, thiazide, carbimazole, clozapine, phenytoin
102
what drugs may cause pancytopenia?
cytotoxic: cyclophosphamide, methotrexate, azathioprine
chloramphenicol
thiazides
carbimazole
clozapine
phenytoin
103
features of myelodysplastic syndromes?
cytopenias
hypercellular BM
defective cells e.g. ringed sideroblasts
30% -\> AML
usually in elderly
BM failure: infection, bleeding, bruising, anaemia
splenomegaly
104
Pelger Huet Anomaly?
AML/ CML
myelodysplastic syndrome
105
Mx of myelodysplastic syndrome?
supportive: transfusions, EPO, G-CSF
Immunosuppression
Allogeneic BMT: may be curative
106
features of essential thrombocythaemia?
Thrombosis:
arterial- TIA, strokes, peripheral emboli
venous- DVT, PE, Budd Chiari
bleeding: (abnormal pl fn)
e. g. mucous membranes
erythromelalgia: episodes of burning pain and redness in the feet
107
Ix of essential thromboythaemia?
platelets \> 600 (often \>1000)
BM: increased megakaryocytes
50% JAK2 +ve
108
mx of essential thrombocythaemia?
Platelets 400-1000: aspirin alone
Platelets \> 1000 or thrombosis: hydroxycarbamide
Anagralide: inhibits pl maturation
109
Essential thrombocythaemia assoc w?
progression to AML/ Myelofibrosis
110
Features of polycythaemia vera?
**hyperviscosity:**
headaches, visual disturbances, tinnitus, thrombosis (arterial/ venous)
**histamine release**:
aquagenic pruritus
**erythromelalgia:**
sudden severe burning in hands and feet w redness of skin
**splenomegaly, hepatomegaly**
**gout**
111
Ix of Polycythaemia vera?
99% JAK2 +ve
high RBC, Hb, Hct
high WCC/ Pl
BM: hypercellular w erythroid marrow
low EPO
112
Mx of polycythaemia vera?
Aim to keep Hct \<0.45 to reduce thrombosis risk
Aspirin 75mg OD
Venesection if young
Hydroxycarbamide if older/ higher risk
113
prognosis of polycythaemia vera?
thrombosis and haemorrhage
30% -\> myelofibrosis
5% -\> AML
114
Differential of polycythaemia?
true polycythaemia:
Polycythaemia vera
secondary to hypoxia (smoking, altitude, COPD) or high EPO (renal cyst/ tumour)
Pseudopolycythaemia: low plasma vol
Acute- dehydration, shock, burns
chronic- smoking, diuretics
115
differential for thrombocythaemia?
primary: essential thrombocythaemia
secondary to
- bleeding, infection, chronic inflammation (RA, IBD)
trauma/ surgery, hyposplenism/ splenectomy
116
Features of primary myelofibrosis?
elderly
massive hepatosplenomegaly
due to extramedullary haemotopoiesis in liver and spleen
Hypermetabolism: FLAWS
BM Failure: anamia, infection, bleeding
117
Ix of Myelofibrosis?
Film: leukoerythroblastic w tear drop poikilocytes
cytopenias
BM: dry tap (neep trephine biopsy)
50% JAK2+ve
118
Mx of primary myelofibrosis?
supportive: blood products
Splenectomy
Allogeneic BMT may be curative
119
What Drugs increase risk of VTE?
