Haematology 2 Flashcards
1
Q
What is polycythaemia?
A
Erythrocytosis of any cause (high red blood cell count) and increased haemoglobin and packed cell volume (PCV)
2
Q
Describe the epidemiology of polycythaemia
A
95% of patients have the JAK2 mutation
3
Q
What is the difference between absolute and relative polycythaemia?
A
Absolute = increased number of RBCs Relative = normal number of RBCs but reduction in plasma
4
Q
What is the difference between primary and secondary absolute polycythaemia?
A
Primary = increased sensitivity of BM cells to EPOSecondary = more circulating EPO
5
Q
What are 2 causes of primary absolute polycythaemia?
A
- Polycythaemia rubra vera = genetic mutation in JAK2 gene
- Primary familial and congenital polycythaemia = genetic mutation in EPO receptor gene
6
Q
What are 8 causes of secondary absolute polycythaemia?
A
- Chronic hypoxia2. Erythropoietin producing tumour (e.g. renal carcinoma)3. High altitude4. COPD5. Sleep apnoea6. PKD7. Renal artery stenosis8. Kidney cancer
7
Q
What are 3 causes of relative polycythaemia?
A
- Obesity2. Dehydration3. Excessive alcohol consumption
8
Q
What are 2 signs of polycythaemia?
A
- Hypertension2. Angina
9
Q
What is a sign of polycythaemia rubra vera that is not seen in secondary polycythaemia?
A
Hepatosplenomegaly
10
Q
What are 9 symptoms of polycythaemia?
A
- Easy bleeding/bruising2. Fatigue3. Dizziness4. Headaches5. Blurred vision6. Plethoric complexion7. Itching especially after contact with water8. Tinnitus9. Erythromelalgia (burning sensation in fingers/toes)
11
Q
What are 3 investigations for patients with polycythaemia?
A
- FBC2. BM biopsy3. Genetic testing for JAK2 gene
12
Q
What is the difference between FBC for polycythaemia rubra vera and secondary polycythaemia?
A
Both = low serum EPORubra vera = raised WBC and plateletsSecondary = normal WBC and platelets
13
Q
What is the treatment for polycythaemia?
A
- Blood letting (venesection - removal of 400-500ml of blood)- Low dose aspirin daily- Hydroxycarbamide (for those at risk of thrombus)- Treat the cause
14
Q
What is thrombocytopenia?
A
Deficiency of platelets in the blood
15
Q
Describe the epidemiology of immune thrombocytopenia (ITP)
A
- Mainly seen in children aged 2-6- Primary = often post-viral infections (self-limiting)- Secondary = more common in young women, malignancies and HIV
16
Q
What are 3 causes of ITP?
A
- Reduced platelet production in BM2. Autoimmune destruction of platelets3. Problems of enlarged spleen
17
Q
Describe the pathophysiology of ITP
A
- Autoimmune destruction of platelets due to IgG antibodies- IgG antibodies coat the platelets which are then removed by binding to Fc receptors on macrophages
18
Q
What are 6 symptoms of both ITP and TTP?
A
- Purpura (red/purple spots on skin caused by bleeding underneath)2. Epistaxis3. Easy bruising4. Menorrhagia5. Headache6. Fatigue
19
Q
What are 2 symptoms of ITP?
A
- Gum bleeding2. Vomiting
20
Q
What are 3 investigations for ITP?
A
- FBC2. BM biopsy3. Platelet autoantibodies present in 70% of cases
21
Q
What is the treatment for ITP?
A
- 1st line = corticosteroids e.g. prednisolone - IV IgG (temporarily increases no. of platelets)- Splenectomy- Immunosuppression = oral azathioprine
22
Q
Describe the epidemiology of thrombotic thrombocytopenia (TTP)
A
- Rare- More common in adults- More common in females (3:2)- Associated with HIV, cancer and systemic lupus erythematosus
23
Q
What is the cause of TTP?
A
Deficiency of von Willebrand Factor cleaving protein (vWF-cp) a.k.a ADAMTS 13 (responsible for the degradation of vWF)
24
Q
Describe the pathophysiology of TTP
A
- Lack of vWF-cp results in extensive microvascular clot formation in small vessels in the body- Results in low platelet count and organ damage
25
What are 4 symptoms of TTP?
1. Flu-like symptoms (fever, aches)2. Haemoptysis (coughing up blood)3. Abdominal pain4. Chest pain
26
What is a sign of TTP?
