pass med haematology Flashcards
(471 cards)
1
Q
heparin factors affected
A
prevents activation of 2, 9, 10, 11
2
Q
warfarin factors affected
A
affects synthesis of 2,7, 9, 10
3
Q
DIC factors affected
A
factors 1, 2, 5, 8, 11
4
Q
liver disease factors affected
A
factors 1, 2,5, 7, 9, 10, 11
5
Q
increased APTT, normal PT, normal bleeding time
A
haemophilia
6
Q
increased APTT, normal PT, increased bleeding time
A
von willebrand’s disease
7
Q
increased APTT, increased PT, normal bleeding time
A
vit K deficiecny
8
Q
acute intermittent porphyria genetics
A
aut dom
a defect in porphobilinogen deaminase, an enzyme involved in the biosynthesis of haem. The results in the toxic accumulation of delta aminolaevulinic acid and porphobilinogen
9
Q
clinical fx acute intermittent porphyria
A
abdominal: abdominal pain, vomiting
neurological: motor neuropathy
psychiatric: e.g. depression
hypertension and tachycardia common
10
Q
gender and age AIP
A
female
20-40 yr olds
11
Q
diagnosis AIP
A
classically urine turns deep red on standing
raised urinary porphobilinogen (elevated between attacks and to a greater extent during acute attacks)
assay of red cells for porphobilinogen deaminase
raised serum levels of delta aminolaevulinic acid and porphobilinogen
12
Q
mx AIP
A
avoid triggers
in acute attacks - IV haematin/haem arginate
IV glucose as alternative
13
Q
acute myeloid leukaemia how common
A
most common form of leukaemia in adults
14
Q
primary or secondary AML
A
both, can be secondary transformation from a myeloproliferative disorder
15
Q
clinical fx of AML
A
anaemia: pallor, lethargy, weakness
neutropenia: whilst white cell counts may be very high, functioning neutrophil levels may be low leading to frequent infections etc
thrombocytopenia: bleeding
splenomegaly
bone pain
16
Q
poor prognostic fx AML
A
> 60 years
20% blasts after first course of chemo
cytogenetics: deletions of chromosome 5 or 7
17
Q
25 yr old with DIC/thrombocytopenia
A
type of AML called acute promyelocytic leukaemia
Auer rods (seen with myeloperoxidase stain)
fusion of PML and RAR alpha genes
good prognosis
18
Q
classification of AML
A
French-American-British (FAB)
MO - undifferentiated
M1 - without maturation
M2 - with granulocytic maturation
M3 - acute promyelocytic
M4 - granulocytic and monocytic maturation
M5 - monocytic
M6 - erythroleukaemia
M7 - megakaryoblastic
19
Q
acute promyelocytic leukaemia what
A
M3 subtype of AML
20
Q
APML genes
A
translocation which causes fusion of PML and RAR alpha genes
21
Q
antiphospholipid syndrome definition
A
an acquired disorder characterised by a predisposition to both venous and arterial thromboses, recurrent fetal loss and thrombocytopenia. It may occur as a primary disorder or secondary to other conditions, most commonly SLE
22
Q
pregnancy complications anti-phospholipid syndrome
A
recurrent miscarriage
IUGR
pre-eclampsia
placental abruption
pre-term delivery
venous thromboembolism
23
Q
mx of antiphospholid syndrome pregnancu
A
low dose aspirin - when preg confirmed on urine then LMWH when fetal heart is seen on USS..discontinued at 34 weeks gestation
24
Q
aplastic anaemia characteristics
A
pancytopenia and hypoplastic bone marrow
25
peak incidence of acquired aplastic anaemia
30 yrs old
26
clinical fx aplastic anaemia
tures
normochromic, normocytic anaemia
leukopenia, with lymphocytes relatively spared
thrombocytopenia
may be the presenting feature acute lymphoblastic or myeloid leukaemia
a minority of patients later develop paroxysmal nocturnal haemoglobinuria or myelodysplasia
27
causes aplastic anaemia
idiopathic
congenital: Fanconi anaemia, dyskeratosis congenita
drugs: cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold
toxins: benzene
infections: parvovirus, hepatitis
radiation
28
categories autoimmune haemolytic anaemia
warm and cold types depending on what temp the antibodies best cause haemolysis
29
primary or secondary autoimmune haemolytic anaemia
most commonly idiopathic
secondary to lymphoproliferative disorder, infection or drugs
30
investigations autoimmune haemolytic anaemia
general features of haemolytic anaemia
anaemia
reticulocytosis
low haptoglobin
raised lactate dehydrogenase (LDH) and indirect bilirubin
blood film: spherocytes and reticulocytes
specific features of autoimmune haemolytic anaemia
positive direct antiglobulin test (Coombs' test).
31
warm AIHA
most common type
the antibody (usually IgG) causes haemolysis best at body temperature and haemolysis tends to occur in extravascular sites, for example the spleen
32
warm AIHA causes
idiopathic
autoimmune disease: e.g. systemic lupus erythematosus*
neoplasia
lymphoma
chronic lymphocytic leukaemia
drugs: e.g. methyldopa
33
warm autoimmune haemolytic anaemia mx
treatment of any underlying disorder
steroids (+/- rituximab)
34
cold AIHA
usually IgM and causes haemolysis best at 4 deg C. Haemolysis is mediated by complement and is more commonly intravascular. Features may include symptoms of Raynaud's and acrocynaosis. Patients respond less well to steroids
35
causes of cold AIHA
neoplasia: e.g. lymphoma
infections: e.g. mycoplasma, EBV
36
beta thalassaemia major gene
chromosome 11
absence of beta globulin chains
37
clinical fx beta thalassaemia major
presents in the first year of life with failure to thrive and hepatosplenomegaly
microcytic anaemia - fx of anaemia
38
beta thalassaemia major haemoglobin
HbA2 & HbF raised
HbA absent
39
beta thalassaemia major mx
repeated tranfusion
alongside iron chelation therapy due to possible iron overload resulting in organ failure
40
beta thalassaemia trait define
a reduced production rate of either alpha or beta chains
41
beta thalassaemia trait genetics
aut recessive
42
type of anaemia beta thalassaemia trait
mild hypochromic, microcytic anaemia - microcytosis is characteristically disproportionate to the anaemia
HbA2 raised (> 3.5%)
43
beta thalassaemia trait clinical fx
trick q - usually asx
44
possible causes target cells
Sickle-cell/thalassaemia
Iron-deficiency anaemia
Hyposplenism
Liver disease
45
tear drop poikilocytes possible causes
myelofibrosis
46
spherocytes possible causes
Hereditary spherocytosis
Autoimmune hemolytic anaemia
47
basophilic stippling possible causes
Lead poisoning
Thalassaemia
Sideroblastic anaemia
Myelodysplasia
48
jowell jolly bodies possible causes
hyposplenism
49
heinz bodies possible causes
G6PD deficiency
Alpha-thalassaemia
50
schistocytes possible causes
Intravascular haemolysis
Mechanical heart valve
Disseminated intravascular coagulation
51
pencil poikilocytes possible causes
iron def anaemia
52
burr cells possible causes
uraemia
pyruvate kinase deficiency
53
acanthocytes possible causes
Abetalipoproteinemia
54
hypersegmented neutrophils possible causes
megaloblastic anaemia
55
causes of hyposplenism
post splenectomy
coeliac disease
56
blood films hyposplenism
target cells
Howell-Jolly bodies
Pappenheimer bodies
siderotic granules
acanthocytes
57
iron def anaemia blood films
target cells
'pencil' poikilocytes
58
iron def anaemia + b12/folate def blood film
'dimorphic' film occurs with mixed microcytic and macrocytic cells
59
blood product transfusion complications
- immune
- infective
-lung
- heart
- other
immunological: acute haemolytic, non-haemolytic febrile, allergic/anaphylaxis
infective
transfusion-related acute lung injury (TRALI)
transfusion-associated circulatory overload (TACO)
other: hyperkalaemia, iron overload, clotting
60
non haemolytic febrile reaction patho
Thought to be caused by antibodies reacting with white cell fragments in the blood product and cytokines that have leaked from the blood cell during storage
61
non haemolytic febrile reaction clinical fx
Fever, chills
62
non haemolytic febrile reaction mx
Slow or stop the transfusion
Paracetamol
Monitor
63
minor allergic reaction patho
caused by foreign plasma proteins
64
clinical fx mild allergic reaction
pruritus, urticaria
65
mild allergic reaction mx
Temporarily stop the transfusion
Antihistamine
Monitor
66
anaphylaxis patho
patients with IgA deficiency who have anti-IgA antibodies
67
anaphylaxis clinical fx
Hypotension, dyspnoea, wheezing, angioedema
68
anaphylaxis mx
Stop the transfusion
IM adrenaline
ABC support
oxygen
fluids
69
acute haemolytic reaction patho
results from a mismatch of blood group (ABO) which causes massive intravascular haemolysis. This is usually the result of red blood cell destruction by IgM-type antibodies.
