Haematology Flashcards
1
Q
What is the iron requirement for the foetus?
A
300 mg
2
Q
What is the main reason for mild anaemia during pregnancy?
A
- Increased red cell mass (120-130%)
- Plasma volume increases (150%)
3
Q
Which vitamin increases iron absorption from non-haem food?
A
Vitamin C
4
Q
Which iron supplements are prescribed for pregnant women?
A
Pregaday 100 mg
Prenacare 17 mg
Ferrous sulphate 65 mg (in 200mg dose).
5
Q
What is the additional folate requirement during pregnancy (in mcg/day)?
A
Additional 200 mcg/day
6
Q
When should folate supplementation be prescribed?
A
Before conception and for >12 weeks gestation
7
Q
What is the folate supplement dose during prengnacy?
A
400 ug/Day
8
Q
What is the definition of anaemia in pregnancy for the first trimester in Hb g/L?
A
<110 g/L
9
Q
What are the complications of iron deficiency during pregnancy?
A
IUGR
Prematurity
Postpartum haemorrhage
10
Q
What is the definition of anaemia in pregnancy for the second and thid trimester in Hb g/L?
A
<105 g/L
11
Q
What is the definition of anaemia in pregnancy during the postpartum period in Hb g/L?
A
100 g/L
12
Q
What are the physiological causes of thrombocytopenia during pregnancy?
A
Physiological - gestational/incidental thrombocytopenia
13
Q
What is HELLP syndrome associated with?
A
Pre-eclampsia
14
Q
What is HELLP syndrome?
A
Haemolysis, elevated liver enzymes, Low platelets
15
Q
What is immune thrombocytopenia?
A
Isolated low platelet count
16
Q
What is the first line management for early onset immune thrombocytopenia during pregnancy?
A
IV immunoglobulin
Review treatment options for bleeding and delivery
Steroids
17
Q
What should be assessed and monitored in neonates with a history of maternal ITP?
A
Check cord blood and then daily (IgG antibodies can cross the placenta)
- Nadir low occurs 5 days after delivery
18
Q
In neonates born with a history of maternal ITP, at what day of life does ITP occur (nadir)?
A
Day 5
19
Q
Define microangiopathic syndromes
A
Deposition of platelet in small blood vessels (platelet rich thrombi)
Thrombocytopenia
Fragmentation (Schistocytes) and lysis of RBCs within the vasculature
20
Q
What type of RBC is evident in MAHA?
A
Schistocytes
21
Q
What is the leading cause of maternal mortality?
A
Pulmonary embolism
22
Q
What risk factor is a predictor of VTE and PE during pregnancy?
A
BMI >25 - need to be on heparin from the first trimester
23
Q
What VTE prophylaxis is administered in pregnant women with a BMI >25?
A
Heparin
24
Q
Which prothrombotic factors are increased during pregnancy (4)?
A
Factor VIII
vWF
Fibrinogen
Factor VII
25
Which pro-fibrinolytic factors are reduced during pregnancy?
Protein S
PAI-1/2
26
At what stage postpartum is the highest incidence of PE?
6 weeks
27
What stage during pregnancy is the highest risk of PE?
First trimester
28
Which investigations are safe to perform during pregnancy to assess for PE?
Doppler and VQ
29
What is the prophylactic management pregnant women at risk of VTE?
Heparin and TED stockings
- Low molecular weight heparin
30
Why is low molecular weight heparin safe during pregnancy?
Does not cross the placenta,
31
What should be measured after the 1st trimester in obstetric patients on LMWH?
Anti-Xa
32
What are the complications of pregnancy associated with thrombosis?
- IUGR
-Recurrent miscarriage
-Late foetal loss
-Placental abruption
Severe PET (Pre-eclampsia)
33
What is the diagnostic criteria of antiphospholipid syndrome?
Recurrent miscarriage (>3)
Persistent lupus anticoagulant or anticardiolipin or antiphospholipid antibodies
34
What is the definition of PPH?
* > 500 mL blood loss
* 5% of pregnancies have blood loss >1 L at delivery.
35
What are the two major risk factors for PPH?
Uterine atony
Trauma
36
Define amniotic fluid embolism
* Presumed due to TF in amniotic fluid entering maternal bloodstream – sudden onset fevers, vomiting, shock, DIC.
37
Which serum monoclonal IgG/IgA is associated with multiple myleoma?
Paraprotein/M-spike
Excess of monoclonal (k or lambda) serum free light chains
38
Which two types of serum free light chains are elevated in multiple myeloma?
Kappa/lambda
39
Which urine monoclonal free light chain is elevated in urine in MM?
Bence jones protein
40
Which cell is malignant iN MM?
Plasma cells
41
What is the median age for MM?
67 years - incidence increases with age
42
Which ethnicity is most affected by MM?
Black
43
What is myeloma preceded by?
Monoclonal gammopathy of uncertain significance (MGUS)
44
Which red cell feature is observed on peripheral blood film in patients with lead poisoning, megaloblastic anaemia, and myelodysplasia?
Basophilic RBC stippling
45
Which red cell feature describes a sea urchin with regular spicules (often an artefact)?
Burr cells (echinocytes)
46
Which red cell feature is observed on peripheral blood film in glucose-6-phosphate dehydrogenase deficiency?
Heinz bodies
47
Which red cell feature is observed on peripheral blood film in post-splenectomy/hyposplenism?
Howell-Jolly bodies
48
Howell-Jolly bodies indicate what?
Post-splenectomy or hyposplenism
49
Which hyposegmented neutrophil with 2 lobes is associated with myelodysplastic syndrome?
Pelger Huet Cells
50
Pelger Huet Cells is associated with which haematological syndrome?
Myelodysplastic syndrome
51
Right shift is associated with haematological disorder?
Megaloblastic anaemia
52
Rouleaux formation is associated with what?
Multiple myeloma
53
Which characteristic cell type is associated with microangiopathic anaemia and DIC?
schistocytes
54
Target cells are associated with what?
Liver disease, hyposplenism, thalassaemia, IDA
55
What is the anaemia threshold for men?
<135 g/L
56
What is the anaemia threshold for women?
<115 g/L
57
What are the symptoms of anaemia?
* Fatigue, dyspnoea, faintness, palpitations, headache, tinnitus, anorexia.
58
Which murmur is associated with anaemia?
Ejection systolic murmur (loudest over apex)
59
A high MCV anaemia is associated with what cause of anaemia?
Decreased production of RBCs e.g., folate and B12 deficiency
60
What are the causes of microcytic anaemia?
Thalassaemia
Anaemia of chronic disease
Iron deficiency anaemia
Lead poisoning
Sideroblastic anaemia
61
What are the causes of normocytic anaemia?
Acute blood loss
Anaemia of chronic disease
Bone marrow failure
Renal failure
Hypothyroidism
Haemolysis
Pregnancy
62
What are the causes of macrocytic anaemia (FATRBC)?
Fetus (pregnancy)
Antifolates (e.g. phenytoin)
Thyroid (hypothyroidism)
Reticulocytosis (release of larger immature cells e.g. with haemolysis)
B12 or folate deficiency
Cirrhosis (Alcohol excess or liver disease)
Myelodysplastic syndromes
63
What are the signs of iron deficiency anaemia?
Koilonychia, atrophic gastritis, angular cheilosis, post-cricoid webs (Plummer–Vinson Syndrome); brittle hair and nails.
64
Plummer Vinson syndrome is associated with which haematological condition?
Iron deficiency anaemia
65
What blood film finding is associated with iron deficiency anaemia?
