HAEMATOLOGY Flashcards
(324 cards)
1
Q
What are the possible causes of ALL?
A
- genetic abnormalities, including the occurrence of a Philadelphia chromosome caused by the t(9;22) translocation.
- radiation exposure
- viral infections
- smoking
- folate metabolism polymorphisms.
2
Q
Where are the sanctuary sites in ALL?
A
Testicles and CNS
3
Q
Which population are most commonly affected by ALL?
A
children under 6 years of age
4
Q
What are the features of anaemia seen in ALL?
A
- Pallor
- Fatigue.
- Dizziness.
- Palpitations.
- Dyspnoea.
5
Q
What are the thrombocytopenia features seen in ALL?
A
- Epistaxis.
- Menorrhagia.
- Ecchymosis
- Petechiae
6
Q
What are the features of bone marrow infiltration seen in ALL?
A
- Anaemia
- neutropenia causing recurrent infection
- thrombocytopenia
- Bone pain
7
Q
What are the features of reticula-endothelial infiltration seen in ALL?
A
- Hepatomegaly
- Splenomegaly
- Lymphadenopathy
8
Q
What are the CNS features of ALL?
A
- Headaches, vomiting, nerve palsies
9
Q
What are the FBC findings in ALL?
A
- Anaemia
- Leucocytosis
- Neutropenia
- Thrombocytopenia.
10
Q
What are the findings on a metabolic panel in ALL?
A
- Elevated calcium
- Elevated potassium
- Elevated uric acid
- Elevated lactic dehydrogenase.
11
Q
What are the findings on a blood film in ALL?
A
-Leukaemic blast cells.
12
Q
What are the findings on bone marrow aspiration and trephine biopsy?
A
- Hypercellularity
- Infiltration by leukaemic blast cells.
13
Q
What is the management of ALL?
A
- Induction therapy with steroids or an aspiraginase
- consolidation therapy with maintenance chemotherapy (teniposide and mercaptopurine and methotrexate) if there is no high risk of relapse.
- if high risk of relapse offer additional stem cell transplant
- salvage chemotherapy for relapse or refractory disease
14
Q
What are the poor prognostic factors in ALL?
A
- Male sex.
- WBC level greater than 30 x 109/L at presentation.
- Philadelphia chromosome.
- CNS involvement.
15
Q
What is tumour lysis syndrome?
A
-an oncological emergency characterised by metabolic and electrolyte abnormalities that can occur after the initiation of cancer treatment.
16
Q
What causes tumour lysis syndrome?
A
-rapid breakdown of large numbers of cancer cells, and subsequent release of large amounts of intracellular content into the bloodstream
17
Q
What are the biochemical features of tumour lysis syndrome?
A
- hyperuricaemia
- hyperkalaemia
- hyperphosphataemia
- hypocalcaemia.
18
Q
Which population are most commonly affected by AML?
A
- over 60s
- Down syndrome
19
Q
what are the clinical features of AML?
A
- Pallor.
- Ecchymoses or petechia.
- Fatigue.
- Palpitations.
- Dyspnoea.
- Infections or fever.
- Lymphadenopathy.
- Hepatosplenomegaly.
- Mucosal bleeding.
20
Q
What is seen on FBC in AML?
A
- Anaemia
- Leucocytosis
- Neutropenia
- Thrombocytopenia.
21
Q
What is seen on blood film in AML?
A
- Myeloid blast cells
- Auer rods
- Bi-lobed nuclei in AMPL
22
Q
What is seen on metabolic panel in AML?
A
- Elevated calcium
- Elevated potassium
- Elevated uric acid
- Elevated lactic dehydrogenase.
23
Q
What is seen on bone marrow biopsy in AML?
A
- Hypercellularity
- Myeloid blast cells
24
Q
What is the management of AML?
A
- Offer induction chemotherapy (cytarabine and idarubicin).
- Offer higher dose cytarabine for relapsed AML.
25
What is the management of APML?
- Offer induction chemotherapy (tretinoin [ATRA] and idarubicin).
- Offer arsenic trioxide for relapsed or refractory AMPL.
26
How is tumour lysis syndrome managed?
- Hydration
| - Allopurinol
27
What is the name of the process by which CLL becomes diffuse large B cell non-Hodgkin’s lymphoma?
-Richter's transformation
28
Which population are most affected by CLL?
-It most commonly occurs in older people with a median age of 70.
29
What are the clinical features of CLL?
- Most cases are diagnosed as incidental findings on routine FBC and are therefore asymptomatic.
- Shortness of breath and fatigue.
- Lymphadenopathy.
- Splenomegaly.
- B symptoms (fever, chills, night sweats, weight loss, fatigue).
- Hepatomegaly.
- Petechia.
- Recurrent infections.
30
What is seen on FBC in CLL?
- Elevated WCC greater than 5 x 109/L.
31
What is seen on blood film in CLL?
- Small B-lymphocytes
- Smudge cells
- Spherocytes if active haemolysis.
32
What is stage 0 of the Rai staging system?
-lymphocytosis
33
What is stage 1 of the Rai staging system?
-Lymphocytosis + lymphadenopathy
34
What is stage 2 of the Rai staging system?
-Lymphocytosis + hepatosplenomegaly.
35
What is stage 3 of the Rai staging system?
-Lymphocytosis + Anaemia.
36
What is stage 4 of the Rai staging system?
-Lymphocytosis + Thrombocytopenia.
37
How is CLL managed?
-Asymptomatic patients with early stage CLL (Rai 0 - 2) do not require immediate treatment, close observation is recommended.
- For advanced disease (Rai 3 - 4) without 17p/p53 mutation:
- Initially offer FCR chemoimmunotherapy.
- Offer ibrutinib and adjunct stem cell transplantation for early relapse or refractory disease.
- For advanced disease (Rai 3 - 4) without 17p/p53 mutation:
- Initially offer ibrutinib.
- Offer idelalisib and adjunct stem cell transplantation for early relapse or refractory disease.
38
Which chromosomal abnormality is responsible for CML?
-Philadelphia chromosome, a reciprocal translocation of the long arm of chromosome 22 to chromosome 9.
39
What population are most affected by CML?
- almost exclusively a disease of adults
| - peak of presentation being between 40 and 60 years.
40
What are the clinical features of CML?
-Often diagnosed as incidental findings on routine FBC and are therefore asymptomatic aside from pallor and massive splenomegaly.
41
What are the features of a blast crisis in CML?
- Malaise.
- Fever.
- Weight loss.
- Abdominal discomfort.
- Night sweats.
- Shortness of breath.
- Splenomegaly.
- Petechia, ecchymoses, easy bruising.
- Excessive bleeding.
- Infection.
42
what is seen on FBC in CML?
- Elevated WCC
| - Thrombocytopenia in blast crisis.
43
what is seen on metabolic profile in CML?
- Elevated potassium
- Elevated LDH
- Elevated uric acid.
44
what is seen on blood film in CML?
- Myeloblasts and elevated basophils and eosinophils in chronic phase
- Blast cells > 20% in blast crisis.
45
what is seen on bone marrow biopsy in CML?
- Hypercellularity and granylocytopoiesis in chronic phase
| - Blast cells >20% in blast crisis.
46
what is the management of CLL?
- tyrosine kinase inhibitor e.g. imatinib
- allogenegic haematopoietic stem cell transplant (HSCT) and high dose induction chemotherapy with tyrosine kinase inhibitor for the blast phase, or for disease progression
- Consider the use of interferon if there is relapse after HSCT, or HSCT is contraindicated.
47
what are the clinical features of hairy cell leukaemia?
- Abdominal discomfort.
- Splenomegaly.
- Fatigue.
- Weakness.
- Weight loss.
- Hepatomegaly.
- Pallor.
- Petechiae.
- Recurrent infections.
48
what is seen on FBC in hairy cell leukaemia?