70
clinical fx acute haemolytic reaction
fever
abdo pain
hypotension
71
mx of acute haemolytic reaction
Stop transfusion
Confirm diagnosis
check the identity of patient/name on blood product
send blood for direct Coombs test, repeat typing and cross-matching
Supportive care
fluid resuscitation with saline
72
TACO patho
Excessive rate of transfusion, pre-existing heart failure
73
TACO clinical fx
Pulmonary oedema, hypertension
74
mx TACO
Slow or stop transfusion
Consider intravenous loop diuretic (e.g. furosemide) and oxygen
75
TRALI patho
Non-cardiogenic pulmonary oedema thought to be secondary to increased vascular permeability caused by host neutrophils that become activated by substances in donated blood
76
TRALI clinical fx
Hypoxia, pulmonary infiltrates on chest x-ray, fever, hypotension within 6 hours of transfusion
77
TRALI mx
Stop the transfusion
Oxygen and supportive care
78
packed red cells key points
Used for transfusion in chronic anaemia and cases where infusion of large volumes of fluid may result in cardiovascular compromise. Product obtained by centrifugation of whole blood.
79
platelet rich plasma key points
Usually administered to patients who are thrombocytopaenic and are bleeding or require surgery. It is obtained by low speed centrifugation.
80
platelet concentrate key points
Prepared by high speed centrifugation and administered to patients with thrombocytopaenia.
81
fresh frozen plasma key points
Prepared from single units of blood.
Contains clotting factors, albumin and immunoglobulin.
Unit is usually 200 to 250ml.
Usually used in correcting clotting deficiencies in patients with hepatic synthetic failure who are due to undergo surgery.
Usual dose is 12-15ml/Kg-1.
It should not be used as first line therapy for hypovolaemia.
82
cyroprecipitate key points
Formed from supernatant of FFP.
Rich source of Factor VIII and fibrinogen.
Allows large concentration of factor VIII to be administered in small volume.
83
SAG-Mannitol blood key points
Removal of all plasma from a blood unit and substitution with:
Sodium chloride
Adenine
Anhydrous glucose
Mannitol
Up to 4 units of SAG M Blood may be administered. Thereafter whole blood is preferred. After 8 units, clotting factors and platelets should be considered.
84
which blood products must be cross matched
Packed red cells
Fresh frozen plasma
Cryoprecipitate
Whole blood
85
which blood products can be ABO incompatible in adults
platelets
86
cell saver devices definition
These collect patients own blood lost during surgery and then re-infuse it. There are two main types:
Those which wash the blood cells prior to re-infusion. These are more expensive to purchase and more complicated to operate. However, they reduce the risk of re-infusing contaminated blood back into the patient.
Those which do not wash the blood prior to re-infusion.
87
adv cell saver devices
avoid the use of infusion of blood from donors into patients and this may reduce risk of blood borne infection. It may be acceptable to Jehovah's witnesses
88
contraindicated cell saver devices
in malignant disease for risk of facilitating disease dissemination.
89
immediate or urgent surgery in pts taking warfarin
4 options
1. Stop warfarin
2. Vitamin K (reversal within 4-24 hours)
IV takes 4-6h to work (at least 5mg)
Oral can take 24 hours to be clinically effective
3. Fresh frozen plasma
Used less commonly now as 1st line warfarin reversal
30ml/kg-1
Need to give at least 1L fluid in 70kg person (therefore not appropriate in fluid overload)
Need blood group
Only use if human prothrombin complex is not available
4. Human Prothrombin Complex (reversal within 1 hour)
Bereplex 50 u/kg
Rapid action but factor 6 short half life, therefore give with vitamin K
90
CMV negative products requirement
Cytomegalovirus (CMV) is transmitted in leucocytes. As most blood products (except granulocyte transfusions) are now leucocyte depleted CMV negative products are rarely required.
91
irradiated blood products indication
Irradiated blood products are depleted of T-lymphocytes and used to avoid transfusion-associated graft versus host disease (TA-GVHD) caused by engraftment of viable donor T lymphocytes.
92
granulocyte transfusions
CMV negative and irradicated blood products required
93
intrauterine transfusions
CMV negative and irradicated
94
neonates up to 28 days post expected date of delivery
CMV negative and irradicated
95
Pregnancy: Elective transfusions during pregnancy (not during labour or delivery)
CMV negative
96
bone marrow/stem cell transplants
irradiated blood products
97
immunocompromised
irradiated blood products
98
patients with/prev hodgkin lymphoma
irradiated blood products
99
FFP indications
'clinically significant' but without 'major haemorrhage' in patients with a prothrombin time (PT) ratio or activated partial thromboplastin time (APTT) ratio > 1.5
can be used prophylactically in patients undergoing invasive surgery where there is a risk of significant bleeding
100
universal donor of FFP
AB - as lacks any anti-A or anti-B antibodies
101
cryoprecipitate consists
concentrated Factor VIII:C, von Willebrand factor, fibrinogen, Factor XIII and fibronectin, produced by further processing of Fresh Frozen Plasma (FFP).
102
cryoprecipitate indication
most suited for patients for 'clinically significant' but without 'major haemorrhage' who have a fibrinogen concentration < 1.5 g/L, eg: DIC, liver failure, hypofibrinogenaemia secondary to massive transfusion, emergency for haemophiliacs or VWB disease
an be used prophylactically in patients undergoing invasive surgery where there is a risk of significant bleeding where the fibrinogen concentration < 1.0 g/L
103
prothrombin complex concentrate indication
emergency reversal of anticoagulation in patients with either severe bleeding or a head injury with suspected intracerebral haemorrhage
can be used prophylactically in patients undergoing emergency surgery depending on the particular circumstance
104
transfusion threshold for red cells
- patient with
- patient without ACS
without - 70g/L
with - 80g/L
105
target after transfusion
- patient without ACS
- patient with ACS
without- 70-90g/L
with - 80-100g/L
106
red cells stored
at 4 degrees prior to infusion
107
non urgent scenario how long unit of red cell transferred
90-120 mins
108
burkitt's lymphoma type of cancer
high grade B cell neoplasm
109
burkitt's lymphoma 2 major forms
endemic (African) form: typically involves maxilla or mandible
sporadic form: abdominal (e.g. ileo-caecal) tumours are the most common form. More common in patients with HIV
110
gene burkitt's lymphoma
c-myc gene translocation, usually t(8:14)
111
infection associated with which type of burkitts lymphoma
EBV - african form
112
microscopic findings burkitt's
'starry sky' appearance: lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells
113
burkitt's mx
chemo
114
complication of tx of burkitt's and how prevented
tumour lysis syndrome
Rasburicase - increases renal excretion given before chemo
115
complications of tumour lysis syndrome
hyperkalaemia
hyperphosphataemia
hypocalcaemia
hyperuricaemia
acute renal failure
116
chronic lymphocytic leukaemia complications
anaemia
hypogammaglobulinaemia leading to recurrent infections
warm autoimmune haemolytic anaemia in 10-15% of patients
transformation to high-grade lymphoma (Richter's transformation)
117
richter's transformation
occurs when leukaemia cells enter the lymph node and change into a high-grade, fast-growing non-Hodgkin's lymphoma. Patients often become unwell very suddenly.
118
richter's transformation sx
lymph node swelling
fever without infection
weight loss
night sweats
nausea
abdominal pain
119
chronic lymphoctic leukaemia caused by
a monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%
120
CLL how common
most common form of leukaemia in adults
121
CLL clinical fx
often none: may be picked up by an incidental finding of lymphocytosis
constitutional: anorexia, weight loss
bleeding, infections
lymphadenopathy more marked than chronic myeloid leukaemia
122
CLL FBC
lymphocytosis
anaemia: may occur either due to bone marrow replacement or autoimmune hemolytic anaemia (AIHA)
thrombocytopenia: may occur either due to bone marrow replacement or immune thrombocytopenia (ITP)
123
CLL blood film
smudge cells (also known as smear cells)
124
immunophenotyping CLL
most cases can be identified using a panel of antibodies specific for CD5, CD19, CD20 and CD23
125
chronic myeloid leukaemia genetics
Philadelphia chromosome is present in more than 95% of patients with chronic myeloid leukaemia (CML). It is due to a translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34; q11). This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22. The resulting BCR-ABL gene codes for a fusion protein that has tyrosine kinase activity in excess of norma
126
CML clinical fx
at 60-70 yrs
anaemia: lethargy
weight loss and sweating are common
splenomegaly may be marked → abdo discomfort
an increase in granulocytes at different stages of maturation +/- thrombocytosis
decreased leukocyte alkaline phosphatase
may undergo blast transformation (AML in 80%, ALL in 20%)
127
mx options CML
imatinib is now considered first-line treatment
inhibitor of the tyrosine kinase associated with the BCR-ABL defect
very high response rate in chronic phase CML
hydroxyurea
interferon-alpha
allogenic bone marrow transplant
128
cryoglobulinaemia what
Immunoglobulins which undergo reversible precipitation at 4 deg C, dissolve when warmed to 37 deg C. One-third of cases are idiopathic
129
three types cryoglobulinaemia
type I (25%):
monoclonal - IgG or IgM
associations: multiple myeloma, Waldenstrom macroglobulinaemia
type II (25%)
mixed monoclonal and polyclonal: usually with rheumatoid factor
associations: hepatitis C, rheumatoid arthritis, Sjogren's, lymphoma
type III (50%)
polyclonal: usually with rheumatoid factor
associations: rheumatoid arthritis, Sjogren's
130
clinical fx cryoglobulinaemia
Raynaud's only seen in type I
cutaneous
vascular purpura
distal ulceration
ulceration
arthralgia
renal involvement
diffuse glomerulonephritis
131
cryoglobulinaemia investigations
low complement - esp C4
high ESR
132
cryoglobulinaemia mx
treatment of underlying condition e.g. hepatitis C
immunosuppression
plasmapheresis
133
what is cryoprecipitate
blood product made from plasmacy
134
cryoprecipitate indications
massive haemorrhage and uncontrolled bleeding due to haemophilia
135
composition of cryoprecipitate
factor VII
fibrinogen
von willebrand factor
factor XIII
136
DVT mx
- first line
- active cancer
(DOACs) as first-line treatment for most people with VTE, including as interim anticoagulants before a definite diagnosis is made
the use of DOACs in patients with active cancer, as opposed to low-molecular weight heparin as was the previous recommendation
137
DVT cancer screening
routine cancer screening is no longer recommended following a VTE diagnosis
138
suspected DVT what do
a two-level DVT Wells score should be performed
if >2 likely
if 1 or less unlikely
139
if DVT likely...
