Haematology

Question 1

Exposure to asbestos is a risk factor for

Answer 1

bronchial carcinoma as well as mesothelioma , laryngeal cancer and ovarian cancer

Exposure to asbestos also increases the risk of some benign diseases, including pleural plaques, diffuse pleural thickening, asbestos related benign pleural effusions and asbestosis.

Question 2

*******raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells

Answer 2

desmopressin (DDAVP):

Question 4

Hereditary angioedema (HAE) is an

Answer 4

autosomal dominant

Question 5

It should be suspected in any patient presenting with an acute kidney injury in the presence of a high phosphate and high uric acid level.

Answer 5

TLS , hypocalcemia and hyperkalemia

Question 6

Cisplatin causes which electrolyte abmormality

Answer 6

Hypomagnesemia

Question 7

. This condition is an X-linked recessive disorder characterized by the triad of eczema, recurrent infections, and thrombocytopenia.
history of recurrent infections, which can be explained by the low immunoglobulin M levels.

Answer 7

Wiskott-Aldrich syndrome

Question 8

*** is an X-linked disorder that results in a lack of mature B cells and therefore very low levels of all immunoglobulins.

Answer 8

Bruton’s congenital agammaglobulinaemia

Question 9

Ataxic telangiectasia is an autosomal recessive disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasias, immune deficiency, and increased risk for malignancies.

Answer 9

patients with ataxic telangiectasia may have recurrent infections due to immune deficiency, they do not typically present with thrombocytopenia or eczema

Question 10

is an autosomal recessive disorder characterized by partial albinism, peripheral neuropathy, and neutropenia.

Answer 10

Chediak-Higashi syndrome

Patients with Chediak-Higashi syndrome often have recurrent infections due to impaired neutrophil function

they do not usually present with thrombocytopenia or eczema as seen in this case.

Question 11

**** is a genetic disorder caused by a deletion in chromosome 22q11.2, leading to thymic hypoplasia or aplasia and resulting in T-cell deficiency.

Answer 11

DiGeorge syndrome

Patients with DiGeorge syndrome often have recurrent infections due to their impaired T-cell function, but they do not typically present with thrombocytopenia or eczema.

Question 12

fever, neurological signs, thrombocytopenia, haemolytic anaemia and renal impairment

Answer 12

TTP

Question 13

**** that is secondary to certain bacterial infections (shigella, enterohaemorrhagic E. coli ), therefore the presentation is usually preceded by a period of diarrhoea. The triad of symptoms includes: thrombocytopenia, haemolytic anaemia and renal impairment.

Answer 13

haemolytic-uraemic syndrome is thrombotic microangiopathy

Question 14

. The patient has polycythaemia rubra vera as evidenced by a ruddy complexion, polycythaemia and a positive mutation for JAK2V617F. These patients are at risk of developing myelofibrosis or acute myeloid leukaemia.

Question 15

Type I cryoglobulinaemia

Answer 15

CRAB mnemonic: >65 years old, hypercalcaemia with abdominal pain and dehydration, renal failure, anaemia and bone pain in her back)

coupled with the secondary Raynaud’s phenomenon evidenced by the hand symptoms/signs being indicative of the cryoglobulins which precipitate at cold temperatures. Type I is the only cryoglobulinaemia that presents with Raynaud’s and is also most strongly associated with multiple myeloma out of the three types.

Question 16

Type 2 cryoglobulinemia

Answer 16

A/w hepatitis

Question 17

**** is a monoclonal antibody that binds to HER2 receptors on the cancer cells, thereby suppressing the growth and proliferation of the tumour. It is effective in HER2-positive breast cancers.

