Haematology Flashcards
1
Q
What 2 groups can macrocytic anaemia be split into and what are examples of each?
A
- megaloblastic: B12 deficiency (pernicious), folate deficiency, drugs (sulfonamides), gastrectomy, terminal ileum resection
- normoblastic: liver disease, alcoholism, hypothyroidism, myelodysplasia, anticonvulsants
2
Q
What are 5 blood test abnormalities that may be seen in anti-phospholipid syndrome?
A
- Anti-cardiolipin antibodies
- Lupus anticoagulant
- Anti beta2 glycoprotein 1 antibody
- Prolonged APTT (paradoxical)
- Low platelets
3
Q
What are the criteria for diagnosing hereditary haemorrhagic telangiectasia?
A
2 criteria - possible diagnosis
3 or more - definite diagnosis
the criteria:
1. epistaxis
2. telangiectases multiple at characteristic sites (lips, oral cavity, fingers, nose)
3. visceral lesions e.g. GI telangiectasia (+/- bleeding), pulmonary AVMs, hepatic AVM, cerebral AVM, spinal AVM
4. family history first-degree relative with HHT
4
Q
What is the key histological finding in Hodgkin’s lymphoma?
A
Reed-Sternberg cells (cells of B cell origin, unable to express antibodies)
5
Q
What are the 5 types of Hodkin’s lymphoma and which has a different treatment paradigm?
A
- nodular sclerosis
- mixed cellularity
- lymphocyte-depleted
- lymphocyte-rich
- nodular lymphocyte predominant Hodgkin disease (different treatment, unique entity)
6
Q
What is Pel-Ebstein fever in Hodgkin’s lymphoma?
A
high fever for 1-2 weeks followed by afebrile period of 1-2 weeks
7
Q
What is alcohol induced pain with lymphadenopathy specific for?
A
Hodgkin’s disease
8
Q
What system is sued to stage Hodgkin’s disease?
A
Ann Arbor system
9
Q
What is the treatment for Hodgkin’s lymphoma?
A
radiotherapy and/or chemotherapy
10
Q
What is the commonest inherited theombophilia?
A
Factor V Leiden
11
Q
What are 5 examples of inherited thrombiphilias?
A
- Factor V Leiden
- Prothrombin gene mutation
- Anthrombin III deficiency
- Protein S deficiency
- Protein C deficiency
12
Q
What is an example of an acquired thrombophilia?
A
Antiphospholipid syndrome
13
Q
What are 4 features of polycythaemia?
A
- Pruritus - particularly after warm bath
- Ruddy complexion
- Gout
- Peptic ulcer disease
14
Q
What is the commonest secondary cause of antiphospholipid syndrome?
A
SLE
15
Q
Why does antiphospholipid syndrome cause a paradoxical rise in APTT?
A
ex-vivo reaction of lupus anticoagulant antibodies with phospholipids involved in the coagulation cascade
16
Q
What are 4 diseases associated with anti-phospholipid syndrome?
A
- SLE
- other autoimmune disorders
- lymphoproliferative disorders
- phenothiazindes (rare)
17
Q
What is a key dermatological manifestation of antiphospholipid syndrome?
A
livedo reticularis
18
Q
What is the primary thromboprophylaxis management for antiphospholipid syndrome?
A
low-dose aspirin
19
Q
What is the secondary thromboprophylaxis given in antiphospholipid syndrome?
A
- initial VTE event: lifelong warfarin, target INR 2-3
- recurrent VTE: lifelong warfarin; if whilst taking warfarin add low dose aspirin, target 3-4
- arterial thrombosis: lifelong warfarin target INR 2-3
20
Q
What is immune (idiopathic) thrombocytopenic purpura?
A
immune-mediated reduction in platelet count; antibodies are directed against glycoprotein IIb/IIIa or Ib-V-IX complex
21
Q
What type of hypersensitivity reaction is immune thrombotuopenic purpura?
A
type II
22
Q
What are the key features of immune thrombocytopenia in children?
A
- bruising, petechial or purpuric rash, bleeding less common (if occurs - epistaxis or gingival bleeding)
- more acute than in adult
23
Q
What will investigations show in immune thrombocytopenic purpura in children in children?
