amjo10@yahoo.com
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 Posted: Mon Dec 19, 2005 10:33 pm Post subject: haemotology oncology |
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Question 1 of 84
A 4-year-old boy is admitted after developing a haemarthrosis in his right knee whilst playing in the garden. The following blood results are obtained:
Platelets 220 * 109/l
PT 12 secs
APTT 78 secs
Factor VIIIc
activity Normal
What is the most likely diagnosis?
Antithrombin III deficiency
Von Willebrand's disease
Antiphospholipid syndrome
Haemophilia A
Haemophilia B
A grossly elevated APTT may be caused by heparin therapy, haemophilia or antiphospholipid syndrome. A normal factor VIIIc activity points to a diagnosis of haemophilia B (lack of factor IX)
Haemophilia
Haemophilia is a X-linked recessive disorder of coagulation. Up to 30% of patients have no family history of the condition. Haemophilia A is due to a deficiency of factor VIII whilst in haemophilia B (Christmas disease) there is a lack of factor IX
Features
• haemoarthroses, haematomas
• prolonged bleeding after surgery or trauma
Blood tests
• prolonged APTT
• bleeding time, thrombin time, prothrombin time normal
Up to 10-15% of patients with haemophilia A develop antibodies to factor VIII treatment
Question 2 of 84
A 23-year-old woman presents to her GP due to lethargy. The following blood results are obtained:
Hb 10.4 g/dl
Plt 278 * 109/l
WCC 6.3 * 109/l
MCV 65 fl
HbA2 4.5%
What is the most likely diagnosis?
Beta-thalassaemia major
Sickle cell anaemia
Beta-thalassaemia trait
Hereditary spherocytosis
Acute lymphoblastic leukaemia
A microcytic anaemia in a female should raise the possibility of either gastrointestinal blood loss or menorrhagia. However, there is no history to suggest this and the microcytosis is disproportionately low for the haemoglobin level. This combined with a raised HbA2 points to a diagnosis of beta-thalassaemia trait
Beta-thalassaemia trait
The thalassaemias are a group of genetic disorders characterised by a reduced production rate of either alpha or beta chains. Beta-thalassaemia trait is an autosomal recessive condition characterised by a mild hypochromic, microcytic anaemia. It is usually asymptomatic
Features
• mild hypochromic, microcytic anaemia - microcytosis is characteristically disproportionate to the anaemia
• HbA2 raised (> 3.5%)
Question 3 of 84
Each one of the following is associated with paroxysmal nocturnal haemoglobinuria, except:
Haemolytic anaemia
Positive Ham test
Haemoglobinuria
Aplastic anaemia
Haemarthrosis
Paroxysmal nocturnal haemoglobinuria
Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired disorder leading to haemolysis (mainly intravascular) of haematological cells. It is thought to be caused by increased sensitivity of cell membranes to complement (see below) due to a lack of glycoprotein glycosyl-phosphatidylinositol (GPI). Patients are more prone to venous thrombosis
Pathophysiology
• GPI can be thought of as an anchor which attaches surface proteins to the cell membrane
• complement-regulating surface proteins, e.g. decay-accelerating factor (DAF), are not properly bound to the cell membrane due a lack of GPI
• thrombosis is thought to be caused by a lack of CD59 on platelet membranes predisposing to platelet aggregation
Features
• haemolytic anaemia
• red blood cells, white blood cells, platelets or stem cells may be affected therefore pancytopaenia may be present
• haemoglobinuria: classically dark-coloured urine in the morning (although has been shown to occur throughout the day)
• thrombosis e.g. Budd-Chiari syndrome
• aplastic anaemia may develop in some patients
Diagnosis
• Ham test: acid-induced haemolysis (normal red cells wouldn't)
Management
• blood product replacement
• anticoagulation
• stem cell transplantation
Question 4 of 84
Which one of the following is least likely to cause a warm autoimmune haemolytic anaemia?
Mycoplasma infection
Methyldopa
Chronic lymphocytic leukaemia
Lymphoma
SLE
Mycoplasma infection causes a cold AIHA
Autoimmune haemolytic anaemia
Autoimmune haemolytic anaemia (AIHA) may be divided in to 'warm' and 'cold' types, according to at what temperature the antibodies best cause haemolysis. It is most commonly idiopathic but may be secondary to a lymphoproliferative disorder, infection or drugs. AIHA is characterised by a positive direct antiglobulin test (Coombs' test)
Warm AIHA
In warm AIHA the antibody (usually IgG) causes haemolysis best at body temperature and haemolysis tends to occur in extravascular sites, for example the spleen. Management options include steroids, immunosuppression and splenectomy
Causes of warm AIHA
• autoimmune disease: e.g. SLE
• neoplasia: e.g. lymphoma, CLL
• drugs: e.g. methyldopa
Cold AIHA
The antibody in cold AIHA is usually IgM and causes haemolysis best at 4 deg C. Haemolysis is mediated by complement and is more commonly intravascular. Features may include symptoms of Raynaud's and acrocynaosis. Patients respond less well to steroids
Causes of cold AIHA
• neoplasia: e.g. lymphoma
• infections: e.g. mycoplasma, EBV
Question 5 of 84
Which one of the following causes a macrocytic anaemia with a megaloblastic bone marrow?
Reticulocytosis
Pregnancy
Vitamin B12 deficiency
Liver disease
Hypothyroidism
Macrocytic anaemia
Macrocytic anaemia can be divided into causes associated with a megaloblastic bone marrow and those with a normoblastic bone marrow
Megaloblastic causes
• vitamin B12 deficiency
• folate deficiency
• cytotoxics e.g. hydroxyurea
Normoblastic causes
• alcohol
• liver disease
• hypothyroidism
• pregnancy
• reticulocytosis e.g. haemolysis
• aplastic anaemia
• myelodysplasia
• drugs: cytotoxics
Question 6 of 84
A 22-year-old man with sickle cell anaemia presents with vomiting, abdominal pain and a rash. Blood results are as follows:
Hb 4.6 g/dl
Reticulocytes 3%
Infection with a parvovirus is suspected. What is the likely diagnosis?
Thrombotic crisis
Sequestration crisis
Transformation to myelodysplasia
Haemolytic crisis
Aplastic crisis
The sudden fall in haemoglobin without an associated reticulocytosis is typical of an aplastic crisis, usually secondary to parvovirus infection
Sickle-cell crises
Sickle cell anaemia is characterised by periods of good health with intervening crises
Four main types of crises are recognised:
• thrombotic, 'painful crises'
• sequestration
• aplastic
• haemolytic
Thrombotic crises
• also known as painful crises or vaso-occlusive crises
• precipitated by infection, dehydration, deoxygenation
• infarcts occur in various organs including the bones (e.g. avascular necrosis of hip, hand-foot syndrome in children, lungs, spleen and brain
Sequestration crises
• sickling within organs such as the spleen or lungs causes pooling of blood with worsening of the anaemia
• acute chest syndrome: dyspnoea, chest pain, pulmonary infiltrates, low pO2 - the most common cause of death after childhood
Aplastic crises
• caused by infection with parvovirus
• sudden fall in haemoglobin
Haemolytic crises
• rare
• fall in haemoglobin due an increased rate of haemolysis
Question 7 of 84
A 72-year-old women is found to have a marked lymphocytosis associated with smudge cells on the blood film. A diagnosis of chronic lymphocytic leukaemia is suspected. Which one of the following is the investigation of choice?