Answer 17

Trastuzumab

Question 18

****is a type of selective oestrogen receptor degrader that binds to and breaks down oestrogen receptors

Answer 18

Fulvestrant

Question 19

This is characterised by a leukocytosis over 50 * 109/L. Typically, there is a neutrophil predominance. This reaction occurs in a variety of conditions, such as infections, reactions to medications, diabetic ketoacidosis, but also certain malignancies, including lung adenocarcinoma

Answer 19

Leukemoid reaction

Leucocyte alkaline phosphatase is raised, unlike in chronic myeloid leukaemia (CML) or acute myeloid leukaemia (AML) where it is lowered.

Question 20

Infectious mononucleosis would have presented with signs of infection and is generally seen in younger patients, with lymphadenopathy, fever and sore throat. It would cause a***** leukocyte alkaline phosphatase, not elevated.

Answer 20

low

Question 21

CKD is the most common cause of *** deficiency

Answer 21

antithrombin III

Question 22

Antithrombin III inhibits several clotting factors, primarily thrombin, factor X and factor IX. It mediates the effects of heparin

Answer 22

Autosommal dominant - Antithrombin 3 defriciency

Question 23

Beta Thalassemia

Answer 23

HbA2 levels are elevated in beta thalassaemia major and minor. It is a variant of haemoglobin A with two delta chains replacing the normal two beta chains. It is found in small amounts in healthy adults at around 1.5 - 3% of total haemoglobin. It is increased in beta thalassaemia because of reduced production of haemoglobin beta chains.

Question 24

. This is the investigation of choice when an anaphylactic reaction is likely. Guidance is that levels should be taken at the time of the reaction, as soon as possible after emergency treatment has commenced, with a second level taken ideally within one to two hours (but no later than four).

Answer 24

Mast cell tryptase is incorrect

Question 25

The occurrence of shortness of breath and headaches in conjunction with discordance between the peripheral oxygen saturation and pO2 of oxygen on the blood gas suggests

Answer 25

methaemoglobinaemia.

Question 26

********is used in the treatment of lidocaine toxicity. Lidocaine toxicity is not likely in this case as this will typically present with neurological symptoms including numbness, tingling, vertigo and seizures.

Answer 26

Lipid emulsion therapy

Question 27

Ascorbic acid is used in the management of congenital methaemoglobinaemia.

Question 28

Dicobalt edetate and hydroxocobalamin are both treatments for cyanide poisoning

Answer 28

cyanide poisoning tends to cause raised peripheral oxygen saturations with low circulating pO2 along with a cherry-red hue on the skin.

Question 29

Acquired causes drugs: sulphonamides, nitrates (including recreational nitrates e.g. amyl nitrite 'poppers'), dapsone, sodium nitroprusside, primaquine chemicals: aniline dyes

Answer 29

Methaemoglobinemia

Question 30

. This is a reversal agent for the anticoagulant agent dabigatran

Answer 30

Idarucizumab

Question 31

. Antibiotic prophylaxis with***** during cyclophosphamide treatment is designed to prevent Pneumocystis jirovecii pneumonia.

Answer 31

Septrin

Question 32

******* are sometimes taken in such patients as they remain elevated for up to 12 hours following an acute episode of anaphylaxis

Answer 32

Serum tryptase level

Question 33

Low haptoglobin levels are found in haemolytic anaemias

Question 34

is now considered first-line treatment ,inhibitor of the tyrosine kinase associated with the BCR-ABL defectvery high response rate in chronic phase CML

Answer 34

imatinib

Question 35

Leukaemoid reaction high leucocyte alkaline phosphatase score

Answer 35

toxic granulation (Dohle bodies) in the white cells 'left shift' of neutrophils i.e. three or fewer segments of the nucleus

Question 36

t(8;14) seen in Burkitt's lymphoma

Answer 36

MYC oncogene is translocated to an immunoglobulin gene

Question 37

Common variable immunodeficiency - low antibody levels, specifically in immunoglobulin types IgG, IgM and IgA. → recurrent chest and other infections

Answer 37

Bruton's agammaglobulinaemia is a rare X-linked recessive immune disorder resulting in poor B-cell development. Whilst it also presents with recurrent infections and low immunoglobulins of all classes, it is much less common overall than CVID and mainly affects male patients due to the X-linked nature of its inheritance.