- pancytopenia
49
what is seen on blood film in hairy cell leukaemia?
-Hairy cells.
50
what is seen on bone marrow biopsy in hairy cell leukaemia?
- Hairy cells
| - Reticulin fibres.
51
How is hairy cell leukaemia managed?
- purine analogue (clabridine or pentostatin) for symptomatic patients.
- rituximab for relapsed or refractory disease.
- splenectomy for massive splenomegaly, splenic rupture, or marked thrombocytopenia.
52
How is hereditary spherocytosis inherited?
-autosomal dominant
53
what are the clinical features of hereditary spherocytosis?
- Pallor.
- Jaundice.
- Gallstones and biliary colic.
- Splenomegaly.
- Fatigue.
- Hydrops fetalis.
54
what is seen on FBC in hereditary spherocytosis?
- Normal or mild reduction in Hb
- Normal or mild reduction in MCV
- Normal WCC
- Normal platelets.
55
what is seen on blood film in hereditary spherocytosis?
- raised reticulocytes
- Spherocytes are small and lack central pallor
- Pincer cells (mushroom-shaped)
- Post-splenectomy Howell jolly bodies which have a purple (basophilic) spot.
56
what is the definitive diagnostic test hereditary spherocytosis?
-eosin-5-maleimide (EMA) binding test with reduced intensity
57
how is hereditary spherocytosis treated?
- Perform red cell transfusions in neonates with jaundice, or in infants, children and adults with mild-to-moderate symptoms.
- Perform splenectomy with a preoperative pneumococcal vaccination where there are severe symptoms.
- Offer lifelong phenoxymethylpenicillin prophylaxis post-splenectomy.
58
how is B-thalassaemia inherited?
-autosomal recessive
59
what are the features of B-thalassaemia major?
- Presents after 6 months of life.
- Pallor.
- Skeletal changes (large head with frontal and parietal bossing, chipmunk facies).
- Misaligned teeth.
- Hepatosplenomegaly.
- Failure to thrive.
- Gallstones.
- Lethargy.
60
what are the features of B-thalassaemia minor?
- asymptomatic
| - mild pallor
61
what is seen on FBC in B-thalassaemia?
-Variable reduced Hb count.
62
what is seen on blood film in B-thalassaemia?
- Microcytic red cells
- Hypochromic red cells.
- variable elevation of reticulocyte count
63
what is seen on Hb analysis in major B-thalassaemia?
- Absent HbA
| - Elevated HbF and HbA2
64
what is seen on Hb analysis in intermediate B-thalassaemia?
- Decreased HbA
| - Elevated HbF and HbA2.
65
what is seen on Hb analysis in minor B-thalassaemia?
- Mostly HbA
| - Elevated HbF and HbA2
66
what is seen on skull x-ray in intermediate and major B-thalassaemia?
- Expansion of marrow
| - ’Hair on end’ appearance.
67
how is minor B-thalassaemia managed?
-Avoid iron supplementation unless there is evidence of iron deficiency.
68
how is intermedia B-thalassaemia managed?
- Offer acute red cell transfusions during symptomatic anaemia.
- Offer iron chelation therapy (subcutaneous desferrioxamine) for iron overload due to repeat transfusions.
- Offer splenectomy in transfusion dependent cases.
69
how is major B-thalassaemia managed?
- Offer lifelong transfusions.
- Offer iron chelation therapy (subcutaneous desferrioxamine) for iron overload due to repeat transfusions.
- Offer splenectomy in transfusion dependent cases.
- Offer stem cell transplantation in HLA-matched siblings as a curative therapy.
- Offer genetic counselling in all patients.
70
what are the clinical features of 2 gene deletion a-thalassaemia?
- Fatigue.
- Dizziness.
- Shortness of breath.
71
what are the clinical features of 3 gene deletion a-thalassaemia?
- Gallstones.
- Growth retardation.
- Jaundice.
- Splenomegaly in Hb Constant Spring.
72
what are the features of hydrops fetalis in a-thalassaemia?
- Pale.
- Oedematous.
- Enormous livers and spleens.
73
what is seen on FBC in a-thalassaemia?
- Low Hb
- Low MCV
- Low MCH.
74
what is seen on blood film in a-thalassaemia?
- Hypochromic red cells
- Microcytic red cells
- Basophilic stippling in Hb Constant Spring.
75
how is a-thalassaemia treated?
- Offer folic acid supplementation.
- Offer acute and chronic red blood cell transfusions.
- Offer iron chelation therapy (desferrioxamine) for patients with iron overload.
- Offer splenectomy and preoperative vaccination and postoperative phenoxymethylpenicillin for painful splenomegaly, hypersplenism, and associated pancytopenia.
76
how is sickle cell disease inherited?
-autosomal recessive
77
what is the genotype for sickle cell anaemia?
-HbSS
78
what is the genotype for sickle cell trait?
-HbAS.
79
what are the complications of sickle cell anaemia?
- infection
- poor growth and delayed sexual maturation
- cardiomegaly
- leg ulcers
- cholecystitis
- priapism
- hepatomegaly
- retinopathy
80
what are the clinical features of sickle cell anaemia?
- Painful swelling across joints of hands and feet (dactylitis).
- Jaundice.
- Pallor.
- Tachycardia.
- Failure to thrive.
- Pneumonia-like syndrome of chest pain, fever, dyspnoea, tachypnoea.
- Bone pain.
- Leg ulcers.
- Systolic flow murmur secondary to anaemia.
- Visual floaters.
- Protuberant abdomen secondary to splenomegaly
81
what is seen on FBC in sickle cell anaemia?
- Reduced Hb (normal for patient)
- Raised MCV
- Raised WCC in infection.
82
what is seen on blood film in sickle cell anaemia?
- Sickle-shaped cells
- Target cells
- Howell-Jolly bodies (hyposplenism).
83
what is seen on plain x-ray in sickle crisis?
- Infarction
- Avascular necrosis of the femoral head
- Third and fourth metacarpals are markedly shorter
- Fifth proximal phalanx is markedly shorter.
84
how is sickle cell anaemia diagnosed?
- CVS or amniocentesis when both parents carry the recessive sickle cell gene
- haemoglobin isoelectric focusing (Hb IEF) or high performance liquid chromatography (HPLC)
- cellulose acetate electrophoresis for diagnosis in older children and adults.
- a sickle solubility test (Sickledex) for rapid diagnosis
85
what is the chronic management of sickle cell anaemia?
- Offer the pneumococcal polysaccharide vaccine (PPV) every 5 years.
- Other vaccinations include the influenza vaccine, Hepatitis B vaccine, and meningitis ACWY vaccine.
- Offer penicillin prophylaxis (or oral erythromycin) to protect against infection.
- Offer folic acid supplementation (5 mg once daily) to prevent deficiency caused by increased folate turnover.
- Offer hydroxycarbamide to prevent acute painful crisis and acute chest syndrome in people with recurrent episodes.
- Avoid triggers such as dehydration, cold and high altitudes, and strenuous exercise.
- Women should avoid the combined oral hormonal contraceptive pill.
- Offer malaria prophylaxis for people with sickle cell disease, as it is likely to be severe due to splenic hypofunction.
86
what is the management of acute painful sickle crisis?
- Offer analgesia depending on the severity (paracetamol for mild pain, codeine for moderate pain, opioids for severe pain).
- Offer fluid replacement for intravascular volume depletion.
- Perform a blood transfusion for life-threatening acute painful crisis .
87
what is the management of acute chest syndrome?
- Offer oxygen therapy at a rate of 2 L/minute for patients with moderate hyperaemia.
- Offer broad spectrum antibiotics because bacterial pneumonia cannot always be ruled out.
- Offer analgesia depending on the severity of pain.
- Arrange cross match for exchange transfusion as soon as the patient is on ITU.
88
how is G6PD deficiency inherited?