Immunophenotyping
Bone marrow aspiration
Protein electrophoresis
White cell scan
Bone marrow trephine
Immunophenotyping will demonstrate the cells to be B-cells (CD19 positive). CD5 and CD23 are also characteristically positive in chronic lymphocytic leukaemia
Chronic lymphocytic leukaemia
Chronic lymphocytic leukaemia (CLL) is caused by a monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%)
Features
• often none
• constitutional: anorexia, weight loss
• bleeding, infections
• lymphadenopathy more marked than CML
Complications
• hypogammaglobulinaemia leading to recurrent infections
• warm autoimmune haemolytic anaemia in 10-15% of patients
• transformation to high-grade lymphoma (Richter's transformation)
Investigations
• blood film: smudge cells
• immunophenotyping
Question 8 of 84
A 42-year-old female is noted to have a Hb of 18.4 g/dL. Which one of the following is least likely to be the cause?
Polycythaemia rubra vera
COPD
Uterine fibroids
Haemochromatosis
Dehydration
Haemochromatosis is not associated with polycythaemia. Blood tests typically reveal a raised ferritin and iron, associated with a transferrin saturation of greater than 60% and a low total iron binding capacity
Polycythaemia
Polycythaemia may be relative, primary (polycythaemia rubra vera) or secondary
Relative causes
• dehydration
• stress: Gaisbock syndrome
Primary
• polycythaemia rubra vera
Secondary causes
• COPD
• altitude
• obstructive sleep apnoea
• excessive erythropoietin: cerebellar haemangioma, hypernephroma, hepatoma, uterine fibroids
To differentiate between polycythaemia rubra vera (PRV) and secondary polycythaemia red cell mass studies are needed. In PRV total red cell mass in males > 35 ml/kg and in women > 32 ml/kg
Question 9 of 84
A 12-year-old boy is noted to bleed excessively during an elective dental extraction. Following the procedure, examination reveals petechial skin haemorrhages. Blood results show:
Hb 12.3 g/dl
Plt 255 * 109/l
WBC 7.9 * 109/l
PT 13.3 secs
APTT 39 secs
Factor VIII
activity 87%
What is the most likely diagnosis?
Disseminated intravascular coagulation
Idiopathic thrombocytopenic purpura
Von Willebrand's disease
Haemophilia A
Haemophilia B
The combination of a petechial skin rash combined with a slightly elevated APTT and reduced factor VIII activity make Von Willebrand's disease the most likely diagnosis
Von Willebrand's disease
Von Willebrand's disease is the most common inherited bleeding disorder. It is inherited in an autosomal dominant fashion and characteristically behaves like a platelet disorder i.e. epistaxis and menorrhagia are common whilst haemoarthroses and muscle haematomas are rare
Role of von Willebrand factor
• large glycoprotein which forms massive multimers up to 1,000,000 Da in size
• promotes platelet adhesion to damaged endothelium
• carrier molecule for factor VIII
Types
• type 1: partial reduction in vWF
• type 2: abnormal form of vWF
• type 3: total lack of vWF
Investigation
• prolonged bleeding time
• APTT may be prolonged
• factor VIII levels may be moderately reduced
• defective platelet aggregation with ristocetin
Management
• tranexamic acid for mild bleeding
• DDAVP
• factor VIII concentrate
Question 10 of 84
Which one of the following types of Hodgkin's lymphoma carries the best prognosis?
Lymphocyte predominant
Mixed cellularity
Nodular sclerosing
Hairy cell
Lymphocyte depleted
Hodgkin's lymphoma: histological classification
Hodgkin's lymphoma is a malignant proliferation of lymphocytes characterised by the presence of the Reed-Sternberg cell. It has a bimodal age distributions being most common in the third and seventh decades
Histological classification
• nodular sclerosing: most common, good prognosis
• mixed cellularity: good prognosis
• lymphocyte predominant: best prognosis
• lymphocyte depleted: least common, worst prognosis
Question 11 of 84
A 33-year-old male patient with a history of recurrent nose bleeds, iron-deficiency anaemia and dyspnoea is found to have a pulmonary AV malformation on pulmonary angiography. What is the likely underlying diagnosis?
Haemophilia A
Hereditary haemorrhagic telangiectasia
Mantle cell lymphoma
Wegener's granulomatosis
Down's syndrome
Hereditary haemorrhagic telangiectasia
Also known as Osler-Weber-Rendu syndrome, hereditary haemorrhagic telangiectasia is an autosomal dominant condition characterised by (as the name suggests) multiple telangiectasia over the skin and mucous membranes. Twenty percent of cases occur spontaneously without prior family history
Features
• telangiectasia develop is skin, mucous membranes and internal organs
• associated with pulmonary AV malformations in 10%
• red lesions often seen on lips and buccal mucosa
• may present as iron-deficiency anaemia secondary to bleeding in the GI tract or nasal mucosa
Question 12 of 84
A blood film shows Howell-Jolly bodies, target cells and siderocytes. What is the most likely diagnosis?
Iron-deficiency anaemia
Intravascular haemolysis
Hyposplenism
Megaloblastic anaemia
Myelofibrosis
Target cells may also be seen in iron-deficiency anaemia but the presence of Howell-Jolly bodies points towards hyposplenism
Blood films: typical pictures
Hyposplenism e.g. post-splenectomy
• target cells
• Howell-Jolly bodies
• Cabot's rings
• siderotic granules
• acanthocytes
• schizocytes
Iron-deficiency anaemia
• target cells
• 'pencil' poikilocytes
• if combined with B12/folate deficiency a 'dimorphic' film occurs with mixed microcytic and macrocytic cells
Myelofibrosis
• 'tear-drop' poikilocytes
Intravascular haemolysis
• schistocytes
Megaloblastic anaemia
• hypersegmented neutrophils
Question 13 of 84
Which one of the following is least associated with a macrocytic anaemia?
Chronic renal failure
Haemolysis
Vitamin B12 deficiency
Liver disease
Hypothyroidism
Chronic renal failure is associated with a normochromic, normocytic anaemia
Macrocytic anaemia
Macrocytic anaemia can be divided into causes associated with a megaloblastic bone marrow and those with a normoblastic bone marrow
Megaloblastic causes
• vitamin B12 deficiency
• folate deficiency
• cytotoxics e.g. hydroxyurea
Normoblastic causes
• alcohol
• liver disease
• hypothyroidism
• pregnancy
• reticulocytosis e.g. haemolysis
• aplastic anaemia
• myelodysplasia
• drugs: cytotoxics
Question 14 of 84
A 55-year-old women is referred to the haematology clinic with easy bruising and recurrent epistaxis. She is otherwise well. Blood tests reveal the following:
Hb 12.9 g/dl
Platelets 19 * 109/l
WCC 6.6 * 109/l
The patient refuses consent for a bone marrow examination. What is the most appropriate initial management?
Platelet transfusion
Oral prednisolone
No treatment
ABVD chemotherapy
Splenectomy
The likely diagnosis in this patient is idiopathic thrombocytopenic purpura. The first line treatment in such patients is high-dose prednisolone. Bone marrow examination would demonstrate increased megakaryocytes
ITP: investigation and management
Idiopathic thrombocytopenic purpura (ITP) is an immune mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb-IIIa or Ib complex
Investigations
• antiplatelet autoantibodies (usually IgG)
• increased megakaryocytes in the marrow
Management
• oral prednisolone (80% of patients respond)
• splenectomy if platelets < 30 after 3 months of steroid therapy
• IV immunoglobulins
• immunosuppressive drugs e.g. cyclophosphamide
Question 15 of 84
Which one of the following haematological malignancies is associated with Reed-Sternberg cells?