Question 38

Wiskott-Aldrich syndrome, like SCID, also affects both T-cells and B-cells. As well as recurrent infections, it is also linked to eczema and thrombocytopaenia, it is X-linked recessive,disease

Answer 38

SCID, as the name implies, is a much more severe immunodeficiency than the presentation described here, affecting both T-cells and B-cells. The most common form is X-linked SCID, usually due to mutations in the gene coding the common gamma chain of multiple interleukin receptors. Patients are afflicted with significant infections from infancy and do not survive into childhood unless the condition is diagnosed early and treated with bone marrow transplantation

Question 39

Thymoma is a/w

Answer 39

Associated with myasthenia gravis (30-40% of patients with thymoma) red cell aplasia dermatomyositis also : SLE, SIADH

Question 40

B' symptoms in Hodgkin's lymphoma are associated with a poor prognosis

Answer 40

weight loss > 10% in last 6 months fever > 38ºC night sweats

Question 41

Hereditary angioedema (HAE) is pathophysiologically separate from anaphylaxis and is treated differently.

Answer 41

Therapeutic options are: intravenous infusion of human C1-esterase inhibitor or subcutaneous injection of the bradykinin receptor inhibitor icatibant

Question 42

NICE updated their guidelines on the investigation and management of venous thromboembolism (VTE) in 2020. Some of the key changes include recommending the following:

Answer 42

the use of direct oral anticoagulants (DOACs) as first-line treatment for most people with VTE, including as interim anticoagulants before a definite diagnosis is made the use of DOACs in patients with active cancer, as opposed to low-molecular weight heparin as was the previous recommendation routine cancer screening is no longer recommended following a VTE diagnosis

Question 43

Disproportionate microcytic anaemia - think

Answer 43

beta-thalassaemia trait

Question 44

Post-infectious haemolysis can occur with

Answer 44

atypical pneumonias such as Mycoplasma (cold-agglutinin disease) and infections that induce hypersplenism such as mononucleosis.

Question 45

Pyruvate kinase deficiency is the next most common inherited metabolic disorder after G6PD deficiency.

Answer 45

Haemolysis in these patients tends to be triggered in times of significant physiological stress.

Question 46

Some drugs causing haemolysis (G6PD deficiency)

Answer 46

anti-malarials: primaquine ciprofloxacin sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas

Question 47

Rates of bacterial contamination of platelet transfusion are relatively speaking high, given that platelets are stored at between 20-24ºC. Risk of bacterial contamination of the platelet pool increases with increasing time ex vivo and is the main factor contributing to the short shelf life of platelets.

Answer 47

If no active bleeding or planned invasive procedure A threshold of 10 x 109 except where platelet transfusion is contradindicated or there are alternative treatments for their condition For example, do not perform platelet transfusion for any of the following conditions: Chronic bone marrow failure Autoimmune thrombocytopenia Heparin-induced thrombocytopenia, or Thrombotic thrombocytopenic purpura.

Question 48

Combined B- and T-cell disorders:

Answer 48

SCID WAS ataxic (SCID, Wiskott-Aldrich syndrome, ataxic telangiectasia)

Question 49

Polycythaemia rubra vera - around 5-15% progress to myelofibrosis or AML

Answer 49

AML varient acute promyelocytic leukaemia can present as DIC

Question 51

Burkitt's lymphoma - translocation

Answer 51

t(8:14) The condition being described here is Burkitt's lymphoma, given the demographic, positive Epstein-Barr virus and the 'starry sky' appearance on microscopy - lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells. Burkitt's lymphoma is associated with the c-myc gene translocation, usually t(8:14).