-x-linked
89
What exposures can cause an acute haemolytic episode in G6PD deficiency?
- Sulfones such as Dapsone, which is used to treat dermatitis herpetiformis.
- Sulfonamides such as trimethoprim.
- Antimalarials such as primaquine.
- Nitrofurantoin.
- Fluoroquinolone such as ciprofloxacin.
- Fava beans.
- Surgery.
- Infection.
90
what are the clinical features of G6PD deficiency?
- Usually asymptomatic outside of acute haemolytic episodes.
- Jaundice.
- Gallstones.
- Pallor.
- Dark urine.
- Tachycardia.
- Nausea.
- Cataract.
91
what is seen on FBC in G6PD deficiency?
- Reduced Hb
| - Increased MCHC.
92
what is seen on blood film in G6PD deficiency?
- Bite cells
- Heinz bodies.
- elevated reticulocytes
93
how is G6PD deficiency with severe anaemia managed?
- Offer folic acid 5 mg orally once daily for 3 weeks.
- Offer a packed red blood cell transfusion in patients with heart failure or severe symptoms.
- Offer erythropoeitin (epoeitin alfa) for patients with impaired renal function.
94
how is G6PD deficiency in neonates with prolonged indirect hyperbilirubinaemia managed?
- Offer phototherapy which transforms bilirubin into isomers that are more easily excretable, making breakdown products that do not require conjugation in the liver.
- Plasma exchange should be considered early on where there is acute ongoing haemolysis.
95
how is pyruvate kinase deficiency inherited?
- autosomal recessive
96
what is seen on blood film in pyruvate kinase deficiency?
- Burr cells (echinocytes)
- distorted prickle cells
- reticulocytosis
97
how is pyruvate kinase deficiency managed?
- Blood transfusions may be necessary during infections and pregnancy.
- Splenectomy is usually advised for patients requiring frequent transfusions
98
which antibody is present in warm haemolytic anaemia?
IgG
99
what are the causes of warm haemolytic anaemia?
- idiopathic
- Other autoimmune diseases such as SLE.
- Malignancy, such as chronic lymphocytic leukaemia.
- Drugs, including methyldopa.
100
which antibody is present in cold haemolytic anaemia?
IgM
101
what are the causes of cold haemolytic anaemia?
- idiopathic
- Infection such as Mycoplasma pneumoniae, and Epstein-Barr virus.
- Malignancy, such as lymphoma
102
what are the clinical features of warm haemolytic anaemia?
- Signs of anaemia such as pallor, fatigue, shortness of breath, and dizziness.
- Jaundice.
- Splenomegaly.
- Malar butterfly rash and arthralgia in SLE.
103
what are the clinical features of cold haemolytic anaemia?
- Signs of anaemia such as pallor, fatigue, shortness of breath, and dizziness.
- Raynaud’s phenomenon.
- Acrocyanosis.
104
what is seen on FBC in autoimmune haemolytic anaemias?
- Low Hb
- Raised WCC if underlying infection or malignancy
- Low platelets in SLE.
105
in which autoimmune haemolytic anaemia is Donath-Landsteiner antibody present?
-cold haemolytic anaemia
106
how is autoimmune haemolytic anaemia managed?
- Treat underlying condition
- Offer folic acid 1 mg orally daily.
- Offer high dose oral steroids (prednisolone 1 mg/kg/day) to reduce both production of the red cell autoantibody and destruction of antibody coated cells.
- Consider splenectomy if steroid treatment is unsuccessful.
- Consider immunosuppressive agents (rituximab) in patients who fail to respond to splenectomy.
- Offer supportive care such as folic acid supplementation and red blood cell transfusion.
- Patients with cold autoimmune haemolytic anaemia should avoid cold exposure.
107
what are the clinical features of paroxysmal nocturnal haemoglobinuria?
- Dark urine at night and in the morning.
- Tiredness.
- Shortness of breath.
- Palpitations.
- Abdominal pain.
- Dysphagia and odynophagia.
- Erectile dysfunction.
- Headache, vomiting, papilloedema, coma.
- Infections.
108
what are the features of Budd-chiari syndrome?
- Right upper quadrant pain.
- Liver enlargement.
- Ascites.
109
what is seen on FBC in paroxysmal nocturnal haemoglobinuria?
- reduced Hb
- reduced platelets
- increased reticulocytes
110
how is paroxysmal nocturnal haemoglobinuria managed?
- eculizumab
- Offer a red blood cell transfusion if the haemoglobin falls below 85 g/l.
- Offer an erythropoiesis stimulating agent (epoeitin alfa) in patients with aplastic anaemia or kidney damage.
-Offer alteplase in the acute stage of thrombosis followed by lifelong prophylactic
anticoagulation with LMWH (dalteparin).
-Offer ferrous sulfate for iron deficiency.
111
what investigations should be performed antenatally to prevent haemolytic disease of the newborn?
- Determine maternal blood type at first antenatal visit and at 28 weeks: RhD negative.
- Can determine foetal blood type from amniocentesis: RhD positive.
- Measure peak systolic velocity of foetal MCA to assess the severity of anaemia
- Perform a rosette test to determine if foetal maternal haemorrhage
- Perform a Kleihauer test
112
what is the Kleihauer test?
- The Kleihauer test involves a blood film of maternal blood that is treated with acid, which elutes HbA.
- HbF is resistant to this treatment and can be seen when the film is stained with eosin.
- If large doses of foetal red cells are present in the maternal circulation, higher dose of anti-D immunoglobulin will be necessary.
113
what is seen on foetal USS in hydrops fetalis?
- Subcutaneous oedema
- Ascites
- Pleural effusion
- Pericardial effusion.
114
what is seen on post-natal cordocentesis in haemolytic disease of newborn?
- Anaemia with a high reticulocyte count
- A positive direct antiglobulin test
- A raised serum bilirubin.
115
how is haemolytic disease of newborn managed antenatally?
-Offer anti-D immunoglobulin to all women with Rh negative blood and no known priorsensitisation at 28 weeks gestation and then within 72 hours of the end of pregnancy (whether by delivery, abortion, or ectopic pregnancy).
- Offer immediate anti-D immunoglobulin followed by a Kleihauer test following:
- -Antepartum haemorrhage (painful vaginal bleeding before 12 weeks, painless vaginal bleeding after 12 weeks)
- -abdominal trauma.
- -Amniocentesis or chorionic villus sampling.
- -External cephalic version.
116
how is haemolytic disease of newborn managed postnatally?
-Offer immediate exchange transfusion and phototherapy for a foetus with acute bilirubin encephalopathy.
-Consider intravascular intrauterine blood transfusions in a RhD positive foetus, elevated
middle cerebral artery flow, or elevated amniotic bilirubin levels.
-Consider exchange transfusion, phototherapy or intravenous immunoglobulin for neonates with erythroblastosis
117
which cell is the hallmark of classical Hodgkin's lymphoma?
-Reed–Sternberg cells
118
which cell is the hallmark of nodular lymphocyte predominant Hodgkin's lymphoma?
-popcorn cell
119
what are the clinical features of Hodgkin's lymphoma?
- Painless and persistent lymphadenopathy.
| - B symptoms
120
what are B symptoms?
- Fever.
- Night sweats.
- Weight loss.
- Pruritus.
- Alcohol-induced pain.
121
what are the symptoms of superior vena cava syndrome?
- Dyspnoea.
- Cough.
- Orthopnoea.
- Dilated neck veins.
122
what investigations are needed to diagnose Hodgkin's lymphoma?
- Inflammatory markers: raised ERS
- bone marrow biopsy: Reed-Sternberg cells
- CXR: mediastinal widening/lymphadenopathy
- PET/CT
123
what is stage 1 of the Cotswolds Modification to Ann Arbor Classification?