Acute lymphoblastic leukaemia
Non-Hodgkin's lymphoma
Hodgkin's lymphoma
Hairy cell leukaemia
Myeloma
Hodgkin's lymphoma
Hodgkin's lymphoma is a malignant proliferation of lymphocytes characterised by the presence of the Reed-Sternberg cell. It has a bimodal age distributions being most common in the third and seventh decades
Features
• lymphadenopathy (75%) - painless, non-tender, asymmetrical
• systemic (25%): weight loss, pruritus, night sweats, fever (Pel-Ebstein)
• alcohol pain in HL
• normocytic anaemia, eosinophilia
• LDH raised
Question 16 of 84
Which of the following translocations is associated with acute promyelocytic leukaemia?
t(15;17)
t(9;17)
t(9;22)
t(15;22)
t(17;22)
Acute promyelocytic leukaemia
Candidates are not normally expected to be able to differentiate the different subtypes of acute myeloid leukaemia (AML) for the MRCP. An exception to this is acute promyelocytic leukaemia (APML, the M3 subtype of AML). The importance of identifying APML lies in both the presentation (classically disseminated intravascular coagulation) and management
APML is associated with the t(15;17) translocation which causes fusion of the PML and RAR-alpha genes.
Features
• presents younger than other types of AML (average = 25 years old)
• DIC or thrombocytopenia often at presentation
• good prognosis
Question 17 of 84
Each one of the following may cause eosinophilia, except:
Allergic bronchopulmonary aspergillosis
Extrinsic allergic alveolitis
Churg-Strauss syndrome
Psoriasis
Toxocara infection
Eosinophilia
Causes of eosinophilia may be divided into pulmonary, infective and other
Pulmonary causes
• asthma
• allergic bronchopulmonary aspergillosis
• Churg-Strauss syndrome
• Loffler's syndrome
• tropical pulmonary eosinophilia
• eosinophilic pneumonia
• hypereosinophilic syndrome
Infective causes
• nematodes: Toxocara, Ascaris, Strongyloides
• cestodes: Echinococcus
Other causes
• drugs: sulfasalazine, nitrofurantoin
• psoriasis/eczema
• eosinophilic leukaemia (very rare)
Question 18 of 84
Which one of the following features is least recognised in thrombotic thrombocytopenic purpura?
Fever
Microangiopathic haemolytic anaemia
Renal failure
Thrombocytopenia
Livedo reticularis
Livedo reticularis is not commonly seen in thrombotic thrombocytopenic purpura. It occurs more commonly in conditions such as antiphospholipid syndrome and cholesterol embolism
Thrombotic thrombocytopenic purpura
Pathogenesis of thrombotic thrombocytopenic purpura (TTP)
• abnormally large and sticky multimers of von Willebrand's factor cause platelets to clump within vessels
• in TTP there is a deficiency of caspase which breakdowns large multimers of von Willebrand's factor
• overlaps with haemolytic uraemic syndrome (HUS)
Features
• rare, typically adult females
• fever
• fluctuating neuro signs (microemboli)
• microangiopathic haemolytic anaemia
• thrombocytopenia
• renal failure
Causes
• post-infection e.g. urinary, gastrointestinal
• pregnancy
• drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir
• tumours
• SLE
• HIV
Question 19 of 84
Which one of the following is the most common inherited thrombophilia?
Protein S deficiency
Antithrombin III deficiency
Protein C deficiency
Activated protein C resistance
von Willebrand's disease
Activated protein C resistance is the most common inherited thrombophilia. It is due to a mutation in the Factor V Leiden gene. Heterozygotes have a 5-fold risk of venous thrombosis whilst homozygotes have a 50-fold increased risk
Thrombophilia: causes
Inherited
• activated protein C resistance (factor V Leiden)
• antithrombin III deficiency
• protein C deficiency
• protein S deficiency
Acquired
• antiphospholipid syndrome
• the Pill
Question 20 of 84
Haemophilia B is due to a deficiency in:
Factor VI
Factor VII
Factor VIII
Factor IX
Factor X
Haemophilia
Haemophilia is a X-linked recessive disorder of coagulation. Up to 30% of patients have no family history of the condition. Haemophilia A is due to a deficiency of factor VIII whilst in haemophilia B (Christmas disease) there is a lack of factor IX
Features
• haemoarthroses, haematomas
• prolonged bleeding after surgery or trauma
Blood tests
• prolonged APTT
• bleeding time, thrombin time, prothrombin time normal
Up to 10-15% of patients with haemophilia A develop antibodies to factor VIII treatment
Question 21 of 84
Which one of the following conditions is not associated with a low platelet count?
Thrombotic thrombocytopenic purpura
Immune thrombocytopenic purpura
Disseminated intravascular coagulation
Henoch-Schonlein purpura
Hypersplenism
Henoch-Schonlein purpura (HSP) is an IgA mediated small vessel vasculitis. There is a degree of overlap with IgA nephropathy (Berger's disease). HSP is usually seen in children following an infection. It is associated with a normal platelet count
Thrombocytopenia
Causes of severe thrombocytopenia
• ITP
• DIC
• TTP
• haematological malignancy
Causes of moderate thrombocytopenia
• heparin induced thrombocytopenia (HIT)
• drug-induced (e.g. quinine, diuretics, sulphonamides, aspirin, thiazides)
• alcohol
• liver disease
• hypersplenism
• viral infection (EBV, HIV, hepatitis)
• pregnancy
• SLE/antiphospholipid syndrome
Question 22 of 84
Interferon alpha is a recognised treatment for which one of the following haematological disorders?
Acute lymphoblastic leukaemia
Myelofibrosis
Burkitt's lymphoma
Hairy cell leukaemia
Acute myeloid leukaemia
Interferons (IFN) are cytokines released by the body in response to viral infections and neoplasia. They are classified according to cellular origin and the type of receptor they bind to. IFN-alpha and IFN-beta bind to type 1 receptors whilst IFN-gamma binds only to type 2 receptors.
IFN-alpha is produced by leucocytes and has an antiviral action. It has been shown to be useful in the management of hepatitis B & C, Kaposi's sarcoma, metastatic renal cell cancer and hairy cell leukaemia
Hairy cell leukaemia
Hairy cell leukaemia is a rare malignant proliferation disorder of B cells. It is more common in males (4:1)
Features
• pancytopenia
• splenomegaly
• skin vasculitis in 1/3 patients
• 'dry tap' despite bone marrow hypercellularity
• tartrate resistant acid phosphotase (TRAP) stain positive
Management
• interferon-alpha or deoxycoformycin
Question 23 of 84
A patient with a history of recurrent thromboembolic events develops a deep vein thrombosis despite full anticoagulation with heparin. Which one of the following causes of thrombophilia is associated with resistance to heparin?
Protein S deficiency
Antithrombin III deficiency
Protein C deficiency
Lupus anticoagulant
Activated protein C resistance
Heparin works by binding to antithrombin III, enhancing its anticoagulant effect by inhibiting the formation of thrombin and other clotting factors. Patients with antithrombin III deficiency may therefore by resistant to heparin treatment
Antithrombin III deficiency
Antithrombin III deficiency is an inherited cause of thrombophilia occurring in approximately 1:2,000 of the population. Inheritance is autosomal dominant
Antithrombin III inhibits several clotting factors, primarily thrombin, factor X and factor IX. It mediates the effects of heparin
Antithrombin III deficiency comprises a heterogeneous group of disorders, with some patients having a deficiency of normal antithrombin III whilst others produce abnormal antithrombin III
Features
• recurrent venous thromboses
• arterial thromboses do occur but is uncommon
Management
• thromboembolic events are treated with lifelong warfarinisation
• heparinisation during pregnancy
• antithrombin III concentrates (often using during surgery or childbirth)
Question 24 of 84
Which one of the following features is least associated with Waldenstrom's macroglobulinaemia?