COCP
HRT
Antipsychotics esp olanzapine
120
Risk factors for developing ALL/AML
ionising radiation- radiotx
chemotx
benzene
MDS/ myeloproliferative disorders
Downs: signficantly increased risk of AML
121
t(15;17)
excess of abnormal promyelocytes
DIC
PML-RARA fusion protein
Acute promyelocytic leukaemia
122
ALL
- peak age incidence
- clinical features
peak incidence in childhood
BM failure - pancytopenia
hepatosplenomegaly
**lymphadenopathy**
**thymic enlargement**
**testicular enlargement**
**bone pain**
123
ALL Ix
Blood count and film, bone marrow aspirate (\>20% blasts)
high WCC (lymphoblasts). low RBC/platelets/ neutrophils
· Immunophenotyping – matters as T (15%) and B-lineage (85%) ALL may be treated differently
· Cytogenetic/molecular genetic analysis - Ph positive need imatinib, treatment must be tailored to the prognosis
· Blood group, LFTs, creatinine, electrolytes, calcium, phosphate, uric acid, coagulation screen
CXR + CT: mediastinal + abdominal LNs
LP: CNS involvement
124
Mx of ALL
· Specific therapy – systemic or CNS-directed chemotherapy
· Supportive care – blood products, abx, general medical care, prophylaxis for Pneumocystis jirovecii infection (co trimoxazole)
· Hyperuricaemia: hydration, urine alkalinization and allopurinol or rasburicase
· Hyperphosphataemia; Al(OH)3, calcium
· Hyperkalemia: fluids, diuretics
· Extreme leukocytosis (WBC \> 200 × 109/l): leukapheresis, sometimes haemodialysis
BMT: best option for younger adults
125
AML
- typical features
- more specific features
- Blood film features
BM failure- effects of pancytopenia
Splenomegaly, hepatomegaly
Gum infiltration if monoblasts/ monocytic
Skin infiltration/ CNS involvement + hypoK
Blood film: circulating blasts (\>20%) with granules**. auer rods.**
if unclear- immunophenotyping
126
AML
- age of incidence
- mutations seen
- pathognomonic features
bimodal incidence: peak in under 2s and in 65-70yos
many mutations assoc with AML
t(5;8), inv(16), t(8;21), trisomy 8, trisomy 21
\>20% myeloblasts on BM + **Auer Rods**
127
treatment of AML
Supportive care:
blood products, abx, FFP/Cryoprecipitate if DIC, allopurinol, fluid and electrolytes to prevent tumour lysis syndrome
Chemotherapy
Consider Allo BMT in young / autologous HSCs
Specific for acute promyelocytic leukaemia: ATRA
128
Ix in CML?
PCR for **BCR-ABL** (philadelphia chr) fusion gene
Ph Chr +ve in 80%
t(9;22)
high WCC, FBC: low Pl, Hb
Blood film: neutrophils, myelocytes, basophilia
Can monitor disease and treatment response with FBC, BCR-ABL:ABL ratio
129
Treatment of CML
**Imatinib\***
a BCR-ABL tyrosine kinase inhibitor
or
if resistant -2nd line: Dasatinib/ Nilotinib
young patients- possible allogeneic SCT
130
how to monitor disease and response to therapy in CML
FBC and WCC count
cytogenetics and detection of Ph chr - reduction in % of Ph Chr expressed
RT-PCR of BCR-ABL fusion transcript. can calculate BCR-ABL: ABL ratio
successful therapy means this will drop
e.g. complete response: 0% Ph +ve
partial response 1-35% Ph +ve
BCR-ABL transcripts reduce from 100% to the best - 0.001%
131
chronic phase vs accelerated phase vs blast phase of CML?
no of blasts in BM/blood
chronic (80% of pts): \<5% blasts
indolent
Accelerated: 10%-19% blasts
increasing manifestations e.g. splenomegaly
Blast crisis: \>20% blasts
median survival 3-6 months
resembles acute leukaemia
132
what translocation is assoc w CML?
t (9;22)
Philadelphia chr
- \> formation of BCR-ABL fusion gene
- \> constitutive tyrosine kinase activity
133
Blood film- tear drop poikilocytes (dacrocytes) and leukoerythroblasts
Dry tap on BM biopsy
extramedullary haemopoiesis - massive splenomegaly (budd chiari syndrome may present), hepatomegaly
pancytopenia: anaemia, thrombocytopenia, neutropenia
hypermetabolic state: weight loss, fatigue, night sweats, hyperuricaemia
myelofibrosis
134
t(9;22)
produces philadelphia chrosome (BCR-ABL gene)
seen in CML
expresses a fusion oncogene with tyrosine kinase activity
can be detected using FISH
135
features of CML?
