Haematology/Oncology Flashcards

Question

Why must Vitamin B12 be replaced before folate?

Answer 1

Prevent precipitation of subacute degeneration of the spinal cord.

Answer 2

- Anaemia - Reticulocytosis - Low haptopglobins - Raised LDH and indirect bilirubin - Blood film: spherocytes and reticulocytes - Positive direct antiglobulin test (coomb's test).

Answer 3

- Most common type - Haemolysis best at body temp - Antibody usually IgG - Haemolysis at extravascular sites e.g. spleen

Answer 4

- Antibody usually IgM - Haemolysis best at 4 degrees Celsius - Haemolysis mediated by complement and usually intravascular - Raynaud's and acrocyanosis may be sx.

Answer 5

- Neoplasia: lymphoma, CLL - Autoimmune: SLE - Idiopathic - Drugs e.g. methyldopa

Answer 6

- Neoplasia: lymphoma - Infection: mycoplasma, EBV

Answer 7

- Treat underlying disorder - Steroid (+/- rituximab) 1st line - Cold AIHA responds less well to steroids.

Answer 8

Autosomal recessive condition that results in synthesis of abnormal haemoglobin chains termed HbS. More common in Afro-Carribean descent. Sx don't tend to develop until 4-6months when HbSS takes over from metal haemoglobin.

Answer 9

HbAA = normal haemoglobin HbAS = sickle cell trait HbSS = sickle cell disease HbSC = milder form of sickle cell disease

Answer 10

Polar amino acid glutamate is switched for non-polar valine in each of the 2 beta chains (codon 6). This decreases the water solubility of deoxygenated haemoglobin. Deoxygenated Hb polymerise to cause RBCs to sickle. (present shaped).

Answer 11

Haemoglobin electrophoresis

Answer 12

- Hydroxyurea - increased HbF levels to prevent painful crises occurring. - Pneumococcal polysaccharide vaccine every 5 years.

Answer 13

- Thrombotic - Acute chest syndrome - Anaemic (aplastic, sequestration) - Infection

Answer 14

- Vaso-occlusive, painful - Can be precipitated by infection - clinical dx - infarcts in various organs and bone e.g. AVN of hip, brain, lungs, spleen, hand-foot syndrome in children.

Answer 15

- Infarction of lung parenchyma - Sx: dyspnoea, low pO2, chest pain, pulmonary infiltrates on CXR - Mx: analgesia, O2, antibiotics, transfusion to improve oxygenation - most common cause of death after childhood

Answer 16

- Infection with parvovirus - Sudden drop in Hb - Bone marrow suppression causes decreased reticulocyte count

Answer 17

- Sickling within organs e.g. spleen, lungs - This leads to blood pooling which worsens anaemia - Raised reticulocyte count

Answer 18

Exchange transfusion

Answer 19

Red cells fail to completely form haem within mitochondria, leading to iron deposits in mitochondria that form a ring round the nucleus (ring sideroblast). Congenital or acquired.

Answer 20

Delta-aminolevulinate synthase-2 deficiency

Answer 21

Alcohol Myelodysplasia Lead Anti-TB medication

Answer 22

- FBC: hypochromic, microcytic anaemia (more so in congenital). - Iron studies: Raised ferritin, raised iron, raised transferrin saturation - Blood film: basophilic stippling of RBCs - Bone marrow: Prussian blue staining shows ring sideroblasts

Answer 23

Supportive Treat underlying cause Pyridoxine may help

Answer 24

Acquired disorder leading to haemolysis of haematological cells. Mainly intravascular haemolysis Increased sensitivity of cell membranes to complement due to a lack of glycosyl-phosphatidylinositol. More prone to venous thrombosis due to a lack of CD59 on platelet membranes predisposing to aggregation.

Answer 25

- haemolytic anaemia - pancytopenia - Haemoglobinuria (dark coloured urine most often in morning) - Thrombosis (e.g. Bidd-Chiari syndrome) - Aplastic anaemia

Answer 26

Gold standard = Flow cytometry of blood to detect low levels of CD59 and CD55. Ham's test: acid induced haemolysis (normal RBCs would not).

Answer 27

- Blood product replacement - Anticoagulation - Eculizumab (directed agains terminal protein C5) being trialled - Stem cell transplantation.