Raynaud's phenomenon
Bone pain
Visual loss
Hepatosplenomegaly
Monoclonal IgM paraproteinaemia
Waldenstrom's macroglobulinaemia
Waldenstrom's macroglobulinaemia is an uncommon condition seen in older men. It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein
Features
• monoclonal IgM paraproteinaemia
• systemic upset: weight loss, lethargy
• hyperviscosity syndrome e.g. visual disturbance
• hepatosplenomegaly
• lymphadenopathy
• cryoglobulinaemia e.g. Raynaud's
Question 25 of 84
Which one of the following is most useful in differentiating between a leukaemoid reaction and chronic myeloid leukaemia?
Haemoglobin level
Neutrophil count
Platelet count
Leucocyte alkaline phosphatase score
Osmotic fragility test
Leukaemoid reaction
The leukaemoid reaction describes the presence of immature cells such as myeloblasts, promyelocytes and nucleated red cells in the peripheral blood. This may be due to infiltration of the bone marrow causing the immature cells to be 'pushed out' or sudden demand for new cells
Causes
• severe infection
• severe haemolysis
• massive haemorrhage
• metastatic cancer with bone marrow infiltration
A relatively common clinical problem is differentiating chronic myeloid leukaemia from a leukaemoid reaction. The following differences may help:
Leukaemoid reaction
• high leucocyte alkaline phosphatase score
• toxic granulation (Dohle bodies) in the white cells
• 'left shift' of neutrophils i.e. three or less segments of the nucleus
Chronic myeloid leukaemia
• low leucocyte alkaline phosphatase score
Question 26 of 84
Which one of the following malignancies may be associated with HTLV-1?
Adult T-cell leukaemia
Colorectal cancer
Burkitt's lymphoma
Medullary thyroid cancer
Breast cancer
Haematological malignancies: infections
Viruses
• EBV: Hodgkin's and Burkitt's lymphoma
• HTLV-1: Adult T-cell leukaemia/lymphoma
• HIV-1: High-grade B-cell lymphoma
Bacteria
• Helicobacter pylori: gastric lymphoma (MALT)
Protozoa
• malaria: Burkitt's lymphoma
Question 27 of 84
A 24-year-old nulliparous female with a history of recurrent deep vein thrombosis presents with shortness of breath. The full blood count and clotting screen reveals the following results:
Hb 12.4
Plt 144
WBC 7.5
PT 14 secs
APTT 38 secs
What is the most likely underlying diagnosis?
Third generation oral contraceptive pill use
Protein C deficiency
Antithrombin III deficiency
Antiphospholipid syndrome
Activated protein C resistance
The combination of a prolonged APTT and thrombocytopenia make antiphospholipid syndrome the most likely diagnosis
Antiphospholipid syndrome
Antiphospholipid syndrome is an acquired disorder characterised by a predisposition to both venous and arterial thromboses, recurrent fetal loss and thrombocytopenia. It may occur as primary disorder or secondary to other conditions, most commonly systemic lupus erythematous (SLE)
A key point for the exam is to appreciate that antiphospholipid syndrome causes a paradoxical rise in the APTT. This is due to an ex-vivo reaction of the lupus anticoagulant autoantibodies with phospholipids involved in the coagulation cascade
Features
• venous/arterial thrombosis
• recurrent fetal loss
• livedo reticularis
• thrombocytopenia
• prolonged APTT
• other features: pre-eclampsia, pulmonary hypertension
Associations other than SLE
• other autoimmune disorders
• lymphoproliferative disorders
• phenothiazines (rare)
Management
• after arterial/venous thrombosis risk of further event is 30% per year, therefore anticoagulate, INR 3-4
Question 28 of 84
Which of the following is a cause of extravascular haemolysis?
Hereditary spherocytosis
G6PD deficiency
Disseminated intravascular coagulation
Mismatched blood transfusion
Haemolytic uraemic syndrome
Haemolytic anaemias: by site
In intravascular haemolysis free haemoglobin is released which binds to haptoglobin. As haptoglobin becomes saturated haemoglobin binds to albumin forming methaemalbumin (detected by Schumm's test). Free haemoglobin is excreted in the urine as haemoglobinuria, haemosiderinuria
Intravascular haemolysis: causes
• mismatched blood transfusion
• G6PD deficiency
• red cell fragmentation: heart valves, TTP, DIC, HUS
• paroxysmal nocturnal haemoglobinuria
• cold autoimmune haemolytic anaemia
Extravascular haemolysis: causes
• haemoglobinopathies: sickle cell, thalassaemia
• hereditary spherocytosis
• haemolytic disease of newborn
• warm autoimmune haemolytic anaemia
Question 29 of 84
Which one of the following drugs is most likely to cause hypercalcaemia?
Bendrofluazide
Ramipril
Spironolactone
Atenolol
Simvastatin
Bendroflumethiazide
Bendroflumethiazide (bendrofluazide) is a thiazide diuretic which works by inhibiting sodium absorption at the beginning of the distal convoluted tubule (DCT). Potassium is lost as a result of more sodium reaching the collecting ducts. Bendroflumethiazide has a role in the treatment of mild heart failure although loop diuretics are better for reducing overload. The main use of bendroflumethiazide currently is as a first-line agent in hypertension (part of the effect is due to vasodilation)
Common adverse effects
• dehydration
• postural hypotension
• hypokalaemia, hypercalcaemia
• gout
• impaired glucose tolerance
• impotence
Rare adverse effects
• thrombocytopenia
• agranulocytosis
• photosensitivity rash
• pancreatitis
Question 30 of 84
Which of the following is most associated with thymomas?
Myelodysplasia
Thrombocytopenia
Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Red cell aplasia
Thymoma
Thymomas are the most common tumour of the anterior mediastinum
Associated with
• myasthenia gravis (30-40% of patients with thymoma)
• red cell aplasia
• dermatomyositis
• also : SLE, SIADH
Causes of death
• compression of airway
• cardiac tamponade
Question 31 of 84
A 15-year-old girl presents with a palpable purpuric over her buttocks accompanied by polyarthralgia following a recent sore throat. What is the most likely diagnosis?
Rubella
Measles
Erythema multiforme
Idiopathic thrombocytopenic purpura
Henoch-Schonlein purpura
Henoch-Schonlein purpura
Henoch-Schonlein purpura (HSP) is an IgA mediated small vessel vasculitis. There is a degree of overlap with IgA nephropathy (Berger's disease). HSP is usually seen in children following an infection
Features
• palpable purpuric rash (with localized oedema) over buttocks and extensor surfaces of arms and legs
• abdominal pain
• polyarthritis
• features of IgA nephropathy may occur e.g. haematuria, renal failure
Question 32 of 84
Which one of the following haematological malignancies is most commonly associated with the t(9;22) translocation?
Chronic myeloid leukaemia
Acute promyelocytic leukaemia
Acute lymphoblastic leukaemia
Burkitt's lymphoma
Mantle cell lymphoma
Haematological malignancies: genetics
Below is a brief summary of the common translocations associated with haematological malignancies
t(9;22) - Philadelphia chromosome
• present in > 95% of patients with CML
• this results in part of the Abelson proto-oncogene being moved to the BCR gene on chromosome 22
• the resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal
• poor prognostic indicator in ALL
t(15;17)
• seen in acute promyelocytic leukaemia (M3)
• fusion of PML and RAR-alpha genes
t(8;14)
• seen in Burkitt's lymphoma
• MYC oncogene is translocated to an immunoglobulin gene
t(11;14)
• Mantle cell lymphoma
• deregulation of the cyclin D1 (BCL-1) gene
Question 33 of 84
Regarding the Ann-Arbor classification of Hodgkin's lymphoma, which one of the following would be staged as IIIB?