Microcytic, hypochromic, anisocytosis, poikilocytosis pencil cells
66
What are the commonest cause of blood-loss related iron deficiency anaemia?
– Meckel’s diverticulum (older children)
– Peptic ulcers / Gastritis (chronic NSAID use)
– Polyps/colorectal Ca (most common cause in adults >50yrs)
– Menorrhagia (women <50 yrs)
– Hookworm infestation (developing countries)
67
What is the management for a patient >60 years with IDA?
Referred for 2ww colorectal cancer pathway
68
What is the 1st line management for IDA?
Oral ferrous sulphate
69
What are the side effects associated with iron sulphate supplementation?
Nausea, abdominal discomfort, diarrhoea/constipation, black stools.
70
What is the management of IDA in sepsis and severe infection?
Blood transfusions
71
Which inflammatory markers are associated with down-regulating EPO receptor production?
IFNs, TNF and IL-1
72
Il-6 stimulates the production of which hormone in anaemia of chronic disease?
Hepcidin
73
What role/effect does hepcidin have?
Reduces gastrointestinal iron absorption (transferrin inhibition) + iron accumulation in macrophages
74
What are the common causes of anaemia of chronic disease?
* Chronic infection e.g., TB, osteomyelitis.
* Vasculitis
* Rheumatoid arthritis
* Malignancy
75
What are ring sideroblasts?
Non-haem iron in mitochondria
76
Ring sideroblasts are associated with what?
Ineffective erythropoiesis - hemosiderosis
77
What are the causes of sideroblastic anaemia?
* Myelodysplastic disorders, following chemotherapy, irradiation, alcohol excess, anti-TB drugs, or myeloproliferative disease.
78
Which drug is used to treat sideroblatic anaemia?
pyridoxine
79
What is pyridoxine?
Vitamin b6
80
TIBC in IDA?
Raised
81
Ferritin level in IDA?
Low
82
TIBC in anaemia of chronic disease?
Low
83
Ferritin level in anaemia of chronic disease?
Raised
84
TIBC in hereditary haemochromatosis?
Low
85
Ferritin level in hereditary haemochromatosis?
Raised
86
What is the TIBC in pregnancy?
Raised
87
Transferrin saturation reflects what?
Serum iron
88
Which TIBC % is indicative of iron deficiency?
<20%
89
What type of protein in ferritin?
Acute phase protein
90
A low reticulocyte in pancytopenia is indicative of what?
Aplastic anaemia/bone marrow failure syndromes e.g., Fanconi Anaemia/dyskeratosis congenita
91
What are the sources of vitamin b12 (cobalamin)?
Red meat, dairy, and eggs
92
What autoantibody is associated with pernicious anaemia?
Anti-intrinsic factor antibodies
93
Pernicious anaemia is associated with reduced absorption of vitamin B12 from which part of the gastrointestinal tract?
Terminal ileum
94
Which cell secretes intrinsic factor?
Parietal cells
95
What are the three main causes of Vitamin B12 deficiency?
Gastric bypass (inadequate parietal cells)
Achlorhydria-induced malabsorption
Terminal ileum disease - Crohn's disease, ileal resections, bacterial overgrowth, topical sprue, tapeworm
96
Which mouth signs are associated with vitamin B12 deficiency?
Glossitis, angular cheilosis
97
What are the neuropsychiatric findings associated with Vitamin B12 deficiency?
Irritability, depression, psychosis, and dementia
98
What are the neurological findings are associated with vitamin B12 deficiency?
Paraesthesia, peripheral neuropathy
99
What is the most common cause of macrocytic anaemia in Western countries (aged >40 years)?
Pernicious anaemia – autoimmune atrophic gastritis – achlorhydria
100
What are the specific investigations performed for suspected pernicious anaemia?
Parietal cell antibodies (90%), intrinsic factor antibodies (50%); Schilling Test.
101
What is the management for dietary-associated vitamin B12 deficiency?
Replenish stores with IM hydroxocobalamin (B12) in 6 injections over 2 weeks
102
What is the management for autoimmune-associated with Vitamin b12 deficiency?
3-monthly IM injections
103
What markers are raised in haemolytic anaemia?
Unconjugated bilirubin
Urobilinogen
LDH
Reticulocyte count
104
What marker is low in intravascular haemolytic anaemia?
Haptoglobin
105
What is Methaemalbuminaemia ?
Haem + albumin in blood
106
Where does extravascular haemolytic anaemia occur?
Spleen - removal in reticuloendothelial system
107
What are the consequences of of haemolysis?
Erythroid hyperplasia state
Increased folate demand
Anaemia
Reticulocyte count
108
What is the inheritance pattern of G6PDD?
X-linked
109
Which class of drugs are associated with potentiating G6PDD?
Oxidative drugs:
- Drugs can induce haemolytic anaemia.
- Dapsone
- Primaquine (Antimalarials)
- Sulphonamides (Antibiotics)
- High-dose aspirin
* Exposure to fava/broad beans and mothballs
110
Which class of ABx is associated with G6PDD?
Sulphonamides
111
Which clinical manifestation is associated with intravascular haemolysis?
Dark urine - indicative of haemoglobinuria
112
What two types of findings are detected on a peripheral blood smear in G6PDD?
1 - Bite cells
2. Heinz bodies
113
Define Heinz bodies?
Fragments of denatured oxidised haemoglobin
114
Define bite cells?
Hemi-ghosts, nucleated RBCs, blister cells
115
What is the management of acute haemolysis associated with G6PDD?
Acute haemolysis - supportive care with folic acid
* Haemoglobin <70 g/L – Blood transfusion.
Neonatal jaundice - phototherapy
116
What is the inheritance pattern with pyruvate kinase deficiency?
Autosomal recessive - mutation in chromosome 1q21
117
What is the role of pyruvate kinase in RBCs?
PK converts phosphoenolpyruvate to pyruvate - decreases RBC ATP production
118
What is the consequence of decreased RBC ATP production in pyruvate kinase deficiency?
Decreases RBC ATP production (intracellular potassium + water loss) - Extravascular haemolysis.
119
Why is there a blueberry muffin rash in pyruvate kinase deficiency?
Indicative of extramedullary haemopoesis
120
What is the neonatal presentation of pyruvate kinase deficiency?
* Hyperbilirubinaemia and anaemia
* Worsening pallor in the first week
* Poor suckling
* Lethargy and poor weight gain
* Neonatal jaundice
- Kernicterus
* Blueberry muffin rash – indicates extramedullary haemopoiesis.
121
What characteristic finding is associated with pyruvate kinase deficiency in older children?
Hepatosplenomegaly
122
What is the inheritance pattern of sickle cell disease?
Autosomal recessive
123
Which codon is implicated in sickle cell disease?
Codon 6 of the beta-globin chain of human haemoglobin
124
What single amino acid substitution is associated with sickle cell disease?
Glu to Valine
(GAG to GTG mutation)
125
What triggers polymerisation of haemoglobin in RBCs in sickle cell disease?
Deoxygenation
126
Sickle cell disease is protective of what?
falciparum malaria
127
Which ethnicity is a risk factor of sickle cell disease?
Afro-Caribbean ethnicity
128
What is the genotype of sickle cell anaemia?
HbSS (Homozygous)
129
What is the genotype of sickle cell trait?
HbAs - asymptomatic except under stress e.g., cold, exercise
130
What is the consequence of deoxyHbs?
Results in damaged membrane cytoskeleton - vaso-occlusion
131
What are the two severe forms of sickle cell disease?
* Sickle-haemoglobin C disease
* Sickle B thalassaemia
132
What is the diagnostic investigation of sickle cell disease?