-Involvement of a single lymph node region (Waldeyer ring, spleen, thymus) or involvement of a single extralymphatic site
124
what is stage 2 of the Cotswolds Modification to Ann Arbor Classification?
- Involvement of two or more lymph node regions on the same side of the diaphragm
- localised contiguous involvement of one extranodal organ or site and lymph node regions on the same side of the diaphragm.
125
what is stage 3 of the Cotswolds Modification to Ann Arbor Classification?
- Involvement of lymph node regions on both sides of the diaphragm
- may be accompanied by involvement of the spleen, or by localised involvement of only one extranodal organ site or both.
126
what is stage 4 of the Cotswolds Modification to Ann Arbor Classification?
-Diffuse or disseminated involvement of one or more extra nodal organs or tissues.
127
how is early classical (stage 1 or 2) Hodgkin's lymphoma managed?
-Offer ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) chemotherapy.
128
how is advanced classical (stage 3 or 4) Hodgkin’s lymphoma managed?
-Offer ABVD chemotherapy and radiotherapy.
129
how is early nodular lymphocyte predominant Hodgkin's lymphoma managed?
-radiotherapy
130
how is advanced nodular lymphocyte predominant Hodgkin's lymphoma managed?
-Offer R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy.
131
which organisms are associated with the development of non-hodgkin's lymphoma?
- EBV
- Hep C
- H.pylori
132
what are the clinical features of non-hodgkin's lymphoma?
- Lymphadenopathy
- Hepatomegaly
- Splenomegaly
- Small bowel lymphomas present with diarrhoea, vomiting, abdominal pain, and weight loss
- Waldeyer’s ring lymphoma causes sore throat/obstructed breathing
- Systemic B symptom features – night sweats, fever, weight loss
- Pancytopenia from marrow involvement – anaemia, infection, bleeding (low platelets)
133
what is seen on FBC in non-hodgkin's lymphoma?
- Thrombocytopenia
- Lymphocytosis
- Pancytopenia.
134
what is seen on blood film in non-hodgkin's lymphoma?
- Nucleated red cells
- Left shift (increase in immature cells)
- Blast cells in mantle cell lymphoma.
135
what is seen on lumbar puncture in non-hodgkin's lymphoma?
- Abnormal cells
- Low glucose
- High protein
- High pressure.
136
what is stage 1 of the modified Ann Arbor staging system?
-single lymph node group.
137
what is stage 2 of the modified Ann Arbor staging system?
-Multiple lymph node groups on same side of diaphragm.
138
what is stage 3 of the modified Ann Arbor staging system?
-Multiple lymph node groups on both sides of diaphragm
139
what is stage 4 of the modified Ann Arbor staging system?
-multiple extra nodal sites or lymph nodes and extra nodal disease
140
how is diffuse large B-cell lymphoma managed?
-Offer R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone)
141
how is early follicular lymphoma managed?
-Offer radiotherapy
142
how is advanced follicular lymphoma managed?
-R-CVP (rituximab, cyclophosphame, vincristine and prednisolone)
143
How is Burkitt's lymphoma managed?
- CODOX-M (cyclophosphamide, vincristine, doxorubicin and methotrexate)
- IVAC (ifosfamide, etoposide and cytarabine)
144
how is mantle cell lymphoma managed?
-hyper-CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone)
145
how is peripheral T cell lymphoma and angioimmunoblastic T-cell lymphoma managed?
-offer CHOP
146
what are the causes of iron deficiency anaemia?
- Decreased iron intake due to impaired absorption (achlorhydria, gastric surgery, or coeliac disease).
- Increased iron loss due to menstrual bleeding, gastrointestinal bleeding (peptic ulcer disease, diverticulosis, ulcerative colitis).
- Increased iron deficiency in children and pregnant women, and inadequate iron intake.
147
what are the sources of iron in an infants diet?
- Breast milk (low iron content but 50% of the iron is absorbed)
- Infant formula (supplemented with adequate amounts of iron)
- Cow’s milk (higher iron content than breast milk but only 10% is absorbed)
- Solids introduced at weaning, e.g. cereals (cereals are supplemented with iron but only 1% is absorbed).
148
which substance increases iron absorption?
-vitamin c
149
which substances can reduce iron absorption?
- tannin in tea
| - phytates in foods such as chapattis.
150
what are the symptoms of iron deficiency anaemia?
- Fatigue.
- Dyspnoea.
- Headache.
- Cognitive dysfunction.
- Restless leg syndrome.
- Vertigo.
- Pruritus.
- Dysphagia (in association with oesophageal web which occurs in Patterson-Brown-Kelly or Plummer-Vinson syndrome).
- Syncope.
- pica in children
151
what are the signs of iron deficiency anaemia?
- Koilonychia
- Alopecia.
- Conjunctival pallor.
- Angular stomatitis.
- Atrophic glossitis.
- Dry and rough skin.
- Systolic flow murmur.
152
what is seen on blood film in iron deficiency anaemia?
- Microcytic red cells
- Hypochromic red cells
- Pencil cells.
153
what is seen on iron profile in iron deficiency anaemia?
- Low serum iron
- Low serum ferritin
- Low transferrin saturation
- Increased total iron-binding capacity.
154
which patients with iron deficiency anaemia should be referred for upper and lower GI endoscopy?
- people over 60
- men of any age with a Hb less than 120 g/l of any age
- postmenopausal women with a Hb of less than 100 g/l.
155
how is iron deficiency anaemia treated?
- Prescribe oral iron replacement therapy (ferrous sulfate 200 mg three times daily).
- Offer ferrous gluconate for people in whom ferrous sulfate is not tolerated.
- In children, the best tolerated preparations are Sytron (sodium iron edetate) or Niferex (polysaccharide iron complex)
156
when should IV iron be considered for iron deficiency?
Patients:
- Who do not respond to, or are intolerant to oral iron replacement therapy.
- During the second and third trimester, but it should be avoided during the first trimester.
- Who are found to have iron-deficiency prior to surgery in whom the time interval for normal iron is too short.
157
when should an FBC be repeated following treatment for iron deficiency anaemia?
-after 2-4 weeks of iron supplement treatment
158
why might a patient fail to respond to oral iron therapy?
- Lack of compliance.
- Continuing haemorrhage .
- Incorrect diagnosis (thalassaemia trait).
159
what are the clinical features of anaemia of chronic disease?
- Systemic features of underlying condition:
- -Fever.
- -Weight loss
- -Night sweats.
- -Anorexia.
- -Myalgia and arthralgia.
- -Hepatosplenomegaly.
- Features of anaemia:
- -Pallor.
- -Weakness.
- -Decreased exercise tolerance.
- -Shortness of breath.
160
what is seen on iron profile in anaemia of chronic disease?
- Low serum iron
- Raised ferritin
- Low transferrin saturation
- Low total iron-binding capacity.
161
how is anaemia of chronic disease treated?
- Treat the underlying disease.
- Offer red blood cell transfusion in symptomatic patients.
- Consider erythropoiesis-stimulating agents (epoeitin alfa) as second line treatment whereby the underlying disease is not responsive to treatment, and there is symptomatic anaemia.
162
what are the acquired causes of sideroblastic anaemia?
- Myelodysplasia.
- Myeloproliferative disorders.
- Myeloid leukaemia.
- Isoniazid.
- Rheumatoid arthritis.
- Alcohol
163
what are the clinical features of sideroblastic anaemia?
- Pallor
- Weakness
- Decreased exercise tolerance
- Shortness of breath
164
what is seen on iron profile in sideroblastic anaemia?
- Raised serum iron
- Raised serum ferritin
- Raised transferrin saturation
- Normal total-iron binding capacity.
165
what is seen on a blood film in sideroblastic anaemia?
- Microcytic red cells
- Hypochromic red cells.
- ring sideroblasts that stain with Perls' reaction
166
how is sideroblastic anaemia managed?