Answer 28

- Viral: HIV, EBV, Hepatitis - Haematological malignancy: myelodysplastic malignancy, aplastic anaemia - Drugs: cytotoxic, carbimazole, clozapine - Benign ethnic neutropenia - Rheumatological conditions - SLE - Severe sepsis - Haemodialysis

Answer 29

- Asthma - Churg- Strauss - Loffler's syndrome - Allergic bronchopulmonary aspergillosis - tropical pulmonary eosinophilia - eosinophilic pneumonia - Hypersosinophilic syndrome

Answer 30

- Schistosomiasis - Nematodes: toxocara, ascaris, strongyloids - cestodes: echinococcus

Answer 31

- Drugs: sulfasalazine, nitrofurantoin - Psoriasis, eczema - Eosinophilic leukaemia

Answer 32

Common complication of cancer therapy, usually chemo. Neutrophil count <0.5 x10(9) + temp >38 or clinical features of sepsis. Usually occurs 7-14days post chemo.

Answer 33

Coagulase negative, gram positive bacteria, usually staph epidermidis (indwelling lines in chemo patients).

Answer 34

Fluoroquinolone

Answer 35

- Early empirical antibiotics - don't wait for WBC. - 1st line Tazocin - 2nd line Meropenem +/- vancomycin - Test for fungal infections if not better by 4-6 days - G-CSF in selected patients.

Answer 36

- Malignancy of lymphoid cells that affect B and T cell lineage. - Arresting of lymphoid cell maturation and proliferation of lymphoblasts (immature cells). - Results in bone marrow and tissue infiltration - Most common childhood cancer - 2-5years peak incidence - 80% of childhood leukaemia

Answer 37

- French-American-British (FAB) L1 type - Common ALL - pre-B phenotype - Low initial WBC - del(9p)

Answer 38

- FAB L3 type - T or B cell surface markers - Philadelphia translocation, t(9;22) - Age <2 or >10yrs - High initial WBC - Males - CNS involvement - Non Caucasian

Answer 39

- Malignancy associated with the Philadelphia chromosome. - Translocation between long arm of chromosome 9 and chromosome 22 (t(9;22)(q34;q11)). - ABL proto-oncogene on 9 fuses with BCR gene on 22 creating fusion protein that increases activity of tyrosine kinase. - 60-70yrs

Answer 40

- Anaemia; lethargy - Weight loss and sweating - Marked splenomegaly - abdo discomfort - Increase in granulocytes of different maturation levels +/- thrombocytosis - Reduced leukocyte alanine phosphatase - May undergo blast transformation (AML in 80% and ALL in 20%)

Answer 41

- 1st line = Imatinib ( tyrosine kinase inhibitor) - Hydroxyurea - Interferon-alpha - Allogenic bone marrow transplant

Answer 42

Monoclonal proliferation of well differentiated lymphocytes, almost always B cells (99%). Most common leukaemia in adults

Answer 43

- may be asymptomatic - Constitutional: weight loss, anorexia - bleeding - infection - lymphadenopathy

Answer 44

- FBC: * lymphocytosis * anaemia (bone marrow replacement or AIHA) * thrombocytopenia (bone marrow replacement or ITP) - Blood film: smudge cells (smear cells) - Immunotyping is key ix, uses panel of antibodies for CD5, CD19, CD20, CD23

Answer 45

- Progressive marrow failure (worsening anaemia/thrombocytopenia) - massive (>10cm) or progressive lymphadenopathy - massive (>6cm) or progressive splenomegaly - progressive lymphocytosis (>50% in 2 months or doubled in < 6months) - Systemic sx ( wt loss >10% in prev 6 months, fever >38 for 2/52, extreme fatigue, night sweats) - Autoimmune cytopenias e.g. ITP

Answer 46

- Monitor with regular blood counts if no indication for rx. - 1st line = fludarabine + cyclophosphamide + rituximab (FCR) - 2nd line = Ibrutinib

Answer 47

- Male - >70yrs - Lymphocyte >50 - Prolymphocytes making up >10% of count - lymphocytic doubling time <12months - Increased LDH - CD38 expression positive - TP53 mutation - deletion of short arm of chromosome 17

Answer 48

Deletion of long arm of chromosome 13

Answer 49

- Anaemia - Hypogammaglobulinaemia; recurrent infections - Warm AIHA - Transformation to high grade lymphoma

Answer 50

Complication of CLL Leukaemia cells enter lymph node and switch to high grade, fast growing non-Hodgkin's lymphoma Become unwell very quickly. - Lymph node swelling - fever without infection - weight loss - night sweats - nausea - abdominal pain

Answer 51

High grade B cell neoplasm - 2 forms: endemic (African) form in mandible/maxilla or sporadic form with abdominal tumours, more common in those with HIV. - c-myc gene translocation t(8;14)

Answer 52

EBV More strongly associated with African form than sporadic.