Systemic: FLAWS
massive HSM -\> abdo discomfort
Bruising/ bleeding
Gout
Hyperviscosity
136
treatment of CLL
many patients undergo watchful waiting if asymptomatic with slowly progressive disease
1st line: alemtuzumab anti-CD52 (depletes lymphocytes)
Ibrutinib - Brutons Tyrosine kinase inhibitor
supportive: abx, vaccination, e.g. aciclovir, PCP prophylaxis, IVIG, pneumovax
young patients: allogeneic SCT
Autoimmune phenomena: 1st line steroids. 2nd line Rituximab
Radiotx - debulking LNs/ splenomegaly
Chemotx: fludarabine, cyclophosphamide, Rituximab
137
what may undergo richter transformation to DLBCL?
CLL
hairy cell leukaemia
138
CLL prophylaxis and treatment of infections
Aciclovir
PCP prophylaxis for those receiving fludarabine or alemtuzumab
IVIG for those w hypogammaglobulinaemia and recurrent bacterial infections
Immunisation against pneumococcus and seasonal flu
139
CLL autoimmune phenomena e.g. AIHA
mx?
1st line steroids
2nd line rituximab
140
Features of CLL?
often asymptomatic incidental finding
symmetrical painless Lymphadenopathy
HSM
Anaemia
B symptoms: FLAWS
141
complications of CLL?
AIHA, ITP
Infection: bacterial, zoster
Marrow failure/ infiltration
142
Smear cells seen in?
CLL
(most often assoc w abnormally fragile lymphocytes)
143
ix of CLL?
high WCC, lymphocytes
Smear cells
low serum Ig
+ve DAT: if AIHA
Rai or Binet staging
Diagnosis via immunophenotyping to distinguish from NHL
144
Hodgkins Lymphoma
- how does it present
- associated with which virus
- affects which age groups
presents as **asymmetrical painless lymphadenopathy.**
most often single node and spreads contiguously to adjacent LNs
+/- obstructive/mass effect symptoms -\> SVC/ bronchial obstruction
**B symptoms** may be present: fever\>38, night sweats, weight loss (\>10% over 6mo)
pain in affected nodes after alcohol
assoc w **EBV**
bimodal age incidence - **20-30** and **\>60**
**itch, Pel Ebstein fever, hepato/splenomegaly**
145
Reed sternberg cell
binucleate/ owl eyed cell on a background of lymphocytes and reactive cells
LN/ BM biopsy - cells stain with CD15 and CD30
Hodgkins Lymphoma
146
Staging of Hodgkins Lymphoma
I; one group of nodes
· II; \>1 group of nodes same side of the diaphragm
· III; nodes above and below the diaphragm
· IV; extra nodal spread (other organs)
· Suffix A if none of below, B if any of below
o Fever, night sweats
o Unexplained Weight loss \>10% in 6 months
\*\*RMB that spleen is considered a LN
147
Pel Ebstein fever assoc w?
fevers which cyclically increase then decrease over an average period of one or two weeks.
Hodgkins lymphoma
148
Ix of Hodgkins Lymphoma
FBC, film, ESR, LFT, LDH, Ca
- high ESR or low Hb = worse prognosis
LN excision biopsy or FNA
- **Reed sternberg cells (Owls eyes nuclei)**
Staging: CT/MRI Chest, Abdo, pelvis
BM biopsy if B symptoms of stage 3/4 disease
149
treatment of Hodgkins Lymphoma
Chemotherapy
Radiotherapy
Chemotherapy:
ABVD: adriamycin, bleomycin, vinblastine, dacarbazine
2-4 cycles in stage 1/2, 6-8 in stage 3
given at 4 wkly intervals
prognosis excellant esp in the young. preserves fertility but can cause long term pulmonary fibrosis, cardiomyopathy
Radiotherapy:
HL is highly responsive to radiotx
usually given at the end of chemo to small area of diseased nodes
risk of collateral damage: BrCa, Leukaemia/ MDS, lung/skin Ca
150
what are the chemotherapy drugs used in hodgkins lymphoma tx?