proximal leg vein USS within 4 hours
if +ve = diagnosis made
-ve = D dimer arranged, if this is -ve alternative diagnosis should be considered
if proximal leg USS cannot be carried out within 4 hours...a D dimer performed and intermit therapeutic anticoagulation (DOAC) started while waiting for USS (which should be performed within 24 hours)
if scan is -ve but D dimer +ve = stop intermit therapeutic anticoag and offer repeat proximal leg USS 6-8 days later
140
if DVT is unlikley
perform D dimer within 4 hours, if not intermit anticoag used in meantime
if -ve = alternative diagnosis considered
if +ve = proximal vein USS within 4 hours, if this USS can not be carried out within 4 hours - intermit anticoag...USS carried out within 24 hours
141
D dimer tests how work
a point-of-care (finger prick) or laboratory-based test
age-adjusted cut-offs should be used for patients > 50 years old
142
how long anticoag DVT
if provoked (obvious precipitating event) - only 3 months, 6 if active cancer
if unprovoked - 6 mths
143
how assess risk of bleeding
ORBIT score
144
DOAC indications
- prevention of stroke in non valvular AF with one of the following risk factors -
prior stroke or transient ischaemic attack
age 75 years or older
hypertension
diabetes mellitus
heart failure
- prevention of VTE following hip/knee surgery
- tx of DVT and PE
145
dabigatran
- MOA
- excretion
- reversal
direct thrombin inhibitor
majority renal
Idarucizumab
146
rivaroxaban
- MOA
- excretion
- reversal
direct factor Xa inhibitor
majority liver
Andexanet alfa
147
apixaban
- MOA
- excretion
- reversal
direct factor Xa inhibitor
majority faecal
andexanet alfa
148
edoxaban
- MOA
- excretion
- reversal
direct factor Xa inhibitor
majority faecal
no authorised reversal
149
normal clotting
he activation of the coagulation cascade yields thrombin that converts fibrinogen to fibrin; the stable fibrin clot being the final product of hemostasis. The fibrinolytic system breaks down fibrinogen and fibrin. Activation of the fibrinolytic system generates plasmin (in the presence of thrombin), which is responsible for the lysis of fibrin clots. The breakdown of fibrinogen and fibrin results in polypeptides (fibrin degradation products). In a state of homeostasis, the presence of plasmin is critical, as it is the central proteolytic enzyme of coagulation and is also necessary for fibrinolysis.
150
DIC pathophysiology
In DIC, the processes of coagulation and fibrinolysis are dysregulated, and the result is widespread clotting with resultant bleeding. Regardless of the triggering event of DIC, once initiated, the pathophysiology of DIC is similar in all conditions. One critical mediator of DIC is the release of a transmembrane glycoprotein (tissue factor =TF). TF is present on the surface of many cell types (including endothelial cells, macrophages, and monocytes) and is not normally in contact with the general circulation, but is exposed to the circulation after vascular damage.
Upon activation, TF binds with coagulation factors that then triggers the extrinsic pathway (via Factor VII) which subsequently triggers the intrinsic pathway (XII to XI to IX) of coagulation.
151
DIC septic conditions
TF is released in response to exposure to cytokines (particularly interleukin 1), tumour necrosis factor, and endotoxin.
152
DIC extensive trauma
TF is also abundant in tissues of the lungs, brain, and placenta.
153
causes of DIC
sepsis
trauma
obstetric complications e.g. aminiotic fluid embolism or hemolysis, elevated liver function tests, and low platelets (HELLP syndrome)
malignancy
154
DIC blood picture
↓ platelets
↓ fibrinogen
↑ PT & APTT
↑ fibrinogen degradation products
schistocytes due to microangiopathic haemolytic anaemia
155
heparin blood results
normal PT
prolonged APTT
normal bleeding time
normal platelet
156
aspirin blood results
normal PT
normal APTT
prolonged bleeding time
normal platelet
157
warfarin blood results
prolonged PT
normal APTT
normal bleeding time
normal platelet
158
most common inherited thrombophilis
factor V Leiden (activated protein C resistance)
159
factor V leiden patho
gain of function mutation in factor V leiden protein
missense mutation resulting in activated factor V becoming inactivated more slowly by activated protein C than normal
160
factor V leiden risk
heterozygote - 4/5 fold risk of venous thrombosis
homozygotes - 10 fold risk
161
different inherited thombophilias
factor V leiden
prothrombin gene mutation
protein C defiency
protein S deficency
antithrombin III deficiency
162
fanconi anaemia inheritance
aut recessive
163
clinical fx fanconi anaemia
aplastic anaemia
neurological fx
short stature
thumb/radius abnormalities
cafe au lait spots
164
fanconi anaemia increased risk
acute myeloid leukaemia
165
G6PD deficiency geographical risk
mediterranean and africa
166
G6PD deficiency inheritence
x linked recessive
167
G6PD deficiency crisis precipitating (causing haemolysis)
drugs (anti-malarials: primaquine
ciprofloxacin
sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas)
infections
broad (fava) beans
168
G6PD deficiency patho
G6PD is the first step in the pentose phosphate pathway, which converts glucose-6-phosphate→ 6-phosphogluconolactone
this reaction also results in nicotinamide adenine dinucleotide phosphate (NADP) → NADPH
NADPH is important for converting oxidizied glutathine back to it's reduced form
reduced glutathine protects red blood cells from oxidative damage by oxidants such as superoxide anion (O2-) and hydrogen peroxide
↓ G6PD → ↓ reduced NADPH → ↓ reduced glutathione → increased red cell susceptibility to oxidative stress
169
clinical fx G6PD deficiency
neonatal jaundice is often seen
intravascular haemolysis
gallstones are common
splenomegaly may be present
170
blood film G6PD def
heinz bodies
bite and blister cells
171
diagnosis G6PD defiency
G6PD enzyme assay
- checked 3 months after an acute episode of haemolysis
172
drugs thought to be safe G6PD deficiency
penicillins
cephalosporins
macrolides
tetracyclines
trimethoprim
173
comparison of G6PD def and hereditary spherocytosis
see table
174
causes of graft versus host disease
allogeneic bone marrow transplant
solid organ transplant
transfusion in immunocompromised
175
graft versus host disease patho
T cells in donor tissue mount an immune response towards host cells
176
GVHD versus Rejection
It is not to be confused with transplant rejection (in which recipient immune cells activate an immune response toward the donor tissue
177
graft v host disease prognosis
poor
178
diagnosis of GVHD criteria
Billingham:
The transplanted tissue contains immunologically functioning cells
The recipient and donor are immunologically different
The recipient is immunocompromised
179
risk factors graft v host
Poorly matched donor and recipient (particularly HLA)
Type of conditioning used prior to transplantation
Gender disparity between donor and recipient
Graft source (bone marrow or peripheral blood source associated with higher risk than umbilical cord blood)
180
acute GVHD
- onset
- affects what
- prognosis
onset within 100 days of transplantation
skin, liver, GI
if multi organ - worse prognosis
181
chronic GVHD
- onset
- what affect
can arise de novo or following acute disease
after 100 days following transplant
v varied - lung, eye, skin, GI, or other
182
clinical fx acute GVHD
Painful maculopapular rash (often neck, palms and soles), which may progress to erythroderma or a toxic epidermal necrolysis-like syndrome
Jaundice
Watery or bloody diarrhoea
Persistent nausea and vomiting
Can also present as a culture-negative fever
183
clinical fx chronic GVHD
Skin: Many manifestations including poikiloderma, scleroderma, vitiligo, lichen planus
Eye: Often keratoconjunctivitis sicca, also corneal ulcers, scleritis
GI: Dysphagia, odynophagia, oral ulceration, ileus. Oral lichenous changes are a characteristic early sign (2)
Lung: my present as obstructive or restrictive pattern lung disease
184
investigations GVHD
LFT - cholestatic jaundice or USS to rule out other causes
abdo USS - ribbon sign
lung function
biopsy of affected tissue
185