Nodes on both sides of diaphragm with pruritus
Two or more lymph nodes on the same side of the diaphragm with pruritus
Nodes on both sides of diaphragm with night sweats
Two or more lymph nodes on the same side of the diaphragm with night sweats
Two or more lymph nodes on the same side of the diaphragm with no systemic symptoms
Hodgkin's lymphoma: staging
Hodgkin's lymphoma is a malignant proliferation of lymphocytes characterised by the presence of the Reed-Sternberg cell. It has a bimodal age distributions being most common in the third and seventh decades
Ann-Arbor staging of Hodgkin's lymphoma
• I: single lymph node
• II: 2 or more lymph nodes/regions on same side of diaphragm
• III: nodes on both sides of diaphragm
• IV: spread beyond lymph nodes
Each stage may be subdivided into A or B
• A = no systemic symptoms other than pruritus
• B = weight loss > 10% in last 6 months, fever > 38c, night sweats (poor prognosis)
Question 34 of 84
Burkitt's lymphoma is associated with a mutation in which one of the following genes?
Cyclin D1 gene
PML gene
BCR-ABL gene
RAR-alpha gene
MYC gene
Haematological malignancies: genetics
Below is a brief summary of the common translocations associated with haematological malignancies
t(9;22) - Philadelphia chromosome
• present in > 95% of patients with CML
• this results in part of the Abelson proto-oncogene being moved to the BCR gene on chromosome 22
• the resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal
• poor prognostic indicator in ALL
t(15;17)
• seen in acute promyelocytic leukaemia (M3)
• fusion of PML and RAR-alpha genes
t(8;14)
• seen in Burkitt's lymphoma
• MYC oncogene is translocated to an immunoglobulin gene
t(11;14)
• Mantle cell lymphoma
• deregulation of the cyclin D1 (BCL-1) gene
Question 35 of 84
What is the most common complication seen in patients with polycythaemia rubra vera?
Chronic myeloid leukaemia
Osteosarcoma
Myelodysplasia
Myelofibrosis
Acute myeloid leukaemia
Polycythaemia rubra vera: management
Polycythaemia rubra vera is a myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets.. It has peak incidence in the sixth decade, with typical features including hyperviscosity, pruritus and splenomegaly
Management
• venesection - first line treatment
• hydroxyurea -slight increased risk of secondary leukaemia
• phosphorus-32 therapy
Prognosis
• 30% of patients progress to myelofibrosis
• 5% of patients progress to acute leukaemia
Question 36 of 84
Which one of the following is the most likely result if a fetus is homozygous for alpha-thalassaemia?
Anencephalic fetus
Normal pregnancy
Prematurity
Hydrops fetalis
Macrosomia
Alpha-thalassaemia
Alpha-thalassaemia is due to a deficiency of alpha chains in haemoglobin
Overview
• 2 separate alpha-globulin genes are located on each chromosome 16
Clinical severity depends on the number of alpha chains present
If 1 or 2 alpha chains are absent then the blood picture would be hypochromic and microcytic, but the Hb level would be typically normal
Loss of 3 alpha chains results in a hypochromic microcytic anaemia with splenomegaly. This is known as Hb H disease
If all 4 alpha chains absent (i.e. homozygote) then death in utero (hydrops fetalis, Bart's hydrops)
Question 37 of 84
Which one of the following anti-hypertensives is most associated with haemolytic anaemia?
Methyldopa
Verapamil
Hydralazine
Losartan
Sodium nitroprusside
Drug-induced haemolytic anaemia
Drug-induced haemolytic anaemia can be classified according to three different mechanisms:
Type I - antibody against drug-red cell membrane complex
• penicillin
Type II - deposition of complement via a drug-protein-antibody complex onto the red cell membrane
• quinidine
• rifampicin
Type III - true autoimmune haemolytic anaemia - role of drug not known
• methyldopa
• L-dopa
• mefanamic acid
Question 38 of 84
The most common tumour causing bone metastases is:
Breast
Lung
Colorectal
Prostate
Testicular
Bone metastases
Most common tumour causing bone metastases (in descending order)
• prostate
• breast
• lung
Most common site (in descending order)
• spine
• pelvis
• ribs
• skull
• long bones
Question 39 of 84
Which one of the following is least associated with paraproteinaemia?
Myeloma
Lymphoma
Amyloidosis
Waldenstrom's macroglobulinaemia
Sarcoidosis
Paraproteinaemia
Causes of paraproteinaemia
• myeloma
• monoclonal gammopathy of uncertain significance (MGUS)
• benign monoclonal gammopathy
• Waldenstrom's macroglobulinaemia
• amyloidosis
• CLL, lymphoma
• heavy chain disease
• POEMS
Benign monoclonal gammopathy
• non-lymphoid malignancy (e.g. colon, breast)
• infections (CMV, hepatitis)
• autoimmune disorders (RA, SLE)
Question 40 of 84
Which one of the following is least associated with small cell lung cancer?
Bad prognosis
Cushing's syndrome
PTH-related peptide secretion
Hyponatraemia
Lambert-Eaton syndrome
PTH-related peptide secretion is seen in squamous cell lung cancer
Lung cancer: small cell
Small cell cancer
• usually central
• arise from APUD cells
• associated with ectopic ADH, ACTH secretion
• ADH --> hyponatraemia
• ACTH --> Cushing's
• ACTH secretion can cause bilateral adrenal hyperplasia, the high levels of cortisol can lead to hypokalaemic alkalosis
• Lambert-Eaton syndrome: antibodies to voltage gated calcium channels causing myasthenic like syndrome
Management
• usually mets by time of diagnosis
• surgery: only used for debulking
• radiotherapy: only used for debulking
• chemotherapy: good response to combination chemo, may extend life by c. 4 months
Question 41 of 84
A 28-year-old female with a history of sickle cell anaemia presents with shortness of breath and chest pain. Chest x-ray shows bilateral infiltrates in the bases. Arterial blood gases on room air are as follows:
pH 7.39
pCO2 4.6
pO2 8.2
What is the likely diagnosis?
Myocardial infarction
Haemolytic crisis
Thrombotic crisis
Acute sickle chest syndrome
Pulmonary embolism
This presentation is typical of acute sickle chest syndrome
Sickle-cell crises
Sickle cell anaemia is characterised by periods of good health with intervening crises
Four main types of crises are recognised:
• thrombotic, 'painful crises'
• sequestration
• aplastic
• haemolytic
Thrombotic crises
• also known as painful crises or vaso-occlusive crises
• precipitated by infection, dehydration, deoxygenation
• infarcts occur in various organs including the bones (e.g. avascular necrosis of hip, hand-foot syndrome in children, lungs, spleen and brain
Sequestration crises
• sickling within organs such as the spleen or lungs causes pooling of blood with worsening of the anaemia
• acute chest syndrome: dyspnoea, chest pain, pulmonary infiltrates, low pO2 - the most common cause of death after childhood
Aplastic crises
• caused by infection with parvovirus
• sudden fall in haemoglobin
Haemolytic crises
• rare
• fall in haemoglobin due an increased rate of haemolysis
Question 42 of 84
What is the most useful marker of prognosis in myeloma?