ABVD
Adriamycin, Bleomycin, Vinblastine, Dacarbazine/DTIC
cycles given at 4 wkly intervals
SE: Adriamycin- cardiomyopathy
Bleomycin- Pulm fibrosis
151
Tx of Hogdkins Lymphoma in relapse patients
Autologous SCT
+ Intensive chemo
152
153
Of the common B cell non-hodgkin lymphomas,
which are high grade?
which are low grade?
High Grade:
V aggressive: Burkitt's
Aggressive: Diffuse Large B cell, Mantle Cell
Low Grade:
Indolent-
Follicular, small lymphocytic/ CLL, marginal zone lymphoma, mantle zone lymphoma
154
affects middle aged/ elderly
\*Large T cell lymphocytes
Aggressive
Often with associated reactive cell population esp eosinophils
Lymphadenopathy and extranodal sites
Peripheral T Cell lymphoma
155
what lymphoma is associated with longstanding coeliac disease?
EATL
Enteropathy Associated T cell lymphoma
156
what lymphoma is associated with mycosis fungoides?
Cutaneous T cell lymphoma
157
Affects mainly children/ young adults
Histology shows large 'epitheliod' lymphocytes
t(2;5) and Alk-1 protein expression
Aggressive.
Anaplastic large cell lymphoma
158
What immunodeficiency is associated with burkitts lymphoma?
HIV / post transplant patients
159
MALT (mucosal associated lymphoid tissue) lymphoma / Marginal zone NHL
- what sites are normally affected?
- treatment?
mainly at extranodal sites. e.g. gut, lung, spleen, thyroid, parotid
arise in response to chronic antigen stimulation
treatment involves removing the antigenic stimulation e.g. H pylori eradication
160
what is the H pylori triple therapy for eradication?
omeprazole, clarithromycin and amoxicillin
161
what causes constant antigenic stimulation, predisposing the patient to small bowel T cell lymphoma?
Coeliac disease
-\> enteropathy associated T-cell Non-Hodgkins Lymphoma (EATL)
162
a lymphoma caused by HTLV-1 infection
HTLV-1 infects T cells
common in the Carribean and Japanese population
what lymphoma is associated?
Adult T cell leukaemia/ lymphoma
\*nuclei of ATL cells have characteristic cloverleaf appearance
163
what virus is associated with Adult T cell leukaemia/ lymphoma?
HTLV-1
164
Known risk factors of lymphoma:
## Footnote
constant antigenic stimulation (will increase risk of DNA replication error)
infection (direct viral infection of lymphocytes e.g. EBV)
loss of T cell function (e.g. HIV)
165
Gastric MALToma
what causes the chronic antigenic stimulation that may lead to gastric MALToma
Helicobacter pylori
-\> marginal zone non-hodgkins lymphoma of the stomach
166
Lymphoma
- what is it?
- where may it be found?
Lymphomas are neoplastic tumours of lymphoid cells.
usually found in lymph nodes, bone marrow and or blood (via the lymphatic system)
and in lymphoid organs such as the spleen, MALT
167
why are lymphocytes particularly at risk of neoplasm/ malignancy?
rapid cell proliferation in immune response risks DNA replication error
dependent on apoptosis (in the germinal centre) -\> apoptosis may get switched off in the germinal centre, there may be acquire DNA mutations in the pro apoptotic genes
DNA molecules are cut and rejoined and undergo deliberate point mutation to generate immunoglobulin and T cell receptor diversity -\> potential for recombination errors and new point mutations
168
what causes constant antigenic stimulation that may result in marginal zone lymphoma of the thyroid gland?
Hashimoto's Disease
169
What causes chronic antigenic stimulation that may predispose to developing parotid lymphoma?
Sjogren's syndrome
-\> marginal zone non-hodgkins lymphoma of the parotids
170
Spread of neoplasia in Hodgkins vs Non Hodgkins Lymphoma?
Hodgkins: spreads contiguously to adjacent LNs
Non Hodgkins: spreads discontinuously
171
Treatment for DLBCL
6-8 cycles of Rituximab-CHOP
aim of therapy is curative
if relapse-\> 2nd line tx: autologous SCT
-\> same regimen for other high grade non hodgkin lymphomas
172
what drugs does R-CHOP consist of?
