Haematology Flashcards
(227 cards)
1
Q
probability of VTE recurrence?
A
20% in the first 2 years
4% pa thereafter
2
Q
4 potential consequences of VTE
A
1) death
2) recurrance
3) thrombophlebitic syndrome
4) pulmonary hypertension
3
Q
components of Virchow’s triad
A
1) Blood
2) Blood flow
3) Vessel wall
4
Q
the coagulation system:
Triggered by ___(1)__
Generates __(2)____
Which converts _(3)____ to __(4)__ (the clot)
A
1) Tissue Factor
2) thrombin
3) fibrinogen
4) fibrin
5
Q
give 4 examples of things which make blood vessel walls prothrombotic?
A
inflammation
malignancy
trauma
infection
6
Q
what is the mechanism of thrombosis due to stasis? - 4 steps
A
1) accumulation of activated factors
2) promotes platelet adhesion
3) promotes leukocyte adhesion and transmigration
4) hypoxia produces inflammatory effect on endothelium
7
Q
What confers the highest risk of thrombosis?
a) factor V leiden
b) Antithrombin deficiency
c) FH of thrombosis
d) deficiency of Factor VII
e) 3 hour plane journey
A
b)
factor V leiden does confer some thrombosis but not as much
FH is important
8
Q
What 3 groups of people are especially at risk of VTE
A
1) pregnant
2) Surgery
3) malignancy
9
Q
How does Heparin work?
A
- immediate
- potentiates action of antithrombin
10
Q
what are the long term effects of heparin?
A
injections
risk of osteoporisis
11
Q
Name 2 types of immediate acting anticoagulants
A
Heparins
Direct acting factor Xa or IIa inhibtors (e.g. rivaroxaban & Dabigatran)
12
Q
What is used to monitor Warfarin levels?
A
INR - international normalised ratio - which is derived from the prothrombin time
13
Q
For therapeutic anticoagulation what should you give?
A
- must be immediate acting, so wither LMWH such as tinzaparin, or rivaroxaban / apixaban
- also give warfarin at the same time for long term anticoagulation
14
Q
What agent is used in thrombolysis and give some common examples
A
TPA - tissue plasminogen activator
alteplase, reteplase, tenecteplase
15
Q
what is D-dimer a breakdown product of and what does mesuring it tell you
A
Breakdown product of fibrin so gives you an indication of clot breakdown. A negative D-dimer suggests that a clot is highly unlikely, but a positive test requires further investigation
16
Q
What are causes of Microcytic Anaemia? (LOW MCV)
A
FAST
Fe deficient anaemia
Anaemia of chronic disease
Sideroblastic anaemia
Thalassaemia
17
Q
What are causes of normocytic anaemia
A
Acute Blood Loss Anaemia of chronic disease Bone marrow failure Renal Failure Hypothyroidism Haemolysis Pregnancy
18
Q
What are causes of Macrocytic anaemia?
A
FATRBC
Foetus (pregnancy) Alcohol and antifolates (e.g. phenytoin) Thyroid (hypothyroidism) Reticulocytosis B12 or folate deficiency Cirrhosis (alcohol or liver disease)
19
Q
Give 5 signs of iron deficiency anaemia
A
kolionchia (spoon nails) atrophic glossitis angular cheilitis post-cricoid webs brittle hair & nails
20
Q
What would you see on a blood film in iron deficiency anaemia?
A
microcytic, hypochromic, anisocytes (varying size), poikilocytosis (shape), pencil cells
21
Q
What 2 ways might you have decreased absorption of Fe leading to IDA?
A
1) post gastric surgery
2) coeliac
22
Q
Give 5 examples of types of GI blood loss leading to IDA
A
1) GI Ca / polyps
2) Meckel’s diverticulum
3) Peptic ulcer / gastritis
4) Hookworm
5) menorrhagia
23
Q
What is the most common cause of Fe-deficiency anaemia in women <50?
A
menorrhagia related
24
Q
Give some differentials if you find Acanthocytes ona blood film
A
abetalipoproteinaemia
liver disease
hyposplenism
25
What does acanthocytosis mean?