GI bleeding
27
What are 6 investigations for patients with thrombocytopenia?
1. Normal coagulation screen
2. Blood smear = fragmented erythrocytes
3. U&E = raised creatinine
4. Raised bilirubin
5. Raised reticulocyte count (immature RBCs)
6. Urinalysis = proteinuria and haematuria
28
What is the treatment for TTP?
- IV plasma exchange- Steroids = IV methylprednisolone- Rituximab (monoclonal antibody)- Folic acid
29
What should you absolutely not do for patients with TTP?
Platelet transfusions
30
What is Von Willebrand Disease?
A deficiency in vWF a.k.a pseudohaemophilia
31
Describe the epidemiology of VWD
- Most common hereditary coagulopathy- More common in females- Poorer prognosis in blood type O
32
What is the cause of VWD?
- vWF deficiency- Can be congenital or acquired
33
What is the function of vWF?
- Assists platelet plug formation- vWF binds to factor VIII to protect it from liver protein C destruction (prevents clearance of factor VIII from plasma)
34
What are the types of VWD?
- Type 1: most common (60-80%); autosomal dominance; defect in QUANTITY of vWF- Type 2- Type 3- Platelet type: most rare
35
What are 3 symptoms of VWD?
1. Epistaxis2. Menorrhagia3. Spontaneous bleeding
36
What are 6 investigations for patients with VWD?
1. FBC2. Fibrinogen level3. Platelet count = normal4. Clotting screen5. Plasma vWF = decreased6. Factor VIII levels = decreases
37
What is the treatment for VWD?
- Stop any antiplatelet drugs and NSAIDs- Tranexamic acid (for minor bleeds)- COC (for menorrhagia)- Desmopressin (increase vWF levels)- Platelet transfusions
38
What is haemophilia A?
Factor VIII deficiency
39
Describe the epidemiology of haemophilia A
- 5 times more common than haemophilia B- Mainly affects men (X linked recessive disorder)
40
What are the types of haemophilia A?
- Mild = >5% FVIII activity- Moderate = 1-5% FVIII activity- Severe = <1% FVIII activity
41
What are 2 signs of haemophilia A and B?
1. Haematoma (collection of blood outside blood vessels)2. Hemarthrosis (bleeding into joint spaces - happens in severe)
42
What are 4 symptoms of haemophilia A and B?
1. Severe bleeding following injury (happens in moderate)2. Easy bruising3. Haematuria4. Severe epistaxis
43
What are 3 investigations for patients with haemophilia A and B?
1. Prothrombin time (PTT) = normal2. Activated partial thromboplastin time (APTT) = prolonged3. Plasma factor VIII/IX = reduced
44
Why is PTT normal and APTT is prolonged in patients with haemophilia A and B?
Factors VIII and IX are not in the extrinsic pathway so PTT is not affected whereas APTT is
45
What is the treatment for haemophilia A and B?
- IV factor VIII and IX- Fresh frozen plasma containing factor VIII/IX- Desmopressin (boosts FVIII/IX activity)- Hep A vaccinations
46
What is a complication of haemophilia A and B?
Joint deformities and arthritis from recurrent bleeding into joints
47
What is haemophilia B?
Factor IX deficiency
48
What are the types of haemophilia B?
- Mild = 6-30% FIX levels- Moderate = 1-5% FIX levels- Severe = <1% FIX levels (50% of cases)
49
What is disseminated intravascular coagulopathy?
Widespread activation of coagulation cascade and platelet activation
50
What are 8 causes of DIC?
1. Sepsis2. Crush syndrome3. Malignancy e.g. leukaemia4. Amniotic fluid embolism5. Abruptio placentae6. Infection e.g. meningitis7. Haemolytic transfusion reactions8. Liver disease
51
Describe the pathophysiology of DIC
- Initial thrombosis following bleeding- Occurs when the balance between forming new clots and breaking down clots is tipped in favour of forming clots = widespread clotting = organ ischaemia- Depletion of clotting factors leads to bleeding
52
What are 2 signs of DIC?
1. GI bleed2. ARDS (adult respiratory distress syndrome)
53
What are 8 symptoms of DIC?
1. Spontaneous bleeding at venepuncture/IV sites2. Epistaxis3. Bruising4. Rash5. Purpura (red/purple spots on skin caused by bleeding underneath)6. Confusion and Shock7. Shortness of breath8. Haemoptysis (coughing up blood)
54
What are 2 investigations for DIC?