Answer 53

- 'Starry sky' appearance - Lymphocyte sheets interspersed with macrophage containing dead apoptotic tumour cells

Answer 54

- Chemotherapy (often induces tumour lysis syndrome (TLS)) - Rasburicase often given before chemo to prevent TLS.

Answer 55

- Hyperkalaemia - Hyperphosphataemia - Hypocalcaemia - Hyperuricaemia - Acute renal failure

Answer 56

Malignant proliferation of lymphocytes characterised by the presence of Reed-Sternberg cell. Bimodal presentation - common in 3rd and 7th decade.

Answer 57

- Lymphadenopathy: (neck>axillary>inguinal), usually painless, non-tender, asymmetrical. ETOH induced lymph node pain <10% patients. - Systemic B sx: night sweats, fever, pruritus, wt loss - Mediastinal mass

Answer 58

- normocytic anaemia (hypersplenism, bone marrow replacement, Coomb's test positive haemolytic anaemia) - Eosinophilia (caused by production of cytokines e.g. IL5) - Increased LDH - Lymph node biopsy (Reed-Sternberg cells are diagnostic.

Answer 59

Diagnostic for Hodgkin's Lymphoma - Large cells that are either multi-nucleated or have a bilobed nucleus with prominent eosinophilic inclusion like nucleoli - 'Owl's eye appearance'.

Answer 60

- Nodular sclerosing - 70%, good prognosis, F>M, lacunar cells. - Mixed cellularity - 20%, good prognosis, large number of Redd-Sternberg cells. - Lymphocyte prodominant - 5%, best prognosis - Lymphocyte depleted - rare, worst prognosis

Answer 61

- B symptoms (fever>38, wt loss >10% in last 6/12, night sweats) - >45yrs - Stage IV disease - Hb <105 - Lymphocyte count <600/ul or <8% - male - albumin <40 - WBC >15000/ul

Answer 62

- Ann Arbour staging - Lugano Classification

Answer 63

- Chemotherapy: * ABVD (doxorubicin + bleomycin + vinblastine + dacarbazine) is standard regime. * BEACOPP (bleomycin + etoposide + doxorubicin + cyclophosphamide + vincristine + procarbazine + prednisolone) better remission but increased toxicity. - Radiotherapy - Combination therapy (chemo + radio) - Hematopoietic cell transplantation (used in refractory/relapsed classic Hodgkin Lymphoma)

Answer 64

Secondary malignancy especially solid tumours e.g. lung and breast.

Answer 65

- Type of B cell lymphoma - Translocation of t(11;14) causing an over expression of cyclin D1 (BCL-1) gene. - CD5+, CD19+, CD22+, CD23-, CD10- all associated - widespread lymphadenopathy - poor prognosis

Answer 66

- Malignant proliferation of lymphocytes - Encompasses all other types of lymphoma that are not Hodgkin's Lymphoma. - 6th most common cancer in UK - Can affect B or T cells - Elderly typically affected - M>FW - Low grade better prognosis - High grade worse prognosis but higher cure rate

Answer 67

- Elderly - Caucasians - Hx of viral infection - Family hx - Chemical agents (pesticides, solvents) - Hx of chemo or radiotherapy - Immunodeficiency (HIV, transplant, diabetes) - Autoimmune disease ( SLE, Sjogren's, coeliac)

Answer 68

- Painless lymphadenopathy (non-tender, rubbery, asymmetrical) - B sx (develop later than in Hodgkin's) - Extranodal disease (more common than in Hodgkin's) - testicular mass - hepatomegaly, splenomegaly

Answer 69

- Excisional node biopsy is diagnostic - CT CAP for staging - HIV testing - FBC and blood film - ESR (useful prognostic indicator) - Ix relevant to extranodal sx.