Spiky / thorny / spicules RBCs
26
describe basophilic stippling
RBCs have small dots at the periphery - which are ribosomes
27
Give 5 causes of basophilic stippling
1) lead poisoning
2) myelodysplasia
3) liver disease
4) thalassaemia
5) megaloblastic anaemia
28
What are Burr cells and what might they indicate?
Echinocytes - irregularly shaped/spikes cells which can arise from uraemia, GI bleeding, stomach carcinoma
29
What are Heinz bodies and what might they indicate?
inclusions within RBCs of denatures Hb. Can occur in G6PD deficiency and chronic liver disease
30
what are howell jolly bodies
Remnants of DNA in RBCs
31
what 3 main things might the presence of howell jolly bodies indicate?
1) Splenectomy/hyposplenism - e.g. due to sickle cell, coeliac, congenital, UC/Chrons
2) megaloblastic anaemia
3) hereditary spheocytosis
32
describe leucoerythroblastic anaemia
Due to bone marrow INFILTRATION
- results in nucleated (immature) RBCs
- poikilocytosis
- teardrop cells
- Also primitive WBCs
33
What cells does Pelger Huet anomoly affect?
Neutrophils
34
What is the name of the anomoly when a neutrophil is hyposegmented?
What might this indicate?
Pelger-Huet anomoly
CONGENITAL - lamin B receptor mutation
ACQUIRED - myelogenous leukaemia, myelodysplastic syndromes
35
What does 'polychromasia' mean?
RBCs of varying colours due to varying amount of Hb content - showing immature/inappropariate release from the BM
36
Reticulocytes increase in___ and decrease in___
Increase: haemolytic anaemia
Decrease: aplastic anaemia & chemotherapy
37
What does a 'right shift' on a blood film mean
Hypermature WBCs - so hypersegmented (>5 lobes to the nuclei) and polymorphic
38
What might hypermature, polymorphic WBCs be called, and what disease could itpoint towards?
'right shift'
- megaloblastic anaemia
- uraemia
- liver disease
39
What is the name for when RBCs are stacked on another?
Rouleaux formation
40
What does a Rouleaux formation on a blood film suggest?
- chronic inflammaiton
- paraproteinaemia
- myeloma
41
Give 5 differentials if you see schistocytes on blood film
1) microangiopathic anaemia e.g. DIC
2) HUS
3) TTP
4) pre-eclampsia
42
What blood film finding is typical for DIC?
schistocytes
43
Give 2 differentials for spherocytosis
1) Hereditary spherocytosis
| 2) AI haemolytic anaemia (Coombs +)
44
Describe stomatocytes
The central white bit is straight or curved into a 'smile'
45
Give 2 differentials for stomatocytosis
1) hereditary stomatocytosis
| 2) high alcohol consumption / liver disease
46
What 4 differentialswhen target cells are seen on blood film?
1) Iron deficiency anaemia
2) liver disease
3) hyposplenism
4) thalassaemia
47
What is the most common hypercoagualability disorder in Europeans?
Factor V leiden
48
What are the numbers for anaemia in Men and Women?
Men - <135 g/L
| Women - <115 g/L
49
5 symptoms of anaemia
```
fatigue
dyspnoea
headaches
palpitations
faitness
(tinnitus, anorexia)
```
50
General causes of anaemia (3)
1) Increased LOSS of RBCs
2) Reduced PRODUCTION of RBCs
3) Increased plasma volume (pregnancy)
51
What are the side effects of oral iron for IDA?
nausea, abdo discomfort, diarrhoea/constipation, black stools
52
What is anaemia of chronic disease in one sentence?
cytokine driven inhibition of RBC production
53
Give 4 causes of anaemia of chronic disease
1) malignancy
2) vasculitis
3) RA
4) Chronic infection e.g. TB, parasitic
54
Why do you get anaemia in renal failure?
EPO deficiency
55
what is sideroblastic anaemia and how do you diagnose it?
Ineffective erythropoiesis leading to iron overload, resulting in haemosiderosis.
56
treatment for sideroblastic anaemia
treat the cause and pyridoxine (vitamin B6)
57
What clotting factors are affected in haemophilia A, B and C?
A- 8
B- 9 (one after 8)
C- 11 (one after 9, then the one after)
58
Draw the clotting cascade!