A
FBC - isolated thrombocytopenia
bone marrow examination - only required if atypical features e.g. LN enlargement/splenomegaly, high/low WCC, failure to resolve/respond to treatment
24
Q
What is the management of immune thrombocytopenic purpura in chidlren?
A
- resolves spontaneously in 80% of children within 6 months with or without treatment
- avoid activties that may result in trauma e.g. team sports
- if platelet count <10 or significant bleeding, options: oral/IV corticosteroid, IVIG, platelet transfusion in emergency
25
What should be administered during cardiac arrest if pulmonary embolism is suspected & how does this cahnge the CPR algorithm?
thrombolytic drugs e.g. alteplase - if given, CPR should be continued for extended period 60-90 min
26
What is the classical genetic abnormality in chronic myeloid leukaemia?
* **Philadelphia** chromosome
* = translocation between long arm of chromosome 9 and 22
* results in ABL proto-oncogene being fused with BCR gene - BCR-ABL gene codes for fusion protein with increased tyrosine kinase activity
27
At what age does chronic myeloid leukaemia present?
60-70 years
28
What are the key presenting clinical features of chronic myeloid leukaemia?
* **anaemia**: lethargy
* **weight loss** and **sweating**
* **splenomegaly** → abdo discomfort
* increase in **granulocytes** at different stages of maturation +/- **thrombocytosis**
* decreased **leukocyte alkaline phosphatase**
* may undergo **blast transformation** (AML in 80%, ALL in 20%)
29
What is the first-line management of chronic myeloid leukaemia?
**imatinib** - inhibits tyrosine kinase associated with BCR-ABL defect
30
What are 4 options for treatment of chronic myeloid leukaemia?
* imatinib
* hydroxyurea
* interferon-alpha
* allogenic bone marrow transplant
31
What are 2 types of acute leukaemia and when do they classically present?
* Acute myeloid leukaemia - **adulthood**
* Acute lymphoblastic leukaemia - **childhood (2-5 years)**
32
What is the most common type of childhood malignancy?
acute lymphoblastic leukaemia (ALL)
33
What are the clinical features of acute lymphoblastic leukaemia?
* anaemia - lethargy and pallor
* neutrophenia - infections
* thrombocytopenia - bruising, petechiae
* bone pain
* splenomegaly
* hepatosplenomegaly
* fever
* testicular swelling
34
What are 3 types of acute lymphoblastic leukaemia?
1. common ALL (75%) - CD10 present, pre-B phenotype
2. T-cell ALL
3. B-cell ALL
35
What are 5 **poor** prognostic factors for ALL?
1. age < 2 years or >10 years
2. WBC <20 at diagnosis
3. T or B cell surface markers
4. non-Caucasian
5. male sex
36
Which patient group does haemolytic uraemic syndrome usually present in?
young children
37
What is the triad of symptoms seen in haemolytic uraemic syndrome?
1. acute kidney injury
2. microangiopathic haemolytic anaemia
3. thrombocytopenia
38
What is the class cause of primary haemolytic uraemic syndrome?
* Shiga toxin-producing E coli (STEC) 0157:H7
39
In addition to STEC, what are 3 other causes of secondary haemolytic uraemic syndrome?
1. pneumococcal infection
2. HIV
3. SLE, drugs, cancer
40
What causes primary (atypical) HUS?
complement dysregulation
41
What are 3 investigations to perform in haemolytic uraemic syndrome?
1. FBC - anaemia (microangiopathic haemolytic anaemia), thrombocytopenia, fragmented blood film
2. U+E - AKI
3. stool culture - PCR for Shiga toxins, looking for STEC
42
What will blood film show in haemolytic uraemic syndrome?
fragmented: schistocytes and helmet cells
43
What will Coombs test show in haemolytic uraemic syndrome?
negative
44
What is the management of haemolytic uraemic syndrome?
* supportive - fluids, blood transfusion, dialysis if required
* plasma exchanged in severe cases NOT associated with diarrhoea
* eculizumab in adult atypical HUS
45
What are 4 types of crises in sickle cell anaemia?
1. **thrombotic** a.k.a. 'vaso-occlusive' 'painful crises'
2. **acute chest syndrome**
3. **anaemic** aplastic or sequestration
4. **infection**
46
What are 3 things that can precipitate a vaso-occlusive / thrombotic sickle cell crisis?