Question 52

Leucocyte alkaline phosphatase is low in CML but raised in myelofibrosis

Question 53

HUS or TTP? Neuro signs point towards TTP

Answer 53

The combination of neurological features, renal failure, pyrexia and thrombocytopaenia point towards a diagnosis of thrombotic thrombocytopenic purpura

Question 54

This condition is characterised by the triad of chronic complement-mediated haemolysis, thrombosis, and bone marrow failure.

Answer 54

paroxysmal nocturnal haemoglobinuria (PNH). Eculizumab is a recombinant monoclonal antibody that inhibits terminal complement activation at the C5 protein and thereby reduces complement-mediated cell damage

Question 56

Indications for splenectomy in HS include

Answer 56

severe symptomatic anaemia, transfusion dependence, or gallstone disease.

Question 57

Itching and tingling of the lips, tongue and mouth are the most common symptoms of oral allergy syndrome

Question 58

Flow cytometry of blood could potentially be useful in diagnosing certain types of leukaemia or lymphoma by identifying abnormal populations of white blood cells

Question 59

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

Answer 59

excessive erythropoietin: cerebellar haemangioma, hypernephroma, hepatoma, uterine fibroids*

Question 60

In true polycythaemia the total red cell mass in males > 35 ml/kg and in women > 32 ml/kg

Answer 60

To differentiate between true and relative polycythemia

Question 61

Target cells and Howell-Jolly bodies may be seen in coeliac disease →

Answer 61

hyposplenism

Question 62

Heinz bodies are large inclusion bodies within the RBCs composed of denatured haemoglobin, and are associated with

Answer 62

glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Question 63

Teardrop-shaped RBCs are seen in.

Answer 63

myelofibrosis

Question 64

Schistocytes are fragmented or broken RBCs which are seen in.

Answer 64

haemolysis

Question 65

It is recognised that many people who are allergic to latex are also allergic to fruits, particularly banana, pineapple, avocado, chestnut, kiwi fruit, mango, passion fruit and strawberry.

Answer 65

Latex-fruit syndrome

Question 66

Drug-induced pancytopaenia

Answer 66

cytotoxics antibiotics: trimethoprim, chloramphenicol anti-rheumatoid: gold, penicillamine carbimazole* anti-epileptics: carbamazepine sulphonylureas: tolbutamide

Question 67

Non-haemolytic febrile reaction During BT

Answer 67

due to white blood cell HLA antibodies often the result of sensitization by previous pregnancies or transfusions paracetamol may be given

Question 68

Transfusion-associated circulatory overload (TACO)

Answer 68

A relatively common reaction due to fluid overload resulting in pulmonary oedema. As well as features of pulmonary oedema the patient may also by hypertensive, a key difference from patients with TRALI.

Question 69

Platelets are stored at room temperature, which increases the risk of bacterial proliferation.

Answer 69

Common contaminants include Staphylococcus epidermidis and Bacillus cereus.

Question 70

Dohle bodies in the white cells

Answer 70

. Dohle bodies are blue-grey, oval cytoplasmic inclusions found in neutrophils during toxic states or infections. They are characteristic of a leukaemoid reaction, which is a reactive process mimicking leukaemia, typically occurring in response to severe infection, inflammation, or malignancy. Their presence strongly suggests a reactive process

Question 71

Hyposplenism Causes

Answer 71

splenectomy sickle-cell coeliac disease, dermatitis herpetiformis Graves' disease systemic lupus erythematosus amyloid Features Howell-Jolly bodies siderocytes

Question 72

TTP is caused by the failure to cleave

Answer 72

vWF normally

Question 73

Leukodepletion is a filtration process designed to remove nearly all white blood cells from blood products before they are transfused. Its primary aim is to reduce the risk of cytomegalovirus (CMV) transmission through the removal of monocytes and other blood-borne viruses.

Answer 73

It is recommended for patients who are immunocompromised, like ours. CMV infection can present in several ways in immunocompromised patients, including colitis and retinitis. However, the case described is more closely aligned with TA-GVHD.