Rituximab (anti CD20)
Cyclophosphamide
Adriamycin
Oncovin aka Vincristine
Prednisolone
173
features of multiple myeloma
CRAB
hypercalcaemia - stones, bones, groans, moans
renal impairment
anaemia
bone pain, osteolytic lesions, fractures, osteoporosis
174
Ix of Multiple myeloma
serum Ca, high ESR, high Urea/Cr
\*NORMAL ALP
MRI whole body
blood film shows Rouleaux formation
Urine electrophoresis: **bence-jones protein**
serum protein electrophoresis: dense narrow band
BM aspirate: \>10% plasma cells
Xray: Punched out lytic lesions, Pepper pot skull, vertebral collapse, fractures
175
Diagnosis of Multiple Myeloma?
1 major and 1 minor criteria or 3 minor criteria + signs or symptoms
**Major criteria**
Plasmacytoma (as demonstrated on evaluation of biopsy specimen)
30% plasma cells in a bone marrow sample
Elevated levels of M protein in the blood or urine
**Minor criteria**
10% to 30% plasma cells in a bone marrow sample.
Minor elevations in the level of M protein in the blood or urine.
Osteolytic lesions (as demonstrated on imaging studies).
Low levels of antibodies (not produced by the cancer cells) in the blood.
176
what is the first investigation you want to do when you suspect Multiple myeloma?
serum protein electrophoresis
- paraprotein detected
177
myeloma bone disease: possible complications
80-90% have lytic lesions
pathological fractures
spinal cord compression leading to paralysis
hypercalcaemia
bone pain -\> affecting QOL, independence, mobility
too many osteoclasts (from increased IL6) and not enough active osteoblasts
178
what investigations for myeloma bone disease
X ray - for lytic lesions
MRI- High sensitivity for marrow infiltration, response monitoring possible, expensive & limited availability
CT – full body CT is the standard used in Imperial to diagnose as it detects very small lesions (high sensitivity). Good for radiotherapy planning but higher radiation dose
PET - detects active disease
179
why does multiple myeloma cause renal failure?
free light chains cause injury to kidneys - active inflammatory mediators in the proximal tubule epithelium
-\> leads to amyloidosis (AL chains)
cast nephropathy
180
treatment of multiple myeloma
supportive for CRAB symptoms including bisphosphonates
Auto-SCT - curative, best for younger patients
steroids
Classical cytostatic drugs (relatively low dose) eg. melphalan
Proteasome inhibitors – prevent misfolded proteins from being degraded, which accumulates in myeloma cells (esp effective as myeloma produces a lot of proteins)
e.g. bortezomib
IMIDs – thalidomide, lenalidomide, pomalidomide (also used in MDS). Reduces cell turnover by affecting transcription factor relevant for plasma cells
181
mx of AKI due to Myeloma?
rehydration +/- dialysis
182
Mx of hypeviscosity due to myeloma?
Plasmapheresis (remove light chains)
183
Poor prognostic indicators of multiple myeloma?
high B2-microglobulin
low albumin
184
mx of cord compression secondary to myeloma?
Radiotx
+ dexamethasone
185
Mx of high calcium in myeloma?
hydration, frusemide, bisphosphonates
186
mx of infections secondary to multiple myeloma?
broad spec abx +/- IVIg if recurrent
187
Diagnosis of Multiple Myeloma?
Clonal BM plasma cells ≥ 10%
presence of serum and or urinary monoclonal protein
end organ damage: CRAB (1 or more)
Ca high (\>2.6 mM)
Renal insufficiency
Anaemia (\<10g/dL)
Bone lesions
188
what amyloid is assoc w Multiple Myeloma?
AL Amyloid
189
Echo findings of AL amyloidosis?
Sparkling appearance on echo
190
Diagnosis of Amyloidosis?
Biopsy of affected tissue -\>
Apple green birefringence w Congo Red stain under polarized light
191
indications for splenectomy?
trauma
rupture e.g. EBV
AIHA
ITP
Hereditary spherocytosis
hypersplenism
192
complications of splenectomy?
redistributive thrombocytosis -\> early VTE
Gastric dilatation (ileus)
left lower lobe collapse: v common
increased susceptibility to infections:
encapsulated bacteria meningococcus, pneumo, Hib
193
Blood film after splenectomy?