Look to khan acadamy video for good explanation again
59
What is the negative feedback mechanisms for the clotting cascade?
1) thrombin stimulates production of plasmin from plasminogen, which breaks down fibrin crosslinks
2) thrombin stimulates generation of antithrombin which decreases thrombin production but also impedes activated Xa
60
What does factor XIII do?
stimulates cross link formation between fibrin strands to make a stable clot
61
Which sides of the clotting cascade do you use PT and PTT
```
PT = extrinsic
PTT = intrinsic (table tennis)
```
62
Which sides of the clotting ascade are heparin and warfarin affected
```
extrinsic = warfarin (W, PT)
intrinsic = heparin (PTT, HEP)
```
63
What is haemophilia A a deficiency of?
Factor VIII
64
What is haemophilia B a deficiency of?
Factor IX
65
What are 5 causes of DIC?
1) malignancy
2) sepsis
3 trama
4) obstetric complication
5) toxins
66
What is TTP due to a LACK of?
ADAMTS13
67
If you are ADAMTS13 negative what would this indicate?
TTP
68
What toxin can induce Haemolytic uraemic syndrome?
E. Coli 0157
69
What is the treatment for HUS?
plasma exchange
70
What happens in factor V leiden?
factor Va is not broken down, meaning increased production of thrombin --> increased risk of VTE
71
Acute leukaemia GENERALLY is the overprodcution of
BLAST CELLS - immature
72
What are the symptoms of BM failure
ANAEMIA - faigue, SOB, chest pain
THROMBOCYTOPENIA - bleeding
NEUTROPENIA - infection
73
What are risk factors for leukaemia?
- chemotherapy
- radiotherapy
- Downs syndrome
74
What cells are prominent in AML?
neutrophils
monocytes
macrophages
75
What are Auer rods found in?
AML
76
What cells feature heavily in ALL?
T and b cells
77
What is a faggot cell, and what might it indicate?
"bundle of twigs"
| Acute promyelocytic leukaemia (M3 - subtype of AML)
78
if you see a leukaemia with gum infiltration what should you think of?
Subtype of AML - M4 and M5
79
what mutation causes the majority of CML?
philadelphia chromosome - 9:22
| BCR-ABL fusion gene
80
What can you now use to treat CML and how does it work?
tyrosine kinase inhibitors - e.g. imatinib
| targets the BCR-ABL fusion gene which inhibits the disease process
81
what are smear cells on a FBC film indicative of?
CLL
82
What is it called when CLL is associated with other autoimmune problems such as ITP?
Evans syndrome
83
what is first line treatment for symptomatic CLL?
chlorambucil
84
What are myelodysplastic syndromes characterised by?
development of a clone of bone marrow stem cells with abnormal maturation resulting in: 1) functionallydefective blood cells and 2) reduction in number
85
give 3 major morphological features you may find in the blood in MDS?
1) WBCs - pelger huet cells - bilobed / immature neutrophils
2) platelets - micromegakaryocytes, hypolobated nuclei
3) RBCs = ring sideroblasts
86
by definition all patients with myelodysplastic syndrome have
<20%
87
what does RCMD-RS mean? and what haematological illness might you find it?
refractory cytopenia with multilienage dysplasia - with ringed sideroblasts - MDS
88
whats the difference between RAEB-I and RAEB-II?
Refractory anaemia with excess blasts-I = cytopenias with <5% blasts in blood and NO auer rods, and 5-9% blasts in the BM
RAEB-II = in blood: cytopenia OR 5-19% blasts OR auer rods, in BM dysplasia with 10-19% blasts or auer rods
89
What % of people develop AML from MDS?
50% in
90
what supportive treatment can be offered for MDS?
- blood transfusions
- EPO
- GCSF injections
- Abx
91
What kind of age distrbution does Myelodysplasia have?
elderly population - over 60 generally
92
What is the mortality of MDS?
rule of thirds:
1/3 die of infection
1/3 die of bleeding
1/3 die of acute leukaemia
93
what are the most common causes of aplastic anaemia?
1) idiopathic (70%)
2) inherited (10%)
3) secondary to malignancy / radiation / drugs / chemo (10-15%)
94
What is the supportive treatment for AA?