Question 74

refers to a technique where plasma is separated from blood cells in a sample. This process can be employed to produce fresh frozen plasma for transfusions or treat plasma in conditions like Guillain-Barre syndrome before it is returned to the patient's circulation.

Answer 74

Plasmapheresis

Question 75

involves separating platelets from whole blood. It might be utilised as part of treatment strategies for essential thrombocytopenia or in generating platelet concentrates for transfusion in cases of severe thrombocytopenia.

Answer 75

Platelet apheresis

Question 76

Just a summary on Haemopoeisis: 1) Myeloid produces- RBC, Platelets, Granulocytes (Neutrophil, Eosinophil,Basophil) 2) Lymphoid prouces- a) B lymphocyte (precursor to plasma cell and Ig); b) T-lymphocyte; c) NK cells

Answer 76

CML is mainly a problem with B cell - hence plasma cell and Ig are affected predominantly Option 5 (immature lymphocytes) would essentially include T lymphoctes as well, hence being the undesirable option

Question 77

The presence of haemolysis with blister cells and Bite cells on the blood film is highly suggestive of

Answer 77

G6PD deficiency

Question 78

A mutation in this gene is associated with Gardener syndrome which causes multiple colonic polyps along with skull osteomas, thyroid cancer, and epidermoid cysts Autosomal dominant familial colorectal polyposis

Answer 78

APC

Question 79

A mutation in this gene is associated with Li-Fraumeni syndrome. This causes a high incidence of sarcomas and leukaemia rather than prostate cancer.

Answer 79

p53

Question 80

KRAS gene mutations are associated with

Answer 80

pancreatic cancers

Question 81

Renal cell carcinoma and non-small cell lung carcinoma are associated with ******mutations

Answer 81

EGFR gene

Question 82

painful vaso-occlusive crises should be diagnosed clinically - there isn't one test that can confirm them although tests may be done to exclude other complications

Question 83

coagulase-negative, Gram-positive bacteria are the most common cause, particularly Staphylococcus epidermidis in *******

Answer 83

Neutropenia sepsis

Question 84

desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells

Question 85

Paraneoplastic neurological syndromes rarely associate with lymphoma, with the exception of cerebellar degeneration and dermatomyositis.

Answer 85

myalgia and skin manifestations makes paraneoplastic dermatomyositis

Question 86

patients with antithrombin III deficiency have a degree of resistance to heparin anti-Xa levels should be monitored carefully to ensure adequate anticoagulation

Question 87

The presence of pancytopenia with DIC should immediately alert you to the possibility of

Answer 87

acute promyelocytic leukaemia (APML) ;t(15;17) APML is treated with all-trans retinoic acid (ATRA) to force immature granulocytes into maturation to resolve a blast crisis prior to more definitive chemotherapy.

Question 88

Sodium 2-mercaptoethane sulfonate (mesna) is often used before the administration of cyclophosphamide to prevent haemorrhagic cystitis.

Answer 88

Urinary symptoms including haemorrhagic cystitis are some of the main dose-limiting toxicities of cyclophosphamide. One of the metabolites of cyclophosphamide, acrolein, is toxic to the urothelium. Mesna binds to acrolein to form a non-toxic compound.

Question 89

Acquired causes of Methaemoglobinemia

Answer 89

drugs: sulphonamides, nitrates (including recreational nitrates e.g. amyl nitrite 'poppers'), dapsone, sodium nitroprusside, primaquine chemicals: aniline dyes

Question 90

Imaging should be performed within 1 week if there are symptoms suspicious for spinal metastases but no neurological symptoms, and within 24 hours if there are symptoms suggestive of malignant spinal cord compression.

Answer 90

Spinal mets

Question 91

*******is characteristically associated with Protein C deficiency. Protein C is a vitamin K-dependent anticoagulant protein, which acts by inactivating factors Va and VIIIa, thus preventing the formation of thrombin. In patients with Protein C deficiency, starting warfarin therapy can lead to an imbalance between procoagulant and anticoagulant factors, predisposing them to thrombotic events and causing skin necrosis.