Calcium level
Urine Bence-Jones protein levels
Alkaline phosphotase
ESR
B2-microglobulin
Myeloma: management and prognosis
Interferon has been shown to improve survival - not used much in clinical practice
Prognosis
• B2-microglobulin is a useful marker of prognosis: raised levels imply poor prognosis
Question 43 of 84
A 35-year-old female who is 34 weeks pregnant presents with a swollen, painful right calf. A deep vein thrombosis is confirmed on Doppler scan. What is the preferred anticoagulant?
Clopidogrel
Aspirin
Intravenous heparin
Warfarin
Subcutaneous heparin
Pregnancy: DVT/PE
Overview
• pregnancy is hypercoagulable state
• majority occur in last trimester
Pathophysiology
• increase in factors VII, VIII, X and fibrinogen
• decrease in protein S
• uterus presses on IVC causing venous stasis in legs
Management
• warfarin contraindicated
• S/C low-molecular weight heparin preferred to IV heparin (less bleeding and thrombocytopenia)
Question 44 of 84
What is the best diagnostic test for paroxysmal nocturnal haemoglobinuria?
Glucose-6-phoshate dehydrogenase levels
Osmotic fragility test
Red cell pyruvate kinase level
PAS staining of erythrocytes
Ham's test
Paroxysmal nocturnal haemoglobinuria
Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired disorder leading to haemolysis (mainly intravascular) of haematological cells. It is thought to be caused by increased sensitivity of cell membranes to complement (see below) due to a lack of glycoprotein glycosyl-phosphatidylinositol (GPI). Patients are more prone to venous thrombosis
Pathophysiology
• GPI can be thought of as an anchor which attaches surface proteins to the cell membrane
• complement-regulating surface proteins, e.g. decay-accelerating factor (DAF), are not properly bound to the cell membrane due a lack of GPI
• thrombosis is thought to be caused by a lack of CD59 on platelet membranes predisposing to platelet aggregation
Features
• haemolytic anaemia
• red blood cells, white blood cells, platelets or stem cells may be affected therefore pancytopaenia may be present
• haemoglobinuria: classically dark-coloured urine in the morning (although has been shown to occur throughout the day)
• thrombosis e.g. Budd-Chiari syndrome
• aplastic anaemia may develop in some patients
Diagnosis
• Ham test: acid-induced haemolysis (normal red cells wouldn't)
Management
• blood product replacement
• anticoagulation
• stem cell transplantation
Question 45 of 84
Which of the following factors is associated with a good prognosis in acute myeloid leukaemia?
Older age at presentation
Acute promyelocytic subtype
25% blast following first course of chemotherapy
Deletion of chromosome 5
Deletion of chromosome 7
Acute myeloid leukaemia
Poor prognostic features
• > 60 years
• > 20% blasts after first course of chemo
• cytogenics: deletions of chromosome 5 or 7
Classification - French-American-British (FAB)
• MO - undifferentiated
• M1 - without maturation
• M2 - with granulocytic maturation
• M3 - acute promyelocytic
• M4 - granulocytic and monocytic maturation
• M5 - monocytic
• M6 - erythroleukaemia
• M7 - megakaryoblastic
Acute promyelocytic leukaemia M3
• associated with t(15;17)
• fusion of PML and RAR-alpha genes
• presents younger than other types of AML (average = 25 years old)
• DIC or thrombocytopenia often at presentation
• good prognosis
Question 46 of 84
Which of the following is a cause of intravascular haemolysis?
Hereditary spherocytosis
Sickle cell anaemia
Paroxysmal nocturnal haemoglobinuria
Haemolytic disease of the newborn
Warm autoimmune haemolytic anaemia
Haemolytic anaemias: by site
In intravascular haemolysis free haemoglobin is released which binds to haptoglobin. As haptoglobin becomes saturated haemoglobin binds to albumin forming methaemalbumin (detected by Schumm's test). Free haemoglobin is excreted in the urine as haemoglobinuria, haemosiderinuria
Intravascular haemolysis: causes
• mismatched blood transfusion
• G6PD deficiency
• red cell fragmentation: heart valves, TTP, DIC, HUS
• paroxysmal nocturnal haemoglobinuria
• cold autoimmune haemolytic anaemia
Extravascular haemolysis: causes
• haemoglobinopathies: sickle cell, thalassaemia
• hereditary spherocytosis
• haemolytic disease of newborn
• warm autoimmune haemolytic anaemia
Question 47 of 84
'Tear-drop' poikilocytes are typically seen in:
Intravascular haemolysis
Iron-deficiency anaemia
Myelofibrosis
Liver disease
Post-splenectomy
Blood films: typical pictures
Hyposplenism e.g. post-splenectomy
• target cells
• Howell-Jolly bodies
• Cabot's rings
• siderotic granules
• acanthocytes
• schizocytes
Iron-deficiency anaemia
• target cells
• 'pencil' poikilocytes
• if combined with B12/folate deficiency a 'dimorphic' film occurs with mixed microcytic and macrocytic cells
Myelofibrosis
• 'tear-drop' poikilocytes
Intravascular haemolysis
• schistocytes
Megaloblastic anaemia
• hypersegmented neutrophils
Question 48 of 84
Each one of the following may cause sideroblastic anaemia, except:
Anti-tuberculosis medication
Alcohol
Pyridoxine
Lead
Myelodysplasia
Sideroblastic anaemia
Overview
• red cells contain abnormal iron granules in the mitochondria around the nucleus: ring sideroblasts
• peripheral blood cells are hypochromic whilst increased marrow iron
• may be congenital or acquired
• congenital cause: delta-aminolevulinate synthase-2 deficiency
Acquired causes
• myelodysplasia
• alcohol
• lead
• anti-TB medications
Investigations
• hypochromic microcytic anaemia (more so in congenital)
• bone marrow: sideroblasts and increased iron stores
Management
• supportive
• pyridoxine may help
Question 49 of 84
Which one of the following investigations is most likely to be abnormal in a patient with haemophilia A?
APTT
Prothrombin time
Bleeding time
Thrombin time
Platelet count
Haemophilia
Haemophilia is a X-linked recessive disorder of coagulation. Up to 30% of patients have no family history of the condition. Haemophilia A is due to a deficiency of factor VIII whilst in haemophilia B (Christmas disease) there is a lack of factor IX
Features
• haemoarthroses, haematomas
• prolonged bleeding after surgery or trauma
Blood tests
• prolonged APTT
• bleeding time, thrombin time, prothrombin time normal
Up to 10-15% of patients with haemophilia A develop antibodies to factor VIII treatment
Question 50 of 84
What is the most common inherited bleeding disorder?
Haemophilia A
Activated protein C resistance
Haemophilia B
Antithrombin III deficiency
von Willebrand's disease
Von Willebrand's disease
Von Willebrand's disease is the most common inherited bleeding disorder. It is inherited in an autosomal dominant fashion and characteristically behaves like a platelet disorder i.e. epistaxis and menorrhagia are common whilst haemoarthroses and muscle haematomas are rare
Role of von Willebrand factor
• large glycoprotein which forms massive multimers up to 1,000,000 Da in size
• promotes platelet adhesion to damaged endothelium
• carrier molecule for factor VIII
Types
• type 1: partial reduction in vWF
• type 2: abnormal form of vWF
• type 3: total lack of vWF
Investigation
• prolonged bleeding time
• APTT may be prolonged
• factor VIII levels may be moderately reduced
• defective platelet aggregation with ristocetin
Management
• tranexamic acid for mild bleeding
• DDAVP
• factor VIII concentrate
Question 51 of 84
Each one of the following is a recognised complication of blood transfusion, except:
Iron overload
ARDS
Hypokalaemia
Clotting abnormalities
Febrile reaction
Blood transfusion complications
Complications
• haemolytic: immediate or delayed
• febrile reactions
• transmission of viruses, bacteria, parasites
• hyperkalaemia
• iron overload
• ARDS
• clotting abnormalities
Immediate haemolytic reaction
• e.g. ABO mismatch
• massive intravascular haemolysis
Febrile reactions
• due to white blood cell HLA antibodies
• often the result of sensitization by previous pregnancies or transfusions
Causes a degree of immunosuppression
• e.g. patients with colorectal cancer who have blood transfusions have a worse outcome than those who do not
Question 52 of 84
A 72-year-old woman with a past history of chronic lymphocytic leukaemia presents with lethargy. The following blood results are obtained:
Hb 7.9 g/dl
Plt 158 * 109/l
WCC 24.0 * 109/l
Blood film: normochromic, normocytic anaemia
What complication has most likely occurred?