mx GVHD
IV steroids, 2nd line 0 anti TNF
(can be topical if just cutaneous)
186
granulocyte colony stimulating factors use
increase neutrophil counts in patients who are neutropenic secondary to chemotherapy or other factors
187
granulocyte colony stimulating factors examples
filgrastim
perfilgrastim
188
philadelphia chromosome
t(9;22)
present in > 95% of patients with CML
this results in part of the Abelson proto-oncogene being moved to the BCR gene on chromosome 22
the resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal
poor prognostic indicator in ALL
189
t(15;17)
seen in acute promyelocytic leukaemia (M3)
fusion of PML and RAR-alpha genes
190
t(8;14)
seen in Burkitt's lymphoma
MYC oncogene is translocated to an immunoglobulin gene
191
t(11;14)
Mantle cell lymphoma
deregulation of the cyclin D1 (BCL-1) gene
192
t(14;18)
follicular lymphoma
increased BCL-2 transcription
193
EBV risk
Hodgkin's and Burkitt's lymphoma, nasopharyngeal carcinoma
194
HTLV-1 risk
acute T cell leukaemia/lymphoma
195
HIV-1 risk
high grade B cell lymphoma
196
H.pylori risk
gastric Lymphoma MALT
197
malaria risk
burkitt's lymphoma
198
hereditary causes of hareditary haemolytic anaemia
membrane: hereditary spherocytosis/elliptocytosis
metabolism: G6PD deficiency
haemoglobinopathies: sickle cell, thalassaemia
199
acquired haemolytic anaemias immune causes
immune causes (Coombs-positive)
autoimmune: warm/cold antibody type
alloimmune: transfusion reaction, haemolytic disease newborn
drug: methyldopa, penicillin
200
acquired haemolytic anaemias non immune causes
(Coombs-negative)
microangiopathic haemolytic anaemia (MAHA): TTP/HUS, DIC, malignancy, pre-eclampsia
prosthetic heart valves
paroxysmal nocturnal haemoglobinuria
infections: malaria
drug: dapsone
Zieve syndrome
rare clinical syndrome of Coombs-negative haemolysis, cholestatic jaundice, and transient hyperlipidaemia associated with heavy alcohol use, typically following a binge
typically resolves with abstinence from alcohol
201
intravascular haemolysis how work
free haemoglobin is released which then binds to haptoglobin. As haptoglobin becomes saturated haemoglobin binds to albumin forming methaemalbumin (detected by Schumm's test). Free haemoglobin is excreted in the urine as haemoglobinuria, haemosiderinuria
202
causes of intravascular haemolysis
mismatched blood transfusion
G6PD deficiency*
red cell fragmentation: heart valves, TTP, DIC, HUS
paroxysmal nocturnal haemoglobinuria
cold autoimmune haemolytic anaemia
203
causes of extravascular haemolyssi
haemoglobinopathies: sickle cell, thalassaemia
hereditary spherocytosis
haemolytic disease of newborn
warm autoimmune haemolytic anaemia
204
haemophilia inheritance
x linked recessive
205
haemophilia a and b
a - def of factor VIII
b - factor IX
206
clinical fx haemophilia
haemoarthroses
haematomas
prolonged bleeding after surgery or trauma
207
blood tests haemophilia
prolonged APTT
bleeding time, thrombin time, prothrombin time normal
208
hereditary angioedema inheritence
aut dom
209
hereditary angioedema patho
low plasma levels of C1 inhibitor protein. this is a multifunctional serine protease inhibitor...uncontrolled release of bradykinin...oedema of tissues
210
inv hereditary angioedema
C1-INH level is low during an attack
low C2 and C4 levels are seen, even between attacks. Serum C4 is the most reliable and widely used screening tool
211
clinical fx hereditary angioedema
attacks may be proceeded by painful macular rash
painless, non-pruritic swelling of subcutaneous/submucosal tissues
may affect upper airways, skin or abdominal organs (can occasionally present as abdominal pain due to visceral oedema)
urticaria is not usually a feature
212
mx hereditary angioedema
acute - IV C1-inhibitor concentrate, fresh frozen plasma (FFP) if this is not available
prophylaxis: anabolic steroid Danazol may help
213
epidemiology hereditary spheroctyosis
northern european
214
inheritance hreditary spherocytosis
aut dom
215
hered spherocytosis patho
the normal biconcave disc shape is replaced by a sphere-shaped red blood cell
red blood cell survival reduced as destroyed by the spleen
216
presentation hereditary spherocytosis
failure to thrive
jaundice, gallstones
splenomegaly
aplastic crisis precipitated by parvovirus infection
degree of haemolysis variable
MCHC elevated
217
diagnosis hereditary spherocytosis
'patients with a family history of HS, typical clinical features and laboratory investigations (spherocytes, raised mean corpuscular haemoglobin concentration [MCHC], increase in reticulocytes) do not require any additional tests
if the diagnosis is equivocal the BJH recommend the EMA binding test and the cryohaemolysis test
for atypical presentations electrophoresis analysis of erythrocyte membranes is the method of choice
218
mx herediatry spherocytosis
- acute and long term
acute haemolytic crisis:
treatment is generally supportive
transfusion if necessary
longer term treatment:
folate replacement
splenectomy
219
hodgkins lymphoma def
a malignant proliferation of lymphocytes characterised by the presence of the Reed-Sternberg cell
220
hodgkins age affects
30 and 70 - bimodal
221
type of hodgkins
most to least common
nodular sclerosing - good prog
mixed cellularity - good prog
lymphocyte predominant - best prog
lymphocyte depleted - worst prog
222
nodular sclerosing more common in
women
223
nodular sclerosing associated
with lacunar cells
224
mixed cellularity associated with
large number of reed-sternerg cells
225
hodgkins worse prognosis B sx
'B' symptoms also imply a poor prognosis
weight loss > 10% in last 6 months
fever > 38ºC
night sweats
226
hodgkins poor prognosis other sx
age > 45 years
stage IV disease
haemoglobin < 10.5 g/dl
lymphocyte count < 600/µl or < 8%
male
albumin < 40 g/l
white blood count > 15,000/µl
227
risk factors hodgkins
HIV
EBV
228
clinical fx hodgkins
lymphadenopathy (75%)
most commonly in the neck (cervical/supraclavicular) > axillary > inguinal
usually painless, non-tender, asymmetrical
alcohol-induced lymph node pain is characteristic of Hodgkin's lymphoma but is seen in less than 10% of patients
systemic - 'B symptoms' (25%)
weight loss
pruritus
night sweats
fever (Pel-Ebstein)
other possible presentations include a mediastinal mass
may be symptomatic (e.g. cough) or found incidentally on a chest x-ray
229
diagnosis hodgkins
normocytic anaemia
may be multifactorial e.g. hypersplenism, bone marrow replacement by HL, Coombs-positive haemolytic anaemia etc
eosinophilia
caused by the production of cytokines e.g. IL-5
LDH raised
lymph node biopsy
Reed-Sternberg cells are diagnostic: these are large cells that are either multinucleated or have a bilobed nucleus with prominent eosinophilic inclusion-like nucleoli (thus giving an 'owl's eye' appearance)
230
staging hodgkins
Ann-Arbor staging of Hodgkin's lymphoma
I: single lymph node
II: 2 or more lymph nodes/regions on the same side of the diaphragm
III: nodes on both sides of the diaphragm
IV: spread beyond lymph nodes
A = no systemic symptoms other than pruritus
B = weight loss > 10% in last 6 months, fever > 38c, night sweats (poor prognosis)
231
hodgkins main mx and types
chemo - 2 combos
ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine): considered the standard regime
BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone): alternative regime with better remission rates but higher toxicity
232
hodgkins other modes of tx
radiotherapy
combined modality therapy (CMT)
chemotherapy followed by radiotherapy
hematopoietic cell transplantation
may be used for relapsed or refractory classic Hodgkin lymphoma
233
complications of tx hodgkins/prognosis
complications of treatment are therefore more of an issue for these patients as prognosis good
secondary malignancies are a risk, in particular solid tumours: breast and lung
234
causes of hyposplenism
splenectomy
sickle-cell
coeliac disease, dermatitis herpetiformis
Graves' disease
systemic lupus erythematosus
amyloid
235
blood film hyposplenism
Howell-Jolly bodies
siderocytes
236
ITP patho
an immune-mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex.