1. infection
2. dehydration
3. deoxygenation e.g. high altitude
47
What are 5 sites where infarction can occur in a sickle cell vaso-occlusive (thrombotic) crisis?
1. avascular necrosis of hip
2. hand-foot syndrome (children)
3. lungs
4. spleen
5. brain
48
What is acute chest syndrome in sickle cell disease?
vaso-occlusion within the pulmonary microvasculature leading to infarction in the lung parenchuma
49
What is the management of acute chest syndrome in sickle cell disease?
* pain relief
* respiratory support e.g. oxygen therapy
* antibiotics
* transfusion - improves oxygenation
50
What causes aplastic crises in sickle cell disease?
infection with parvovirus
51
How will aplastic crises in sickle cell disease manifest on blood tests?
* sudden fall in Hb
* **reduced** reticulocyte count (bone marrow suppression)
52
What is a sequestration crisis in sickle cell disease?
* sickling within organs such as spleen or lungs causing pooling of blood with worsening of the anaemia
* may present with splenomegaly, abdominal pain, clinical anaemia
53
How will a sequestration crisis in sickle cell disease manifest on blood tests?
worsening of anaemia, INCREASED reticulocyte count
54
How can aplastic and sequestration crises be differentiated in sickle cell disease, on the basis of blood tests?
reticulocyte count increased in sequestration, reduced in aplastic
55
What are 6 PRC transfusion reactions?
1. Non-haemolytic febrile reaction
2. Minor allergic reaction
3. Anaphylaxis
4. Acute haemolytic reaction
5. Transfusion-associated circulatory overload (TACO)
6. Transfusion-related acute lung injury (TRALI)
56
What are the features of non-haemolytic febrile reaction in response to blood transfusion?
fever, chills
| 10-30% caused by platelet transfusion
57
What is the management of a non-haemolytic febrile reaction?
slow or stop transfusion, paracetamol, monitor
58
What is thought to cause non-haemolytic febrile transfusion reaction?
HLA antibodies reacting with white cell fragments in the blood product and cytokines that have leaked from the blood cell durting storage - often due to sensitisation by previous pregnancies / transfusions
59
What is thought to cause minor allergic reactions to blood transfusion?
foreign plasma proteins
60
What are the features of a minor allergic reaction to blood transfusion?
pruritis, urticaria
61
What is the management of minor allergic reaction to blood transfusion?
* temporarily stop transfusion
* antihistamine
* monitor
* once symptoms resolve, transfusion may be continued
62
What can cause anaphylaxis in response to blood transfusion?
patients with IgA deficiency who have anti-IgA antibodies
63
What is the management of anaphylaxis in response to blood transfusion?
permanently discontinue - administer IM adrenaline - supportive care; antihistamine, steroids and bronchodilators, IVF
64
What causes an acute haemolytic transfusion reaction?
mismatch of blood group (ABO) causng massive intravascular haemolysis - usually result of red blood cell destruction by IgM type antibodies
65
How quickly do acute haemolytic transfusion reaction symptoms develop and what are they?
* within minutes
* fever, abdominal / chest pain, agitation, hypotension
66
What is the management of acute haemolytic transfusion reaction?
* stop transfusion
* confirm diagnosis - check patient ID / blood product
* send blood for direct Coomns test, repeat typing and cross-matching
* IVF resuscitation
* inform lab
67
What are 2 possible complications of acute haemolytic transfusion reaction?
* intravascular coagulation
* renal failure
68
What are 2 things that can pre-dispose to transfusion-associated circulatory overload?
1. excessive rate of transfusion
2. pre-exisitng heart failure
69
What is a key difference in TACO that is not seen in TRALI?
patients may be hypertensive in TACO
70
What is the management of TACO?
slow or stop transfusion
consider IV loop diuretic and O2
71
What is transfusion-related acute lung injury (TRALI)?
* non-cardiogenic pulmonary oedema
* thought secondary to increased vascular permeabiliy caused by host neutrophils
* activated by substances in donated blood
* develop hgypoxaemia / acute respiratory distress syndrome
72
How quickly does TRALI develop?
within 6 hours of transfusion
73
What are 4 key features of TRALI?
1. hypoxia
2. pulmonary infiltrates on CXR
3. fever
4. hypotension
74
What is the management of TRALI?
stop transfusion, oxygen, supportive care
75
What are 4 ways that the risk of vCJD from blood transfusion has been reduced?