- blood products (leuodepleted)
- Abx
- iron chelation
95
what are 3 complications of immunosuppressive therapy for aplastic anaemia?
1) relapse of AA (35% over 15 years)
2) clonal haem disorders: MDS / leukaemia / PNH (20% risk over 20 years)
3) Solid tumours (3% risk)
96
What is the risk of relapse of Aplastic anaemia if treated with immunosuppression
35% over 15 years
97
what is the most common form of aplastic anaemia?
Fanconi anaemia
98
Name some congenital abnormalies found in 70% children with fanconi anaemia
- short
- weird thumbs
- cafe au lait spots
micro / hydrocephaly
- hypogonadism
- developmental delay
99
a patient presenting with skin pigmentation, nail dystrophy and leukoplakia is likely to have...?
Dyskeratosis congenita
100
What is leucoplakia? and what haematological disorder does it feature in
Development of white lesions on gums, inside mouth and sometimes tongue - feature of Dyskeratosis congenita
101
Name a drug that promotes bone marrow recovery
oxymetholone
102
What is the main chromosomal abnormality featuring in idiopathic aplastic anaemia and dyskeratosis congenita?
short telomeres
103
how is dyskeratosis congenta inherited?
X-linked
104
what is the definition of lymphomas?
a neoplastic (malignant) tumour of lymphoid cells
105
in lymphomas where are tumours usually found?
- lymph nodes, bone marrow and blood
- sometimes spleen and GALT (MALT)
- occasionally anywhwhere - skin, breast
106
give 3 reasons why the adaptive immune system results in the risk of lymphoma
1) Rapid cell proliferation
2) dependent on apoptosis (90% normal cells die)
3) antigen specificity in T cells and B cells is by cutting & rejoining DNA (VDJ) - increasing point mutations/ translocations
107
What is the general molecular basis of lymphoma?
- tanslocations involving the Ig locus --> area where promoter is highly active (making LOADS OF t AND b CELLS NORMALLY) --> if oncogene is translocated closely downstream of the promoter you get upregulation of oncogene expression
108
Give 3 examples of lymphoma oncogenes
bcl2
bcl6
Myc
109
give 3 risk factors/causes for lymphoma
1) constant antigenic stimulation
2) infection (direct viral infection of lymphocytes)
3) loss of T cell function (HIV - immunosuppression)
110
why is chronic antigen stimulation a risk factor for lymphoma and give 3 examples of conditions which relate to this
antigen stimulation triggers lymphocyte proliferation so there's more chance of mutation
1) Chronic gut infection with H. pylori - GALT lymphoma
2) Sjogrens syndrome - (saliva gland) parotid lymphoma
3) Coeliacs (with uncontrolled diet) - small bowel T cell lymphom, EATL (enteropathy associatedT cell lymphoma) - v aggressive
111
What is the classic example of a virus which infects t CELLS BY DIRECT VERTICAL TRANSMISSion, and what can this lead to?
HTLV1
| adult T cell leukaemia lymphoma
112
WHy do HIV patients have a higher risk of lymphoma? what type particularly?
have 60 fold increase in risk of B cell Non Hodgkins lymphoma, due to the loss of T cell regulation of EBV infected B cells
113
What cells does EBV infect?
B lymphocytes
114
Why are post-transplant lymphomas a thing
- give patients immunosuppressants like cyclosporin & steroids to prevent T cell mediated organ rejection
- this also allows uncontrolled EBV infected B lymphocyte proliferation resulting in lymphoma
115
what antigens do you look for in immunohistochemistry when diagnosing lymphoma, and what information can this tell you?
CD markers - over 100 types
can tell you what type of lymphoma and what stage of development
116
What is the most common type of lymphoma? (what%?)
B cell type non-hodgkins lymphoma - 80-85%
117
What is a t(11;14) chromosomal translocation diagnostic for?
Mantle cell lymphoma - the translocation causes overexpression of cyclin D1 - leading to unregulated overgrowth of B cells
118
What is it called when a low grade lymphoma changes into a high grade?
Richter transformation
119
What markers are typically present in B cell lymphomas which are detected with immunochemistry?
CD5 & CD23
120
Which lymphoma typically has a starry sky appearance on a histological examination?