Answer 70

Lugano Classification

Answer 71

- Dependent on subtype - Rituximab used in combination with conventional chemo regimes in a lot of NHL (must screen for Hep B first as may reactivate)

Answer 72

- Bone marrow infiltration - Superior vena cava obstruction - Metastasis - Spinal cord compression - Complications secondary to rx.

Answer 73

Rare malignant proliferation disorder of B cells M>F - pancytopenia - splenomegaly - skin vasculitis in 1/3 patients - 'dry tap' despite bone marrow hypercellularity - tartrate resistant acid phosphotase (TRAP) stain positive

Answer 74

- chemotherapy is first-line: cladribine, pentostatin - immunotherapy is second-line: rituximab, interferon-alpha

Answer 75

Immune-mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex. More chronic in adults, acute in children often following infection.

Answer 76

- symptomatic patients: * petechiae, purpura * bleeding (e.g. epistaxis) * catastrophic bleeding (e.g. intracranial) is not a common presentation - may be incidental on blood tests

Answer 77

- full blood count: isolated thrombocytopenia - blood film - bone marrow examination is no longer used routinely - antiplatelet antibody testing has poor sensitivity and doesn't affect clinical management so is not commonly done

Answer 78

- 1st line: oral prednisolone - pooled normal human immunoglobulin (IVIG) may also be used (raises the platelet count quicker than steroids, therefore may be used if active bleeding or an urgent invasive procedure is required) - splenectomy is now less commonly used

Answer 79

ITP in association with autoimmune haemolytic anaemia

Answer 80

- typically peripheral - most common type of lung cancer in non-smokers, although the majority of patients who develop lung adenocarcinoma are smokers

Answer 81

- typically peripheral - anaplastic, poorly differentiated tumours with a poor prognosis - may secrete β-hCG

Answer 82

- typically central - associated with parathyroid hormone-related protein (PTHrP) secretion → hypercalcaemia - strongly associated with finger clubbing - cavitating lesions are more common than other types - hypertrophic pulmonary osteoarthropathy (HPOA)

Answer 83

Primary immunodeficiency disorder characterised by a defect in B-cell function, leading to impaired production of immunoglobulins.

Answer 84

- Low antibody levels, specifically in immunoglobulin (Ig) types IgG, IgM and IgA. - Recurrent chest infections. - May also predispose to autoimmune disorders and lymphoma

Answer 85

- Autosomal dominant condition associated with low plasma levels of the C1 inhibitor (C1-INH, C1 esterase inhibitor) protein. - C1-INH is a multifunctional serine protease inhibitor - the probable mechanism behind attacks is uncontrolled release of bradykinin resulting in oedema of tissues.

Answer 86

- C1-INH level is low during an attack - low C2 and C4 levels are seen, even between attacks. Serum C4 is the most reliable and widely used screening tool

Answer 87

- attacks may be proceeded by painful macular rash - painless, non-pruritic swelling of subcutaneous/submucosal tissues - may affect upper airways, skin or abdominal organs (can occasionally present as abdominal pain due to visceral oedema) - urticaria is not usually a feature

Answer 88

- HAE does not respond to adrenaline, antihistamines, or glucocorticoids - IV C1-inhibitor concentrate, fresh frozen plasma (FFP) if this is not available - prophylaxis: anabolic steroid Danazol may help

Answer 89

- myelofibrosis - leukaemoid reactions - polycythaemia rubra vera - infections - steroids, Cushing's syndrome - pregnancy, oral contraceptive pill

Answer 90

- chronic myeloid leukaemia - pernicious anaemia - paroxysmal nocturnal haemoglobinuria - infectious mononucleosis

Answer 91

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

Answer 92

t(14;18) translocation causes increased BCL-2 transcription

Answer 93

Factor V Leiden (activated protein C resistance) is the most common inherited thrombophilia. Mutation in the Factor V Leiden protein resulting in activated factor V (a clotting factor) is inactivated 10 times more slowly by activated protein C than normal. Heterozygotes have a 4-5 fold risk of VTE Homozygotes have a 10 fold risk of VTE

Answer 94

- Abnormally large and sticky multimers of von Willebrand's factor cause platelets to clump within vessels - deficiency of ADAMTS13 (a metalloprotease enzyme) which breakdowns ('cleaves') large multimers of von Willebrand's factor - overlaps with haemolytic uraemic syndrome (HUS)

Answer 95

- rare, typically adult females - fever - fluctuating neuro signs (microemboli) - microangiopathic haemolytic anaemia - thrombocytopenia - renal failure

Answer 96

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

Answer 97

- no antibiotics - may worsen outcome - 1st line: plasma exchange is the treatment of choice - steroids, immunosuppressants - vincristine

Answer 98

- 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. - Peak incidence in the sixth decade - hyperviscosity, pruritus and splenomegaly.