237
ITP adults v child
an acute thrombocytopenia that may follow infection or vaccination. In contrast, adults tend to have a more chronic condition
238
ITP epidemology
older females
239
clinical fx ITP
may be detected incidentally following routine bloods
symptomatic patients may present with
petechiae, purpura
bleeding (e.g. epistaxis)
catastrophic bleeding (e.g. intracranial) is not a common presentation
240
investigations ITP
full blood count: isolated thrombocytopenia
blood film
241
mx ITP
oral prednisolone
pooled normal human immunoglobulin (IVIG) may also be used
it raises the platelet count quicker than steroids, therefore may be used if active bleeding or an urgent invasive procedure is required
splenectomy is now less commonly used
242
evan's syndrome
ITP in association with autoimmune haemolytic anaemia (AIHA)
243
iron def anaemia patho
Iron is needed to make the haemoglobin in red blood cells, therefore a deficiency of iron leads to a reduction in red blood cells/haemoglobin i.e. anaemia
244
peak age iron def anaemka
pre school age
245
causes iron def anaemia
blood loss - menorrhagia or GI bleed in colon cancer
inadequate diet - vegans and beg
poor gi absoprtion - coliac
increased iron requirements - pregnancy
246
clinical fx iron def anaemia
Fatigue
Shortness of breath on exertion
Palpitations
Pallor
Nail changes: this includes koilonychia (spoon-shaped nails)
Hair loss
Atrophic glossitis
Post-cricoid webs
Angular stomatitis
247
iron def anaemia inv
FBC - hypochromic microcytic anaemia
low serum ferritin
(can be false negative as rises in inflammation)
TIBC/transferin will be high
blood film - anisopoikilocytosis, target cells and pencil poikilocytes
endoscopy
248
referral when iron def anaemia
Post-menopausal women with a haemoglobin level ≤10 and men with a haemoglobin level ≤11 should be referred to a gastroenterologist within 2 weeks.
249
iron def anaemia mx
underlying causes managed
oral ferrous sulfate
iron rich diet - dark green leafy veg, meat, iron foritifed bread
250
common s/e of iron supplements
nausea
abdo pain
constipation
diarrhoea
251
iron def anaemia v anaemia of chronic disease
serum iron
<8 in IRON, <15 in ACD
TIBC
high in IRON, low in ACD
Transferrin saturation
low in IRON, low in ACD
ferritin
low in IRON, high in ACD
252
idiopathic thrombocytopenia purpura patho
an immune mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb-IIIa or Ib complex
253
idiopathic thrombocytopenia purpura inv
antiplatelet autoantibodies (usually IgG)
bone marrow aspiration shows megakaryocytes in the marrow.
254
idiopathic thrombocytopenia purpura rule out
leukaemia
255
mx idiopathic thrombocytopenic purpura
oral prednisolone (80% of patients respond)
splenectomy if platelets < 30 after 3 months of steroid therapy
IV immunoglobulins
immunosuppressive drugs e.g. cyclophosphamide
256
decreased haptoglobin
intravascular haemolysis
257
MCHC increased
hereditary spherocytosis
autoimmune haemolytic anaemia
258
MCHC decreased
microcytic anaemia
259
abdo pain and neuro signs ddx
acute intermittent porphyria
lead poisoning
260
lead poisoning patho
defective ferrochelatase and ALA dehydratase function.
261
lead poisoning clinical fx
abdominal pain
peripheral neuropathy (mainly motor)
neuropsychiatric features
fatigue
constipation
blue lines on gum margin
262
inv lead poisoning
blood level - >10 mcg/dl
microcytic anameia
blood film - basophilic strippling and clover leaf
raised serum and urine levels of delta aminolaevulinic acid
urine coproporphyrin increased
263
mx lead poisoning
chelating agents - dimercaptosuccinic acid (DMSA)
D-penicillamine
EDTA
dimercaprol
264
infective causes of generalised lymphadenopathy
infectious mononucleosis
HIV, including seroconversion illness
eczema with secondary infection
rubella
toxoplasmosis
CMV
tuberculosis
roseola infantum
265
neoplastic causes of generalised lymphadenopathy
leukaemia
lymphoma
266
other causes of generalised lymphadenopathy
autoimmune conditions: SLE, rheumatoid arthritis
graft versus host disease
sarcoidosis
drugs: phenytoin and to a lesser extent allopurinol, isoniazid
267
lymphatic drainage of ovaries
para-aortic lymphatics
268
uterus lymphatic drainage
within broad ligament to iliac LN's
269
cervic ln drainage
laterally through the broad ligament to the external iliac nodes, along the lymphatics of the uterosacral fold to the presacral nodes and posterolaterally along lymphatics lying alongside the uterine vessels to the internal iliac nodes.
270
megaloblastic causes of macrocytic anaemia
vitamin B12 deficiency
folate deficiency
e.g. secondary to methotrexate
271
normoblastic causes of macrocytic anaemia
alcohol
liver disease
hypothyroidism
pregnancy
reticulocytosis
myelodysplasia
drugs: cytotoxics
272
aged 0-24 yrs symptoms urgent referral
within 48 hours to investigate for leukaemia -
Pallor
Persistent fatigue
Unexplained fever
Unexplained persistent infections
Generalised lymphadenopathy
Persistent or unexplained bone pain
Unexplained bruising
Unexplained bleeding
273
methaemoglobinaemia patho
haemoglobin which has been oxidised from Fe2+ to Fe3+. This is normally regulated by NADH methaemoglobin reductase, which transfers electrons from NADH to methaemoglobin resulting in the reduction of methaemoglobin to haemoglobin. There is tissue hypoxia as Fe3+ cannot bind oxygen, and hence the oxidation dissociation curve is moved to the left
274
congenital causes methaemoglobinaemia
haemoglobin chain variants: HbM, HbH
NADH methaemoglobin reductase deficiency
275
acquired causes methaemoglobinaemia
drugs: sulphonamides, nitrates (including recreational nitrates e.g. amyl nitrite 'poppers'), dapsone, sodium nitroprusside, primaquine
chemicals: aniline dyes
276
clinical fx methoglobinaemia
'chocolate' cyanosis
dyspnoea, anxiety, headache
severe: acidosis, arrhythmias, seizures, coma
normal pO2 but decreased oxygen saturation
277
mx methoglobinaemia
NADH methaemoglobinaemia reductase deficiency: ascorbic acid
IV methylthioninium chloride (methylene blue) if acquired
278
MGUS causes
paraproteinaemia
279
MGUS mistaken for
myeloma
280
MGUS risk of
eventually develop myeloma
281
clinical fx MGUS
usually asymptomatic
no bone pain or increased risk of infections
around 10-30% of patients have a demyelinating neuropathy
282
myeloma V MGUS
normal immune function
normal beta-2 microglobulin levels
lower level of paraproteinaemia than myeloma (e.g. < 30g/l IgG, or < 20g/l IgA)
stable level of paraproteinaemia
no clinical features of myeloma (e.g. lytic lesions on x-rays or renal disease)
283
causes of microcytic anaemia
iron-deficiency anaemia
thalassaemia*
congenital sideroblastic anaemia
anaemia of chronic disease (more commonly a normocytic, normochromic picture)
lead poisoning
284
normal Hb, microcytic, no risk of thalassaeia
polycythiamia rubra vera which may cause iron def secondary to bleeding
285
microcytic anaemia urgent referral
if new onset in elderly pts
286
myelodysplastic syndrome definition
encompass a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, and a risk of progression to acute myeloid leukaemia (AML).
287
median age of diagnosis myelodysplastic syndrom
70-75
288
primary or secondary myelodysplastic syndrome
Around 90% of cases are primary with the remaining 10% secondary to causes such as chemotherapy and radiotherapy. Secondary MDS typically develops around 5 years post-treatment.
289
patho MDS
ineffective hematopoiesis leading to peripheral cytopenias despite a typically hypercellular bone marro
290
common presentations MDS
fatigue, weakness, and pallor due to anaemia; recurrent infections due to neutropenia; and easy bruising or bleeding due to thrombocytopenia. Some patients may be asymptomatic and are diagnosed incidentally on routine blood counts.
291
diagnosis MDS
peripheral blood counts, bone marrow examination, and cytogenetic analysis. Bone marrow biopsy typically shows dysplastic changes in hematopoietic cells and a varying degree of blasts. Cytogenetic analysis can identify specific chromosomal abnormalities that may have prognostic implications.