Burkitt's lymphoma
121
Name an intermediate grade B cell lymphoma
Burkitt's lymphoma
122
What are 4 common low grade B cell lymphomas?
1) Mantle zone
2) follicular
3) small lymphocytic lymphoma / chromic lymphocytic leukaemia
4) marginal zone
123
Name a high grade (rapid growth, very ill, masses develop quickly) B cell lymphoma
Diffuse large B cell lymphoma
124
What type of lymphoma do you see sheets of large lymphoid cells
Diffuse large B cell lymphoma
125
anaplastic large cell lymphoma mainly affects who?
children / young adults
126
what's the difference between Hodgkin and non-Hodgkin terms of spread characteristics?
Hodgkin's = Spreads CONTINUOUSLY to adjacent lymph nodes, whereas non-Hodgkins spreads discontinuously,
127
what do Reed-Sternberg cells indicate?
Classical Hodgkin Lymphoma
128
what is the incidence of Hogkins lymphoma?
Bimodal - young 20-29 and another peak >60
129
describe the staging for lymphoma
I - one group of nodes
II - >1 group of nodes same side of diaphragm
III - nodes above and below diaphragm
IV- extranodal spread
then suffix A = no extra red flags
B - unexplained weight loss >10% in 6 months / night sweats / fever
130
What is the treatment for hodgkins lymphoma?
ABVD chemotherapy (2 or 6 cycles)
+/- radiotherapy
PET scans to check for persistance of active disease
131
What is the current chemotherapy reigeme for Hodgkins lymphoma?
ABVD - given at 4 weekly intervals
Adriamycin
Bleomycin
Vinblastine
DTIC
132
What is the advantage of ABVD over MOPP chemotherapy?
preserves fertility
133
What are 2 negative long term SEs of ABVD treatment for HL?
- pulmonary fibrosis
| - cardiomyopathy
134
What is a typical presentation of Non hodgkins lymphoma?
- painless lymphadenopathy
- compression symptoms
- B symptoms (fever, weight loss, night sweats)
135
What is the main change to the FBC in pregnancy?
macrocytic anaemia
| --> RBC mass rises (120-130%) and plasma volume rises (150%) so net dilution
136
How does pregnancy affect iron requirements?
Demand increases due to fetus and red cell mass increase -
foestus = 300mg
RBC expansion = 500mg
so increase daily intake RDA: 30-60mg supplements + 400mcg folic acid daily
137
What can maternal anaemia be a risk for in pregnancy?
Low birth weight
Miscarriage
Puerperal sepsis (infection of the uterus post partum)
138
What can iron deficiency in pregnancy be a risk for (3 things)
1. IUGR (intrauterine growth restriction)
2. prematurity
3. postpartum haemorrhage
139
what is the WHO recommendation for iron supplementation in pregnancy?
30-60mg Fe
| + 400 mcg folic acid - however this isnt advised in the UK
140
what is the benefit of taking folic acid supplements during pregnancy?
reduces the risk of neural tube defects
141
WHat happens to the platelet count in pregnancy?
Thrombocytopenia
| in 13% women falls below 150 x 10(9)/L
142
Give 3 main causes of thrombocytopena in pregnancy
1) gestational (physiological)
2) pre-eclampsia
3) ITP
- can also be due to microangiopathic syndromes or others like BM failure, leukaemia, hypersplenism, DIC
143
what are the 5 general criteria for gestational thrombocytopenia?
1. Mild and asymptomatic thrombocytopenia typically >70 x 10(9) /L
2. no past Hx of thrombocytopenia
3. happens during late gestation
4. no association with foetal thrombocytopenia
5. spontaneous resolution after delivery .
144
what proportion of women with pre-eclampsia get thrombocytopenia?
50%
145
What are the Tx options for ITP in pregnancy?
1. IV Immunoglobulin
2. Steroids
3. Anti D if Rh D +
146
What are the 3 most common causes of mortality in pregnancy?
VTE
preeclampsia
haemorrhage
genital tract sepsis
147
Give 4 main coagulation changes in pregnancy?