1. FBC2. Blood smear/film = schistocytes (fragmented RBCs)
55
What do bloods show in patients with DIC?
- Low platelets- Low fibrinogen- High d-dimer- Long PT- Long APTT
56
What is the treatment for DIC?
- Treat underlying cause- Cryoprecipitate (for low fibrinogen)- Platelet transfusion- Red cell transfusion- Fresh frozen plasma
57
What are 2 complications of DIC?
1. Organ failure by infarction2. Death
58
What is the cause of glandular fever (infectious mononucleosis)?
Epstein Barr Virus
59
What are 3 signs of glandular fever?
1. Lymphadenopathy (swollen lymph nodes)2. Tonsillar enlargement3. Splenomegaly
60
What are 3 symptoms of glandular fever?
1. Fever2. Sore throat3. Fatigue
61
What are 2 investigations for patients with glandular fever?
1. Test for heterophile antibodies (Monospot test or Paul-Bunnel test)2. Test for EBV antibodies
62
What is the treatment for glandular fever?
- Usually self-limiting (2-3 weeks)- Advised to avoid alcohol and contact sports- Emergency surgery (if splenic rupture)
63
What is multiple myeloma?
Cancer of plasma cells resulting in excess production of certain immunoglobulins (most often IgG and IgA)
64
Describe the epidemiology of multiple myeloma
- 75+- Afro-Caribbean's- Males- IgG = 55%- IgA = 20%- Close link to monoclonal gammopathy of undetermined significance (MGUS)
65
What is monoclonal gammopathy of undetermined significance (MGUS)?
- Too much of an immunoglobulin is released by abnormal plasma cells- 1% of cases develop into myeloma
66
What are the signs of multiple myeloma?
OLD CRAB:- Old >75- Calcium (high) >2.75mmol/L- Renal impairment- Anaemia- Bone lesions (pepper pot skull)
67
What are 6 symptoms of multiple myeloma?
1. Fatigue2. Dizziness3. Polyuria/polydipsia 4. Constipation5. Abdominal pain6. Back pain
68
What are 6 investigations for patients with multiple myeloma?
1. FBC = anaemia and raised ESR
2. Blood film = rouleaux
3. Serum and urine electrophoresis = Bence Jones protein in urine
4. Xray = pepper pot skull and fractures
5. CT = bone lesions and cord compression
6. Serum protein electrophoresis = presence of M proteins
69
What is the treatment for multiple myeloma?
Palliative disease- Bisphosphonates- Analgesia (avoid NSAIDs)- Chemotherapy/radiotherapy- Blood transfusions- Infection control
70
What are 5 complications of multiple myeloma?
End organ damage:1. Lytic bone lesions2. Infections3. Fractures4. Renal failure5. Proteinuria
71
What is anaemia?
Lower than normal concentration of haemoglobin (Hb <130 in men, <120 in women)
72
What are 4 signs of anaemia?
1. Tachycardia2. Skin pallor3. Conjunctive pallor4. Raised respiratory rate
73
What are 5 symptoms of anaemia?
1. Fatigue2. Headache3. Dizziness4. Dyspnoea (especially on exertion)5. Palpitations
74
What are 4 distinguishing symptoms of anaemia?
1. Jaundice/dark urine (haemolytic anaemia)2. Lemon/yellow skin (B12 deficiency)3. Koilonychia (spoon shaped nails) (iron deficiency)4. Angular stomatitis (irritated cracked sores/inflammation around corners of mouth) (iron/B12 deficiency)
75
What is microcytic anaemia?
Anaemia with a MCV (mean corpuscular volume) of <80fl
76
Describe the epidemiology of microcytic anaemia
- 2-5% of men and post menopausal women- Premenopausal women are at a higher risk due to menses- Iron deficiency anaemia is the most common type of anaemia
77
What are 5 causes of microcytic anaemia?
1. Iron deficiency2. Anaemia of chronic disease3. Thalassaemia4. Sickle cell5. Sideroblastic anaemia
78
What are 6 causes of iron deficiency?
1. Blood loss (e.g. menorrhagia)2. Poor diet3. Malabsorption (e.g. coeliac disease)4. Hookworm5. Pregnancy6. Breastfeeding
79
What are 4 causes of anaemic of chronic disease?
1. Cancer2. HF3. CKD4. Chronic inflammation (e.g. connective tissue disorders)
80
What is thalassaemia?