* Electrophoresis + sickle solubility test
133
Which test at birth is suggestive of sickle cell anaemia?
Guthrie test at birth
134
What cell types are observed in sickle cell diseae?
Sickle and target cells
135
What vasculopathy is associated with sickle cell disease?
Moyamoya diseae
136
What are the cardiorespiratory complications associated with sickle cell disease?
Acute chest syndrome
137
Sickle cell disease is predisposed to which viral infection?
Parvovirus b19
138
What is the first presenting symptom in children for sickle cell disease?
Dactylitis
139
When does HbF switch to HbS?
Between 6 and 12 months
140
When does splenic dysfunction occur in sickle cell disease?
141
What are the clinical manifestations of sickle cell disease in teenagers?
Impaired growth, gallstones, priapism, cognitive impairment (reduction in IQ due to silent cerebral infarction).
142
What is the acute management for sickle cell crises?
Analgesia e.g., paracetamol, NSAIDs, fluids and rest
- Strong opiate analgesia if severe pain risis
- Exchange transfusion for severe acute chest syndrome
143
What is the management for priapism in sickle cell disease?
Oral alpha-adrenergic agents (etilefrine) and analgesia + fluids
144
What prophylactic vaccinations is administered for chronic sickle cell disease?
Pneumococcus (pneumovax), meningococcus, and haemophilus
145
Which ABx is prescribed as part of the chronic management for sickle cell disease?
Penicillin V
146
What monitoring investigation is recommended in children with sickle cell disease?
Transcranial Doppler Screening
147
What intervention is administered to children to reduce the risk of stroke in sickle cell disease?
Exchange transfusion to maintain HbS <30%
148
Which drug indicated in the management of sickle cell disease is associated with increasing foetal haemoglobin?
Hydroxycarbamide
149
What class of drug is Crizanlizumab ?
An anti-P selectin agent
150
Which sickle cell disease drug is associated with reducing the frequency of vaso-occlusive crises?
* Crizanlizumab – An anti-P selectin agent
151
What is the mechanism of action of voxelotor in the management of sickle cell disease?
Inhibits polymerisation of haemoglobin and reduces haemolysis
152
Which drug indicated in the management of sickle cell anaemia is associated with the following mechanism: 'Inhibits polymerisation of haemoglobin and reduces haemolysis'?
voxelotor
153
What is the definitive management of sickle cell disease?
Haematopoeitic stem cell transplantation
154
Beta-thalassaemia causes which type of anaemia?
Microcytic anaemia resulting in ineffective erythropoiesis
155
What is the effect of beta-thalassaemia on alpha-globin chains?
Excess of unmatched alpha-globin chains
156
What are the three types of beta-thalassemia?
Major, intermediate, minor
157
What is the inheritance pattern of beta-thalassaemia?
Autosomal recessive
158
When does symptoms occur in beta-thalassasemia?
3-6 months of life (decline of HbF and increased production of Hba)
159
What is the genotype of beta thal intermedia?
B thal B thal (+)
160
What is the genotype of beta thal major?
B thal B thal (0)
161
What are the clinical manifestations associated with beta-thalassaemia?
* Lethargy
* Abdominal distension
* Failure to gain weight and height.
* Pallor
* Spinal changes – osteopenia related to iron overload and marrow expansion in vertebral bodies.
* Large head
- Frontal and parietal bossing
* Chipmunk facies
* Misaligned teeth
* Hepatosplenomegaly
* Jaundice
o Iron overload gonadal and heart failure.
162
What is the complication of alpha-thalassaemia (foetal)?
Bart's hydrops fatalis
163
What is the characteristic red cell type associated with beta-thalasssaemia?
Tear drops
164
On plain x-ray of skull - finding associated with beta-thalassaemia?
- Widening of diploeic space, facial deformity.
165
What is the gold-standard investigation for beta-thalassaemia?
Haemoglobin Electrophoresis - Raised A2
166
What is the management for beta-thalassaemia trait?
Genetic counselling and iron advice
167
What is the management for beta-thalassaemia intermedia?
* Transfusions at times of symptomatic anaemia
- Serial measurement of liver iron concentration (LIC) over time to measure iron loading and chelation therapy.
o Deferasirox
o Desferrioxamine
168
What is the management for beta-thalassaemia major?
* Regular red cell transfusions and iron chelation therapy
169
Which cell type is affected in multiple myeloma?
Plasma cells
170
Which urine monoclonal free light chain is associated with multiple myeloma?
* Bence Jones Protein
171
Which monoclonal serum free light chains are raised in multiple myleoma?
Kappa or lambda
172
What two processes occur in germinal centres regarding B-Cells?
Somatic hypermutation
Class switch recombination
173
Multiple myeloma is preceded by which condition?
* Monoclonal Gammopathy of Uncertain Significance (MGUS)
174
What is the diagnostic threshold for Serum M-protein for MGUS?
<30 g/L
175
What is the diagnostic threshold for bone marrow clonal plasma cells for MGUS?
<10%
176
What are the three risk factors associated with MGUS?
* Non-IgG M-spike
* M-spike >15g/L
* Abnormal serum free light chain (FLC) ratio
177
Smouldering myeloma is associated with a serum monoclonal protein level of what?
>30 g/L
178
What is the IMWG updated risk stratification model for smouldering myleoma?
* Spike >20 g/L
* Serum FLC Ratio >20
* Bone marrow myeloma cells >20%
179
What are the diagnostic features associated with smouldering myleoma?
M spine >3 g/dL
Urinary M protein >500 mg
PC >10%
No CRAB criteria
180
What uninvolved SFLC ratio is associated with myleoma?
>100
181
What type of amyloidosis can occur at any stage of multiple myeloma, MGUS etc?
AL amyloidosis
182
What are the primary events associated with multiple myeloma?
* Hypodiploidy – additional number of chromosomes
* IGH rearrangements
- t(11;14) IGH/CCND1
- t(4;14) IGH/FGFR3
- t(14;16) IGH/MAF
183
Which cell type is implicated in stimulating bone resorption in multiple myeloma?
Osteoclast activation
184
What are the CRAB criteria associated with multiple myeloma?
* Hypercalcaemia – Calcium >2.75 mmol/L
* Renal disease – Creatinine >177 mol/L or eGFR <40 ml/min
- Due to myeloma light chain deposition.
* Anaemia – Hb <100 g/L or drop by 20g/L
* Bone disease
- One or more bone lytic lesions in imaging
185
Which spinal complication is associated with multiple myleoma?
Metastatic spinal cord compression
and spinal mets
186
Which imaging modality is implicated in multiple myeloma for bone disease?
* Whole-body diffusion-weighted MRI
187
What is the first line investigation for suspected metastatic spinal cord compression in MM?
Spinal MRI
188
What is the first line management for MSCC?
Dexamethasone
189
What is the first line management for hypercalcaemia in MM?
o Management (1st line): IV fluids + IV bisphosphonates (zoledronic acid) + steroids.
190
What are the clinical manifestations associated with hypercalcaemia in MM?
* Calcium (Hypercalcaemia) – Thirst, moans, groans, stones, bones – constipation, muscle weakness, AKI.
191
What is the serum creatine threshold for renal failure in MM?
Serum Creatinine >177 umol/L
192
eGFR threshold for renal failure in MM?
eGFF <40 mL/min.
193
What is the cause of renal failure in multiple myeloma?
o Cast nephropathy is caused by high serum free light chains and BJP deposition in the proximal tubule cells.
194
Site of serum free light chain and BJP deposition in cast nephropathy?
Proximal tubule cells
195
Serum free light chains and BJP interact with which molecule, resulting in PCT obstruction?