Paroxysmal nocturnal haemoglobinuria
Microangiopathic haemolytic anaemia
Sideroblastic anemia
Warm autoimmune haemolytic anaemia
Cold autoimmune haemolytic anaemia
Warm autoimmune haemolytic anaemia occurs in around 10-15% of patients with chronic lymphocytic leukaemia
Chronic lymphocytic leukaemia
Chronic lymphocytic leukaemia (CLL) is caused by a monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%)
Features
• often none
• constitutional: anorexia, weight loss
• bleeding, infections
• lymphadenopathy more marked than CML
Complications
• hypogammaglobulinaemia leading to recurrent infections
• warm autoimmune haemolytic anaemia in 10-15% of patients
• transformation to high-grade lymphoma (Richter's transformation)
Investigations
• blood film: smudge cells
• immunophenotyping
Question 53 of 84
Which one of the following types of Hodgkin's lymphoma carries the worst prognosis?
Nodular sclerosing
Mixed cellularity
Lymphocyte predominant
Lymphocyte depleted
Hairy cell
Hodgkin's lymphoma: histological classification
Hodgkin's lymphoma is a malignant proliferation of lymphocytes characterised by the presence of the Reed-Sternberg cell. It has a bimodal age distributions being most common in the third and seventh decades
Histological classification
• nodular sclerosing: most common, good prognosis
• mixed cellularity: good prognosis
• lymphocyte predominant: best prognosis
• lymphocyte depleted: least common, worst prognosis
Question 54 of 84
In idiopathic thrombocytopenic purpura what are the autoantibodies most commonly directed at?
Platelet activating factor
Glycoprotein IIb/IIIa complex
ATP receptor
Anti-thrombin III receptor
ADP receptor
ITP
Idiopathic thrombocytopenic purpura (ITP) is an immune mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb-IIIa or Ib complex.
ITP can be divided into acute and chronic forms:
Acute ITP
• more commonly seen in children
• equal sex incidence
• may follow an infection or vaccination
• usually runs a self-limiting course over 1-2 weeks
Chronic ITP
• more common in young/middle-aged women
• tends to run a relapsing-remitting course
Evan's syndrome
• ITP in association with autoimmune haemolytic anaemia (AIHA)
Question 55 of 84
Each one of the following is associated with iron-deficiency anaemia, except:
Atrophic glossitis
Onycholysis
Post-cricoid webs
Koilonychia
Angular stomatitis
Iron deficiency anaemia
Features
• koilonychia
• atrophic glossitis
• post-cricoid webs
• angular stomatitis
Blood film
• target cells
• 'pencil' poikilocytes
• if combined with B12/folate deficiency a 'dimorphic' film occurs with mixed microcytic and macrocytic cells
Question 56 of 84
Which one of the following is least associated with the development of aplastic anaemia?
Chloramphenicol
Benzene exposure
Parvovirus
Homocystinuria
Fanconi's anaemia
Aplastic anaemia
Characterised by pancytopaenia and a hypoplastic bone marrow
Peak incidence of acquired = 30 years old
Features
• normochromic, normocytic anaemia
• leukopenia, with lymphocytes relatively spared
• thrombocytopenia
• may be the presenting feature acute lymphoblastic or myeloid leukaemia
• a minority of patients later develop paroxysmal nocturnal haemoglobinuria or myelodysplasia
Causes
• idiopathic
• congenital: Fanconi anaemia, dyskeratosis congenita
• drugs: cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold
• toxins: benzene
• infections: parvovirus, hepatitis
• radiation
Question 57 of 84
The presence or absence of each one of the following is useful in differentiating myeloma from a monoclonal gammopathy of undetermined significance, except:
Bone pain
Paraprotein band
Renal impairment
Beta-2 microglobulin levels
Lytic lesions on x-ray
MGUS
Monoclonal gammopathy of undetermined significance (MGUS, also known as benign paraproteinaemia and monoclonal gammopathy) is a common condition that causes a paraproteinaemia and is often mistaken for myeloma. Differentiating features are listed below. Around 10% of patients eventually develop myeloma at 5 years, with 50% at 15 years
Features
• usually asymptomatic
• no bone pain or increased risk of infections
• around 10-30% of patients have a demyelinating neuropathy
Differentiating features from myeloma
• normal immune function
• normal beta-2 microglobulin levels
• lower level of paraproteinaemia than myeloma (e.g. < 30g/l IgG, or < 20g/l IgA)
• stable level of paraproteinaemia
• no clinical features of myeloma (e.g. lytic lesions on x-rays or renal disease)
Question 58 of 84
Which one of the following is associated with a low leucocyte alkaline phosphatase score?
Myelofibrosis
Polycythaemia rubra vera
Leukaemoid reactions
Chronic myeloid leukaemia
Pregnancy
Leucocyte alkaline phosphatase
Raised in
• myelofibrosis
• leukaemoid reactions
• polycythaemia rubra vera
• infections
• steroids, Cushing's syndrome
• pregnancy, oral contraceptive pill
Low in
• chronic myeloid leukaemia
• pernicious anaemia
• paroxysmal nocturnal haemoglobinuria
• infectious mononucleosis
Question 59 of 84
Which of the following is a good prognostic factor in chronic lymphocytic leukaemia?
Female sex
Lymphocyte doubling time < 12 months
CD38 expression positive
Age > 70 years
Raised LDH
Chronic lymphocytic leukaemia: prognostic factors
Poor prognostic factors (median survival 3-5 years)
• male sex
• age > 70 years
• lymphocyte count > 50
• prolymphocytes comprising more than 10% of blood lymphocytes
• lymphocyte doubling time < 12 months
• raised LDH
• CD38 expression positive
Question 60 of 84
What is the most common monoclonal paraprotein produced in myeloma?
IgE
IgM
IgD
IgG
IgA
Myeloma
Overview
• neoplastic proliferation of bone marrow plasma cells
• peak age = 70 years
• equal sex ratio
Monoclonal products produced
• IgG (50-60%)
• IgA (20-30%)
• light chain disease (20%)
Diagnosis: 2 of the following 3
• monoclonal protein in serum or urine
• increased plasma cells in the bone marrow (> 20%)
• bone lesions
Question 61 of 84
Each one of the following is associated with polycythaemia rubra vera, except:
Splenomegaly
Hyperviscosity
Raised ESR
Hypertension
Pruritus
Polycythaemia rubra vera is associated with a low ESR
Polycythaemia rubra vera: features
Polycythaemia rubra vera is a myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets.. It has peak incidence in the sixth decade, with typical features including hyperviscosity, pruritus and splenomegaly
Features
• hyperviscosity
• pruritus, typically after a hot bath
• splenomegaly
• haemorrhage (secondary to abnormal platelet function)
• plethoric appearance
• hypertension in a third of patients
Investigations
• neutrophils, basophils up in half of patients
• platelets up in half of patients
• a microcytosis may be seen due to iron-deficiency secondary to bleeding
• ESR is low
• leukocyte alkaline phosphotase is increased
Main diagnostic criteria (by the PRV Study Group)
• total red cell mass in males > 35ml/kg, women > 32 ml/kg
• arterial oxygen saturation > 92%
• splenomegaly
Question 62 of 84
Which one of the following is least recognised as a treatment modality in idiopathic thrombocytopenic purpura?