When the body makes an abnormal form/inadequate amount of Hb resulting in defective subunits
81
What is sideroblastic anaemia?
Normal iron levels but body cannot insert iron into Hb
82
What are 4 signs and symptoms of microcytic anaemia due to iron deficiency?
1. Brittle hair and nails2. Atrophic glossitis (tongue inflammation)3. Koilonychia (spoon shaped nails)4. Angular stomatitis (inflammation of corners of mouth)
83
What are 2 signs and symptoms of microcytic anaemia due to thalassaemia?
Asymptomatic (if heterozygotic)
1. Failure to thrive
2. Bone deformities
84
What are 3 investigations for patients with microcytic anaemia due to iron deficiency?
1. FBC = low Hb, low MCV <80fl2. Iron studies = low ferritin/iron, low transferrin saturation but raised transferrin3. Blood film = small, hypochromic cells
85
What are 2 investigations for patients with microcytic anaemia due to chronic disease?
1. FBC = low Hb, low/normal MCV, high ESR2. Iron studies = normal/raised ferritin, low iron, low transferrin saturation
86
What is the investigation for patients with microcytic anaemia due to thalassaemia?
Blood film = microcytic, hypochromic cells
87
What are 2 investigations for patients with microcytic anaemia due to sideroblastic anaemia?
1. FBC = increased iron/ferritin/transferrin2. Blood film = ringed 'sideroblasts'
88
What is the treatment for microcytic anaemia?
- Ferrous sulphate
Thalassaemia:
- Blood transfusions
- Iron chelating agent (for iron overload)
- Ascorbic acid (increased iron excretion in urine)
89
What are 3 complications of microcytic anaemia?
1. Iron overload2. Endocrine dysfunction3. Side effects of ferrous sulphate = black stool, constipation/diarrhoea and nausea
90
What is normocytic anaemia?
Anaemia with a MCV (mean corpuscular volume) of 80-95fl
91
What are 6 causes of normocytic anaemia?
1. Anaemia of chronic disease2. Acute blood loss3. Pregnancy4. Renal failure5. Autoimmune6. Malaria
92
What is the difference between haemolytic and non-haemolytic normocytic anaemia?
Haemolytic = increased destruction of RBCsNon-haemolytic = decreased production of RBCs
93
What are 2 types of haemolytic anaemia?
1. Sickle cell anaemia2. Autoimmune haemolytic anaemia
94
Describe the epidemiology of sickle cell anaemia
- Autosomal recessive condition (abnormal gene for beta-globin on chromosome 11- High proportion in Africa/India/Middle East/Caribbean as having the sickle-cell trait increases the likelihood of surviving malaria
95
Describe the pathophysiology of sickle cell anaemia
- Gene mutation of GAG to GTG
- Causes sickle shaped RBCs (due to abnormal haemoglobin variant HbS)
- These RBCs are more fragile and more easily destroyed
96
Describe the pathophysiology of hereditary spherocytosis causing anaemia
- Often causes aplastic crisis in the presence of parvovirus
- RBCs are round (sphere) shaped (often due to mutation in ANK1 gene)
- These RBCs are more fragile and more easily destroyed
- = anaemia
97
Describe the pathophysiology of malaria causing anaemia
- Sporozoites injected into humans by mosquitos
- These infect hepatocytes
- Develops into schizonts which burst/destroy and infect RBCs
- = fewer RBCs = anaemia
98
When are G6PD deficiency crises triggered?
After infections, medications (nitrofurantoin) or fava (broad) beans
99
Describe the pathophysiology of G6PD deficiency causing anaemia
- Lack of enzyme glucose-6-phosphate dehydrogenase (helps RBCs to work and protects them)
- Deficiency = RBCs break apart = fewer RBCs = anaemia
100
Describe the pathophysiology of autoimmune haemolytic anaemia
- Immune system makes antibodies against RBCs- This causes increased haemolysis
101
Describe the pathophysiology of CKD causing anaemia
- Less EPO is produced so fewer RBCs can be made - = anaemia
102
Describe the pathophysiology of aplastic anaemia
- Immune system attacks health stem cells in the bone marrow- This causes new blood cells to not be produced
103
What is the investigation for patients with normocytic anaemia and what are the results?
FBC:
- Normal MCV 80-95fl
- Low Hb
- Low haematocrit
- Raised bilirubin
- Raised urobilinogen
104
What are 3 investigations for patients with haemolytic normocytic anaemia?