292
tx MDS
supportive care (e.g., blood transfusions, growth factors), disease-modifying therapy (e.g., hypomethylating agents, lenalidomide), immunosuppressive therapy, and hematopoietic stem cell transplantation
293
myelofibrosis definition
a type of myeloproliferative disorder caused by hyperplasia of abnormal megakaryocytes...release of platelet derived growth factor...stimulate fibroblasts
Haematopoeisis develops in liver and spleen
294
clinical fx myelofibrosis
e.g. elderly person with symptoms of anaemia e.g. fatigue (the most common presenting symptom)
massive splenomegaly
hypermetabolic symptoms: weight loss, night sweats etc
295
lab findings myelofibrosis
anaemia
high WBC and platelet count early in the disease
'tear-drop' poikilocytes on blood film
unobtainable bone marrow biopsy - 'dry tap' therefore trephine biopsy needed
high urate and LDH (reflect increased cell turnover)
296
multiple myeloma definition
a haematological malignancy characterised by plasma cell proliferation. It arises due to genetic mutations which occur as B-lymphocytes differentiate into mature plasma cells
297
myeloma age
70 yrs old
298
myeloma clinical fx
CRABBI
Calcium
Renal
Anaemia
Bleeding
Bones
Infection
299
CRABBI explained
Calcium
hypercalcaemia
primary factor: due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells
much less common contributing factors: impaired renal function, increased renal tubular calcium reabsorption and elevated PTH-rP levels
this leads to constipation, nausea, anorexia and confusion
Renal
monoclonal production of immunoglobulins results in light chain deposition within the renal tubules
this causes renal damage which presents as dehydration and increasing thirst
other causes of renal impairment in myeloma include amyloidosis, nephrocalcinosis, nephrolithiasis
Anaemia
bone marrow crowding suppresses erythropoiesis leading to anaemia
this causes fatigue and pallor
Bleeding
bone marrow crowding also results in thrombocytopenia which puts patients at increased risk of bleeding and bruising
Bones
bone marrow infiltration by plasma cells and cytokine-mediated osteoclast overactivity creates lytic bone lesions
this may present as pain (especially in the back) and increases the risk of pathological fractures
Infection
a reduction in the production of normal immunoglobulins results in increased susceptibility to infection
300
investigations myeloma
bloods
protein electrophoresis
bone marrow aspiration
imagin
301
myeloma blood
full blood count: anaemia
peripheral blood film: rouleaux formation
urea and electrolytes: renal failure
bone profile: hypercalcaemia
302
myeloma protein electrophoriesis
raised concentrations of monoclonal IgA/IgG proteins will be present in the serum
in the urine, they are known as Bence Jones proteins
303
myeloma bone marrow aspiration
plasma cells is significantly raised
304
myeloma imagin
whole body MRI
X-rays: 'rain-drop skull' (likened to the pattern rain forms after hitting a surface and splashing, where it leaves a random pattern of dark spots). Note that a very similar, but subtly different finding is found in primary hyperparathyroidism - 'pepperpot skull'
305
major criteria myeloma
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
306
minor criteria myeloma
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.
307
neutropenia count
<1.5 x 10^9
308
neutrophil count severity
Mild 1.0 - 1.5 * 109
Moderate 0.5 - 1.0 * 109
Severe < 0.5 * 109
309
causes of neutropenia
viral
HIV
Epstein-Barr virus
hepatitis
drugs
cytotoxics
carbimazole
clozapine
benign ethnic neutropaenia
common in people of black African and Afro-Caribbean ethnicity
requires no treatment
haematological malignancy
myelodysplastic malignancies
aplastic anemia
rheumatological conditions
systemic lupus erythematosus: mechanisms include circulating antineutrophil antibodies
rheumatoid arthritis: e.g. hypersplenism as in Felty's syndrome
severe sepsis
haemodialysis
310
neutropenic sepsis definition
defined as a neutrophil count of < 0.5 * 109 in a patient who is having anticancer treatment and has one of the following:
a temperature higher than 38ºC or
other signs or symptoms consistent with clinically significant sepsis
311
causes neutropenic sepsis
coagulase-negative, Gram-positive bacteria are the most common cause, particularly Staphylococcus epidermidis
312
prophylaxis neutropenic sepsis
fluroquinolone
313
neutropenic sepsis mx
abx started immediately, not wait for WBC - Tazocin
assessed by a specialist
if patients are still febrile and unwell after 48 hours an alternative antibiotic such as meropenem is often prescribed +/- vancomycin
if patients are not responding after 4-6 days the Christie guidelines suggest ordering investigations for fungal infections (e.g. HRCT), rather than just starting therapy antifungal therapy blindly
there may be a role for G-CSF in selected patients
314
lymphoma definition
the malignant proliferation of lymphocytes which accumulate in lymph nodes or other organs. Lymphoma may be classified as either Hodgkin's lymphoma (a specific type of lymphoma characterized by the presence of Reed-Sternberg cells) or non-Hodgkin's lymphoma (every other type of lymphoma that is not Hodgkin's lymphoma).
315
non hodgkins lymphoma subgroup
either B or T cells
further classified into high or low grade
316
which type lymphoma more common
non hodgkin's
317
non hodgkins age
over 75 yrs usually
can be any age
318
risk fx non hodgkins
Elderly
Caucasians
History of viral infection (specifically Epstein-Barr virus)
Family history
Certain chemical agents (pesticides, solvents)
History of chemotherapy or radiotherapy
Immunodeficiency (transplant, HIV, diabetes mellitus)
Autoimmune disease (SLE, Sjogren's, coeliac disease)
319
non hodgkins sx
Painless lymphadenopathy (non-tender, rubbery, asymmetrical)
Constitutional/B symptoms (fever, weight loss, night sweats, lethargy)
Extranodal Disease - gastric (dyspepsia, dysphagia, weight loss, abdominal pain), bone marrow (pancytopenia, bone pain), lungs, skin, central nervous system (nerve palsies
320
how different non hodgkins v hodgkins
biopsy how differentiate
Lymphadenopathy in Hodgkin's lymphoma can experience alcohol-induced pain in the node
'B' symptoms typically occur earlier in Hodgkin's lymphoma and later in non-Hodgkin's lymphoma
Extra-nodal disease is much more common in non-Hodgkin's lymphoma than in Hodgkin's lymphoma
321
clinical signs non hodgkins
Signs of weight loss
Lymphadenopathy (typically in the cervical, axillary or inguinal region)
Palpable abdominal mass - hepatomegaly, splenomegaly, lymph nodes
Testicular mass
Fever
322
non hodgkins inv
diagnostic - excisional node biopsy
CT TAP
HIV - risk factor
FBC and blood film - normocytic anaemia to rule out leukaemia
ESR - prognostic fx
LDH - prognostic fx
323
non hodgkins staging
Ann arbor
Stage 1 - One node affected
Stage 2 - More than one node affected on the same side of the diaphragm
Stage 3 - Nodes affected on both sides of the diaphragm
Stage 4 - Extra-nodal involvement e.g. Spleen, bone marrow or CNS
with A or B to indicated B symptoms present or not
324
non hodgkins mx
dependent on the specific sub-type of non-Hodgkin's lymphoma and will typically take the form of watchful waiting, chemotherapy or radiotherapy.
Rituximab is used in combination with conventional chemotherapy regimes (e.g. CHOP) for a variety of types of NHL
All patients will receive flu/pneumococcal vaccines
Patients with neutropenia may require antibiotic prophylaxis
325
complications non hodgkins
Bone marrow infiltration causing anaemia, neutropenia or thrombocytopenia
Superior vena cava obstruction
Metastasis
Spinal cord compression
Complications related to treatment e.g. Side effects of chemotherapy
326
prognosis low grade non hodgkins
better
327
prognosis high grade non hodgkins
worse but higher cure rate
328
causes of normocytic anaemia
anaemia of chronic disease
chronic kidney disease
aplastic anaemia
haemolytic anaemia
acute blood loss
329
paroxysmal nocturnal haemoglobinuria definition
an acquired disorder leading to haemolysis (mainly intravascular) of haematological cells. It is thought to be caused by increased sensitivity of cell membranes to complement (see below) due to a lack of glycoprotein glycosyl-phosphatidylinositol (GPI)
330
PNH more prone to
venous thrombosis
331
PNH patho
GPI can be thought of as an anchor which attaches surface proteins to the cell membrane
complement-regulating surface proteins, e.g. decay-accelerating factor (DAF), are not properly bound to the cell membrane due a lack of GPI
thrombosis is thought to be caused by a lack of CD59 on platelet membranes predisposing to platelet aggregation
332
clinical fx HPN
haemolytic anaemia
red blood cells, white blood cells, platelets or stem cells may be affected therefore pancytopaenia may be present
haemoglobinuria: classically dark-coloured urine in the morning (although has been shown to occur throughout the day)
thrombosis e.g. Budd-Chiari syndrome
aplastic anaemia may develop in some patients
333
diagnosis non hodgkins
flow cytometry of blood to detect low levels of CD59 and CD55 has now replaced Ham's test as the gold standard investigation in PNH
334
mx HPN
blood product replacement
anticoagulation
eculizumab, a monoclonal antibody directed against terminal protein C5, is currently being trialled and is showing promise in reducing intravascular haemolysis
stem cell transplantation
335
offer platelet transfusion at what count
<30x10^9 with clinically significant bleeding
if severe bleeding or bleeding at critical sites such as CNS - <100 x 10^9 before transfusing
336
risk of platelet transfusion
bacterila contamination
337
platelet transfusion for thrombocytopenia before surgery aim
> 50×109/L for most patients
50-75×109/L if high risk of bleeding
>100×109/L if surgery at critical site
338
if no active bleeding platelet threshold
10x10^9
339
not perform platelet transfusion for following
Chronic bone marrow failure
Autoimmune thrombocytopenia
Heparin-induced thrombocytopenia, or
Thrombotic thrombocytopenic purpura.