Uromodulin
196
What is the most common precipitating factor of renal failure in MM?
Dehydration from vomiting and diarrhoea (MOST COMMON); infection; and toxicity of antibiotics.
197
what are the complications of bone disease in multiple myeloma?
Pathological fractures .e.g, wedge compression, pepper pot skull
198
What are the infective complications associated with multiple myeloma?
Reactivation of Herpes Zoster
199
What is the diagnostic investigation of multiple myeloma?
* Serum protein electrophoresis (Dense band of monoclonal protein, often IgG or IgA) (2/3rd monoclonal Ig light chain in urine – IgG > IgA)
200
What blood film finding is seen in multiple myeloma?
Rouleaux stacks
201
On bone marrow aspiration and biopsy - which finding is seen?
>10% plasma cells
202
203
What CD markers are raised in MM?
CD38, CD138
204
Why is rituximab ineffective in multiple myeloma?
Rituximab targets CD20 - therefore cannot be used for B-cell depletion
205
What is the high risk translocation in myeloma?
t(4;14)
206
What term describes Lymphoplasmacytic lymphoma ?
Waldenstrom’s macroglobulinemia
207
What is the staging criteria for multiple myeloma?
Durie-Salmon Staging System.
208
What is the first line management for multiple myeloma?
1. Cytostatic drugs (alkylating agents) = High dose Melphalan 200mg/m2 impregnated in autologous SCT.
209
What are alkylating agents (mechanism)?
Nitrogen derivatives that add alkyl groups to DNA
210
What drug is impregnated in Autologous Haemopoietic Stem Cell Transplant for multiple myeloma?
Mephalan
211
What class of drug is Bortezomib?
Proteasome inhibitor
212
Proteasomes regulate misfolded protein production through which process?
ER-associated degradation
213
Which drug is used in inhibiting angiogenesis in myleoma?
Thalidomide
214
Which monoclonal antibody is implicated in the management of myeloma?
Daratumumab
215
Daratumumab binds to which CD marker in myeloma?
CD38
216
What combination therapy is indicated in the management of myeloma?
lenalidomide and dexamethasone
217
Which stain is used for the diagnosis of amyloidosis?
Congo red
218
Which type of renal disease is associated with Al amyloidosis?
Nephrotic syndrome
219
What is the clinical presentation of AL amyloidosis?
* Nephrotic Syndrome (70%) – Proteinuria + peripheral oedema.
* Unexplained heart failure - Determinant of prognosis
- Raised NT-proBNP.
- Abnormal echocardiography and cardiac MRI.
- Sensory neuropathy
- Abnormal liver function tests
- Macroglossia.
220
Which light chain is implicated in AL amyloidosis?
Lambda light chain
221
Which gammopathy is associated in the elderly population within the 7th decade of life?
Waldenstrom’s Macroglobinaemia
222
Infiltration of which type of cells in the bone marrow causes Waldenstrom’s Macroglobinaemia ?
clonal lymphoplasmacytic cells
223
What are is the clinical presentation for Waldenstrom’s Macroglobinaemia ?
* Anaemia – pallor, weakness, fatigue
* Weight loss, fever, night sweats.
* Organomegaly – enlarged lymph nodes, spleen and liver.
* Hyperviscosity syndrome
o Blurring
o Loss of vision
o Headache
o Ataxia
o Dementia
o Stroke
o Coma
224
What is the diagnostic finding seen on serum protein electrophoresis in Waldenstrom’s Macroglobinaemia ?
Presence of IgM monoclonal paraprotein on serum immunofixation.
225
Which paraprotein is seen in Waldenstrom’s Macroglobinaemia ?
IgM monoclonal paraprotein
226
What is the management for hyperviscosity syndrome in Waldenstrom’s Macroglobinaemia ?
Plasmapheresis
227
Which drug is used for the management of Waldenstrom’s Macroglobinaemia ?
Rituximab
228
Which characteristic cells are associated with Hodgkin’s Lymphoma ?
Reed-Sternberg cells
229
Which virus is associated with Hodgkin’s Lymphoma ?
EBV
230
What is the commonest subtype of Hodgkin’s Lymphoma ?
Nodular sclerosing
231
Which is associated with nodular sclerosing Hodgkin’s Lymphoma ?
A mediastinal mass
232
What are the four types of Hodgkin’s Lymphoma ?
1. Nodular sclerosing – 80% - F>M, neck nodes + mediastinal mass – MOST COMMON.
2. Mixed cellularity
3. Lymphocyte rich
4. Lymphocyte depleted – POOR PROGNOSIS.
233
Which Hodgkin’s Lymphoma subtype is associated with a poor prognosis?
Lymphocyte depleted
234
What are the three classical B symptoms?
o Weight loss >10% in 6 months unintentional.
o Night sweats
o Pel–Ebstein fever (>38, cyclic 1-2 weeks)
235
What is the diagnostic investigation of choice for Hodgkin’s Lymphoma ?
Fine needle aspiration
236
Binucleate owl eyes on biopsy is characteristic of which cell type?
Reed-Sternberg cells
237
Which cell stain markers are raised in Hodgkin’s Lymphoma ?
CD15 and CD30
238
What are the two staging classifications for Hodgkin's lymphoma?
Lugano Classification
Ann-Arbor staging
239
What is stage 1 Hodgkin’s Lymphoma ?
One lymph node region
240
What is stage 2 Hodgkin’s Lymphoma ?
Two or more lymph node regions on the same side of the diaphragm
241
What is stage 3 Hodgkin’s Lymphoma ?
2+ in regions on opposite sides of the diaphragm.
242
What is stage 4 of Hodgkin’s Lymphoma ?
Extranodal sites (liver, BM).
243
Stage the following:
Patient with involvement in 3 LN regions above the diaphragm, pain after alcohol and SVC syndrome BUT no weight loss, night sweats etc.
Stage 2a
244
What is the combination chemotherapy for the management of Hodgkin’s Lymphoma ?
* ABVD – Adriamycin, bleomycin, vinblastine, and dacarbazine
245
What is the complication of bleomycin?
Pulmonary fibrosis
246
What is the target of Brentuximab ?
Anti-CD30
247
What is the management for relapsed patients w/myeloma?
Brentuximab
248
Which type of Hodgkin's lymphoma is not associated with EBV, and marked by isolated lymphadenopathy?
Nodular Lymphocyte Predominant Lymphoma
249
Which CD markers are negative and positive in Nodular Lymphocyte Predominant Lymphoma?
CD 20 POSITIVE
cd30/15 negative
250
Which type of Non-Hodgkin’s Lymphoma is fastest growing?
Burkitt's lymphoma
251
Which type of Non-Hodgkin’s Lymphoma is indolent?
Follicular lymphoma
252
Which type of Non-Hodgkin’s Lymphoma is very aggressive?
Burkitt's lymphoma
253
Which type of Non-Hodgkin’s Lymphoma aggressive?
Diffuse large B-cell, Mantle cell
254
Which type of Non-Hodgkin’s Lymphoma is indolent?
Follicular, marginal zone, small lymphocytic.
255
Which mutation is associated with Burkitt's lymphoma?
c-MYC proto-oncogene on chromosome 8
256
Translocation involved in Burkitt's lymphoma?
t(8;14)
257
What are the two types of Burkitt lymphoma?
Endemic and sporadic
258
What is the characteristic clinical manifestation of endemic Burkitt’s lymphoma?
Characteristic jaw involvement and abdominal mass.
-Involves mandible and maxilla.
Associated with spontaneous tumour lysis syndrome.