Howell-Jolly bodies
Pappenheimer bodies
Target cells
194
Mx of Splenectomy/ hyposplenism?
Immunisation: pneumovax, HiB, Men C, yrly flu
Daily Abx: pen V or erythromycin
Warning: Alert card and/or bracelet
195
Causes of hyposplenism?
post splenectomy
SCD
coeliac
IBD
196
Haematological causes of Splenomegaly?
Haemolysis: HS
Myeloproliferative disease: CML, PV, MF
Lymphoproliferative disease: lymphoma, leukaemia
197
infective causes of splenomegaly?
malaria, leishmaniasis, hydatid disease
EBV, CMV
TB, infectious endocarditis
198
Connective tissue causes of splenomegaly?
rheumatoid arthritis
SLE
Sjogrens
199
Causes of splenomegaly?
Haematological: haemolysis, myeloproliferative, lymphoproliferative
Infection: EBV, malaria, leishmaniasis
Portal HTN: cirrhosis, Budd-Chiari
Connective tissue: RA, SLE, sjogrens
Other: Sarcoid, Amyloid,
200
Causes of massive splenomegaly (\>20cm)?
CML
Myelofibrosis
Malaria
leishmaniasis
Gauchers (AR, glucocerebrosidase deficiency)
201
Features of the spleen?
LUQ
lies anterior to ribs 9-11
Dull to percussion
enlarges to RIF
moves inferiorly on resp
cant get above it
medial notch
202
Function of the spleen?
phagocytosis of the old RBCs, WBCs, opsonised bugs
antibody production
haematopoiesis
sequestration of formed blood elements
203
Normal ESR?
20 mm/hr
204
what causes raised ESR?
plasma factors:
- increased fibrinogen: inflammation
- increased globulins: e.g. myeloma
red cell factors:
anaemia
205
differentials for ESR \>100?
Multiple myeloma
SLE
GCA
AAA
Ca prostate
206
differential for basophilia?
parasitic infection
IgE-mediated hypersensitivity: urticarial, asthma
CML
207
Differential for eosinophilia?
parasitic infection
drug reactions
allergies: asthma, atopy, churg-strauss
Skin disease, psoriasis, eczema, pemphigus
208
differential of high monocyte count?
Chronic infection: TB, Brucella, Typhoid
AML
209
Differential of low lymphoctes?
Drugs: steroids, chemo
HIV
210
differential for lymphocytosis?
Leukaemia, lymphoma esp CLL
Viral infections eg. CMV, EBV
Chronic infections TB, Brucella, hepatitis, toxo
211
Differential for neutrophilia?
bacterial infection: left shift, toxic granulation, vacuolation
stress: trauma, burns, surgery, haemorrhage
steroids
inflammation: MI, polyarteritis nodosa
Myeloproliferative disorders e.g. CML
212
differential of neutropenia?
viral infection
Severe sepsis
Drugs: chemo, cytotoxics, carbimazole, sulphonamides
Feltys
213
tartrate resistant acid phosphatase +ve
Hairy cell leukaemia
214
Sudan Black B, MPO +ve
AML
215
Blood film showing target cells?
hyposplenism
thalassaemia
liver disease
216
Heinz bodies?
G6Pd deficiency
217
Acanthocytes?
LAB
Liver disease
Abetalipoproteinaemia
218
Basophilic stippling
Lead poisoning
thalassaemia
219
Burr cells?
Uraemia
220
Howell Jolly bodies?
hyposplenism
221
leukoerythoblastic film?
BM infiltration
222
Pappenheimer bodies?
hyposplenism
223
Pencil cells?
IDA
224
What is the most common inherited bleeding disorder?
## Footnote
Von Willebrand's disease
225
Types of Von Willebrand's disease?
type 1: partial reduction in vWF (80% of patients)
type 2\*: abnormal form of vWF
type 3\*\*: total lack of vWF (autosomal recessive)
226
Investigation of Von Willebrands disease?
prolonged bleeding time
APTT may be prolonged
factor VIII levels may be moderately reduced
defective platelet aggregation with ristocetin
227
Tx for post-thrombotic syndrome?
