Haematology Flashcards
(245 cards)
1
Q
What are the 4 main types of leukaemia ?
A
Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic myeloid leukaemia
Chronic lymphocytic leukaemia
2
Q
What leukaemia most commonly affects children under 5 ?
A
Acute lymphoblastic leukaemia
3
Q
How can leukaemia present ?
A
Fatigue
Fever
Pallor
Petechiae
Abnormal bleeding
Hepatosplenomegaly
4
Q
What are some differentials for a non-blanching rash ?
A
Leukaemia
Meningococcal septicaemia
Vasculitis
Henoch-schonlein purpura
ITP
Non-accidental injury
5
Q
What is acute lymphoblastic leukaemia associated with ?
A
Down’s syndrome
6
Q
How does acute lymphoblastic leukaemia cause pancytopenia ?
A
Affects the lymphocyte precursor cells causing acute proliferation of a single type of lymphocyte usually B cells.
Excessive accumulation of these cells replaces the other cell types in the bone marrow leading to pancytopenia.
7
Q
What occurs in chronic lymphocytic leukaemia ?
A
Slow proliferation of a single type of well-differentiated lymphocyte usually B cells.
8
Q
How does chronic lymphocytic leukaemia present ?
A
Asymptomatic
Infections
Anaemia
Bleeding
Weight loss
9
Q
What is Richter’s transformation ?
A
The rare transformation of chronic lymphocytic leukaemia into high grade B cell lymphoma.
10
Q
What appears on a blood film in chronic lymphocytic leukaemia ?
A
Smear or smudge cells due to ruptured white blood cells that occur while preparing the blood film due to cells being fragile and aged.
11
Q
What are the 3 phases of chronic myeloid leukaemia ?
A
Chronic phase
Accelerated phase
Blast phase
12
Q
What happens in the first phase of chronic myeloid leukaemia ?
A
Often asymptomatic and patients are diagnosed after an incidental finding of a raised white cell count.
13
Q
What happens in the second phase of chronic myeloid leukaemia ?
A
Abnormal blast cells take up a high proportion of the bone marrow and blood cells.
Patients become symptomatic and develop anaemia, thrombocytopenia and immunodeficiency.
14
Q
What happens in the final phase of chronic myeloid leukaemia ?
A
An even higher proprioception of blast cells in the blood
Severe symptoms and panctyopenia
Often fatal
15
Q
What can acute myeloid leukaemia be a transformation of ?
A
A myeloproliferative disorder such as polycythaemia ruby vera or myelofibrosis
16
Q
What is seen on a blood film and biopsy in acute myeloid leukaemia ?
A
High proportion of blast cells
Auer rods in the cytoplasm of blast cells are also characteristic
17
Q
What is the general management of leukaemia ?
A
Chemotherapy and targeted therapies
Examples of targeted therapy - tyrosine kinase inhibitors and monoclonal antibodies
Radiotherapy
Bone marrow transplant
Surgery
18
Q
What are some complications of chemotherapy ?
A
Failure to treat the cancer
Stunted growth and development in children
Infections
Neurotoxicity
Infertility
Secondary malignancy
Cardio toxicity
Tumour lysis syndrome
19
Q
What in tumour lysis syndrome and what does it result in ?
A
Results from chemicals released when cells are destroyed by chemotherapy, resulting in :
- high uric acid
- high potassium
- high phosphate
- low calcium
20
Q
What complications can occur from tumour lysis syndrome ?
A
AKI - uric acid can form crystals in the interstitial space and tubules of the kidneys
Cardiac arrhythmias - from hyperkalaemia
Systemic inflammation - release of cytokines
21
Q
What is tumour lysis syndrome managed ?
A
Very good hydration and urine output before chemotherapy is required
Allopurinol or rasburicase may suppress uric acid levels
22
Q
What are some poor prognostic features of acute myeloid leukaemia ?
A
Over 60 years old
More than 20% blasts after first course of chemo
Deletion of chromosome 5 or 7
23
Q
What are some features of acute myeloid leukaemia ?
A
Anaemia - pallor, lethargy
Neutropenia
Thrombocytopenia- bleeding
Splenomegaly
Bone pain
24
Q
What is the Philadelphia chromosome and what is its relevance ?
A
Translocation between the long arm of chromosome 9 and 22. Results in abnormal tyrosine kinase activity.
It is present on more than 95% of patients with chronic myeloid leukaemia.