1. Blood film = schistocytes
2. Genetic testing during pregnancy and newborn screening heel prick test (for sickle cell anaemia)
3. Blood film = Heinz bodies
105
What are 3 investigations for patients with autoimmune haemolytic anaemia?
1. FBC = normocytic anaemia
2. Blood film = schistocytes
3. Direct Coombs test = positive
106
What is the treatment for normocytic anaemia?
- Treat underlying cause- Improve diet with plenty of vitamins- EPO injections
107
What is the treatment for sickle cell anaemia?
- Avoid dehydration- Ensure vaccines are up to date- Antibiotic prophylaxis to protect against infection (phenoxymethylpenicillin)- Hydroxycarbamide (stimulates production of HbF)- Blood transfusion- Bone marrow transplant
108
What is the main complication of sickle cell anaemia?
Sickle cell crisis
109
What 4 things most commonly occur in a sickle cell crisis?
1. Vaso-occlusive crisis2. Splenic sequestration crisis3. Aplastic crisis4. Acute chest syndrome
110
What is macrocytic anaemia?
Anaemia with a MCV (mean corpuscular volume) of >95fl
111
What is the difference between megaloblastic and non-megaloblastic macrocytic anaemia?
Megaloblastic = impaired DNA synthesis which causes cells to grow into large, abnormal cellsNon-megaloblastic = multiple mechanisms
112
What are 3 causes of megaloblastic macrocytic anaemia?
1. B12 deficiency due to insufficient dietary intake2. B12 deficiency due to pernicious anaemia3. Folate deficiency
113
What are 4 causes of non-megaloblastic macrocytic anaemia?
1. Alcohol2. Hypothyroidism3. Liver disease4. Drugs e.g. azathioprine
114
Describe the pathophysiology of pernicious anaemia
- Antibodies form against parietal cells and intrinsic factor- Lack of intrinsic factor prevents the absorption of vitamin B12 in the ileum- = lack of vitamin B12
115
What are 4 symptoms of macrocytic anaemia?
1. Visual changes2. Mood/cognitive changes3. Peripheral numbness/paraesthesia4. Loss of vibration sense/proprioception
116
What are 2 investigations for patients with macrocytic anaemia?
1. FBC = high MCV (>95fl) and low Hb2. Blood film = large, hypochromic cells and hypersegmented neutrophil polymorphs (in megaloblastic)
117
What is lymphoma?
A group of cancers that affect the lymphocytes inside the lymphatic system
118
Describe the epidemiology of Hodgkin's lymphoma
- 1/5 lymphomas- Bimodal age distribution with peaks around 20 and 75- Male predominance- 5th most common malignancy in the western world
119
What are 3 risk factors for both Hodgkin's and Non-Hodgkin's lymphoma?
1. HIV2. Epstein-Barr virus3. Family history
120
What are 2 risk factors for Hodgkin's lymphoma?
1. Immunosuppression2. Autoimmune conditions e.g. rheumatoid arthritis and sarcoidosis
121
What are 3 risk factors for Non-Hodgkin's lymphoma?
1. H. pylori2. Hepatitis B or C3. Exposure to pesticides and trichloroethylene
122
What is Burkitt lymphoma?
Type of lymphoma associated with HIV, Epstein-Barr virus and malaria
123
What is MALT lymphoma?
Type of lymphoma that affects the mucosa-associated lymphoid tissue usually around the stomach (associated with H. pylori)
124
What is diffuse large B cell lymphoma?
Type of lymphoma that often presents as a rapidly growing painless mass in patients over 65 years
125
What is a sign of Non-Hodgkin's lymphoma?
Hepatosplenomegaly
126
What is the main symptom of Hodgkin's and Non-Hodgkin's lymphoma?
Lymphadenopathy (enlarged lymph nodes)- Felt in neck, axilla or inguinal region- Characteristically non tender and feel rubber- Painful upon drinking alcohol
127
What are 3 B symptoms (systemic symptoms) of Hodgkin's and Non-Hodgkin's lymphoma?
1. Fever2. Weight loss3. Night sweats
128
What are 6 other symptoms of Hodgkin's and Non-Hodgkin's lymphoma?
1. Fatigue2. Itching3. Cough4. Shortness of breath5. Abdominal pain6. Recurrent infections
129
What are 4 investigations for patients with Hodgkin's and Non-Hodgkin's lymphoma?