259
Endemic Burkitt’s lymphoma affects which part of the world?
Equatorial Africa
260
What is the histology appearance of Burkitt’s lymphoma?
‘Starry Sky’ Appearance
261
What is the chemotherapy agent indicated in the management for Burkitt’s lymphoma?
Rituximab (anti-CD20) found on B-cells
262
What is the characteristic clinical presentation of sporadic Burkitt’s lymphoma?
Ascites, ileo-caecal tumours, and can mimic appendicitis.
* Localised lymphadenopathy.
* ~25% present with jaw or facial growths.
263
Which high-grade non-Hodgkin's lymphoma is high-grade and associated with middle-aged and elderly individuals?
Diffuse Large-B cell
264
Sheets of large lymphoid cells is associated with which type of non-Hodgkin's lymphoma ?
Diffuse Large B-cell
265
What is the translocation associated with Mantle cell lymphoma?
t (11;14) translocation
266
What is the histology finding for mantle cell lymphoma?
Angular clefted nuclei
267
What is the translocation for follicular lymphoma?
t (14;18)
268
Which T-cell lymphoma is aggressive and frequently seen in young males?
Anaplastic Large Cell lymphoma
269
What is the translocation associated with Anaplastic Large Cell lymphoma ?
t (2;5)
270
Overexpression of which protein is associated with Anaplastic Large Cell lymphoma ?
overexpression of ALK-1 protein (better prognosis)
271
What type of nuclei is seen in Anaplastic Large Cell lymphoma ?
Horseshoe-shaped nuclei
272
What is the histology associated with peripheral T-cell lymphoma?
Large pleiomorphic cells
273
Adult T-cell leukaemia/lymphoma affects which ethnicity the most?
Japanese and Caribbean population.
274
Which virus is implicated in Adult T-cell leukaemia/lymphoma?
HTLV1
275
Which T-cell lymphoma is associated with Coeliac disease?
Enteropathy-associated T cell lymphoma
276
What is the presentation of Enteropathy-associated T cell lymphoma ?
Abdominal pain, diarrhoea + bowel perforation
277
What is the characteristic presentation of cutaneous T-cell lymphoma?
mycosis fungoides.
Sezary syndrome
278
Sezary syndrome in cutaneous T-cell lymphoma is associated with what on histology?
Cerebriform nuclei
279
What is the Philadelphia chromosome positive myeloproliferative disorder?
Chronic myeloid leukaemia
280
Name three Philadelphia Chromosome Negative myeloproliferative disorders?
Polycythaemia Vera
Myelofibrosis
Essential thrombocytosis
281
Which kinase chimeric fusion protein is characteristic of CML?
BCR-ABL
282
Which mutation is associated with Polycythaemia Vera?
Jak2 mutations
283
What is the role of Jak2?
STAT transcription factor - transcription of genes associated with cell disease
284
What type of mutation is associated with JAK2 and implicated in the pathology of Polycythaemia Vera?
Gain of function
(Activates JAK 2- hyperactivation of the STAT transcription factor pathway independent of cytokine receptor binding)
285
Which two parameters are raised in Polycythaemia Vera?
Raised haemoglobin concentration and raised haematocrit.
286
What are the common causes of relative/ pseudopolycythaemia?
Alcohol, smoking, dehydration e.g., diuretics, burns, enteropathy, D&V, obesity
287
What is Gaisbock’s syndrome (polycythaemia)?
Occurs in young male smokers with HTN – results in reduced plasma volume & apparent rise in RCC.
288
What are the two types of true Polycythaemia ?
Secondary (non-malignant)
Primary (myeloproliferative neoplasm).
289
What is the appropriate causes of secondary polycythaemia?
Chronic lung hypoxia e.g., COPD, high altitude
290
What is the inappropriate cases of secondary polycythaemia?
Renal cell carcinoma, cysts, hydronephrosis
EPO abused by athletes = blood doping
291
What is the main cause of primary polycythaemia?
Polycythaemia Vera
292
Which principal hormone regulates erythropoiesis?
EPO
293
Which specific mutation is implicated in Polycythaemia Vera ?
JAK2 V617F mutation
294
What is the clinical presentation of Polycythaemia Vera ?
* Plethora/ruddy complexion/flushing; retinal/conjunctival vascular enlargement.
- Red nose, gout.
* Splenomegaly (>75%) and hepatomegaly – early satiety and abdominal discomfort.
* Venous or arterial thrombosis
- Myocardial ischemia, stroke, and retinal vein engorgement.
- Budd-Chiari syndrome
* Aquagenic pruritus (contact with water) – Duet to increased histamine release.
* Bleeding: Epistaxis
* Erythromelalgia
* Peptic ulcers
295
What are the symptoms of hyperviscosity associated with Polycythaemia Vera ?
* Headaches, light-headedness, stroke
* Visual disturbances
* Fatigue, dyspnoea
296
On bone marrow trephine biopsy what is found in Polycythaemia Vera?
Increased cellularity affecting erythroid cells
297
What is the diagnostic investigation for Polycythaemia Vera?
JAK2 V716F mutation analysis (present on exon 14)
298
How is blood volume measured in Polycythaemia Vera?
Isotope dilution
299
What is the management for Polycythaemia Vera?
Venesection (Bleeding and IDA stimulate megakaryocytes to produce more platelets) – Reduce viscosity, HCT <45%.
* Hydroxycarbamide (cytoreductive therapy) and low-dose aspirin for maintenance therapy.
* Reduce thrombosis risk: Control HCT, aspirin, keep platelets <400.
300
What term describes an isolated raised platelet count (A myeloproliferative disorder of platelets and megakaryocytes)?
Essential Thrombocythemia
301
What are the symptoms of thrombosis associated with Essential Thrombocythemia?
CVA, gangrene TIA, DVT/PE.
302
What are the symptoms of hyperviscosity associated with Essential Thrombocythemia?
o Headaches
o Light-headedness
o Stroke
o Visual disturbances
o Fatigue
o Dyspnoea
303
Which mutations are associated with Essential Thrombocythemia?
* Mutations (JAK2, calreticulin, MPL)
304
What is the management of Essential Thrombocythemia?
1. Aspirin -To prevent thrombosis.
2. Hydroxycarbamide To suppress platelet count.
3. Anagrelide - Specific inhibition of platelet formation
Side effects: Palpitations + flushing.
305
Which drug specifically inhibits platelet formation in Essential Thrombocythemia?
Anagrelide
306
What is the mechanism of action of Anagrelide?
Inhibits platelet formation in Essential Thrombocythemia
307
What is chromosomal translocation implicated in chronic myeloid leukaemia?
T(9;22) - Robertsonian translocation - BCR-ABL fusion gene
308
Which cell lineage is affected by chronic myeloid leukaemia?
Marked by leucocytosis 50-500 x 109/L.
309
Myeloblasts form which type of cells?
Granulocytes - eosinophil, neutrophil, basophils
310
Which THREE cell types are raised in CML?
Neutrophils and Basophils
+ Platelet count
311
A blast crisis in CML is associated with what >% of blasts?
>20%
312
Which drug is implicated in the short-term management for CML?
imatinib
313
What thrombotic events are associated with CML?
mono-ocular blindness, CVA, bruising, bleeding
(Due to raised platelet count)
314
What is the investigation of choice to confirm the BCL-ABL gene in CML?
FISH metaphase/interphase karyotyping
315
What is the diagnostic investigation for CML?
Cytogenetic testing and detection of the Philadelphia Chromosome.
316
Left shift is associated with what in CML?
Precursor cells present, myelocytes and myeloblasts <5%
317
What class of drug is imatinib?