25
At what age is chronic myeloid leukaemia most common ?
60-70
26
What are some features of chronic myeloid leukaemia ?
Anaemia - lethargy
Weight loss and sweating
Splenomegaly
27
What is the management for chronic myeloid leukaemia ?
Imatinib - first line - inhibitor of tyrosine kinase
28
What are some complications of chronic lymphocytic leukaemia ?
Anaemia
Hypogammaglobulinaemia
Warm autoimmune haemolytic anaemia
Richter’s transformation
29
What symptoms are present in richters transformation ?
Lymph node swelling
Fever without infection
Weight loss
Night sweats
Nausea
Abdominal pain
30
What are some features of acute lymphoblastic leukaemia ?
Anaemia - lethargy and pallor
Neutropenia - severe and recurrent infections
Thrombocytopenia - easy bruising and petechiae
Splenomegaly and hepatomegaly
31
What are some poor prognostic factors of acute lymphoblastic leukaemia ?
Age less than 2 or above 10
WBC more than 20*10^9 at diagnosis
T or B cell surface markers
Non-Caucasian
Male sex
32
What is lymphoma ?
The malignant proliferation of lymphocytes which accumulate in lymph nodes or other organs. Lymphoma may be classified as either Hodgkin’s lymphoma or non-Hodgkin’s
33
What is Hodgkin’s lymphoma ?
A specific type of lymphoma characterised by the presence of reed-sternberg cells
34
What are some risk factors of non-Hodgkin’s lymphoma ?
Elderly
Caucasian
History of viral infection - Epstein Barr virus
Family history
Certain chemical agents
History of chemo or radiotherapy
Immunodeficiency - HIV DM
Autoimmune disease - SLE, sjogrens or coeliac
35
What are some symptoms of non-Hodgkin’s lymphoma ?
Painless lymphadenopathy - non-tender asymmetrical
B symptoms - fever, weight loss, lethargy
Extranodal disease - gastric ( dyspepsia, dysphagia, weight loss ) bone marrow ( pancytopenia, bone pain), lung and skin
36
How is Hodgkin’s lymphoma differentiated from non-Hodgkin’s lymphoma ?
In Hodgkin’s - alcohol induced pain in the nodes
B symptoms occur earlier in Hodgkin’s lymphoma
Extra nodal more common in non-Hodgkin’s
37
What are some signs of non-Hodgkin’s lymphoma ?
Weight loss
Lymphadenopathy
Palpable abdominal mass
Testicular mass
Fever
38
What is aplastic anaemia ?
Characterised by pancytopenia and hypoplastic bone marrow
39
What features are present in aplastic anaemia ?
Nomochromic normocytic anaemia
Leukopenia
Thrombocytopenia
40
What are some causes of aplastic anaemia ?
Idiopathic
Congenital - Franconia anaemia
Drugs - cytotoxics
Toxins
Infections
Radiation
41
What is autoimmune haemolytic anaemia ?
May be divided into warm and cold types according to what temperature the antibodies best cause haemolysis.
42
What causes autoimmune haemolytic anaemia ?
Idiopathic
Secondary to lymphoproliferative disorder, infection or drugs
43
What investigations are performed for autoimmune haemolytic anaemia ?
FBC
Blood film
Coombs’ test
44
What is warm autoimmune haemolytic anaemia ?
Most common type
The antibody causes haemolysis best at body temperature and haemolysis tends to occur in extra vascular sites.
45
What are some causes of warm autoimmune haemolytic disorder ?
Idiopathic
Autoimmune disease
Neoplasia
Drugs
46
What is the management of warm autoimmune haemolytic anaemia ?
Steroids +/- rituximab
47
What causes cold autoimmune haemolytic anaemia ?
Neoplasia - lymphoma
Infections - mycoplasma, EBV
48
What are some features of beta thalassaemia major ?
Presents in the first year of life with failure to thrive and hepatosplenomegaly
Microcytic anaemia
HbA absent
49
What is the management of beta thalassaemia major ?
Repeated transfusion -
Can lead to iron overload - and then organ failure
Iron chelation therapy
50
What is beta thalassaemia trait ?
A group of genetic disorders characterised by a reduced production rate of either alpha or beta chains.
Autosomal recessive
51
What are some features of beta thalassaemia trait /
Mild hypochromic microcytic anaemia
HbA2 raised
52
What do target cells on a blood film indicate ?