1. FBC = anaemia and raised ESR2. Lymph node biopsy3. Lactate dehydrogenase = raised (non specific)4. CT/MRI/PET
130
What are the results of lymph node biopsies in patients with Hodgkin's and non-Hodgkin's lymphoma?
Hodgkin's = Reed-Sternberg cellsNon-Hodgkin's = No Reed-Sternberg cells
131
What are Reed-Sternberg cells?
Abnormally large B cells that have multiple nuclei that have nucleoli inside them
132
What additional investigation is there for patients with Hodgkin's lymphoma?
CXR - wide mediastinum
133
What is Ann Arbor Staging?
Staging for where lymphomas are:
Stage 1 = confined to one region of the lymph nodes
Stage 2 = in more than one region but on the same side of the diaphragm
Stage 3 = affects lymph nodes both above and below diaphragm
Stage 4 = widespread involvement including non-lymphatic organs e.g. lungs/liver
134
What is the treatment for Hodgkin's lymphoma?
- ABVD chemotherapy - Radiotherapy- Steroids- Stem cell/bone marrow transplant
135
What is the treatment for Non-Hodgkin's lymphoma?
- RCHOP chemotherapy- Radiotherapy- Stem cell/bone marrow transplant
136
What are 2 complications of Hodgkin's and Non-Hodgkin's lymphoma treatment?
1. Chemotherapy carries a risk of leukaemia and infertility2. Radiotherapy carries a risk of cancer and damage to tissues and hyperthyroidism
137
What is leukaemia?
Cancer of the bone marrow
138
Describe the pathophysiology of leukaemia
- Immature blast cells uncontrollably proliferate
- This takes up space within the bone marrow leading to infiltration into other tissues
- Lack of space within the bone marrow means that fewer healthy cells can mature and be released into the blood
- = pancytopenia (low RBCs, WBCs and platelets)
139
What is acute myeloid leukaemia?
Proliferation of immature myeloblasts (neutrophils, basophils, eosinophils)
140
Describe the epidemiology of AML
- Presents mostly in the elderly (over 75)- Only 15% 5 year survival
141
What are 3 signs of AML?
1. Hepatosplenomegaly2. Lymphadenopathy3. Failure to thrive
142
What are 5 symptoms of AML?
1. General anaemia symptoms2. Bleeding/bruising3. Infections4. Gum hypertrophy5. Petechiae
143
What are 8 investigations for patients with AML?
1. FBC = anaemia, leukopenia, thrombocytopenia
2. Blood film = high proportion of blast cells
3. Lactate dehydrogenase = raised (non specific)
4. Bone marrow biopsy = auer rods (rods in cytoplasm of blast cells)
5. CXR = mediastinal lymphadenopathy
6. Lymph node biopsy
7. Lumbar puncture (if CNS involvement)
8. CT/MRI/PET
144
What is the treatment for AML?
- Blood/platelet transfusions
- Chemotherapy
- Stem cell/bone marrow transplant
- Antibiotics
145
What is acute lymphoblastic leukaemia?
Proliferation of immature lymphoblasts (B lymphocytes, T lymphocytes)
146
Describe the epidemiology of ALL
- Most common leukaemia in children 0-4 years- Under 5 and over 45- Often associated with Downs Syndrome
147
What are 3 signs of ALL?
1. Hepatosplenomegaly2. Lymphadenopathy3. CNS infiltration = CNS palsies
148
What are 4 symptoms of ALL?
1. General anaemia symptoms2. Bleeding/bruising3. Infections4. CNS infiltrations = headaches
149
What are 7 investigations for patients with ALL?
1. FBC = anaemia, leukopenia/neutropenia, thrombocytopenia
2. Blood film = high proportion of blast cells
3. Lactate dehydrogenase = raised (non specific)
4. Bone marrow biopsy
5. CXR = lymphadenopathy
6. Lumbar puncture (if CNS involvement)
7. CT/MRI/PET
150
What is the treatment for ALL?
- Blood/platelet transfusions
- Chemotherapy (methotrexate)
- Stem cell/bone marrow transplant
- Steroids
- Antibiotics
151
What is chronic myeloid leukaemia?
Proliferation of mature myeloid blood cells (neutrophils, basophils, eosinophils)
152
Describe the epidemiology of CML
- Over 40
- Strong association with the Philadelphia chromosome (translocation of genes between chromosome 9 and 22 - t(9;22) of BCR/ABL gene)
153
What is the chronic phase of CML?