HYPERCOAGULABLE and HYPOFIBRINOLYTIC
- increased thrombin generation
- increased fibrin cleavage
- reduced fibrinolysisi
148
What is a big risk factor for maternal death due to PE?
BMI
| + FHx
149
How should you treat women at high risk of VTW in pregnancy?
```
prophylactic heparin (LMWH)
TED stockings
```
150
Which anticoagulant is advised for pregnant women (and why!)
Heparin - as does not traverse the placenta (whereas warfarin DOES cross the placenta)
151
What type of thrombophilia is associated with recurrant miscarriage. + persistant lupus anticoagulant (LA) / anticardiolipin abs (ACL)?
APLS - antiphospholipid syndrome
152
What type of antibodies are against RBC surface antigens?
IgM antibodies - anti-A & anti-B
153
what type of antibodies are anti-D antibodies?
IgG
154
What are the majority of the population in terms of the RhD antigen?
85% RhD +
| 15% RhD negative
155
What type of blood can RhD + patients recieve?
RhD + and - cells
156
What type of blood can RhD negative patients get?
they lack the RhD antigen
Therefore can MAKE RhD antibodies if exposed to the RhD+ antigens on RBCs
- so best to give RhD -ve patients negative blood, although more important in pregnancy
157
What type of reaction occurs if you give an RhD - patient RhD + blood?
May induce formation of anti-D antibodies (IgG) --> this does not cause agglutinaton of RBCs so not immediate haemolysis and death but delayed haemolytic transfusion reaction
158
What problems in pregnancy can an Rh - mother with anti-D antobodies result in?
If mother exposed to Rh+ blood, can cause haemolytic disease of the newborn (HDN)
or severe fatal anemai and heart failure (hydrops fatalis)
159
What is the standard way to prevent anti-D formation in a RhD- woman
give IM anti-D Ig when at high risk of feto-haemorrhage
160
What blood types should you worry about in pregnant women?
If mother RhD- and foetus RHD + then you'd consider giving woman anti-D Ig
161
What are you checking in a blood antibody screen?
Immune antibodies (IgG) in the blood (not the naturally occurring ABO antibodies that are IgM) that are atypical and occur in 1-3% patients
162
What kind of haemolysis can happen in a blood transfusion where the patient has atypical immune antibodies in their plasma
can form antibody:antigen complexes with transfused RBCs resulting in an extravascular haemolysis in the spleen
163
What group of patients should you give K negative blood to and why?
Women of childbearing potential - because anti-K can cause HDN
164
What are the routine times to give a woman anti-D Ig if she is Rh negative?
28 and 34 weeks
during pregnancy if a sensitising event occurs (abortion, miscarriage, abdo trauma, external cephalic version)
At delivery if the baby is Rhd +
165
What type of plasma can be given to everyone, but it's in short supply?
AB - has no anti-A or anti-B antibodies in it
166
What volume of blood loss should trigger blood transfusion?
30% blood volume lost
167
how much Hb does 1 unit of blood give in a 70-80kg person?
1 unit = 10g/L Hb
168
When should you crossmatch blood sbefore surgery, and when do you not need to bother?
Group and screen firsat and then Must crossmatch if there are antibodies present, but if no antibodies then don't have to - just save sample in the fridge
169
What patients require irradiated blood, and what severe complication can happen if it isn't?
Immunosuppressed patients who cannot destroy incoming donor lymphocytes - this can cause transfusion associated graft vs host disease (TA-GvHD)
170
give 3 indications for giving FFP (fresh frozen plasma)
1. massive transfusion (blood loss > 150ml/min)
2. DIC (with bleeding)
3. Liver disease
171
What is the treatment for reversing warfarin?
PCC - prothrombin complex concentrate
172
Give 3 examples of (immune) causes of acute adverse reactions to a blood transfusion
1. ABO incompatibility
2. allergic / anaphylactic
3. febrile non haemolytic
173
What is TACO?
transfusion associated circulatory overload
174
name some general symptoms that may arise in an acute reaction to a blood transfusion
fever, rigors, flushing, vomiting, dyspnoea, pain, loin pain, chest pain, urticaria, headache, collapse
175
What is the likely diagnosis and treatment in a patient receiving a blood transfusion suddenly becoming febrile and experiencing chills/rigors?