Compression stockings
228
painful, heavy calves
pruritus
swelling
varicose veins
venous ulceration
following previous DVT
Post-thrombotic syndrome
229
What is cryoprecipitate used for?
contains concentrated Factor VIII:C, von Willebrand factor, fibrinogen, Factor XIII and fibronectin
Clinically it is most commonly used to replace fibrinogen
e.g. DIC, liver failure
230
universal donor of FFP?
AB -ve blood
lacks anti-A or anti-B antibodies
231
What is Prothrombin complex concentrate used for?
used for the emergency reversal of anticoagulation in patients with either severe bleeding or a head injury with suspected intracerebral haemorrhage
232
Critical bleeding e.g. CNS
+ Pl \< 100
Mx
immediate platelet transfusion
normally if other bleeding e.g haematemesis, melaena -\> only transfuse if Pl \< 30
233
An 88-year-old male has been formally diagnosed with anorectal cancer. Imaging confirms the cancer is localised to a region inferior to the pectinate line.
If untreated which group of lymph nodes will this cancer likely metastasize to?
Below the pectinate line cancer spreads to the superficial inguinal lymph nodes.
234
stomach cancer drains to which LN first?
Coeliac lymph nodes
235
Ca in the anal canal above pectinate line drains into which LNs?
Internal iliac lymph nodes
236
Ca of glans penis drains into which LNs?
Deep inguinal lymph nodes
237
Ca of testes/ ovaries/ kidney/ adrenal glands drain into which LNs?
Para-aortic lymph nodes
238
Ca of Lateral breast
Upper limb drain into which LNs?
Axillary lymph nodes
239
Ca in
## Footnote
Duodenum
Jejunum drains into which LNs?
Superior mesenteric lymph nodes
240
ca in Descending colon
Sigmoid colon
Upper part of rectum will drain into which LNs?
Inferior mesenteric lymph nodes
241
diagnosis of Hodgkins lymphoma?
This is made by excision of a complete lymph node that is then submitted for detailed histological evaluation.
242
poor prognostic markers of Hodgkins lymphoma?
Lymphocyte depleted Hodgkins lymphoma, advancing age, male sex and stage IV disease
243
Normal blood transfusion threshold?
Transfusion threshold in pts wihth ACS?
Normal: 70g/L
ACS: 80g/L
244
Electrolyte abnormalities in Tumour Lysis syndrome?
High K and PO4
and low Ca
+ high uric acid
245
Which one of the types of Hodgkin's lymphoma carries the best prognosis?
Lymphocyte predominant
246
What is the most common type of Hodgkins Lymphoma?
Nodular sclerosing
247
What drug class is known to precipitate renal failure in patients with multiple myeloma (MM)?
NSAIDs
248
t(11;14)
deregulation of the cyclin D1 (BCL-1) gene
Mantle cell lymphoma
249
t(15;17)
fusion of PML and RAR-alpha genes
seen in acute promyelocytic leukaemia (M3)
250
t(8;14)
## Footnote
MYC oncogene is translocated to an immunoglobulin gene
Burkitt's lymphoma
251
most common type of Hodgkin's lymphoma?
nodular sclerosing
252
platelet transfusions should not be performed in which conditions?
Chronic bone marrow failure
Autoimmune thrombocytopenia
Heparin-induced thrombocytopenia, or
Thrombotic thrombocytopenic purpura.
253
reversal agent for dabigatran?
Idarucizumab
- humanised monoclonal antibody that directly inhibits dabigatran.
254
How to investigate patients w unprovoked clots?
**Investigate for underlying malignancy:**
- physical exam guided by full hx
- CXR
- Blood tests and urinalysis
Consider CT abdo-pelvis in all \>40 w unprovoked DVT/ PE
**Thrombophilia screening:**
consider test for antiphospholipid abs
consider testing for hereditary thrombophilia in pts who have first degree relative who have had DVT/PE