- Can last around 5 years- Often asymptomatic- Patients are diagnosed with a raised white cell count
154
What is the accelerated phase of CML?
- Abnormal blast cells take up a high proportion of the cells in the bone marrow and blood (10-20%)
- Patients become more symptomatic, develop anaemia and thrombocytopenia and become immunocompromised
155
What is the blast phase of CML?
- Very high proportion of abnormal blast cells (>30%) - Severe symptoms and pancytopenia- Often fatal
156
What are 2 signs of CML?
1. Hepatosplenomegaly2. Gout
157
What are 5 symptoms of CML?
1. General anaemia symptoms2. Bleeding/bruising3. Infections4. Weight loss5. Night sweats
158
What are 5 investigations for patients with CML?
1. FBC = anaemia, thrombocytopenia, leucocytosis2. Blood film3. Lactate dehydrogenase = raised (non specific)4. Bone marrow biopsy5. Genetic testing
159
What is the treatment for CML?
- Chemotherapy- Stem cell/bone marrow transplant- Tyrosine kinase inhibitors (imatinib)
160
What is chronic lymphoblastic leukaemia?
Chronic proliferation of mature lymphocytes (B lymphocytes, T lymphocytes - predominantly B lymphocytes)
161
Describe the epidemiology of CLL
- Over 55- Most common type of leukaemia in adults
162
What is a sign of CLL?
Lymphadenopathy
163
What are 4 symptoms of CLL?
Often asymptomatic
1. General anaemia symptoms
2. Infections
3. Weight loss
4. Night sweats
164
What are 4 investigations for patients with CLL?
1. FBC = anaemia, thrombocytopenia, leucocytosis
2. Blood film = smear/smudge cells (aged/fragile WBCs that have ruptured)
3. Lactate dehydrogenase = raised (non specific)
4. Bone marrow biopsy
165
What is the treatment for CLL?
- Watch and wait in early stages- Chemotherapy- Stem cell/bone marrow transplant
166
What are 2 complications of CLL?
1. Can cause warm autoimmune haemolytic anaemia2. Can transform into high-grade lymphoma (Richter's transformation)
167
What is neutropenia?
Low numbers of white blood cells (neutrophils) in the blood
168
What are 4 potential causes of neutropenia?
1. Antibiotics2. Chemotherapy3. Marrow failure4. Liver disease
169
What is neutrophilia?
High white blood cell (neutrophil) count in the blood
170
What are 3 potential causes of neutrophilia?
1. Infection2. Inflammation3. CML
171
What is lymphopenia/lymphocytopenia?
Low numbers of white blood cells (lymphocytes) in the blood
172
What are 5 potential causes of lymphopenia/lymphocytopenia?
1. Steroids2. HIV3. Post-viral4. Marrow failure5. Chemotherapy
173
What is lymphocytosis?
High white blood cell (lymphocyte) count in the blood
174
What are 5 potential causes of lymphocytosis?
1. EBV2. CMV (cytomegalovirus)3. Hepatitis4. Malignancy (CLL/ALL/lymphoma)5. Stress
175
What are 3 potential causes (production failure) of thrombocytopenia?
1. Marrow failure2. Congenital3. Leptospirosis (bacterial disease)
176
What are 6 potential causes (increased removal) of thrombocytopenia?
1. ITP2. TTP3. DIC4. HIT (heparin-induced thrombocytopenia)5. HUS (haemolytic uremic syndrome)6. SLE
177
What is thrombocytosis?
Increased platelet count in the blood
178
What are 5 potential causes of thrombocytosis?
1. Infection2. Inflammation3. Tissue injury4. Splenectomy5. Essential thrombocythemia
179
What is prothrombin time (PT)?
Time taken for a clot to form in a blood sample (tests the extrinsic pathway)
180
Briefly describe the extrinsic pathway of the coagulation cascade
- Initiated by tissue factor- Expressed by immune cells and endothelium- Consists of factors VII, II (prothrombin), V and X- 7 --> 10 --> 10a
181
What is international normalised ratio (INR)?
Calculation based on the results of a prothrombin time that is used to monitor individuals being treated with anticoagulants (e.g. warfarin)
182
What is activated partial thromboplastin time (APTT)?