Sickle cell
Iron deficiency anaemia
Hyposplenism
Liver disease
53
What do tear drop poikilocytes on a blood film indicate ?
Myelofibrosis
54
What do spherocytes on a blood film indicate ?
Hereditary spherocytosis
Autoimmune haemolytic anaemia
55
What does basophilic stripping on a blood film indicate ?
Lead poisoning
Thalassaemia
Sideroblastic anaemia
Myelodysplasia
56
What do Howell jolly bodies on a blood film indicate ?
Hyposplenism
57
What do heinz bodies on a blood film indicate ?
G6PD deficiency
Alpha thalassaemia
58
What do schistocytes on a blood film indicate ?
DIC
Intravascular haemolysis
59
What is non-haemolytic febrile reaction ?
From a blood transfusion
Caused by antibodies reacting with white cell fragments in the blood product and cytokines that have leaked from the blood cells during storage.
60
What are some features of non-haemolytic febrile reaction ?
Fever
Chills
61
What is the management of non-haemolytic febrile reaction ?
Slow or stop the transfusion
Paracetamol
Monitor
62
How can anaphylaxis be caused in patients having a blood transfusion ?
Can be caused by patients with IgA deficiency who have anti-IgA antibodies
63
What is the management of anaphylaxis while having a blood transfusion ?
Stop the transfusion
IM adrenaline
ABC support - oxygen and fluids
64
What can cause transfusion - associated circulatory overload ?
Excessive rate of transfusion and a pre-existing heart failure
65
What is the management of transfusion - associated circulatory overload ?
Slow or stop the transfusion
Consider IV loop diuretics ( furosemide )
66
What is transfusion related acute lung injury ?
Non-cardiogenic pulmonary oedema thought to be secondary to increased vascular permeability caused by host neutrophils that become activated by substances in donated blood.
67
What is the management of transfusion related acute lung injury ?
Stop the transfusion
O2 and supportive care
68
What are packed red cells ?
Transfusion in chronic anaemia and cases where infusion of large volumes of fluid may result in cardiovascular compromise.
69
What is fresh frozen plasma ?
Prepared from single units of blood
Contains clotting factors, albumin and immunoglobulin
70
What is burkitt’s lymphoma ?
High grade B cell neoplasm
71
What is seen on microscopy in burkitt’s lymphoma ?
Starry sky appearance : lymphocyte sheets interspersed with macrophages
72
What is the management of Burkitt’s lymphoma ?
Chemotherapy
Rasburicase is given before chemotherapy
73
What are some complications of tumour lysis syndrome ?
Hyperkalaemia
Hyperphosphataemia
Hypocalcaemia
Acute renal failure
74
What is factor V Leiden ?
Most common inherited thrombophilia.
Activated protein C resistance
75
What does factor V Leiden increase the risk of ?
Venous thrombosis
76
What is G6PD deficiency ?
Commonest red blood cell enzyme defect
77
What is the pathophysiology of G6PD deficiency ?
Decreases G6PD = reduced NADPH = reduced glutathione = increased red cell susceptibility to oxidative stress
78
What are some features of G6PD deficiency ?
Neonatal jaundice
Intravascular haemolysis
Gallstones
Splenomegaly
Heinz bodies I
79
What are some drugs that cause haemolysis ?
Primaquine
Ciprofloxacin
Sulphasalazine
Sulfonylurea
80
What inheritance is G6PD deficiency ?
X linked recessive
81
When does graft versus host disease occur ?
When T cells in the donor tissue mount an immune response toward recipient cells.
82
What features are present in graft versus host disease ?
Painful maculopapular rash
Jaundice
Watery or bloody diarrhoea
Persistent nausea and vomiting
83
What is the management of graft versus host disease ?
Immunosuppression and supportive measures
IV steroids
Anti-TNF
84
What can EBV increase the risk of ?
Hodgkin’s lymphoma
Burkitt’s lymphoma
Nasopharyngeal carcinoma
85
What can H.Pylori increase the risk of ?
Gastric lyphoma ( MALT )
86
What are some hereditary causes of haemolytic anaemia ?
Hereditary spherocytosis / elliptocytosis
G6PD deficiency
Sickle cell
87
What are acquired immune causes of haemolytic anaemia ?
Warm / cold antibody type
Transfusion reaction
Haemolytic disease of a newborn
88
What are acquired non-immune causes of haemolytic anaemia ?