- withdraw drugs and alcohol
- pyridoxine
- folic acid for accompanying folate deficiency
167
what are the clinical features of myeloma?
- Bone pain, typically localised to the back owing to vertebral involvement.
- Symptoms of anaemia (fatigue, shortness of breath).
- symptoms of hypercalcaemia (bone pain, constipation, thirst, polyuria, muscle weakness).
- Symptoms of hyper viscosity (headache, visual disturbances, cognitive impairment).
- Recurrent infections.
168
what is seen on FBC in myeloma?
- Normocytic anaemia
| - Leukopenia and thrombocytopenia in advanced disease.
169
what is seen on blood film in myeloma?
-Rouleaux formation.
170
which tests are diagnostic for myeloma and what is seen?
- serum/urine electrophoresis: Raised concentrations of IgG and IgA.
- serum free light chain assay: Increased concentration of free light chains.
- bone marrow aspirate and biopsy: Monoclonal plasma cell infiltration in the bone marrow greater than 10%.
- whole body MRI:
- -Osteolytic lesions
- -Raindrop appearance.
171
what supportive theory should be given in myeloma?
- correct anaemia with blood transfusion and EPO
- treat hypercalcaemia, kidney injury and hyperviscosity
- treat infection with Abx promptly
- yearly flu and one-off pneumococcal vaccine
- hydration and stop NSAIDs
172
what specific therapy should be given to treat myeloma?
- induction therapy (dexamethasone and bortezomib) followed by stem cell transplantation in transplant candidates.
- bortezomib and thalidomide for patients who are not transplant candidates.
- bisphosphonate (zoledronic acid or disodium pamidronate) for prevention and treatment of bone disease.
173
what is pernicious anaemia?
- an autoimmune disorder
- there is atrophic gastritis
- loss of parietal cells in the gastric mucosa
- consequent failure of intrinsic factor production and vitamin B12 malabsorption.
174
what is subacute combined degeneration of the cord?
- lesions of the nervous system as a result of B12 deficiency
- causes myelin degeneration of the posterior and later columns of the spinal cord.
175
what are the clinical features of subacute combined degeneration of the cord?
symmetrical neuropathy affecting the legs more than the arms
176
what are the clinical features of pernicious anaemia?
- Lemon-yellow tint.
- Glossitis.
- Angular stomatitis.
- Ataxia.
- Paraesthesia.
- Muscle weakness.
- Optic neuropathy.
177
what is seen on FBC in pernicious anaemia?
- low Hb
- MCV greater than 96 fL
- Leucopenia
- Thrombocytopenia.
- Low reticulocyte count.
178
what is seen on blood film in pernicious anaemia?
- Oval macrocytes
| - Hypersegmented polymorphs
179
how is pernicious anaemia managed?
- Administer intramuscular hydroxocobalamin on alternate days until there is no further improvement, then administer intramuscularly every 2 months.
- If gastric cancer is suspected, refer urgently using a suspected cancer pathway referral (for an appointment within 2 weeks).
- Offer oral cyanocobalamin where the cause of vitamin B12 deficiency is thought to be diet related, for vegans this treatment may need to be lifelong.
180
what are the causes of folate deficiency anaemia?
- Malnutrition (folate intake due to poor diet, overcooking of food, and alcoholism).
- Malabsorption (due to coeliac disease, tropical sprue, and Crohn’sdisease).
- Drugs (sulfasalazine, trimethoprim, methotrexate, and phenytoin).
- Increased requirements (pregnancy and lactation, haemolytic anaemia, myelofibrosis,malignancy).
- hereditary folate malabsorption
181
what are the symptoms of folate deficiency anaemia?
- Fatigue.
- Palpitations.
- Shortness of breath.
- Dizziness.
- Headaches.
- Loss of appetite.
- Weight loss.
- Dysphagia.
- Diarrhoea with coeliac disease and Crohn’s disease
182
what are the signs of folate deficiency anaemia?
- Pallor.
- Glossitis.
- Angular stomatitis.
- Tachycardia.
- Tachypnoea.
- Systolic flow murmur.
- Signs of heart failure.
183
what is seen on blood film in folate deficiency anaemia?
- Oval macrocytes
| - Hypersegmented polymorphs.
184
what is the management of folate deficiency anaemia?
- Offer oral folic acid replacement (5mg daily for 4 months)
- Give dietary advice about foods that are good sources of folate, including leafy green vegetables.
- offer packed red cell transfusion for severe anaemia with symptoms of heart failure
185
how should inborn errors of folate metabolism be treated?
- Give betaine for methyl-THF reductase deficient .
| - Give folic acid plus methionine for glutamate formiminotransferase deficiency.
186
what are the causes of macrocytosis without megaloblastic changes?
- pregnancy
- Alcohol excess
- Liver disease
- Reticulocytosis
- Hypothyroidism
- Some haematological disorders (e.g. aplastic anaemia, sideroblastic anaemia, pure red cell aplasia)
- Drugs (e.g. hydroxycarbamide, azathioprine)
- Cold agglutinins due to autoagglutination of red cells (the MCV decreases to normal with warming of the sample to 37°C).
187
what are the causes of normocytic anaemia?
- Acute blood loss
- Anaemia of chronic diseases
- Bone marrow failure
- Renal failure
- Hypothyroidism
- Haemolysis
- Pregnancy
188
what are the symptoms of normocytic anaemia?
- Fatigue
- Dyspnoea
- Faintness
- Palpitations
- Headache
- Tinnitus
- Anorexia
189
what are the signs of normocytic anaemia?
- Pallor
- Hyperdynamic circulation (tachycardia, flow murmurs: ejection-systolic loudest over apex)
- Cardiac enlargement
- Retinal Haemorrhages
190
what are the clinical features of waldenstrom's macroglobulinaemia?
- Asymptomatic.
- Fatigue.
- Anorexia.
- Visual deterioration (hyper-viscosity syndrome)
- Peripheral neuropathy.
- Sinus and bronchial infections.
- Hepatosplenomegaly.
- Lymphadenopathy.
- Raynaud’s phenomenon.
191
what is seen on high resolution serum protein electrophoresis in waldenstroms macroglobulinaemia?
-IgM paraprotein.
192
what is seen on bone marrow biopsy in waldenstroms macroglobulinaemia?
-Intratrabecular monoclonal lymphoplasmacytic infiltration.
193
how is waldenstroms macroglobulinaemia treated?
- Offer plasmapharesis (plasma exchange) for patients with symptomatic hyper-viscosity syndrome.
- Offer dexamethasone and rituximab and cyclophosphamide for low tumour burden.
194
how does an acute haemolytic reaction arise during a transfusion?
-ABO incompatibility secondary to human error
195
what are the clinical features of an acute haemolytic reaction during a transfusion?
- Fever.
- Abdominal, chest, back, or loin pain.
- Hypotension.
- Haemoglobinuria is often present.
196
how is an acute haemolytic reaction during transfusion treated?
- The blood transfusion should be stopped immediately.
- Check the identity of the patient.
- Offer generous fluid replacement with normal saline. The goal urine output is 100 ml/hour.
- Send blood for direct Coombs test.
197
what are the clinical features of a minor allergic reaction during transfusion?
- Pruritus.
- Urticaria.
- Flushing.
198
what are the clinical features of an anaphylactic allergic reaction during transfusion?
- Hypotension.
- Dyspnoea.
- Wheezing.
- Stridor.
199
how are minor allergic reactions during transfusion managed?
- Temporarily discontinue blood transfusion.
| - Offer an antihistamine (diphenhydramine) intravenously.
200
how are anaphylactic reactions during transfusion managed?
- Offer intramuscular adrenaline 1:1000 solution every 5 minutes and children and every 10 minutes in adults. Intravenous adrenaline is reserved for cardiac arrest.
- Intensive care monitoring (intubation and crystalloid fluids) may be required.