Answer 99

- aspirin (reduces the risk of thrombotic events) - venesection (first-line treatment to keep the haemoglobin in the normal range) - chemotherapy * hydroxyurea - slight increased risk of secondary leukaemia * phosphorus-32 therapy

Answer 100

- Oxygen therapy to maintain saturations > 95% - Intravenous fluids to ensure euvolaemia - Adequate pain relief - Incentive spirometry in all patients presenting with rib or chest pain - Antibiotics with cover for atypical organisms - Early consultation with the critical care team and haematology

Answer 101

- Carried on chromosome 17 (BRCA 1) and Chromosome 13 (BRCA 2) - Linked to developing breast cancer (60%) risk. - Associated risk of developing ovarian cancer (55% with BRCA 1 and 25% with BRCA 2). - BRCA2 mutation is associated with prostate cancer in men

Answer 102

- Chronic granulomatous disease - Chediak-Higashi syndrome - Leukocyte adhesion deficiency

Answer 103

- Neutrophil primary immunodeficiency - Lack of NADPH oxidase reduces ability of -phagocytes to produce reactive oxygen species - causes recurrent pneumonias and abscesses, particularly due to catalase-positive bacteria (e.g. Staphylococcus aureus and fungi (e.g. Aspergillus) - Negative nitroblue-tetrazolium test - Abnormal dihydrorhodamine flow cytometry test

Answer 104

- Neutrophil primary immunodeficiency - Microtubule polymerization defect which leads to a decrease in phagocytosis - Affected children have 'partial albinism' and peripheral neuropathy. - Recurrent bacterial infections are seen - Giant granules in neutrophils and platelets

Answer 105

- Neutrophil primary deficiency - Defect of LFA-1 integrin (CD18) protein on neutrophils - Recurrent bacterial infections. - Delay in umbilical cord sloughing may be seen - Absence of neutrophils/pus at sites of infection

Answer 106

- Common variable immunodeficiency - Bruton's (x-linked) congenital agammaglobulinaemia - Selective immunoglobulin A deficiency

Answer 107

- B cell disorder - Low antibody levels, specifically in immunoglobulin (Ig) types IgG, IgM and IgA. - Recurrent chest infections. - May also predispose to autoimmune disorders and lymphona

Answer 108

- Defect in Bruton's tyrosine kinase (BTK) gene that leads to a severe block in B cell development - X-linked recessive. - Recurrent bacterial infections are seen - Absence of B-cells with reduced immunoglogulins of all classes

Answer 109

- Maturation defect in B cells - Most common primary antibody deficiency. - Recurrent sinus and respiratory infections - Associated with coeliac disease and may cause false negative coeliac antibody screen - Severe reactions to blood transfusions may occur (anti-IgA antibodies → anaphylaxis)

Answer 110

Di-George syndrome

Answer 111

- T cell disorder - 22q11.2 deletion, failure to develop 3rd and 4th pharyngeal pouches - Common features include congenital heart disease (e.g. tetralogy of Fallot), learning difficulties, hypocalcaemia, recurrent viral/fungal diseases, cleft palate

Answer 112

- Severe combined immunodeficiency - Ataxic telangiectasia - Wiskott-Aldrich syndrome - Hyper IgM Syndromes

Answer 113

- Many varying causes. Most common (X-linked) due to defect in the common gamma chain, a protein used in the receptors for IL-2 and other interleukins. Other causes include adenosine deaminase deficiency - Recurrent infections due to viruses, bacteria and fungi. - Reduced T-cell receptor excision circles - Stem cell transplantation may be successful