Microangiopathic haemolytic anaemia
Prosthetic heart valves
89
What are some Intravascular causes of haemolytic anaemia ?
Mismatched blood
G6PD deficiency
DIC
90
What are some extra vascular causes of haemolytic anaemia ?
Sickle cell
Thalassaemia
Hereditary spherocytosis
Haemolytic disease of a newborn
91
What is haemophilia ?
X linked recessive disorder of coagulation
92
What factor is deficient in haemophilia A ?
Factor 8
93
What factor is deficient in haemophilia B ?
Lack of 9
94
What are the features of haemophilia ?
Haemoarthroses
Haematomas
Prolonged bleeding
95
What is seen on the blood tests in haemophilia ?
Prolonged APTT
Normal bleeding time, thrombin time, prothrombin time
96
What is hereditary angioedema ?
An autosomal dominant condition associated with low plasma levels of the C1 inhibitor protein.
97
What are some symptoms of hereditary angioedema ?
Attacks may be proceeded by painful macular rash
Painless non-pruritic swelling of subcut/submucosal tissues
98
What is the management of hereditary angioedema ?
IV C1-inhibitor concentrate, fresh frozen plasma
Prophylactic anabolic steroid Danazol may help
99
What is hereditary spherocytosis ?
Autosomal dominant defect of the red blood cell cytoskeleton
The biconcave disc shape is replaced by a sphere shaped red blood cell
100
How does hereditary spherocytosis present ?
Failure to thrive
Jaundice
Gallstones
Splenomegaly
101
What is the management of hereditary spherocytosis ?
Treatment is generally supportive
Transfusion if necessary
Folate replacement and splenectomy
102
What are some factors that indicate a poor prognosis in Hodgkin’s lymphoma ?
Having B symptoms
Age over 45
Stage 4 disease
Low Hb
High lymphocyte count
Male
103
What are some risk factors for Hodgkin’s lymphoma ?
HIV
EBV
104
What are some features of Hodgkin’s lymphoma ?
Lymphadenopathy - painless, non-tender, asymmetrical
B symptoms - weight loss, pruritus, night sweats and fever
105
What are som investigations of Hodgkin’s lymphoma ?
FBC
LDH
Lymph node biopsy
106
What is seen on the investigations in Hodgkin’s lymphoma ?
Normocytic anaemia
LDH raised
Reed - sternberg cells
107
What are some causes of hyposplenism ?
Splenectomy
Sickle cell
Coeliac disease, dermatitis herpetiformis
Graves’ disease
SLE
108
What are some features of hyposplenism ?
Howell-jolly bodies
Siderocytes
109
What is ITP ?
An immune mediated reduction in the platelet count where antibodies are directed against the glycoprotein IIb/IIIa
110
How does ITP present ?
Incident finding
Petechiae and purpura
Bleeding
Catastrophic bleed
111
What investigations should be performed for ITP ?
FBC
Blood film
112
What is the management of ITP ?
Oral prednisolone
Pooled normal human immunoglobulin
113
What are some causes of iron deficiency anaemia ?
Excessive blood loss - Menorrhagia, GI upset
Inadequate dietary intake
Poor intestinal absorption - coeliac
Increased iron requirement - during pregnancy
114
What are some features of iron deficiency anaemia ?
Fatigue
Shortness of breath
Palpitations
Pallor
Nail changes
Hair loss
Angular stomatitis
115
What are some investigations for iron deficiency anaemia ?
FBC
Serum ferritin
Blood film
Total iron-binding capacity
116
What is the management of iron deficiency anaemia ?
Identify and manage underlying causes
Oral ferrous sulfate
Iron rich diet
117
What are some differences between iron deficiency anaemia and anaemia of chronic disease ?
Iron levels are higher in chronic disease
Ferritin is higher in chronic disease
118
What is lymphadenopathy ?
A condition of enlarged lymph nodes, typically indicating an immune response to an infection or malignancy.
119
What are some infective causes of lymphadenopathy ?
Infectious mononucleosis
HIV
Eczema
Rubella
CMV
TB
120
What are some neoplastic causes of lymphadenopathy ?
Leukaemia
Lymphoma
121
What are some other causes of lymphadenopathy ?
Autoimmune conditions - SLE, RA
Graft versus host disease
Sarcoidosis
Drugs - phenytoin
122
What lymphatics do the ovaries drain into ?