ABL Tyrosine kinase inhibitors
318
What are the side effects associated with imatinib?
fluid retention, pleural effusion
319
What is the first line drug of choice for CML?
Imatinib
320
If Imatinib is unsuccessful in CML, what is the next step in management?
Switch to 2nd or 3rd generation TKI – Dasatinib, nilotinib or bosutinib (3rd generation).
321
Name a 2nd generation monocloncal agent for CML management?
Dasatinib
322
What is the definitive management for CML?
Allogenic stem cell transplantation.
323
AML is associated with which cell type?
## Footnote
Associated with Auer Rods
immature blast cells - clonal proliferation of myeloid precursors
324
What is the median age of diagnosis for AML?
65 years
325
Which genetic syndromes are associated with AML?
Trisomy 8 & 21, Fanconi anaemia
326
Which genes are implicated in AML?
RUNX + RUNX1T1
327
Which genetic abnormality is associated with core binding factor in AML?
inv(16), t(16;16)
328
inv(16) t(16;16) in AL, is associated with which cell type?
‘eosinophil-type’ cells remain.
329
Which translocation is associated with APML?
t(15;17) PML-RARA (Susceptible to DIC) - M3 subype
330
Acute promyelocytic leukaemia is associated with an increased predisposition to what?
DIC
331
Inversion of which chromosome causes an arrest in differentiation in AML?
Chromosome 16
332
AML is associated with what haem complications?
1. Anaemia
* Fatigue, pallor, and weakness.
2. Neutropenia
* Infections – fever Immediate broad spectrum ABx.
3. Thrombocytopenia
* Gingival bleeding, ecchymoses, epistaxis or menorrhagia.
333
Which characteristic cell type is seen in AML?
* Auer rods
334
What % of myeloblasts is seen in AML?
>20%
335
What stain is used in the diagnosis of AML?
Sudan-black stain.
336
What is the diagnostic investigation for confirming AML?
Flow cytometry/Immunophenotyping
337
Which investigation is used to identify the specific mutations in AML?
Cytogenetic analysis/FISH
338
Which CD marker is increased in precursor cells in AML?
CD34
339
What is the remission induction protocol for AML?
* Daunorubicin, cytarabine
340
What prophylactic drug is prescribed to mitigate gout (TLS) in AML?
* Allopurinol
341
Which haematological malignancy is associated with an increased risk of disseminated intravascular coagulation?
Acute Promyelocytic Leukaemia
342
What is a type 1 abnormality for Acute Promyelocytic Leukaemia ?
Promote proliferation and survival – FLT3-ITD.
343
What is a type 2 abnormality for Acute Promyelocytic Leukaemia ?
Translocation t(15;17) – PML-RARA (retinoic acid receptor alpha locus on chromosome 17) – blocks differentiation.
344
Which type of abnormality is associated with blocking differentiation?
Type 2
345
What is the hypergranular variant of APML?
Low WCC – neoplastic promyelocytes containing Auer rods = contain violet cytoplasmic densely packed granules (faggot cells).
346
Faggot cells are associated with what?
Acute Promyelocytic Leukaemia
347
What is the immunophenotype for Acute Promyelocytic Leukaemia ?
CD13 and CD33 negative.
348
RT-PCR detection of what is associated with Acute Promyelocytic Leukaemia ?
PML: RARA
349
What is the management for Acute Promyelocytic Leukaemia ?
All-trans retinoic acid and A2O3
350
What CD marker is continuously activated by mutations in CLL?
CD5
351
What is Evan's syndrome?
CLL + Autoimmune haemolytic anaemia + ITP).
352
Bone marrow examination of CLL demonstrates what?
Hypercellular bone marrow
353
What describes CLL transformation to an aggressive large cell lymphoma?
Richter’s transformation
354
Why is there an increased risk of infection in CLL?
* Hypogammaglobinaemia – reduced ability to produce antibodies for immune response – increased risk of infection.
355
Smear/smudge cells are associated with what type of leukaemia?
CLL
356
What characteristic cells are seen in CLL?
Smear/smudge cells
357
Flow cytometry detects which CD markers in CLL?
- CD5+, CD19, CD20, CD23
358
Which mutation is associated with a worse prognosis in CLL?
tp53
359
Which mutation is associated with a good prognosis in CLL?
- IGHV
360
What staging is used for CLL?
Rai and Binet staging
361
What is the management for Rai and Binet Stage A CLL?
Wait and Watch
362
What is stage B Rai and Binet CLL in terms of n number of enlarged lymph node groups?
3 or more areas of lymphoid involvement
363
Cytopenia is associated with which Rai and Binet stage in CLL?
Stage C
364
BLC-2 inhibitors are associated with the management of which type of leukaemia?
CLL
365
Name a BLC-2 inhibitor
Venetoclax
366
What class of drug is Venetoclax?
BLC-2 inhibitor
367
What are the two combination immune chemotherapy implicated in the management for CLL?
* BCL-2 inhibitors – Venetoclax (apoptosis)
* BCR kinase inhibitors – Ibrutinib (BTK); idelalisib (P13K)
368
Ibrutinib is what class of drug used in CLL?
* BCR kinase inhibitors
369
Which genetic syndrome is associated with ALL?
Down’s syndrome
370
What blood film finding is associated with ALL?
>20% lymphoblast (high nucleus: cytoplasmic ratio).
371
What is the diagnostic investigation for ALL?
Immunophenotyping with FISH analysis – CD34+ (B-cell, CD20+, CD19/22; T-cell - CD3+, CD4/8).
372
What are the poor prognostic factors for ALL?
* Age <2 years or >10 years
* WBC <20
* Non–Caucasian
* Male sex
373
What is the induction therapy for ALL?
prednisolone, doxorubicin, vincristine (with l-asparaginase) and consolidation cycles (2-3 years)
374
Why are men treated comparatively longer than females for ALL?
CNS/Testes to management of sanctuary sites - treated for 3 years
375
Which drug is used as part of CNS-directed therapy in ALL?
Intrathecal methotrexate
376
Which class of drug is used to treat AML?
Imatinib (Tyrosine kinase inhibitor/TKI
377
Febrile neutropenia is managed by what?
Filgrastim – CSF + Tazocin
378
Mature B-cells CD negative and positive markers?
* CD19 +ve
* CD5 -ve
* CD3 -ve
379
Mature T-cell CD negative and positive?
* CD19 -ve
* CD5 +ve
* CD3 +VE
* CD4 or CD8 +ve
380
B-CLL positive CD markers?
CD19 +ve
CD5 +ve
381
Which syndrome in CLL is associated with autoimmune haemolytic anaemia and ITP?
Evan's Syndrome
382
What is at an increased risk in myelodysplasia?
AML transformation
383
What differentiates leukaemia and myelodysplasia?
<20% blasts
384
What is the main clinical presentation of myelodysplasia?
Symptoms of Bone Marrow Failure:
* Fatigue – due to anaemia
* Thrombocytopenia + leukopenia
* Skin pallor, mucosal bleeding, and ecchymosis
* Fever, infection, and dyspnoea.
* All patients have <20% blasts (>20% = acute leukaemia).
385
Bone marrow feature in myelodysplasia?
Hypercellular bone marrow
386
What is the definition of myelodysplasia?
Myelodysplastic syndromes are a group of acquired clonal disorders of HSCs - Altered differentiation and proliferation of abnormally maturing myeloid stem cells.
387
What is the definitive management for myelodysplasia?
Allogenic stem cell transplant + intensive chemotherapy
388
Which chemotherapy is indicated for myelodysplasia?