Answer 114

- Defect in DNA repair enzymes - Autosomal recessive. - Features include cerebellar ataxia, telangiectasia (spider angiomas), recurrent chest infections and 10% risk of developing malignancy, lymphoma or leukaemia

Answer 115

- Defect in WASP gene - X-linked recessive. - Features include recurrent bacterial infections, eczema, thrombocytopaenia. - Low IgM levels - Increased risk of autoimmune disorders and malignancy

Answer 116

- Mutations in the CD40 gene - Infection/Pneumocystis pneumonia, hepatitis, diarrhoea

Answer 117

- M3 Subtype of AML. - t(15;17) translocation which causes fusion of the PML and RAR-alpha genes. - presents younger than other types of AML (average = 25 years old) - DIC or thrombocytopenia often at presentation - good prognosis

Answer 118

- all-trans retinoic acid (ATRA) to force immature granulocytes into maturation to resolve a blast crisis prior to more definitive chemotherapy.

Answer 119

Perl's stain

Answer 120

- Potentially deadly condition related to the treatment of high-grade lymphomas and leukaemias. Usually induced post chemotherapy. - breakdown of the tumour cells and the subsequent release of chemicals from the cell. - high potassium and high phosphate level in the presence of a low calcium - acute kidney injury in the presence of a high phosphate and high uric acid level should raise suspicion.

Answer 121

- IV fluids - allopurinol or rasburicase * rasburicase: recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin. Allantoin is much more water-soluble than uric acid and is, therefore, more easily excreted by the kidneys, preferred now for patients at a higher risk of developing TLS * allopurinol: generally used for patients in lower-risk groups - rasburicase and allopurinol should not be given together in the management of tumour lysis syndrome as this reduces the effect of rasburicase

Answer 122

- presence of immature cells such as myeloblasts, promyelocytes and nucleated red cells in the peripheral blood. - may be due to infiltration of the bone marrow causing the immature cells to be 'pushed out' or sudden demand for new cells

Answer 123

- severe infection - severe haemolysis - massive haemorrhage - metastatic cancer with bone marrow infiltration

Answer 124

- high leucocyte alkaline phosphatase score - toxic granulation (Dohle bodies) in the white cells - 'left shift' of neutrophils i.e. three or fewer segments of the nucleus

Answer 125

- defective ferrochelatase and ALA dehydratase function. -abdominal pain - peripheral neuropathy (mainly motor) - neuropsychiatric features - fatigue - constipation - blue lines on gum margin (only 20% of adult patients, very rare in children)

Answer 126

- blood lead level is usually used for diagnosis. Levels greater than 10 mcg/dl are considered significant - microcytic anaemia. - Blood film shows red cell abnormalities including basophilic stippling and clover-leaf morphology - raised serum and urine levels of delta aminolaevulinic acid may be seen making it sometimes difficult to differentiate from acute intermittent porphyria - urinary coproporphyrin is also increased (urinary porphobilinogen and uroporphyrin levels are normal to slightly increased) - in children, lead can accumulate in the metaphysis of the bones although x-rays are not part of the standard work-up

Answer 127

- dimercaptosuccinic acid (DMSA) - D-penicillamine - EDTA - dimercaprol

Answer 128

Breast cancer

Answer 129

Pancreatic

Answer 130

Melanoma Schwannoma

Answer 131

Small cell lung carcinoma Gastric cancer Neuroblastoma

Answer 132

Paraproteinaemia and is often mistaken for myeloma. Benign. Around 10% of patients eventually develop myeloma at 10 years, with 50% at 15 years

Answer 133

- Non-IgM MGUS * most common * may progress to multiple myeloma or AL amyloidosis - IgM MGUS * may progress to Waldenström macroglobulinaemia or lymphoma - Light chain MGUS * increased risk of renal disease or AL amyloidosis

Answer 134

- usually asymptomatic - no bone pain or increased risk of infections - around 10-30% of patients have a demyelinating neuropathy

Answer 135

- 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)

Answer 136

- dehydration - stress: Gaisbock syndrome - Polycythemia vera - COPD - altitude - obstructive sleep apnoea - excessive erythropoietin: cerebellar haemangioma, hypernephroma, hepatoma, uterine fibroids

Answer 137

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red blood cell enzyme defect. - More common in people from the Mediterranean and Africa - X-linked recessive - Many drugs can precipitate a crisis as well as infections and broad (fava) beans