Answer 91

WISN

Question 92

****** is an anti-emetic which blocks the neurokinin 1 (NK1) receptor. It is a substance P antagonists (SPA). It is licensed for chemotherapy-induced nausea and vomiting (CINV) and for prevention of postoperative nausea and vomiting. It is also been shown to be effective in treating clinical depression.

Answer 92

Aprepitant

Question 93

Factor V Leiden mutation is a common genetic thrombophilia that predisposes to venous thromboembolism.

Answer 93

The mutation renders factor V resistant to inactivation by activated protein C (APC), leading to a prothrombotic state. This means that the body is unable to effectively break down blood clots, leading to an increased risk of deep vein thrombosis (DVT) which appears as swelling and pain in the leg, as described in this patient.

Question 94

A low fibrinogen level is the major criteria determining the use of cryoprecipitate in bleeding

Question 95

Granulocytes at different stages of maturation

Answer 95

CML The blood film would show granulocytes at varying maturation stages (myeloblasts to mature neutrophils), reflecting dysregulated myeloid proliferation from the BCR-ABL fusion gene. The splenomegaly results from extramedullary haematopoiesis, typical of CML.

Question 97

Monoclonal IgM paraproteinemia

Answer 97

Waldenstrom's macroglobulinaemia

Question 98

Cytogenetic analysis is the most important prognostic factor in acute myeloid leukaemia (AML).

Answer 98

Specific chromosomal abnormalities are strongly associated with treatment outcomes and survival rates. For example, t(8;21), inv(16), and t(15;17) are associated with favourable prognosis, while complex karyotype, monosomy 5 or 7, and 11q23 abnormalities indicate poor prognosis.

Question 99

Haemophilia A RX

Answer 99

Cryoprecipitate → fibrinogen and factor VIII

Question 100

PCRV : 5-15% chance of progressing to AML ( Increased risk on giving chemo)

Question 101

Causes post-infection e.g. urinary, gastrointestinal pregnancy drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir tumours SLE HIV

Answer 101

TTP

Question 102

β2M is a small protein that forms part of the MHC class I molecule and is present on the surface of all nucleated cells.

Answer 102

In myeloma, elevated levels of β2M reflect both tumour burden and renal function, as it is normally filtered by the glomeruli and reabsorbed by the proximal tubules. Higher levels of β2M (>5.5 mg/L) are associated with poorer prognosis and shorter survival.

Question 103

T wave inversion in the right precordial leads (V1-V4) is associated with raised pulmonary pressures, of which a PE is a known cause.

Answer 103

The raised troponin is likely secondary to right heart strain.

Question 104

CLL Ix

Answer 104

blood film: smudge cells (also known as smear cells) immunophenotyping is the key investigation most cases can be identified using a panel of antibodies specific for CD5, CD19, CD20 and CD23

Question 105

Third-generation combined oral contraceptives (containing gestodene or desogestrel) actually have a higher risk of VTE compared to second-generation ones (containing levonorgestrel).

Question 106

Bony lesions with no Organomegally: Myeloma Organomegally with no bony lesions: Waldenstrom’s

Answer 106

MGUS criteria (1) A monoclonal paraprotein band less than 30 g/l (< 3g/dl); (2) Plasma cells less than 10% on bone marrow examination; (3) No evidence of bone lesions, anemia, hypercalcemia, or chronic kidney disease related to the paraprotein, and (4) No evidence of another B-cell proliferative disorder.

Question 107

we aren't treating with FCR in patient's with CLL, who are asymptomatic and non-progressive, in accordance with NICE guidelines on watchful waiting. The potential risks associated with FCR therapy further support this approach.

Question 108

Golgi adds mannose-6-phosphate to proteins for trafficking to lysosomes