Para-aortic lymphatics
123
What are some megaloblastic causes of macrocytic anaemia ?
Vitamin B12 deficiency
Folate deficiency
Secondary to methotrexate
124
What are some normoblastic causes of macrocytic anaemia ?
Alcohol
Liver disease
Hypothyroidism
Pregnancy
125
What is monoclonal gammopathy of undetermined significance ( MGUS ) ?
A common condition that causes a paraproteinanemia and is often mistaken for myeloma.
126
What are some features of MGUS ?
Usually asymptomatic
No bone pain
increased risk of infection
127
What are some differentiating features of MGUS to myeloma ?
Normal immune function
Normal beta-2 microglobulin levels
Lower level of paraproteinaemia than myeloma
128
What are some causes of microcytic anaemia ?
Iron deficiency anaemia
Thalassaemia
Congenital sideroblastic anaemia
Anaemia of chronic disease
Lead poisoning
129
What is myelodysplastic syndrome ?
Encompasses a heterogeneous group of clonal haematopoietic stem cell disorders characterised by ineffective haematopoeisis, peripheral blood cytopenias and a risk of progression to AML.
130
What causes myelodysplastic syndromes ?
Arises from genetic mutations in haematopoietic stem cells
Primary ( 90%)
Secondary ( 10% ) - chemotherapy and radiotherapy - 5 years post treatment
131
How does myelodysplastic syndrome present?
Fatigue
Weakness
Pallor - anaemia
Recurrent infections
Easy bruising and bleeding
132
What are the treatment option choices for myelodysplastic syndrome ?
Supportive care
DMARDs
Immunosuppressive therapy
Haematoopoietic stem cell transplantation
133
What are some factors that determine treatment for myelodysplastic syndrome ?
Subtype of MDS
Patients age
Overall health
Severity of symptoms
134
What is myelofibrosis ?
A myeloproliferative disorder thought to be caused by hyperplasia of abnormal megakaryocytes
135
What are some features of myelofibrosis ?
Elderly person with symptoms of anaemia ( fatigue )
Massive splenomegaly
Hypermetabolic symptoms - weight loss, night sweats
136
What are the laboratory findings for myelofibrosis ?
Anaemia
High WBC and platelet count
Tear drop poikilocytes on blood film
High urate and LDH
137
What is myeloma ?
A haematological malignancy characterised by plasma cell proliferation.
Occurs as B cells differentiate into mature plasma cells
138
What are the features of myeloma ?
C - calcium ( Hypercalcaemia )
R - renal ( renal damage )
A - anaemia
B - bleeding
B - bones ( pain and pathological fractures )
I - infection
139
How does myeloma cause hypercalcaemia ?
Primarily to increased osteoclastic bone resorption caused by local cytokines released by the myeloma cells
140
How does hypercalcaemia present in myeloma ?
Constipation
Nausea
Anorexia
Confusion
141
How does myeloma cause renal abnormalities ?
Monoclonal production of immunoglobulins results in light chain deposition within the renal tubules. This causes renal damage which presents as dehydration and increasing thirst.
142
How does myeloma cause anaemia ?
Bone marrow crowding suppresses erythropoiesis leading to anaemia which causes fatigue and pallor
143
How does myeloma cause bone abnormalities ?
Bone marrow infiltration by plasma cells and cytokine-mediated osteoclast overactivity creates lytic bone lesions.
Presents as bone pain or increased risk of pathological fractures
144
How does myeloma increase the risk of infection ?
A reduction in the production of normal immunoglobulins results in increased susceptibility to infection.
145
What is neutropenia ?
Low neutrophil count or < 1.5 *10^9
146
What are some viral causes of neutropenia ?
HIV
EBV
Hepatitis
147
What are some drugs that cause neutropenia ?
Cytotoxic
Carbimazole
Clozapine
148
Other than viral causes and medications what are some other causes of neutropenia ?
Myelodysplastic malignancies
Aplastic anaemia
Rheumatological conditions
SLE
RA
Haemodialysis
Severe sepsis
149
What is a common consequence of chemotherapy ?
neutropenic sepsis
150
How is neutropenic sepsis defined ?
Neutrophil count lower than 0.5 *10^9 in a patient having anti-cancer treatment and has one of the following :
- temp higher than 38 degrees
- other signs or symptoms consistent with clinically significant sepsis
151
What causes neutropenic sepsis ?