340
relative causes of polycythaemia
dehydration
stress: Gaisbock syndrome
341
primary cause of polycythaemia
polycythaemia rubra vera
342
secondary causes of polycythaemia
COPD
altitude
obstructive sleep apnoea
excessive erythropoietin: cerebellar haemangioma, hypernephroma, hepatoma, uterine fibroids*
343
polycythaemia vera /rubra vera definition
a myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets
344
polycythaemia vera genetics
a mutation in JAK2 is present in approximately 95% of patients with polycythaemia vera
345
clinical fx polycythaemia vera
pruritus, typically after a hot bath
splenomegaly
hypertension
hyperviscosity
arterial thrombosis
venous thrombosis
haemorrhage (secondary to abnormal platelet function)
low ESR
346
initial tests polycythaemia vera
full blood count/film (raised haematocrit; neutrophils, basophils, platelets raised in half of patients)
JAK2 mutation
serum ferritin
renal and liver function tests
347
if JAK2 mutation -ve other investigations polycythamia evra
red cell mass
arterial oxygen saturation
abdominal ultrasound
serum erythropoietin level
bone marrow aspirate and trephine
cytogenetic analysis
erythroid burst-forming unit (BFU-E) culture
348
JAK2 positive polycythameia vera diagnosis
both criteria -
A1 High haematocrit (>0.52 in men, >0.48 in women) OR raised red cell mass (>25% above predicted)
A2 Mutation in JAK2
349
JAK2 negative polycythaemia vera diagnosis
A1 + S2 _ A3 + either A or B criteria
A1 Raised red cell mass (>25% above predicted) OR haematocrit >0.60 in men, >0.56 in women
A2 Absence of mutation in JAK2
A3 No cause of secondary erythrocytosis
A4 Palpable splenomegaly
A5 Presence of an acquired genetic abnormality (excluding BCR-ABL) in the haematopoietic cells
B1 Thrombocytosis (platelet count >450 * 109/l)
B2 Neutrophil leucocytosis (neutrophil count > 10 * 109/l in non-smokers; > 12.5*109/l in smokers)
B3 Radiological evidence of splenomegaly
B4 Endogenous erythroid colonies or low serum erythropoietin
350
polycythaemia vera mx
aspirin
reduces the risk of thrombotic events
venesection
first-line treatment to keep the haemoglobin in the normal range
chemotherapy
hydroxyurea - slight increased risk of secondary leukaemia
phosphorus-32 therapy
351
polycythaemia vera prognosis
thrombotic events are a significant cause of morbidity and mortality
5-15% of patients progress to myelofibrosis
5-15% of patients progress to acute leukaemia (risk increased with chemotherapy treatment)
352
post thrombotic syndrome definition
complications following a DVT. Venous outflow obstruction and venous insufficiency result in chronic venous hypertension. The resulting clinical syndrome is known as post-thrombotic syndrome.
353
clinical fx post thrombotic syndrome
painful, heavy calves
pruritus
swelling
varicose veins
venous ulceration
354
reduce risk of post thrombotic syndrome
compressions stocking on pts with DVT
355
mx of post thrombotic syndromes
compression stockings
leg elevation
356
when pregnancy dvt/pe
last trimester
357
pathophysiology pregnancy dvt development
increase in factors VII VIII, X, and fibrinogen
decrease in protein S
uterus also presses on IVC...venous stasis in legs
358
pregnancy dvt/pe mx
S/C LMWH
(preferred over IV as less bleeding and thrombocytopenia)
359
chronic granulomatous defect underlying defect
lack of NADPH oxidase...reduced ability of phagocytes to produce reactive oxygen species
360
which organisms more likely affect chronic granulomatous disease
staph aureus and aspergillus
...causes recurrent pneumonias and abscesses
361
chediak-higashi syndrome underlying defect
microtubule polymerisation defect...decrease in phagocytosis
362
chediak-higashi syndrome clinical fx
peripheral neuropathy
partial albinism
recurrent bacterial infections
363
chronic granulomatous disease inv
abnormal dihydrorhodamine flow cytometry test
364
chediak-higashi syndrome blood film
giant granules in neutrophils and platelets
365
leukocyte adhesion deficiency underlying pathology
defect of CD18 protein on neutrophils
366
leukocyte adhesion deficiency clinical fx
recurrent bacterial infections
delay in umbilical cord sloughing
absence of pus at sites of infection
367
neutrophil disorders
chronic granulomatous disorder
chediak higashi
leukocyte adhesion def
368
B cell disorders
common variable immunodeficiency
bruton's
selective IgA def
369
common variable immunodeficiency immunoglobulin levels
low antibodies - IgG, IgM, IgG
370
common variable immunodefiency increased risk
recurrent chest infections
autoimmune disorders
lymphoma
371
bruton's underlying patho
defect in BTK gene...severe block in B cell development
372
bruton's inheritance
x linked recessive
373
bruton's clinical fx
recurrent bacterial inf
374
bruton's tests
absence of B cells
reduced immunoglobulins of all classes
375
selective IgA def underlying patho
maturation defect in B cells
376
selective IgA def how common
most common primary antibody def
377
selective IgA def associated
coeliac disease and may cause false negative coeliac antibody screen
378
selective IgA def and blood transfusions
Severe reactions to blood transfusions may occur (anti-IgA antibodies → analphylaxis)
379
T cell disorder
DiGeorge Syndrome
380
di george syndrome underlying patho
chromosome deletion...failure to develop 3rd and 4th pharngeal pouches
381
clinical fx di george syndrome
congenital heart disease (e.g. tetralogy of Fallot), learning difficulties, hypocalcaemia, recurrent viral/fungal diseases, cleft palate
382
combined b and t cell defect examples
Severe combined immunodef
ataxic telangiectasia
wiskott-aldrich syndrome
hyper-IgM syndromes
383
SCID underlying defect
many
defect in common gamma chain...used to form receptors for IL2 nad other interleukins
384
SCID clinical fx
recurrent infections
385
SCID possible tx
stem cell transplant
386
ataxic telangiectasia defect
defect in DNA repair enzymes
387
ataxic telangiectasia inheritence
aut rec
388
clinical fx ataxic telangiectasia
cerebellar ataxia, telangiectasia (spider angiomas), recurrent chest infection
389
increased risk of.. in ataxic telangiectasia
lymphoma or leukaemia
390
wiskott-aldrich syndrome defect
defect in WASP gene
391
wiskott-aldrich syndrome inheritance
x linked rec
392
clinical fx wiskott-aldrich
recurrent bacterial infections, eczema, thrombocytopaenia.
393
wiskott aldrich antibody levels
low IgM
394
increased risk of..wiskott-aldrich syndrome
autoimmune and malignancy
395
hyper IgM syndromes defect
mutations in CD40 gene
396
hyper IgM syndromes clinical fx
Infection/Pneumocystis pneumonia, hepatitis, diarrhoea
397
sickle cell inheritance
aut recessive
398
sickle cell pathophysiology
synthesis of abnormal Hb chain = HbS
if homozygous = HbSS
if hetero = HbAS
if inherited one HbS+abnormal Hb = HbSC
glutmate substituted for valine in each of the two beta chains...decreased water solubility of deoxy-Hb.