Hydroxyurea and low dose cytarabine
389
A hypocellular bone marrow is seen in which haematological disorder?
Aplastic anaemia
390
Which blood types are affected in aplastic anaemia?
All blood types - suppression or stem or progenitor hemopoietic stem cells
391
Which BMF cause is associated with impaired DNA repair inter-strand crosslinks?
Fanconi Anaemia
392
Which cause of BMF is associated with mutations in telomere length?
Dyskeratosis congenita
393
What is the consequence of mutated telomere length in dyskeratosis congenita?
Premature cell death - pulmonary fibrosis and liver cirrhosis
394
Which haematological condition is associated with red cell aplasia?
* Diamond–Blackfan Anaemia
395
Pathogenesis of Diamond–Blackfan Anaemia ?
Red cell aplasia
396
What type of anaemia is associated with Diamond–Blackfan Anaemia?
Macrocytic anaemia with reticulocytopenia + elevated foetal haemoglobin
397
Which primary immunodeficiency is associated with neutropenia (a form of SCID)?
* Kostmann’s syndrome
398
Kostmann’s syndrome affects which cell type?
Neutropenia (neutrophil progenitors)
399
Which criteria is used to diagnose severe aplastic anaemia?
Camitta criteria
400
What is the Camitta criteria (3 components)?
1. Reticulocytes <1% (<20 x 109/L)
2. Neutrophils <0.5 x 109/L
3. Platelets < 20 x 109/L
401
What are the diagnostic tests for confirming severe aplastic anaemia?
Peripheral blood - pancytopenia (reduced reticulocyte count)
Bone marrow - Hypocellular + fat
402
What is the most common inhertiited aplastic anaemia?
Fanconi anaemia
403
Which genes are implicated in Fanconi anaemia?
FA-A, -B, -C and -D
404
What disease is characterised by a short stature, hypopigmented spots and cafe au lait spots, abnormality of thumbs, hypogonadism and aplastic anaemia?
Fanconi anaemia
405
Which derm manifestation is associteatead with Fanconi anaemia?
* Hypopigmented spots and café-au-lait spots
406
What is the triad of symptoms associated with dyskeratosis congenita?
1. Oral leucoplakia
2. Nail dystrophy
3. Reticular hyperpigmentation
407
What is the most common complication associated with Fanconi anaemia?
Bone marrow failure
408
What is the commonest clinical presentation in Dyskeratosis congenita?
Bone marrow failure
409
Which gene is associated with dyskeratosis congenita?
DKC1 gene encoding for dyskerin protein
410
Which haematological disorder is associated with an autosomal recessive disorder marked by pancytopenia and exocrine pancreatic dysfunction?
Schwachman–Diamond Syndrome
411
What is the inheritance pattern for Schwachman–Diamond Syndrome?
Autosomal recessive
412
Which extra-haematological dysfunction is associated with Schwachman–Diamond Syndrome?
Exocrine-pancreatic dysfunction - steatorrhoea, malabsorption, and fat-soluble vitamin deficiency
413
What skeletal abnormalities are associated with Schwachman–Diamond Syndrome?
Short stature, rib-cage abnormalities, slipped femoral epiphysis, spinal and finger deformities.
414
Which congenital bony malformation is associated with Diamond Blackfan anaemia?
triphalangeal thumbs
415
What is the first line management for Diamond Blackfan Anaemia?
corticosteroid therapy and chronic blood transfusions
416
Which protein is implicated in hereditary Elliptocytosis ?
spectrin
417
What is the inheritance pattern associated with hereditary Elliptocytosis ?
Autosomal dominant
418
Which proteins are affected in Hereditary Spherocytosis?
Spectrin and ankyrin
419
What test is used to diagnose Hereditary Spherocytosis ?
Eosin-5-malimide (EMA) binding test
420
What type of anaemia is implicated in Hereditary Spherocytosis ?
Macrocytic anaemia
421
Increased osmotic fragility is associated with which haem disorder?
Hereditary Spherocytosis
422
Hereditary Spherocytosis is susceptible to which virus?
Parvovirus B19
423
What is the presentation of Hereditary Spherocytosis ?
* Splenomegaly (extravascular haemolysis), anaemia, hyperbilirubinaemia
* Triad of jaundice, anaemia and splenomegaly in neonates.
424
Which test is positive in autoimmune haemolytic anaemia?
Coombs test
425
Which immunoglobulin is associated with WARM AIHA?
IgG
426
Which immunoglobulin is associated with cold agglutinin disease?
IgM
427
Which AIHA is associated with Raynaud's phenomenomen?
Cold agglutinin disease
428
What are the associated causes of AIHA?
Lymphoma, infections e.g., EBV, mycoplasma, CLL, SLE
429
Which drug is associated with causing warm AIHA?
Methyldopa
430
What cell type is seen in warm AIHA?
Spherocytes
431
What is the management for warm AIHA?
Steroids, splenectomy, immunosuppression
432
Which autoimmune haemolytic anaemia is associated with IgM erythrocyte agglutination?
Cold agglutinin disease
433
What is the diagnostic investigation for autoimmune haemolytic anaemia?
Coomb Test to detect autoantibodies.
434
Which markers are raised in haemolytic anaemia?
* Raised unconjugated bilirubin
* Raised lactate dehydrogenase
* Raised reticulocytes
435
Which immunosuppressant agents are indicated in the management of warm AIHA?
Mycophenolate Mofetil, azathioprine, cyclophosphamide.
436
What is the definitive management of warm AIHA?
Splenectomy and blood transfusions
437
What is the drug management for CAD?
* Rituximab
438
Which antibodies are associated with paroxysmal cold haemoglobinuria?
Donath-Landsteiner antibodies - marker of complement-mediated haemolysis
439
Donath–Landsteiner antibodies are associated with what?
Paroxysmal Cold Haemoglobinuria
440
What causes Paroxysmal Cold Haemoglobinuria ?
Haemoglobin in the urine caused by a viral infection e.g., measles, syphilis, VZV.
441
Which marker is deficient in non-immune coomb's negative Paroxysmal Nocturnal Haemoglobinuria ?
Loss of protective surface GP1 markers on RBC (platelets and neutrophils)
442
What mediates haemolysis in Paroxysmal Nocturnal Haemoglobinuria ?
Complement
443
What is the characteristic presentation for Paroxysmal nocturnal Haemoglobinuria ?
* Morning haemoglobinuria, thrombosis (+Budd–Chiari syndrome – hepatic v thromb).
444
Which test is used to diagnose Paroxysmal Nocturnal Haemoglobinuria ?
Ham's test ( in vitro acid-induced lysis)
445
The Ham's test is used to diagnose which condition?
Paroxysmal Nocturnal Haemoglobinuria
446
Which monoclonal antibody is used in the management for Paroxysmal Nocturnal Haemoglobinuria?
eculizumab
447
What is the mechanism of action of eculizumab ?
Prevents complement binding RBCs
448
Which haematology condition is characterised by the mechanical destruction of RBCs?
Microangiopathic haemolytic anaemia
449
What are the causes of microangiopathic haemolytic anaemia?
HUS, TTP, DIC, pre-eclampsia
450
In thrombotic thrombocytopenia purpura, antibodies targeting against what ?
ADAMTS13
451
ADAMTS13 causes what?
Thrombotic thrombocytopenia purpura
452
Haemolytic uraemic syndrome is caused by what organism?
E coli 0157
453
What cell type is associated with myelofibrosis?
Dacrocyte (tear drop poikilocytes)
454
Tear drop cells are associated with which pathology?
Myelofibrosis
455
What is the pathogenesis of myleofibrosis?