Febrile non haemolytic transfusion reaction (FNHTR)
| paracetamol +/- slowing/ stopping/ restarting transfusion
176
What is the likely diagnosis if a patient suddenly comes up in an urticarial rash and starts wheezing after a blood transfusion?
Allergy transfusion reaction
| Tx = IV antihistamines
177
what is the cause of an Allergy transfusion reaction
aLLERGY TO PLASMA PROTEIN IN THE particular DONOR - won't necessrily happen again, depends how common the allergen is
178
How might a bacterial contamination of donor blood affect a patient receiving it in a transfusion?
- similar presentation to ABO incompatibility
| - fever, vomiting, flushing, collapse, tachycardia and low blood pressure, (SHOCK)
179
what is the basic mechanism causing TRALI
anti-wbc antibodies in the donor's blood (usually anti HLA or neutrophil) react with the antigens of recepient's WBCs - aggregations get stuck in the pulmonary capillaries and release of neutrophil proteolytic enzymes and toxic 02 metabolites = lung damage
180
describe delayed haemolytic transfusion reaction?
1. 1-3% patients having transfusions develop immune antibody to an antigen they dont have (allmmunisation)
2. Then if transfused again with blood containing the same antigen then patient has Abs which cause RBC destruction - Extravascular haemolysis (IgG - 5-10 days later)
181
Describe the symptoms you might see in TA-GvHD
severe diarrhoea, skin desquamation, bone marrow failure, death
182
which antibodies are able to cross the placenta - potentially causing HDFN
IgG Rh+ antibodies
183
What is the risk of a hyperbilirubinaemia in newborns
kernicterus
184
What is the treatment for neonatal jaundice?
light therapy +/- exchange transfusion
185
Describe how the prophylactic anti-D Ig injection works?
--> anti-D Ig coat the RhD+ RBCs, which are then removed by mother's reticuloendothelial system BEFORE they can sensitise mother to produce anti-D antibodies --> Must give anti-D Ig injection within 72 hours of the sensitising event
186
give some examples of "sensitising events" during pregnancy which are indications for anti-D Ig
basically where FMH is likely to occur (fetal maternal haemorrhage)
- -> spontaneous miscarriages
- -> amniocentesis & CVS
- --> abdo trauma
- -> external cephalic version
- -> stillbirth / intrauterine death
187
apart from anti-D , what 2 other antibodies can cause severe HDN
anti-K (Kell)
| anti-c
188
What levels of Hb are classed as anaemia in men and women?
Men; <135g/L
| Women: <115 g/L
189
Causes of Macrocytic anaemia
```
FATRBC
pregnancy
Antifolates
HypoThyroidism
Reticulocytosis
B12 defciency
Cirrhosis - alcohol/liver disease
```
190
Causes of microcytic anameia
```
FAST
Fe iron deficiency
Anaemia of chronic disease
Sideroblastic anaemia
Thalassaemia
```
191
CAUSES OF NORMOCYTIC Anaemia
```
Acute blood loss
Anaemia of chronic disease
Hypothyroidism
Renal Failure
Bone Marrow Failure
Pregnancy
haemolysis
```
192
Give the signs you would see on a blood film that would be consistent with iron deficiency anaemia
Microcytic, hypochromic, poikilocytosis, anisocytosis, pencil cells
193
Causes of Iron deficiency anaemia
Bleeding until proven otherwise, but consider all:
1. Blood loss - tends to be GI e.g. gastric ulcer, meckel's diverticulum, malignancy, menorrhagia
2. increased use - pregnancy, children growing
3. decreased intake - e.g. elderly malabsorption, prematurity
4. malabsorption - coeliacs, post surgery
5. intravascular haemolysis - MAHA, NPH
194
Is ferritin high or low in anaemia of chronic disease
High (unless co-existing Fe-deficiency) - because Fe gets sequestered in macrophages to protect it from invading bacteria
195
how do you diagnose sideroblastic anaemia
look for ringed sideroblasts in the bone marrow
196
What are ringed sideroblasts?
erythrocyte precursors with iron deposited in the mitochondria which makes a ring around the nucleus
197
describe a megaloblastic blood film
macrocytic anaemia, hypersegmented polymorphs, leucopenia, thrombocytopenia,
198
What causes megaloblastic anaemia
due to inhibition of DNA synthesis during RBC production. E.g. cytotoxic drugs, folate deficiency, B12 deficiency.