Time taken for a clot to form in a blood sample (tests the intrinsic and common pathways)
183
Briefly describe the intrinsic pathway of the coagulation cascade
- Consists of factors VIII, IX, XI and XII- 12 --> 11 --> 9 --> 8 --> 10 --> 10a
184
Briefly describe the common pathway of the coagulation cascade
- Consists of factors I, II (prothrombin), V, VII and X- 10a --> 2 --> 2a (thrombin) --> fibrinogen --> fibrin (reinforced by factor XIII)
185
Describe the epidemiology of HIV
- HIV-1 is the most common- HIV-2 is rare outside West Africa
186
Describe the pathophysiology of HIV
- HIV is an RNA retrovirus
- Virus enters T helper cells and binds to CD4 receptors
- Endocytoses RNA and enzymes
- Reverse transcriptase is used to turn RNA into DNA
- Integrase uses to integrate the viral DNA into the hosts
- Protein synthesis of viral proteins and RNA which leave via exocytosis and take part of the CD4 cell cytoplasm
- This repeats, increasing the viral copies and reducing the number of CD4 T helper cells
187
What are 3 methods of transmission of HIV?
1. Unprotected anal, vaginal or oral sexual activity
2. Mother to child at any stage of pregnancy birth or breastfeeding (vertical transmission)
3. Mucous membrane, blood or open wound exposure to infected blood or bodily fluids such as sharing needles, needle-stick injuries or blood splash in an eye
188
What are AIDS-defining illnesses?
Those associated with end-stage HIV where the CD4 count has dropped to a level that allows for unusual opportunistic infections and malignancies to appear
189
What are 6 examples of AIDS-defining illnesses?
1. Kaposi's sarcoma2. Pneumocystis jirovecii pneumonia (PCP)3. Cytomegalovirus infection4. Candidiasis (oesophageal or bronchial)5. Lymphomas6. TB
190
What are 3 methods of testing for HIV?
1. Antibody blood test (repeat testing required)2. Testing for the P24 antigen3. PCR testing for HIV RNA levels (gives a viral load)
191
What are 2 methods of monitoring HIV?
1. CD4 count2. Viral load
192
What is the normal range and end stage HIV/AIDS range for CD4 count?
Normal = 500-1200 cells/mm3End stage HIV/AIDS = <200 cells/mm3
193
What classes as an 'undetectable' viral load?
Viral load below the labs recordable range, usually 50-100 copies of HIV RNA per ml of blood
194
What are the 2 aims of HIV treatment?
1. Achieve a normal CD4 count2. Achieve an undetectable viral load
195
What is the main method of treatment for HIV?
Combination of antiretroviral therapy (ART)
196
What are 5 high active anti-retrovirus therapy (HARRT) medication classes?
1. Protease inhibitors (PIs)2. Integrase inhibitors (IIs)3. Nucleoside reverse transcriptase inhibitors (NRTIs)4. Non-nucleoside reverse transcriptase inhibitors (NNRTIs)5. Entry inhibitors (EIs)
197
What 2 other medications are given to patients with HIV?
1. Prophylactic co-trimoxazole given to patients with CD4 <200/mm3 to protect against PCP2. Statins given to reduce the risk of developing CVD
198
What 2 preventative/screening things should be done for patients with HIV?
1. Yearly cervical smears for women2. Up to date vaccines for annual influenza, pneumococcal, hep A/B, tetanus, diphtheria and polio
199
What are 2 complications of HIV?
1. Increased risk of developing CVD2. Predisposed to cervical human papillomavirus (HPV) infection and cervical cancer
200
What is tumour lysis syndrome?
Collection of metabolic disturbances occurring with rapid destruction of neoplastic cells
201
Describe the epidemiology of tumour lysis syndrome
Occurs more frequently with aggressive treatment of haem malignancies e.g. Non Hodgkin lymphoma and acute leukaemia
202
Describe the pathophysiology of tumour lysis syndrome
- Chemotherapy given causes cancer cells too break down
- Cancer cells release their contents e.g. uric acid into the blood stream
- Uric acid can form crystals in the interstitial tissue and tubules of kidneys to cause damage/loss of function
203
What does tumour lysis syndrome cause?
- Hyperuricaemia
- Hyperkalaemia
- Hyperphosphatemia
- Hypocalcaemia
- AKI
204
What is the treatment for tumour lysis syndrome?
- Allopurinol (xanthine oxidase inhibitor) to reduce uric acid levels- IV fluid and correct electrolytes