Answer 138

↓ G6PD → ↓ reduced NADPH → ↓ reduced glutathione → increased red cell susceptibility to oxidative stress

Answer 139

- neonatal jaundice is often seen - intravascular haemolysis - gallstones are common - splenomegaly may be present - Heinz bodies on blood films. Bite and blister cells may also be seen

Answer 140

G6PD enzyme assay - levels should be checked around 3 months after an acute episode of hemolysis, RBCs with the most severely reduced G6PD activity will have hemolysed → reduced G6PD activity → not be measured in the assay → false negative results

Answer 141

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

Answer 142

- Reactive: platelets are an acute phase reactant - platelet count can increase in response to stress such as a severe infection, surgery. Iron deficiency anaemia can also cause a reactive thrombocytosis - Malignancy - Essential thrombocytosis - myeloproliferative disorder e.g. chronic myeloid leukaemia or polycythaemia rubra vera - hyposplenism

Answer 143

Myeloproliferative disorders which overlaps with chronic myeloid leukaemia, polycythaemia rubra vera and myelofibrosis. Megakaryocyte proliferation results in an overproduction of platelets.

Answer 144

- platelet count > 600 * 109/l - both thrombosis (venous or arterial) and haemorrhage can be seen - a characteristic symptom is a burning sensation in the hands - a JAK2 mutation is found in around 50% of patients

Answer 145

- hydroxyurea (hydroxycarbamide) is widely used to reduce the platelet count - interferon-α is also used in younger patients - low-dose aspirin may be used to reduce the thrombotic risk

Answer 146

Abnormality in enzymes responsible for the biosynthesis of haem Results in overproduction of intermediate compounds (porphyrins)

Answer 147

- Most common hepatic porphyria - defect in uroporphyrinogen decarboxylase - may be caused by hepatocyte damage e.g. alcohol, oestrogens - classically photosensitive rash with bullae, skin fragility on face and dorsal aspect of hands - urine: elevated uroporphyrinogen and pink fluorescence of urine under Wood's lamp - manage with chloroquine

Answer 148

Autosomal codominant condition which causes an increased risk of thrombosis - venous thromboembolism - skin necrosis following the commencement of warfarin: when warfarin is first started biosynthesis of protein C is reduced. This results in a temporary procoagulant state after initially starting warfarin, normally avoided by concurrent heparin administration. Thrombosis may occur in venules leading to skin necrosis

Answer 149

Useful for food allergies and also pollen Easy to perform and inexpensive Uses histamine positive control and sterile water negative control Can be read after 15mins

Answer 150

Useful for food allergies, inhaled allergens (e.g. Pollen) and wasp/bee venom Determines the amount of IgE that reacts specifically with suspected or known allergens, for example IgE to egg protein. Results are given in grades from 0 (negative) to 6 (strongly positive) Used when skin prick tests are not suitable

Answer 151

Useful for contact dermatitis. Patches are removed 48 hours later with the results being read by a dermatologist after a further 48 hours

Answer 152

Haemoglobin which has been oxidised from Fe2+ to Fe3+. This is normally regulated by NADH methaemoglobin reductase, which transfers electrons from NADH to methaemoglobin resulting in the reduction of methaemoglobin to haemoglobin. There is tissue hypoxia as Fe3+ cannot bind oxygen, and hence the oxidation dissociation curve is moved to the left

Answer 153

Congenital: - haemoglobin chain variants: HbM, HbH - NADH methaemoglobin reductase deficiency Acquired: - drugs: sulphonamides, nitrates (including recreational nitrates e.g. amyl nitrite 'poppers'), dapsone, sodium nitroprusside, primaquine - chemicals: aniline dyes

Answer 154

- 'chocolate' cyanosis - dyspnoea, anxiety, headache - severe: acidosis, arrhythmias, seizures, coma - normal pO2 but decreased oxygen saturation

Answer 155

- NADH methaemoglobinaemia reductase deficiency: ascorbic acid - IV methylthioninium chloride (methylene blue) if acquired

Answer 156

Alpha-fetoprotein + beta-HCG

Answer 157

Aflatoxin (produced by Aspergillus)

Answer 158

Aniline dyes

Answer 159

Nitrosamines

Answer 160

Vinyl chloride