In dexoygenated state - HbS polymerases and causes red cells to sickle (sickle at a higher oxygen level)
these cells are fragile and haemolyse..block vessels and cause infarction
399
sickle cell epidemiology
african descent = heterozygous...protection from malaria
400
when in life develop sickle cell sx
when homozygous...4-6mths in when abnormal HbSS takes over from fetal Hb
401
definitive diagnosis sickle cell
haemoglobin electrophoresis
402
sickle cell crisis mx
analgesia e.g. opiates
rehydrate
oxygen
consider antibiotics if evidence of infection
blood transfusion
exchange transfusion: e.g. if neurological complications
403
long term mx of sickle cell
hydroxyurea - increases HbF levels...prophylactically prevent painful episodes
pneumococcal vaccine
404
type of crisis in sickle cell
thrombotic, 'vaso-occlusive', 'painful crises'
acute chest syndrome
anaemic
aplastic
sequestration
infection
405
thrombotic crises precipitated
infection, dehydration, deoxygenation (e.g. high altitude)
406
examples clinical presentations thrombotic crisis
avascular necrosis of hip
hand foot sundrome
infarcts in lung, spleen, brain
407
acute chest syndrome patho
vaso occlusion within pulmonary microvasculature...infarction
408
clinical fx acute chest syndrome
dyspnoea, chest pain, low o2
inv - CXR - pulmonary infiltrates
409
acute chest syndrome mx
pain relief
respiratory support e.g. oxygen therapy
antibiotics: infection may precipitate acute chest syndrome and the clinical findings (respiratory symptoms with pulmonary infiltrates) can be difficult to distinguish from pneumonia
transfusion: improves oxygenation
410
aplastic crisis caused by
infection with parvovirus
411
aplastic crises investigations
sudden drop in Hb
reduced reticulocyte count
412
sequestration crises patho
sickling within organs such as lungs or spleen...pooling of blood and worsening of anaemia
413
sequestration crises blood results
increased reticulocyte
414
sickle cell crisis general mx
analgesia e.g. opiates
rehydrate
oxygen
consider antibiotics if evidence of infection
blood transfusion
indications include: severe or symptomatic anaemia, pregnancy, pre-operative
do not rapidly reduce the percentage of Hb S containing cells
exchange transfusion
indications include: acute vaso-occlusive crisis (stroke, acute chest syndrome, multiorgan failure, splenic sequestration crisis
rapidly reduce the percentage of Hb S containing cells
415
sideroblastic anaemia patho
red cells fail to form haem...leads to deposits of iron in mitochondria = forms a ring sideroblast around nucleus
416
causes of sideroblastic anaemia
congenital causes - delta-aminolevulinate synthase-2 deficiency
acquired - myelodysplasia, alcohol, lead, anti-TB meds
417
sideroblastic anaemia inv
hypochromic microcytic anaemia
iron studies - high ferritin, high iron, high transferrin sat
basophilic strippling of red cell
bone marrow staining - sideroblasts
418
sideroblastic anaemia mx
supportive
treat any underlying cause
pyridoxine may help
419
massive splenomegaly possible causes
myelofibrosis
chronic myeloid leukaemia
visceral leishmaniasis (kala-azar)
malaria
Gaucher's syndrome
420
other causes of splenomegaly
portal hypertension e.g. secondary to cirrhosis
lymphoproliferative disease e.g. CLL, Hodgkin's
haemolytic anaemia
infection: hepatitis, glandular fever
infective endocarditis, thalassaemia
rheumatoid arthritis (Felty's syndrome)
421
sickle cell large or small spleen?
majority of adults will have atrophied spleen due to repeated infarctions
422
causes of severe thrombocytopenia
ITP
DIC
TTP
haem malignancy
423
causes of moderate thrombocytopenia
heparin induced thrombocytopenia (HIT)
drug-induced (e.g. quinine, diuretics, sulphonamides, aspirin, thiazides)
alcohol
liver disease
hypersplenism
viral infection (EBV, HIV, hepatitis)
pregnancy
SLE/antiphospholipid syndrome
vitamin B12 deficiency
424
pseudothrombocytopenia association
use of EDTA as an anticoagulant
425
platelet count thrombocytosis
high
>400 x 10^9/l
426
possible causes of thrombocytosis
reactive - platelets act as an acute phase reactant...respond to stress/infection/iron def anaemia
malignancy
essential thrombocytosis
hyposplenism
427
essential thrombocytosis definition
one of the myeloproliferative disorders which overlaps with chronic myeloid leukaemia, polycythaemia rubra vera and myelofibrosis
428
essential thrombocytosis patho
megakaryocyte prolferation..overproduction of platelets
429
fx of essential thrombocytosis to diagnose
platelet >600
both thrombosis and haemorrhage
burning sensation in hands
JAK2 mutation in 50% of pts
430
essential thrombocytosis mx
hydroxyurea - reduce platelet count
low dose aspirin -
431
causes of inherited thrombophilias
factor V Leiden (activated protein C resistance)
prothrombin gene mutation
deficiencies -
antithrombin III deficiency
protein C or S deficiency
432
most common cause of thrombophilia
factor V Leiden (activated protein C resistance)
433
acquired cause of thrombophilia
antiphospholipid syndrome
COCP
434
patho of thrombotic thrombocytopenic purpura
defiency of enzymes which breaksdown von willebrand factor. so these factors cause platelets to clump within vessels
435
TTP overlaps with
HUS
436
clinical fx TTP
rare, typically adult females
fever
fluctuating neuro signs (microemboli)
microangiopathic haemolytic anaemia
thrombocytopenia
renal failure
437
causes of TTP
post-infection e.g. urinary, gastrointestinal
pregnancy
drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
tumours
SLE
HIV
438
thymoma
- how common
- tumour of
most common tumour of anterior mediastinum
439
thymoma when detected
60-70 years old
440
thymoma associations
myasthenia gravis (30-40% of patients with thymoma)
red cell aplasia
dermatomyositis
also : SLE, SIADH
441
causes of death from thymoma
airway compression
cardiac tamponade
442
MoA of tranexamic acid
reversibly binds to lysine receptor sites on plasminogen or plasmin...prevents plasmin from degrading fibrin
443
indications tranxemaic acid
menorrhagia
bleeding trauma if given in 1st 3 hours (IV bolus following by infusion)
444
when tumour lysis syndrome tx what
high grade lymphomas or leukaemias
usually triggered by combo chemo
or with steroid tx alone
445
TLS patho
he breakdown of the tumour cells and the subsequent release of chemicals from the cell
446
TLS electrolytes
2 high one low
high potassium and phosphate, low calcium
447
when suspect TLS
AKI
high phosphate
high uric acid
448
prevention TLS
IV fluids
allopurinol or rasburicase
449
which prophylactic tx for high risk pts of TLS and how work
rasburicase - a recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin. Allantoin is much more water-soluble than uric acid and is, therefore, more easily excreted by the kidneys
450
TLS grading
Cairo-bishop scoring system
451
clinical tumour lysis syndrome diagnosis
laboratory tumour lysis syndrome plus one or more of the following:
increased serum creatinine (1.5 times upper limit of normal)
cardiac arrhythmia or sudden death
seizure
452
general risks of VTE
increased risk with advancing age
obesity
family history of VTE
pregnancy (especially puerperium)
immobility
hospitalisation
anaesthesia
central venous catheter: femoral >> subclavian
453
underlying conditions causing increased risk of VTE
malignancy
thrombophilia: e.g. Activated protein C resistance, protein C and S deficiency
heart failure
antiphospholipid syndrome
Behcet's
polycythaemia
nephrotic syndrome
sickle cell disease
paroxysmal nocturnal haemoglobinuria
hyperviscosity syndrome
homocystinuria
454
medications causing higher risk of VTE
COCP
HRT (more if combined)
raloxifene and tamoxifen
antipsychotics esp olanzapine
455
how vit b12 absorbed
It is absorbed after binding to intrinsic factor (secreted from parietal cells in the stomach) and is actively absorbed in the terminal ileum. A small amount of vitamin B12 is passively absorbed without being bound to intrinsic factor.
456
causes of vit b12 def
pernicious anaemia: most common cause
post gastrectomy
vegan diet or a poor diet
disorders/surgery of terminal ileum (site of absorption)
Crohn's: either diease activity or following ileocaecal resection
metformin (rare)
457
clinical fx of vit b12 def
macrocytic anaemia
sore tongue and mouth
neurological symptoms
the dorsal column is usually affected first (joint position, vibration) prior to distal paraesthesia
neuropsychiatric symptoms: e.g. mood disturbances
458
vit b12 def mx
if no neuro - IM hydroxocobalamin 3x/wk for 2 wks then 1/3mths
if def in folic acid - treat b12 first
459
most common inheritable bleeding disorder
von willebrand disease
460
von willebrand's inheritance
aut dom USUALLY
461
clinical fx von willebrand
epistaxis
menorrhagia
haemoarthroses
muscle haematomas
462
von willebrand's patho
promotes platelet adhesion to damaged endothelium
also carrier molecule for factor VIII
463
what are 3 types of von willebrands
type 1: partial reduction in vWF (80% of patients)
type 2*: abnormal form of vWF
type 3**: total lack of vWF (autosomal recessive)
464
von willebrands inv
prolonged bleeding time
APTT may be prolonged
factor VIII levels may be moderately reduced
defective platelet aggregation with ristocetin
465
von willebrands mx
mild bleeding - tranxemic acid
desmopressin - raises level of vWF
factor VIII concentrate
466
waldenstrom's macroglobulinaemia age and sex
older men
467
patho waldenstrom's macroglobulinaemia
It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein
468
clinical fx waldenstrom's macroglobulinaemia
systemic upset: weight loss, lethargy
hyperviscosity syndrome e.g. visual disturbance
the pentameric configuration of IgM increases serum viscosity
hepatosplenomegaly
lymphadenopathy
cryoglobulinaemia e.g. Raynaud's
469
waldenstroms macroglobulinaemia inv
monoclonal IgM paraproteinaemia
bone marrow biopsy is diagnostic
infiltration of the bone marrow with lymphoplasmacytoid lymphoma cells
470
waldenstrom's macroglobulinaemia mx
rituximab-based combo chemo
471