Coagulase - negative, gram positive bacteria ( staph epidermidis )
- usually due to indwelling lines in patients with cancer
152
What is the management of neutropenic sepsis ?
ABx - do not wait for WBC ( tazocin or piperacillin )
Add vancomycin is central venous access
If not responded in 48 hours change to meropenem
153
Which is the more common lymphoma ?
Non-Hodgkin’s
154
What are some risk factors for non-Hodgkin’s lymphoma ?
Elderly
Caucasian
History of viral illness
FH
Certain chemical agents - pesticides
History of chemotherapy or radiotherapy
155
What are some symptoms of non-Hodgkin’s lymphoma ?
Painless lymphadenopathy
B symptoms - fever, weight loss, night sweats
Gastric upset
Bone pain
Nerve palsies
156
What are some signs of non-Hodgkin’s lymphoma ?
Signs of weight loss
Lymphadenopathy
Palpable abdominal mass
Testicular mass
Fever
157
What are some investigations of non-Hodgkin’s lymphoma ?
Excision all node biopsy
CT chest abdomen pelvis
HIV test
FBC and blood film
ESR
158
What is stage 1 non-Hodgkin’s lymphoma ?
Involvement of a single node legion
159
What is stage 2 non-Hodgkin’s lymphoma ?
Involvement of two or more lymph nodes on the same side of the diaphragm
160
What is stage 3 non-Hodgkin’s lymphoma ?
Involvement of lymph nodes on both sides of the diaphragm which may have involvement of the spleen or extra-lymphatic organ
161
What is stage 4 non-Hodgkin’s lymphoma ?
Diffuse and disseminated involvement of one or more extralymphatic organs with or without lymph node involvement
162
What is the management of non-Hodgkin’s lymphoma ?
Watchful waiting
Chemotherapy or radiotherapy
163
What are some complications of non-Hodgkin’s lymphoma ?
Bone marrow infiltration causing anaemia, neutropenia or thrombocytopenia
Superior vena cava obstruction
Metastasis
Spinal cord compression
Side effects of chemo
164
What are some causes of normocytic anaemia ?
Anaemia of chronic disease
CKD
Aplastic anaemia
Haemolytic anaemia
Acute blood loss
165
What are some causes of polycythaemia ?
Polycythaemia rubera vera
COPD
Altitude
Obstructive sleep apnoea
Excessive erythropoietin
166
What is polycythaemia vera ?
A myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume often by overproduction of neutrophils and platelets.
Mutation in the JAK2
167
What are some features of polycythaemia Vera ?
Pruritus
Splenomegaly
HTN
Hyperviscosity
Haemorrhage
Low ESR
168
Following history and examination what tests should be performed when suspecting polycythaemia ?
FBC / blood film
JAK2 mutation
Serum ferritin
Renal and liver function tests
169
What criteria is needed to be met for a polycythaemia Vera diagnosis ?
High haematocrit or raised red cell mass
Mutation in the JAK2
170
What is the management of polycythaemia Vera ?
Aspirin - reduces thrombotic events
Venesection - keep Hb in normal range
171
What can polycythaemia Vera develop into ?
Myelofibrosis
Acute leukaemia
172
When does post-thrombotic syndrome develop ?
A complication of a DVT
173
How does post-thrombotic syndrome occur ?
Post DVT - Venous outflow obstruction and insufficiency resulting in chronic venous hypertension
174
What are some features of post-thrombotic syndrome ?
Painful, heavy calves
Pruritus
Swelling
Varicose veins
Venous ulceration
175
What helps reduce the risk of post-thrombotic syndrome as well as its management ?
Compression stockings
176
Why can DVT occur in pregnancy ?
Pregnancy causes a hypercoagulable state
There is an increase in factors VII,VIII, X and fibrinogen
Uterus presses on IVC causing venous stasis in legs
177
What is the management of a DVT in pregnancy ?
S/C low molecular weight heparin preferred to IV heparin
Warfarin contraindicated
178
What is chronic granulomatous disease ?
Primary Neutrophil immunodeficiency
179
What is the underlying defect in chronic granulomatous disease ?
Lack of NAPDH oxidase reduces the ability of phagocytes to produce reactive oxygen species
180
How does chronic granulomatous disease present ?
Recurrent pneumonia and abscesses ( particularly staph aureus and aspergillus )
181
What are some B cell primary immunodeficiency ?