1. leucodepletion to reduce vCJD infectivity
2. plasma derivated have been fractionated from imported plasma (not UK donors)
3. FFP for children / certain adult groups imported
4. recipients of blood transfusion excluded from donating blood
76
What are 4 secondary causes of polycythaemia which are due to **excessive erythropoietin**?
1. cerebellar haemangioma
2. hypernephroma
3. hepatoma
4. uterine fibroids
77
How can you differentiate between **true** (primary or secondary) polycythaemia and **relative** polycythaemia (dehydration / stress)?
**red cell mass studies** are sometimes used. In true polycythaemia the total red cell mass in males > 35 ml/kg and in women > 32 ml/kg (not in relative PC)
78
What are 2 relative causes of polycythaemia?
1. dehydration
2. stress (Gaisbock syndrome)
79
What is primary polycythaemia called?
polycythaemia rubra vera
80
What are 4 secondary causes of polycythaemia?
1. COPD
2. altitude
3. OSA
4. excessive EPO
81
What is a cause of episodic RUQ pain in a patient with hereditary spherocytosis?
**biliary colic** - chronic haemolysis -> gallstone formation (differential - splenic rupture)
82
What is the inheritance pattern of hereditary spherocytosis?
autosomal dominant
83
What are 7 aspects of the presentation of hereditary spherocytosis?
1. failure to thrive
2. jaundice
3. gallstones
4. splenomegaly
5. aplastic crisis precipitated by parvovirus infection
6. degree of haemolysis variable
7. MCHC elevated
84
When are no additional tests required for a diagnosis of hereditary spherocytosis?
* patients with family history of HS
* typical clinical features
* typical laboratory investigations: spherocytes, raised mean corpuscular haemoglobin concentration (MCHC), high reticuloctes
85
If diagnosis is equivocal based on initial presentation and lab tests, what is the diagnostic test for hereditary spherocytosis?
**EMA binding test** and cryohaemolysis test
86
What is the method of choice for diagnosing hereditary spherocytosis with atypical presentations?
electrophoresis analysis of erythrocyte membranes
87
What is the management of an acute haemolytic crisis in hereditary spherocytosis?
supportive, transfuse if necessary
88
What are 2 aspects of the long term management of hereditary spherocytosis?
1. folate replacement
2. splenectomy
89
Which region of the world is hereditary spherocytosis more common?
North European
90
What are 4 types of Hodgkin's lymphoma and their relative frequencies?
1. Nodular sclerosing - 70% (commonest)
2. Mixed cellularity (20%)
3. Lymphocyte predominant (5%)
4. Lymphocyte depleted (rare)
91
What is the order of prognosis of the 4 types of Hodgkin's lymphoma from best to worst?
1. Best: Lymphocyte predominant
2. Good: nodular sclerosing
3. Good: mixed cellularity
4. Worst: lymphocyte depleted
92
Which type of Hodgkin's lymphoma is associated with lacunar cells?
nodular sclerosing
93
Which type of Hodgkin's lymphoma is associated with a large number of Reed-Sternberg cells?
mixed cellularity
94
What symptoms imply a poor prognosis in Hodgkin's lymphoma?
B symptoms - weight loss >10% in last 6 months, fever >38, night sweats
95
What are 7 factors associated with a poor prongosis in Hodgkin's lymphoma other than b symptoms?
1. age > 45 years
2. stage IV disease
3. Hb <10.5
4. lymphocytes < 600 or 8%
5. male
6. albumin < 40
7. WCC < 15 000
96
Of blood transfusion and exchange transfusion in sickle cell crises, which can rapidly reduce the percentage of Hb S containing cells?
exchange transfusion (not blood)
97
When should you admit patients with features of a sickle cell crisis?
* all children with fever - particularly if unexplained
* low threshold for all children
* temperature over 38
* any chest symptoms
98
What are 4 blood test findings in iron deficiency anaemia?
1. low ferritin (can be raised during inflammatory states)
2. increased total iron binding capacity (TIBC)
3. low serum iron
4. reduced transferrin saturation (but increased transferrin)
99
What type of anaemia is IDA?
hypochromic microcytic anaemia
100
For how long should patients continue taking iron after iron deficiency has been corrected?