- Offer adjunct bronchodilators (salbutamol inhaled), antihistamines (intravenous diphenhydramine) and corticosteroids (methylprednisolone sodium succinate).
201
what are the clinical features of febrile non-haemolytic reaction during transfusion?
- Fever.
| - Chills.
202
what is the management of febrile non-haemolytic reaction during transfusion?
- Discontinue Transfusion until a haemolytic reaction can be ruled out.
- Offer an antipyretic (paracetamol).
203
what are the clinical features of Transfusion-Associated Circulatory Overload?
- Hypoxia.
- Hypotension.
- Fine crackles through chest.
- Raised JVP.
- Third heart sound.
- Fever.
204
how is Transfusion-Associated Circulatory Overload managed?
- Stop the transfusion.
| - Offer oxygen and supportive care.
205
what are the clinical features of transfusion related acute lung injury?
- Sudden onset dyspnoea.
- Sudden onset tachypnoea.
- Hypotension.
- Fever.
- tachycardia.
206
what is the management of transfusion related acute lung injury?
- Stop the transfusion.
| - Offer supplemental oxygen.
207
what are the clinical features of delayed haemolytic transfusion reaction?
- Features occur days to weeks following transfusion:
- Anaemia.
- Fever.
- Jaundice.
- Haemoglobinuria.
208
how is delayed haemolytic transfusion reaction treated?
- Send blood for direct Coombs test to confirm the diagnosis.
- If there is no brisk haemolysis, no specific treatment is required.
- If there is brisk haemolysis, treat as an acute haemolytic transfusion reaction, with generous fluid replacement with normal saline, with a goal urine output of 100 ml/hour
209
what are the clinical features of transfusion associated graft-vs-host disease?
- Symptoms develop 8 to 10 days following transfusion:
- Maculopapular rash.
- Fever.
- Diarrhoea.
210
what are the clinical features of thromboangiitis obliterans?
- Current smoking history.
- Paraesthesia.
- Rest pain.
- Cold sensation
- Cyanosis.
- Plantar claudication
- Absent pulses.
- Gangrene of the distal phalanges.
- Positive Allan test whereby both radial and ulnar arteries are occluded resulting in ischaemia.
- in men aged 20-40
211
what is seen on arterial doppler and duplex in thromboangiitis obliterans?
- absence of popliteal, brachial or distal pulses.
- Non-atherosclerotic occluded vessels
- Corkscrew shaped collateral vessels (Martorell’s sign).
212
how is thromboangiitis obliterans managed?
-Urgent smoking cessation is essential.
- For critical ischaemia:
- -Offer nifedipine
- -Offer intravenous antibiotic therapy (metronidazole and benzylpenicillin sodium) for infection or wet gangrene.
- -Offer tramadol for pain relief.
213
define aplastic anaemia
--pancytopenia with hypocellularity
214
which drugs can cause aplastic anaemia?
- Chloramphenicol.
- Phenytoin.
- NSAIDs
- Carbimazole.
- Gold
- Chlorpromazine
- Phenytoin
- Ribavirin
- Tolbutamide
215
what are the clinical features of aplastic anaemia?
- History of recurrent infection.
- History of bleeding or easy bruising.
- Pallor and fatigue.
- Exposure to causative drugs.
- Bleeding gums caused by phenytoin.
- Features of Fanconi syndrome include:
- -Hearing loss or deafness.
- -Short stature.
- -Pigmentation abnormalities (cafe au lait spots).
216
what is required on FBC for diagnosis of aplastic anaemia?
- 2 or more cytopenias
- Hb less than 100 g/l
- Platelet count less than 50 x 109/L
- Neutrophil count less than 1.5 x 109/L.
217
what is seen on bone marrow biopsy in aplastic anaemia?
- Hypocellular marrow
| - No abnormal cell population.
218
how is aplastic anaemia treated?
- immunosuppression with anti-thymocyte globulin and ciclosporin
- allogenic stem cell transplant
219
what are the three pre-disposing factors in Virchow's triad that may result in thrombus formation?
- changes in the intimal surface of the blood vessel
- changes in the pattern of blood flow
- changes in the blood constituents
220
what is provoked DVT?
-associated with a transient risk factor e.g. surgery, immobility, pregnancy, OCP, trauma
221
what us unprovoked DVT?
-occurs in the absence of a transient risk factor, or a risk factor that is persistent and not easily correctable
222
what is the risk factors for DVT?
- History of DVT
- Cancer
- Increasing age (60+)
- Male sex
- Heart failure
- Acute infection
- Thrombophilia
- Vasculitis
- Varicose veins
- Smoking
223
what are the clinical features of DVT?
- Unilateral localised pain that is throbbing in nature, and may be worse on dorsiflexion (Homan’s sign).
- Unilateral calf swelling that is typically 3 cm larger than the other calf.
- Skin changes, including oedema, redness, and warmth.
224
what Wells score would indicate that DVT is likely?
2 points or more
225
how should DVT diagnosed on the basis of the Wells score be treated?
- Offer a proximal leg vein ultrasound scan within 4 hours.
- If unavailable, offer interim therapeutic anticoagulation with LMWH (dalteparin) and a proximal leg vein ultrasound scan within 24 hours.
226
how should those patients unlikely to have a DVT based on the Wells score?
- d-dimer
- If positive, offer a proximal leg vein ultrasound scan with the results available within 4 hours.
- If negative, stop interim therapeutic anticoagulation and consider an alternative diagnosis.
227
the activity of which clotting factors is monitored with PT?
-II, V, VII and X
228
the activity of which clotting factors is monitored with APtT?
-II, V, VIII, IX, X, XI and XII
229
what are the clinical features of haemophilia?
- Presence of risk factors, including a family history of haemophilia, and male sex.
- Painful swelling of muscles and joints, decreased range of motion, erythema, and increased local warmth.
- Bleeding into iliopsoas presents as lower abdominal, lower back, or upper thigh pain, with a characterise gait (flexed hip and inward rotation).
- Prolonged bleeding following heel prick or circumcision.
- Mucocutaenous bleeding such as epistaxis, bleeding from gums following dental procedures.
- Excessive bruising.
- Bulging fontanelle, decreased oral intake, and hypo-activity in intracranial bleeding.
- Menorrhagia in females.
- GI bleeding
- signs of anaemia
230
How does the APTT present in haemophilia?
-prolonged
231
how is mild bleeding in haemophilia A managed?
- Offer factor 8 concentrate (where there are no antibodies against the clotting factor) or desmopressin
- offer a bypassing agent (factor VIIa) if antibodies present
232
how is mild bleeding in haemophilia B managed?
- Offer factor 9 concentrate
| - offer a bypassing agent (factor VIIa) if antibodies present
233
what are the clinical features of von Willebrand disease?
- Bleeding from minor wounds
- Post-operative bleeding
- Lymphoproliferative disorders (multiple myeloma, Waldenstrom’s macroglobulinaemia)
- Aortic stenosis
- Myeloproliferative disorders
- Hypothyroidism
234
how is von Willebrand disease diagnosed?
- measure vWF antigen
| - vWF function assay (RCo)
235
how is type 1 von Willebrand disease treated?
- Offer desmopressin for mild bleeding (type 1 or 2, but avoid in type 2b).
- Offer tranexamic acid for bleeding that involves mucosal membranes (menorrhagia).
236
how is type 2 von Willebrand disease treated?
- Offer desmopressin for mild bleeding (not in type 2b) to determine whether the patient responds to desmopressin.
- Offer vWF-containing concentrates for type 2b disease or if the patient does not respond to desmopressin
237
how is type 3 von Willebrand disease treated?
-Offer vWF-containing concentrates for active severe haemorrhage or for patients undergoing surgical procedures.
238
what are the causes of vitamin K deficiency?
- malabsorption
- warfarin therapy
- haemorrhagic disease of the newborn
239
what are the clinical features of vitamin K deficiency?