199
What are 3 megaloblastic causes of macrocytic anaemia
B12 deficiency, folate deficiency, cytotoxic drugs
200
what is pernicious anaemia?
autoimmune atropohic gastritis, resulting in attack of the parietal cells so absence of HCL and
201
how do you diagnose pernicious anaemia?
Anti-parietal cell antibodies
- Anti-IF antibodies
(used to do schillings test but outdated now)
202
Treatment for B12 deficiency?
IM hydroxocobalamin (B12)
203
causes of folate deficiency
Diet - e.g. not eating enough fresh leafy veg
Malabsorption - Coeliacs
Drugs - alcohol, methotrexate, trimethoprim
Increased turnover e.g. pregnancy, malignancy, renal dialysis
204
What signs in the blood would you see in intravascular haemolysis?
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Increased bilirubin
increased urobilinogen
increased LDH
reticulocytosis (so increased MCV and polychromasia)
may have pigmented gallstones
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increased free plasma Hb
decreased haptoglobin (as it binds free Hb)
Haemoglobulinuria
Haem + albumin in the blood
205
What is the inheritance of G6PD deficiency?
X linked recessive
206
What things precipitate a haemolytic episode in G6PD deficiency?
oxidants: drugs - primaquine, aspirin, fava beans, acute infection,
207
What does G6PD help synthesise to protect RBCs from oxidate damage normally?
glutathione
208
What signs might you see in G6PD deficiency?
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Heinz bodies on a blood film,
(Neonatal) jaundice
Dark urine
splenomegaly
gall stones common
```
209
how is spherocytosis inherited
autosomal dominant
210
spectrin deficiency is seen in which haemolytic disorders?
Hereditary spherocytosis
| Hereditary elliptocytosis
211
what is the mutation causing sickle cell disease
single base mutation on codon 6 of beta-chain - GAG-->GTG (Glu --> Val) creasing HbS
212
Why does SSD only manifest at 3 months of age?
corresponds to decreasing levels of Fetal Hb (HbF)
213
How is sickle cell diagnosed?
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Heel prick test
Blood film - sickle cells and taget cells
sickle solubility test
elelctrphoresis
Family history
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214
Which antibodies stick to RBCs in paroxysmal cold haemaglobinuria?
Donath-Lansteiner antibodies
215
what are the RBC markers that indicate a patient has paroxysmal nocturnal haemaglobinuria
GPI marker on the surface membrane
216
what are the most serious complications of Paroxysmal nocturnal haemaglobinuria?
Thrombosis - PE, DVT, thrombosis in the hepatic veins - Budd-Chiari, superior and anterior mesenteric veins: ischaemia
217
Treatment for PNH?
- iron and folate
- prophylactic Abx
- monoclonal antibody therapy (prevents complement binding the the RBCs causing lysis) -> eculizumab EXPENSIVE!! `
218
What infection causes HUS?
E coli
219
What is Osler-Weber-Rendu syndrome?
aka hereditary haemorrhagic telangectasia - autosomal dominant condition characterised by abnormal blood vessels in mucous membranes and organs - get lots of nosebleeds
220
Give 2 examples of congenital disorders which are a vascular cause of bleeding disorders
1. osler-weber-rendu syndome
| 2. Ehler-Danlos
221
what is deficient in Haemophilia A?
Factor VIII
222
What is deficient in Haemophilia B?
Factor IX
223
What is the manaement of von willebrands disease?
Desmopressin (stimulated more VWF)
| VWF + F VIII concentrates
224
What is storage pool disease?
congenital condition causing reduced platelet function resulting in increased bleeding. aka gray platelet syndrome
225
Which clotting factors are affected by vitamin K deficiency?
2, 7, 9 and 10 and protein C/S
226
DVT prophylaxis =
injections of LMWH (eg enoxaparin/clexane) + TED stockings
227
Treatment of a PE/DVT=
LMWH (175 units/kg) + Warfarin +/- NOAC - stop LMWH once INR in therapeutic range (2.5)