Common variable immunodeficiency
Bruton’s agammaglobulinaemia
Selective IgA deficiency
182
What is deficient in common variable immunodeficiency ?
Antibodies - IgG, IgM and IgG
183
How does common variable immunodeficiency present ?
Recurrent chest infections
184
What is the underlying defect in Bruton’s agammaglobulinaemia ?
Defect in Bruton’s tyrosine kinase gene that leads to a severe block in b cell development
185
What pattern of inheritance is Bruton’s agammaglobulinaemia ?
X linked recessive
186
How does Bruton’s agammaglobulinaemia present ?
Recurrent bacterial infections
187
What is deficient in Bruton’s agammaglobulinaemia ?
Absence of b cells with reduced immunoglobulins of all classes
188
What is the underlying defect in selective immunoglobulin A deficiency ?
Maturation defect in b cells
189
How does selective immunoglobulin A deficiency present ?
Recurrent sinus and respiratory infections
190
What is selective immunoglobulin A deficiency associated with ?
Coeliac disease
191
What is DiGeorge syndrome ?
T cell primary immunodeficiency disorder
192
What is the underlying defect in DiGeorge syndrome ?
22q11.2 deletion
Failure to develop 3rd and 4th pharyngeal pouches
193
What are some common features in DiGeorge syndrome ?
Congenital heart disease - tetralogy of fallot
Learning difficulties
Hypocalcaemia
Recurrent viral/fungal diseases
Cleft palate
194
What is a combined b and T cell disorder ?
Severe combined immunodeficiency
195
What is the most common underlying defect for severe combined immunodeficiency ?
Defect in the common gamma chain, a protein used in receptors for IL-2 and other interleukins
196
How does severe combined immunodeficiency present ?
Recurrent infections due to viruses, bacteria and fungi
197
What is sickle cell anaemia ?
An autosomal recessive condition that results for synthesis of an abnormal haemoglobin chain termed HbS.
198
What is the pathophysiology of sickle cell anaemia ?
Polar amino acid glutamate is substituted by a non-polar valine in each of the 2 beta chains. This decreases water solubility. The cells are fragile and haemolyse which can block blood vessels and cause infarction.
199
What is the definitive investigation for sickle cell anaemia ?
Haemoglobin electrophoresis
200
What is the management of a sickle cell crisis ?
Analgesia
Rehydrate
Oxygen
ABx if infection
Blood transfusion
201
What is the longer term management of sickle cell anaemia ?
Hydroxyurea - increases the HbF levels and is used in prophylactic treatment as well
Pneumococcal vaccine every 5 years
202
What are some types of sickle cell crisis ?
Thrombotic - vaso-occlusive - painful crises
Acute chest syndrome
Anaemic
Infection
203
What precipitates a vaso-occlusive crisis in sickle cell anaemia ?
Infection
Dehydration
Deoxygenation ( high altitude )
204
What is acute chest syndrome ?
Vaso-occlusion within the pulmonary micro vasculature causing an infarction in the lung parenchyma.
205
How does acute chest syndrome present ?
Dyspnoea
Chest pain
Pulmonary infiltrates on CXR
Low pO2
206
What is the management of acute chest syndrome ?
Pain relief
Respiratory support
ABx
Transfusion
207
What causes an aplastic crises ?
Caused by an infection with parvovirus
208
What are some features of an aplastic crisis ?
Sudden fall in haemoglobin
Bone marrow suppression causes a reduced reticulocyte count
209
What is a sequestration crises ?
Sickling within organs such as the spleen or lungs causes pooling of blood with worsening of the anaemia
210
What is sideroblastic anaemia ?
A condition where red cells fail to completely form haem, whose biosynthesis takes place partly in the mitochondria. This leads to deposits of iron in the mitochondria that form a ring around the nucleus called a ring sideroblast.
211
What are some causes of sideroblastic anaemia ?
Delta-aminolevulinate synthase-2 deficiency
Myelodysplasia
Alcohol
Lead
Anti-TB medications
212
What investigations are used for sideroblastic anaemia ?
FBC
Iron studies
Blood film
Bone marrow
213
What is the management of sideroblastic anaemia ?
Supportive
Treat for underlying cause
Pyridoxine
214
What are some causes of splenomegaly ?