- Bruising.
- Haematuria.
- GI bleeding.
- Cerebral bleeding.
240
what are the APTT and PT in vitamin K deficiency?
-prolonged
241
how is vitamin k deficiency treated?
- phytomenadione (vitamin K1) 10mg intravenously for mild bleeding.
- vitamin K 1 mg intramuscularly to all neonates to prevent haemorrhagic disease of the newborn.
242
which disease states trigger coagulation activation in DIC?
- septicaemia
- malaria
- malignancy
- burns, surgery, trauma, shock, intravascular haemolysis, dissecting aortic aneurysm
- amniotic fluid embolus, placental abruption and retained products of conception
- severe organ destruction
243
what are the features of circulatory collapse in DIC?
- Oliguria.
- Hypotension.
- Tachycardia.
- Dyspnoea.
244
what are the signs of thrombosis in DIC?
- Purpura fulminans.
- Gangrene.
- Acral cyanosis.
- Delirium or coma.
245
what are the signs of bleeding in DIC?
- Petechia.
- Ecchymosis.
- Bleeding from the mouth and nose.
- Haematuria
246
what is seen on FBC in DIC?
-reduced platelet count
247
how do the APTT and PT appear in DIC?
-prolonged
248
how should DIC be managed?
- Treat the underlying cause.
- Administer a platelet transfusion when the platelet count is less than 20 x 109/l.
- Administer fresh frozen plasma (FFP) for replacement of coagulation factors when significant bleeding is present.
- Anti-thrombin and protein C concentrates have been used, particularly in severe meningococcal septicaemia with purpura fulminans.
249
Name the thrombophilias
- Factor V Leiden
- Anti-thrombin deficiency
- protein C and S deficiency
- prothrombin gene mutation G20210A
250
what are the causes of acquired thrombophilia?
- SLE
- anti-phospholipid syndrome
- increased homocysteine
- PNH
- nephrotic syndrome
- myeloproliferative disorders
- DIC
251
which thrombophilia patients should be offered LMWH prophylaxis?
- admitted with medical illness
- cancer before surgery
- major trauma
- pregnant
252
what is thrombocytopenia?
-a platelet count <150 × 109/L.
253
which medications can cause ITP?
- Heparin.
- Quinine.
- Sulfonamides.
- Vancomycin
254
which conditions is ITP associated with?
- Systemic lupus erythematosus.
- Rheumatoid arthritis.
- HIV.
- H.pylori infection.
255
what are the clinical features of ITP?
- Bruising
- Petechiae.
- Haemorrhagic bullae.
- Bleeding gums.
- Epistaxis.
- Menorrhagia.
- Preceding viral illness in children.
- Absent hepatosplenomegaly.
256
what is seen on bone marrow biopsy in adults with ITP?
-increased megakaryocytes
257
when should a bone marrow biopsy be conducted in a child with ITP?
- Any atypical clinical features
- anaemia
- neutropenia
- hepato-splenomegaly
- marked lymphadenopathy
- treatment with steroids planned
258
how is ITP treated in children?
- in most, it is acute, benign and self-limiting, usually remitting spontaneously within 6–8 weeks.
- if persistent, give steroids, IVIG, mycophenolate or rituximab
259
how is ITP treated in adults?
- prednisolone
- IVIG
- splenectomy
260
what is the pentad of TTP?
- Microangiopathic haemolytic anaemia.
- Thrombocytopenia with purpura.
- Acute renal insufficiency (less marked than HUS).
- Neurological insufficiency (more marked than HUS).
- Fever.
261
what are the clinical features of TTP?
- Non-specific prodrome.
- Coma.
- Focal abnormalities.
- Seizures.
- Headache.
- Confusion.
- Fever.
- Nausea and vomiting.
- Diarrhoea.
- Abdominal pain
- Purpura/Ecchymosis
- Menorrhagia
262
how is TTP treated?
- Administer plasma exchange plus prednisolone as the mainstay of treatment.
- Offer caplacizumab as an adjunctive therapy in adults. It blocks the interaction between vWF and platelets.
- Offer immunosuppression (vincristine or rituximab) in patients who do not respond to initial treatment.
263
what are the the 3 main causes of red cell aplasia in children?
- Congenital red cell aplasia (’Diamond–Blackfan anaemia’)
- Transient erythroblastopenia of childhood
- Parvovirus B19 infection
264
what is seen on investigation of red cell aplasia?
- Low reticulocyte count despite low Hb
- Normal bilirubin
- Negative direct antiglobulin test (Coombs test)
- Absent red cell precursors on bone marrow examination.
265
how is diamond-blackfan anaemia treated?
- Treatment is by oral steroids
- monthly red blood cell transfusions are given to children who are steroid unresponsive and some may also be offered stem cell transplantation
266
how do bone marrow failure syndromes present in children?
- Anaemia due to reduced red cell numbers
- Infection due to reduced white cell numbers (especially neutrophils)
- Bruising and bleeding due to thrombocytopenia.
267
how is fanconi anaemia inherited?
-autosomal recessive
268
how does fanconi's anaemia present?
- short stature
- abnormal radii and thumbs
- renal malformations
- microphthalmia
- pigmented skin lesions
- bone marrow failure
269
how is fanconi's anaemia treated?
bone marrow transplantation
270
how is Shwachman–Diamond syndrome inherited?
-autosomal recessive
271
what are the clinical features of Shwachman–Diamond syndrome?
- bone marrow failure
- pancreatic exocrine failure
- skeletal abnormalities
272
what is febrile neutropenia?
-Temperature recorded >38 in a patient with an absolute neutrophil count <1.0 x 109/L
273
which patients are at risk of neutropenic sepsis?
- Those with neutropenia
- Cytotoxic chemotherapy
- Haematological malignancies – leukaemia, myelodysplasia, myelofibrosis
- Bone marrow failure – aplastic anaemia
- Rare inherited syndrome with isolated neutropenia – cyclical neutropenia
274
how does neutropenic sepsis present?
- Febrile
- May initially look well due to inability to form an inflammatory response
- General malaise
- Sweats/rigors
- Cough, sore throat, diarrhoea and abdominal pain
- Pain or erythema around central venous catheter
275
what are the clinical signs of neutropenic sepsis?
- Pyrexia
- Tachycardia
- Hypotension
- Raised respiratory rate
276
what investigations should be done for suspected neutropenic sepsis?
- blood gas including glucose and lactate
- blood culture
- FBC
- CRP
- Creatinine, urea and electrolytes
- LFTs
- clotting
- urinalysis
277
how is neutropenic sepsis managed?
- oxygen as indicated
- IV broad spectrum Abx e.g tazocin and gent
- IV fluid bolus and monitoring of fluid balance
278
how does hyperviscosity present?
- Lethargy
- Headaches
- Confusion
- Visual disturbance and retinal haemorrhage
- Cranial nerve defects
- Ataxia
- Chest and abdominal pain
- Dyspnoea and cough
279
how is hyperviscosity syndrome managed?
- Venesection
| - plasma/leukopheresis
280
what are the clinical features of polycythaemia vera?
- Asymptomatic.
- Headache.
- Fatigue.
- Pruritus, which is evoked by warm water, such as after a bath.
- Erythromelalgia, a painful burning and redness of the fingers, palms, heel and toes.
- Gout.
281
what is seen on FBC in polycythaemia vera?
- Hb greater than 165 g/l in men and 160 g/l in women
- Haematocrit > 49% in men and 48% in women
- Low MCV
- Raised WCC
- Raised platelets.
282
which mutation is associated with polycythaemia vera?
V617F mutation in JAK2 gene
283
what is seen on bone marrow biopsy in polycythaemia vera?
-Hypercellularity with prominent erythroid, granulocytic and megakaryocytic proliferation.