Plasma exchange
Splenectomy
IV immunoglobulin
Cyclophosphamide
Oral prednisolone
ITP: investigation and management
Idiopathic thrombocytopenic purpura (ITP) is an immune mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb-IIIa or Ib complex
Investigations
• antiplatelet autoantibodies (usually IgG)
• increased megakaryocytes in the marrow
Management
• oral prednisolone (80% of patients respond)
• splenectomy if platelets < 30 after 3 months of steroid therapy
• IV immunoglobulins
• immunosuppressive drugs e.g. cyclophosphamide
Question 63 of 84
What is the best diagnostic test for hereditary spherocytosis?
Ham's test
PAS staining of erythrocytes
Glucose-6-phoshate dehydrogenase levels
Osmotic fragility test
Direct Coombs' test
Hereditary spherocytosis
Basics
• most common hereditary haemolytic anaemia in northern Europeans
• autosomal dominant defect of RBC cytoskeleton
• biconcave disc --> spherocyte
• red cell survival reduced, destroyed by spleen
Presentation
• e.g. failure to thrive
• jaundice, gallstones
• splenomegaly
• aplastic crisis precipitated by parvovirus infection
• degree of haemolysis variable
Diagnosis
• osmotic fragility test
Management
• folate replacement
• splenectomy
Question 64 of 84
Von Willebrand factor acts as a carrier molecule for which clotting factor?
Factor V
Factor VII
Factor VIII
Factor IX
Factor X
Von Willebrand's disease
Von Willebrand's disease is the most common inherited bleeding disorder. It is inherited in an autosomal dominant fashion and characteristically behaves like a platelet disorder i.e. epistaxis and menorrhagia are common whilst haemoarthroses and muscle haematomas are rare
Role of von Willebrand factor
• large glycoprotein which forms massive multimers up to 1,000,000 Da in size
• promotes platelet adhesion to damaged endothelium
• carrier molecule for factor VIII
Types
• type 1: partial reduction in vWF
• type 2: abnormal form of vWF
• type 3: total lack of vWF
Investigation
• prolonged bleeding time
• APTT may be prolonged
• factor VIII levels may be moderately reduced
• defective platelet aggregation with ristocetin
Management
• tranexamic acid for mild bleeding
• DDAVP
• factor VIII concentrate
Question 65 of 84
Which one of the following is the most common type of Hodgkin's lymphoma?
Lymphocyte predominant
Nodular sclerosing
Lymphocyte depleted
Mixed cellularity
Hairy cell
Hodgkin's lymphoma: histological classification
Hodgkin's lymphoma is a malignant proliferation of lymphocytes characterised by the presence of the Reed-Sternberg cell. It has a bimodal age distributions being most common in the third and seventh decades
Histological classification
• nodular sclerosing: most common, good prognosis
• mixed cellularity: good prognosis
• lymphocyte predominant: best prognosis
• lymphocyte depleted: least common, worst prognosis
Question 66 of 84
Which one of the following is least associated with microcytic anaemia?
Iron deficiency
Hypothyroidism
Thalassaemia
Sideroblastic anaemia
Anaemia of chronic disease
Microcytic anaemia
Causes
• iron-deficiency anaemia
• thalassaemia*
• congenital sideroblastic anaemia
• anaemia of chronic disease (more commonly a normocytic, normochromic picture)
• lead poisoning
*in beta-thalassaemia minor the microcytosis is often disproportionate to the anaemia
A question sometimes seen in the MRCP gives a history of a normal haemoglobin level associated with a microcytosis. In patients not at risk of thalassaemia, this should raise the possibility of polycythaemia rubra vera which may cause an iron-deficiency secondary to bleeding
Question 67 of 84
Lambert-Eaton myasthenic syndrome is most commonly seen in:
Large cell lung cancer
Squamous cell lung cancer
Lung adenocarcinoma
Small cell lung cancer
Lung carcinoid
Lambert-Eaton syndrome
Lambert-Eaton myasthenic syndrome is seen in association with small cell lung cancer, and to a lesser extent breast and ovarian cancer. It may also occur independently as an autoimmune disorder. Lambert-Eaton myasthenic syndrome is caused by an antibody directed against pre-synaptic voltage gated calcium channel in the peripheral nervous system
Features
• repeated muscle contractions lead to increased muscle strength
• limb girdle weakness (affects lower limbs first)
• hyporeflexia
• autonomic symptoms: dry mouth, impotence, difficultly micturating
• ophthalmoplegia and ptosis not commonly a feature (unlike in myasthenia gravis)
EEG
• incremental response to repetitive electrical stimulation
Management
• guanidine is sometimes used
• plasma exchange may be beneficial
Question 68 of 84
Which one of the following malignancies may be associated with the Epstein-Barr virus?
Medullary thyroid cancer
Breast cancer
Adult T-cell leukaemia
Colorectal cancer
Burkitt's lymphoma
Haematological malignancies: infections
Viruses
• EBV: Hodgkin's and Burkitt's lymphoma
• HTLV-1: Adult T-cell leukaemia/lymphoma
• HIV-1: High-grade B-cell lymphoma
Bacteria
• Helicobacter pylori: gastric lymphoma (MALT)
Protozoa
• malaria: Burkitt's lymphoma
Question 69 of 84
Which one of the following is least associated with eosinophilia?
Churg-Strauss syndrome
Nematode infection
Histoplasmosis
Allergic bronchopulmonary aspergillosis
Asthma
Eosinophilia
Causes of eosinophilia may be divided into pulmonary, infective and other
Pulmonary causes
• asthma
• allergic bronchopulmonary aspergillosis
• Churg-Strauss syndrome
• Loffler's syndrome
• tropical pulmonary eosinophilia
• eosinophilic pneumonia
• hypereosinophilic syndrome
Infective causes
• nematodes: Toxocara, Ascaris, Strongyloides
• cestodes: Echinococcus
Other causes
• drugs: sulfasalazine, nitrofurantoin
• psoriasis/eczema
• eosinophilic leukaemia (very rare)
Question 70 of 84
Which one of the following is not associated with thrombophilia?
Protein S deficiency
Antithrombin III deficiency
Protein C deficiency
Activated protein C resistance
von Willebrand's disease
Thrombophilia: causes
Inherited
• activated protein C resistance (factor V Leiden)
• antithrombin III deficiency
• protein C deficiency
• protein S deficiency
Acquired
• antiphospholipid syndrome
• the Pill
Question 71 of 84
Which one of the following therapeutic options is least recognised in the treatment of aplastic anaemia?
Interferon-alpha
Stem cell transplantation
Antilymphocyte globulin
Haematopoietic growth factors
Platelet transfusion
Aplastic anaemia: management
Supportive
• blood products
• prevention and treatment of infection
• haematopoietic growth factors
Antilymphocyte globulin (ALG)
• prepared in animals (e.g. rabbits or horses) by injecting human lymphocytes
• is highly allergenic and may cause serum sickness (fever, rash, arthralgia)
• therefore steroid cover usually given
• ciclosporin may also be given
Stem cell transplantation
• allogeneic transplants have a success rate of up to 80%
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