3 months
101
How can you differentiate between CLL and CML?
* **chronic lymphocytic leukaemia** - lymphocytosis with mature lymphocytes and smudge cells on peripheral smear
* **chronic myeloid leukaemia** - increased numbers of granulocytes at all stages of development, splenomegaly + high platelets
102
What is the inheritance pattern of beta-thalassaemia?
autosomal recessive
103
What are 2 features on blood tests of beta-thalassaemia trait?
* mild hypochromic, microcytic anaemia - microcytosis disproportionate to anaemia
* HbA2 raised (>3.5%)
104
What is the mechanism of action of dabigatran?
direct thrombin inhibitor
105
What is the reversal agent for dabigatran?
idarucizumab
106
Which drugs can andexanet alfa be used as the reversal agent?
rivaroxaban + apixaban
107
What is the mechanism of action of rivaroxaban / apixaban / edoxaban?
direct factor Xa inhibitor
108
What is the excretion of different DOACs?
* dabigatran: renal
* rivaroxaban: liver
* apixaban: faecal
* edoxaban: faecal
109
At what partial pressure of oxygen do patients with HbAS (one normal, one abnormal chain) RBCs sickle?
2.5-4 kPa
110
At what partial pressure of oxygen do patients with HbSS (two abnormal chains) RBCs sickle?
pO2 5-6 kPa
111
How is a definitive diagnosis of sickle cell disease made?
haemoglobin electrophoresis
112
What are 2 causes of benign paraproteinaemia?
1. monoclonal gammopathy of undetermined significance (MGUS)
2. transient paraproteinaemia (e.g. after infection)
113
What are 4 malignant causes of paraproteinaemia?
1. multiple myeloma
2. Waldenstrom macroglobulinaemia
3. primary amyloidosis
4. B-cell lymphoproliferative disorders e.g. CLL, non-Hodgkin lymphoma
114
What are 5 clinical features of paraproteinaemia?
1. hyperviscosity syndrome
2. neuropathy e.g. sensory, motor, autonomic
3. renal dysfunction
4. haematologic abnormalities e.g. anaemia, thrombocytopenia, leukopenia
5. bone pain or pathologic fractures
115
What are 3 key aspects of the management of polycythaemia vera?
1. **aspirin** - reduces risk of thrombotic events
2. **venesection** - first line to normalise Hb
3. **chemotherapy** - hydroxyurea, phosphorus-32 therapy
116
What are 2 options for chemotherapy for polycythaemia rubra vera?
1. hydroxyurea
2. phosphorus-32 therapy
117
What are 3 key risks in polycythaemia vera?
1. **thrombotic** events
2. progression to **myelofibrosis**
3. progression to **acute leukaemia** (chemotherapy increases risk)
118
What are 5 features of post-thrombotic syndrome after DVT?
1. painful, heavy calves
2. pruritus
3. swelling
4. varicose veins
5. venous ulceration
119
What is the advice regarding compression stockings and post-thrombotic syndrome?
NICE advise do not offer elastic compression stockings to prevent PTS or VTE recurrence - but recommended once PTS has developed
120
What are 5 causes of microcytic anaemia?
1. iron-deficiency anaemia
2. thalassaemia
3. congenital sideroblastic anaemia
4. anaemia of chronic disease (but more commonly normocytic)
5. lead poisoning
121
What does normal Hb with microcytosis raise the possibility of?
polycythaemia rubra vera
122
In which condition can a microcytosis be disproportionate to the anaemia?
beta thalassaemia
123
In which condition are 'tear drop' poikilocytes generally seen?
myelofibrosis (flat, elongated RBCs)
124
In which condition are smear cells generally seen on a blood film?
chronic lymphocytic leukaemia (CLL)
125
In what 2 conditions are spherocytes seen on a blood film?
1. hereditary spherocytosis
2. autoimmune haemolytic anaemia
126
What are 2 conditions in which target cells (RBCs) are seen on blood film?
1. iron-deficiency anaemia
2. hyposplenism
127
In which condition are Auer rods classically seen?
acute promyelocytic leukaemia
128
What is the more common form of acute leukaemia in adults?
acute myeloid leukaemia
129
What are 5 features of acute myeloid leukaemia?