284
what are the major criteria for diagnosis of polycythaemia vera?
- Hb greater than 165 g/l in men and 160 g/l in women.
| - Presence of V617F mutation.
285
what are the minor criteria for diagnosis of polycythaemia vera?
- Bone marrow biopsy showing hypercellularity.
| - Low serum erythropoeitin.
286
how is polycythaemia vera managed?
- venesection
- hydorxycarbamide
- low dose aspirin
- radioactive phosphorus or busulfan if intolerant of other therapy
287
what are the clinical features of essential thrombocythaemia?
- Asymptomatic.
- Erythromelalgia, a painful burning of the extremities which increases with exposure to heat and improves with cold.
- Splenomegaly.
- Livedo reticularis, a purplish discolouration of the skin, usually the legs, described as net-like in appearance.
- Headache, dizziness, and syncope.
- History of thrombosis.
- History of bleeding.
288
what is seen on peripheral blood film in essential thrombocythaemia?
- Giant platelets
- Megakaryocyte fragments
- Howell-Jolly bodies.
289
how is essential thrombocytaemia managed?
- smoking cessation and weight control
- aspirin
- hydroxycarbamide, busulfan or interferon alfa for high risk patients
- plateletpharesis
290
what are the causes of myelodysplasia?
- primary
- chromosomal abnormality (5q deletion)
- chemotherapy or radiotherapy
- tobacco
- benzene exposure
- Congenital neutropenia, such as Shwachman-Diamond’s syndrome or Down’s syndrome.
291
what are the clinical features of myelodysplasia?
- Asymptomatic.
- Fatigue.
- Exercise intolerance.
- Pallor.
- Petechia.
- Purpura.
- Bacterial infections.
- Hepatosplenomegaly.
- Lymphadenopathy.
292
what is seen on FBC in myelodysplasia?
- one or more cytopenias
| - low reticulocytes
293
what is seen on bone marrow biopsy in myelodysplasia?
-Hyper-cellular marrow.
294
how is myelodysplasia managed?
- monitor asymptomatic cytopenia
- haematopoietic growth factors (epoeitin alfa) as first line for symptomatic cytopenias with no 5q deletion.
- thalidomide analogue (lenalidomide) as first line for symptomatic cytopenias with a 5q deletion.
- allogenic HSCT for high-risk disease in patients with good health and a compatible donor.
295
what are the clinical features of myelofibrosis?
- Weight loss.
- Night sweats.
- Low-grade fever.
- Cachexia.
- Fatigue.
- Pruritus.
- Splenomegaly.
- Ascites.
- Oesophageal varices.
-Joint and bone pain.
hepatomegaly
296
what is seen on blood film in myelofibrosis?
- Teardrop shaped poikilocytes
| - Myelocytes and promyelocytes.
297
what is seen on bone marrow aspiration and biopsy in myelofibrosis?
- unable to aspirate marrow due to marrow fibrosis
| - increased reticulin deposit
298
how is myelofibrosis treated?
- folic acid and pyridoxine if asymptomatic
- stem cell transplant
- allopurinol for hyperuricaemia
- splenectomy for painful splenomegaly
- ruxolitinib
299
what are the indications for LMW heparin?
- VTE prophylaxis in hospital patients
- First-line DVT treatment
- First-line PE treatment
- First-line therapy to improve revascularisation and prevent intracoronary thrombus progression in ACS.
300
how does LMW heparin work?
- Activates antithrombin III
- inactivates Factor Xa
- inhibits prothrombin activator
- inhibits thrombin activation.
301
what are the adverse effects of LMW heparin?
- bleeding
- injection site reactions
- thrombocytopenia
302
when should caution be exercised when giving LMW heparin?
- clotting disorders
- severe uncontrolled hypertension
- after surgery or trauma
- renal impairment
303
how is LMWH monitored?
-Monitor APTT with unfractioned heparin, FBC and renal profile in all cases and platelet count monitored in prolonged therapy.
304
what are the indications for warfarin?
- To prevent clot extension and recurrence in DVT and PE
- To prevent stroke in atrial fibrillation
- To prevent stroke after heart valve replacement.
305
what is the mechanism of action of warfarin?
- Inhibits Vitamin K Epoxide Reductase
- this inhibits the reduction of Vitamin K epoxide to its active hydroquinone form.
- This interferes with the post-translational γ-carboxylation of glutamic acid residues in clotting factors II, VII, IX and X.
306
what are the adverse effects of warfarin?
- Bleeding especially in genetically susceptible individuals who have lower CYP2C9 activity
- skin necrosis
- blue-toe syndrome
- liver dysfunction.
307
in which patients should the use of warfarin be avoided?
- patients at immediate risk of haemorrhage
- pregnancy as it causes fetal malformations
- liver disease where patients are less able to metabolise drug and are at risk of over-anticoagulation/bleeding.
308
which factors potentiate warfarin?
- macrolides and azoles (inhibit hepatic drug metabolism)
- cephalosporins (inhibit the reduction of vit k)
- sulfonamides (depress intestinal flora)
- NSAIDs (interfere with platelet function
- liver disease
309
which factors reduce the effect of warfarin?
- aminoglycosides (induce hepatic metabolism)
- vitamin k
- cholestyramine (reduce absorption)
- pregnancy
310
how is warfarin reversed with major bleeding?
- stop warfarin
- give prothrombin complex concentrate
- 5mg vitamin K
311
how is warfarin monitored?
- INR is the PT of a person on warfarin divided by that of a control.
- Target INR is 2.5 above and below this value increase the risk of haemorrhage and thromboembolism respectively.
- INR is measured in hospital inpatients and every few days in outpatients commencing warfarin.
- INR measurement becomes less frequent when a stable dose is established.
312
when is dabigatran (factor IIa inhibitor) indicated?
- Prophylaxis of VTE following total knee replacement surgery
- Treatment of DVT and PE.
313
what are the adverse effects of dabigatran?
- Abnormal hepatic function
- haemorrhage
- anaemia
- gastrointestinal disorders
314
when should dabigatran be avoided?
- active bleeding
- antiphospholipid syndrome
- prosthetic heart valves
- malignancy
- oesophageal varices
- recent surgery and peptic ulcer.
315
which drugs does dabigatran interact with?
- Carbamazepine
- Dronaderone
- Ritonavir
- St John’s Wart
- Triazole antifungals.
316
which drug reverses the effect of dabigatran?
Praxbind (idarucizumab)
317
what are the indications for factor Xa inhibitors such as rivaroxaban?
- Prophylaxis of VTE following hip or knee replacement surgery
- Treatment of DVT and PE.
318
what are the adverse effects of factor Xa inhibitors?
- Haemorrhage
- Anaemia
- GI disturbances
- Headache
- Hypotension.
319
in which patients should factor Xa inhibitors be avoided?
- active bleeding
- antiphospholipid syndrome
- prosthetic heart valves
- malignancy
- oesophageal varices
- recent surgery
- peptic ulcer.
320
which drugs do factor Xa inhibitors interact with?
- Carbamazepine
- Dronaderone
- Ritonavir
- St John’s Wart
- Triazole antifungals.
321
what are the indications for fibrinolytic agents?
- ischaemic stroke
- STEMI
- massive pulmonary embolism.
322
what are the adverse effects of fibrinolytic agents?
- Nausea
- Vomiting
- Bruising at injection site
- Hypotension
- Serious bleeding
- Allergic reaction
- Cardiogenic shock
- Cardiac arrest
- Cerebral oedema
- Arrhythmias.
323
in which patients should fibrinolytic agents be avoided?
- Avoid with recent haemorrhage, trauma or surgery
- Avoid streptokinase with previous streptokinase treatment as antibodies develop and block its action
- Intracranial haemorrhage must be excluded with CT.
324
what are the adverse effects of oral iron therapy?
-GI disturbances such as nausea, epigastric pain, constipation