Primary myelofibrosis is a chronic myeloproliferative neoplasm characterised by the clonal proliferation of myeloid cells – results in chronic myeloproliferation and atypical megakaryocytic hyperplasia.
* Bone marrow fibrosis - nonclonal fibroblastic proliferation - Excess collagen deposition derived from fibroblasts.
* Affects elderly
456
What are the clinical manifestations associated with myelofibrosis?
* Constitutional symptoms – fatigue, night sweats, low-grade fever, weight loss.
* Massive Splenomegaly
- Spleen fills the left side of the abdomen and to the pelvic brim – abdominal pain (with referred left shoulder pain), early satiety, weight loss and splenic infarction.
* Cytopenia
* Extramedullary haematopoiesis – portal hypertension, hepatomegaly.
- Can present with Budd-Chiari syndrome.
457
A bone marrow aspirate reveals what in myelofibrosis?
Dry tap (punctio sicca)
458
Which drug reduces spleen volume and is indicated in the management of myelofibrosis?
Ruxolitinib
459
Which measuers the intrinsic pathway?r
APTT
460
What is the first factor for the intrinsic pathway?
Factor 12
461
What is the order of clotting factors in the intrinsic pathway till the beginning of the common pathway?
12 --> 11 --> 9 --> 8 --> 10
462
What factor activates the extrinsic pathway and is released from traumatised vascular wall?
Tissue factor
463
Tissue factor causes which clotting factor to be activated?
VII to VIIa
464
What is the function of clotting factor VIIa in the extrinsic pathway?
VIIa, in the presence of calcium ions results in the activation of X to Xa
465
Which co-factor ion is indicated in the activation of X to Xa medidated by factor VIIa?
Calcium 2+ ions
466
Factor Xa activates which factor in the extrinsic pathway?
V to Va
467
What role does factor Xa play with the formation of thrombin?
Forms the prothombin activator complex
468
What forms the prothrombin activator complex?
Xa, V, Ca2+ co-factor and tissue factor
469
What are the four pro-coagulative effects of thrombin amplification?
Platelet activation
Co-factor activation (V, VIII, IX)
Cleaves fibrinogen into fibrin
Cleaves stabilising factor XIII to XIIIa
470
Which clotting factor is a stabilising factor and forms cross-links between fibrin chains?
XIII
471
Thrombin results in the activation of which stabilising factor?
13
472
Which 3 clotting factors are activated by thrombin?
8, 9 and 5
473
How is warfarin monitored?
INR
474
What are the anti-coagulant factors in the coagulation cascade?
Anti-thrombin, Protein C/S, tissue factor pathway inhibitor
475
What is the average lifespan of a megakarocyte?
10 days
476
Aspirin inhibits which enzyme?
Cyclo-oxygenase
477
Which glycoprotein is implicated in direct platelet adhesion?
Glycoprotein 1A
478
What are the vitamin K dependent factors?
2,7,9,10
479
What is the most common cause of vitamin K deficieincy?
Warfarin
480
What do endothelial cells secrete as part of the first stage of fibrinolysis (2)?
Tissue-type plasminogen activator (t-Pa)
Urokinase-type plasminogen activator (u-Pa)
481
What is the role of t-Pa?
Activates plasminogen into plasmin
482
Plasmin cleaves which clotting factor?
Factor XIII
483
What 2 plasma regulators control plasmin-induced fibrinolysis?
Alpha-2 antiplasmin
Alpha-2-macroglobulin
484
What blocks plasmin formation by inhibiting plasminogen?
PLasminogen activator inhibitor-1 (PAI-1)
485
Which clotting disorder is associated with the greatest thrombotic risk?
Antithrombin-3 deficiency
486
Protein C binds to what?
Binds to thrombomodulin through endothelial Protein C receptor - results in the formation of APC
487
Which protein co-factor activates the activated protein C complex?
Protein S
488
Protein C/S inactivates which two clotting factors?
Factors 5a and 8a
489
Clopidogrel inhibits what?
ADP-R by binding to platelet P2RY12 purinergic receptor
490
What is the management for severe ITP?
corticosteroids and IV immunoglobulin
491
Haemophillia A - inheritance pattern?
X-linked recessive
492
Which factor is deficient in haemophilia A?
Factor 8
493
What bleeding test is prolonged in Haemophilia A/B?
aPTT
494
What is the chronic management for Haemophilia A?
Factor VIII concentrates
495
What is the acute management for haemophilia A?
Recombinant factor VIIIa or concentrate of actovated vitamin-K derived clotting factor with a bypassing agent
496
Haemophilia B is caused by a deficiency in what?
Factor 9
497
Von Willebrand Factor is released from what by endothelial cells?
Weibel-Palade bodies
498
VWF is secreted by what two cell types?
Megakaryocytes and endothelial cells
499
How is VWF stored in megakaryocytes?
Alpha-dense granules
500
What is the inheritance of VWD?
Autosomal inheritance
501
VWF is regulated by which metalloprotease?
ADAMST13
502
What is the role of VWF?
Acts as a carrier for factor 8
503
What is type 1 VWD?
Quantitative deficiency of VWF
504
What is type 2 VWD?
A functional deficiency of VWF (normal levels)
505
Which type of VWD is associated with a near absence of VWF?
Type 3
506
Which cofactor activity assay is the gold-standard investigation for assessing VWF function?
Ristocetin cofactor activity assay
507
What are the confirmatory investigations for the diagnosis of VWD?
vWF antigen and activity assay
Factor VIII assay
Raised APTT
508
Which antifibrinolytic is administered for the treatment of bleeding VWD?
Transexamic acid
509
Which drug is used to manage type 1 VWD?
Desmopressin
510
What is the mechanism of action of desmopression in the management of type 1 VWD?
Induces the secretion of VWF from Weibel-Palade body stores within endothelial cells
511
Heparin increases the activity of what?
Antithrombin-3
512
Antithrombin-3 inactivates waht 4 factors?
Thrombin, 9,10,11
513
How is unfractionated heparin administered?
IV
514
How is LMWH administered?
Subcutaneous injection once daily
515
How is unfractionated heparin monitored?
Anti-Xa assay or APTT
516
What is the reversal agent for heparin?
Protamine sulphate
517
What is the complication associated with the use of heparin?
Heparin-induced thrombocytopenia
- causes paradoxical thrombosis
518
Which specific antibody is implicated in heparin-induced thrombocytopenia?
Anti-platelet factor 4
519
What is the reversal agent for Anti-XA DOACs?
Adnexanet alfa
520
What is the reversal agent for dabigatran?
Idaruziumab
521
Which enzyme is inhibited by warfarin?
Vitamin K Epoxide reductase
522
What are the first factors that are inhibited by warfarin?
Protein C/S
523
What is the reversible agent for warfarin (immediate)?
Prothrombin complex concentrate
524
What are the complications associated with warfarin?
Purple toes, teratogenicity, skin necrosis
525
Which live enzyme inducer is contraindicated or interacts with warfarin?
P450 enzymes e.g., amiodarone and ciprofloxacin
526
Threshold US/CTPA for suspected PE/DVT based on Wells?
>4
527
Investigation for Wells score 4 points or less?
D-dimer
528
What is the minimum duration of treatment for provoked DVT?
3 months
529
What is the minimum duration of treatment for unprovoked?
6 months
530
Why is there a net dilution/anaemia during pregnancy?
Increased red-cell mass (120-130%)
Plasma volume increses by 150%
531
What happens to platelet count during pregnancy?
Decreases
532
Which drug is indicated in the management of cold agglutinin disease?
Chlorambucil