1. Anaemia
2. Neutropenia - may be high WCCs, low functioning neutrophils
3. thrombocytopenia + bleeding
4. splenomegaly
5. bone pain
130
What are 3 poor prognostic features in AML?
1. > 60 years
2. > 20% blasts after first course of chemo
3. cytogenetics: deletions of chromosome 5 or 7
131
What causes acute promyelocytic leukaemia M3 genetically?
associated with t(15;17), fusion of PML and RAR-alpha genes
132
What is the prognosis of acute promyelocytic leukaemia M3 compared with other AML?
good prognosis
133
What age group is commonly affected by acute promeylocytic leukaemia M3?
younger than other AML types - avg 25 years
134
What is often seen at presentation of Acute promyelocytic leukaemia M3?
DIC or thrombocytopenia
135
What classification is used for AML?
French-American-British (FAB) classification, M0-M7
136
When does WHO recommend platelet transfusion is given?
platelet count < 30 with clinically significant bleeding (haematemesis, melaena, prolonged epistaxis)
137
When is a platelet threshold > 30 used?
maximum <100 for patients with severe bleeding or critical sites e.g. CNS
138
Which type of blood product has the highest risk of bacterial contamination?
platelet transfusion
139
What are the platelet thresholds that are aimed for before surgery / invasive procedure?
* most patients: > 50
* high risk of bleeding: 50-75
* surgery at critical site: > 100
140
What is the target level of platelets in someone without active bleeding or any planned procedure?
threshold of 10 (except if platelet transfusion CI / there are alternative treatments)
141
What are 4 conditions when platelet transfusion should not be performed?
1. chronic bone marrow failure
2. autoimmune thrombocytopenia
3. heparin-induced thrombocytopenia
4. thrombotic thrombocytopenic purpura
142
What is the most common inherited bleeding disorder?
von Willebrand's disease
143
What is the inheritance pattern of von Willebrand's disease?
most commonly **autosomal dominan**t (type 3, total lack of vWF = autosomal recessive)
144
What type of bleeding does von Willebrand's disease cause?
behaves like platelet disorder - epistaxis and menorrhagia common, haemarthroses and muscle haematomas rare
145
What is the role of von Willebrand factor?
large glycoprotein which forms massive multimers; promotes platelet adhesion to damaged endothelium. also carrier molecule for factor VIII
146
What are 3 types of von Willebrand's disease?
1. type 1: partial reduction in vWF (80% of patients)
2. type 2: abnormal form of vWF
3. type 3: total lack of vWF
147
What are 4 blood test findings in von Willebrand's disease?
1. prolonged bleeding time
2. prolonged APTT
3. factor VIII levels may be moderately reduced
4. defective platelet aggregation with ristocetin
148
What are 3 aspects of the treatment of von Willebrand's disease?
1. **TXA** - mild bleeding
2. **desmopressin** (DDAVP) - raises vWF levels by induced release from Weibel-Palade bodies in endothelial cells
3. **factor VIII** ceoncentrate
149
What is seen on a blood film in DIC and why?
schistocytes - microangiopathic haemolytic anaemia
150
What are 4 things seen on FBC / clotting profile in DIC?
1. reduced platelets
2. reduced fibrinogen
3. raised PT and APTT
4. raised fibrinogen degradation products
151
How can you distinguish between liver failure and DIC as causes for coagulopathy on blood tests?
* liver failure: all clotting factors low except factor VIII, which is supranormal
* DIC: all clotting factors depleted
152
What are 3 causes why there is a paradoxical increased risk of venous thromboembolism in liver failure despite prolonged PT and APTT?
1. supranormal levels of factor VIII
2. reduced synthesis of protein c and protein s (vitamin K dependent)
3. reduced anti-thrombin synthesis (non-vtamin K dependent)
153
What is the management with antiplatlets/anticoagulation in someone with a history of stable CVD + indication for anticoagulation e.g. AF?
anticoagulant monotherapy without antiplatelets
154
What is the antiplatelet/anticoagulant management of a patient post-ACS / PCI?
* initially give 2 antiplatelets + 1 anticoagulant for 4 weeks - 6 months
* then 1 antiplatelet + 1 anticoagulant for 12 months
155
What is anti-streptolysin O antibody associated with in children?
Henoch-Schonlein purpura