Myelofibrosis
Chronic myeloid leukaemia
Malaria
Portal hypertension
Haemolytic anaemia
Infection - hepatitis
Infective endocarditis
215
What are some causes of severe thrombocytopenia ?
ITP
DIC
Haematological malignancy
216
What are some moderate causes of thrombocytopenia ?
Heparin induced thrombocytopenia
Drug induced
Alcohol
Liver disease
Hypersplenism
Viral infection
Vitamin B12 deficiency
217
What are some causes of thrombocytosis ?
Reactive - stress = severe infection, surgery and iron deficiency anaemia
Malignancy
Essential thrombocytosis
Hyposplenism
218
What is essential thrombocytosis ?
A myeloproliferative disorder which overlaps with chronic myeloid leukaemia, polycythaemia ruba Vera and myelofibrosis.
219
What are some features of essential thrombocytosis ?
Platelet count more than 600*10^9
Both thrombosis and haemorrhage can be seen
Burning sensation in the hands
JAK2 mutation is found in around 50%
220
What is the management of essential thrombocytosis ?
Hydroxyurea
Interferon-alpha
Low dose aspirin - reduce thrombotic risk
221
What are some inherited causes of thrombophilia ?
Factor V Leiden
Antithrombin III deficiency
Protein C and S deficiency
222
What are some acquired causes of thrombophilia ?
Antiphospholipid syndrome
Drugs - COCP
223
What is thrombotic thrombocytopenic purpura ?
Abnormally large and sticky multimers of von Willebrand’s factor cause platelets to clump within vessels
224
What are some features of thrombotic thrombocytopenic purpura ?
Rare
Fever
Fluctuating neuro signs
Thrombocytopenia
225
What are some causes of thrombotic thrombocytopenic purpura ?
Post infection
Pregnancy
Drugs
Tumours
SLE
HIV
226
What is a thymoma ?
Most common tumour of the anterior mediastinum
227
What is associated with a thymoma ?
Myasthenia gravis
Red cell aplasia
Dermatomyositis
228
How is a thymoma lead to death ?
Compression of the airway
Cardiac tamponade
229
What is tranexamic acid ?
A synthetic derivative of lysine
230
What is the primary mode of action of tranexamic acid ?
Antifibrinolytic that reversibly binds to lysine receptor sites on plasminogen and prevents plasmin from binding to and degrading fibrin.
231
When is tranexamic acid given ?
Major haemorrhage
232
What is tumour lysis syndrome ?
A deadly condition related to the treatment of high grade lymphoma and leukaemia.
Usually triggered by the introduction of combination chemotherapy
Causes high potassium and phosphate levels with low calcium.
233
How to prevent tumour lysis syndrome ?
IV fluids
Allopurinol or rasburicase ( not given together )
234
How is clinical tumour lysis syndrome diagnosed ?
Laboratory tumour lysis syndrome + one or more of :
- increased serum creatinine
- cardiac arrhythmias or sudden death
- seizure
235
What are some general risk factors for venous thromboembolism ?
Age
Obesity
Family history
Pregnancy
Immobility
236
What are some underlying conditions that are risk factors for venous thromboembolism ?
Malignancy
Thrombophilia
Heart failure
Antiphospholipid syndrome
Sickle cell anaemia
237
What are some drugs that increase the risk of a VTE ?
COCP
HRT
Raloxifene and tamoxifen
Antipsychotics
238
How is vitamin b12 absorbed in the body ?
Absorbed after binding to intrinsic factor secreted from parietal cells in the stomach and is activity absorbed in the terminal ileum.
239
What are some causes of vitamin b12 deficiency ?
Pernicious anaemia
Post-gastrectomy
Poor diet
Crohn’s
240
What are some features of vitamin b12 deficiency ?
Macrocytic anaemia
Sore tongue and mouth
Mood disturbances
Distal paraesthesia
241
What is the management for vitamin b12 deficiency ?
If no neurological involvement then 1mg of IM hydroxocobalamin
242
What is von willebrand’s disease ?
Most common inherited bleeding disorder
Autosomal dominant
243
What is the role of von willebrand factor ?
Large glycoprotein which forms massive multimers
Promotes platelet adhesion to damaged endothelium
Carrier molecule for factor VIII
244
What abnormalities are seen during investigations in von willebrands disease ?
Prolonged bleeding time
APTT may be prolonged
245
What is the management of von willebrand disease ?
Tranexamic acid
Desmopressin
Factor VIII concentrate
