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Phase 2a Sheffield Medicine > Haematology > Flashcards

Haematology Flashcards

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1
Q

What is HIV?

A
  • HIV is a retrovirus (RNA virus) which infects CD4+ T cells, macrophages and dendritic cells of the immune system.
  • HIV-1 is the most common and virulent.
  • HIV-2 is localised to West Africa
  • There are 40 million cases worldwide.
  • 30% are women in the UK, 70% are men.
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2
Q

Name 3 ways in which HIV can be transmitted?

A
  1. Sexual:in most cases, HIV is transmitted sexually. Men who have sex with men (MSM) are at particular risk.
  2. Parenteral:via needlestick or needle sharing.
  3. Vertical:via breastfeeding or vaginal delivery.
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3
Q

What are some risk factors for HIV infection?

A
  • Regular intercourse with known HIV carrier.
    • Unprotected anal intercourse: 1% risk for the receptive partner
    • Unprotected vaginal intercourse: 0.1% - woman and 0.05% - men
    • Co-infection with a different STI: e.g. gonorrhoea increases the risk
  • Needlestick - 0.3% risk
  • Needle sharing - IV drug users
  • Blood transfusion
  • Vertical transmission
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4
Q

What are the signs of acute infection with HIV?

A

Asymptomaticorflu-like illness, characterised by:

  • Malaise
  • Fever
  • Lymphadenopathy
  • Sore throat
  • Maculopapular rash
  • Diarrhoea
  • Ulcers
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5
Q

What are the signs of clinical latency infection with HIV?

A

May be asymptomatic or present with non-AIDS defining illnesses:

  • Fever
  • Persistent lymphadenopathy
  • Opportunistic infections, e.g. thrush
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6
Q

What are the investigations for HIV?

A
  • Diagnostic combined HIV antibody and p24 antigen test: ELISAto detect antibodies against HIV-1 and HIV-2,andto detect the p24 antigen (capsid protein)
    • May give afalse negativeif less than 4 weeks post-infection as antibody production is yet to occur. P24 antigen is present prior to the HIV antibody. Negative result requires repeat testing at 12 weeks.
  • Confirmatory testing: if initial diagnostic test is positive. Either:
    • Repeat the combined HIV antibody and p24 antigen test OR
    • Western blot: detects the p24 antigen, as well as gp120 and gp41 antibodies
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7
Q

How would you monitor HIV? What is AIDS

A
  • CD4 T-cell count:indicates immune status, with CD4 < 200/mm^3 defining AIDS
  • Viral load (HIV RNA):can be used for diagnosis, and the result is often in the millions in early infection. It is used for monitoring and response to antiretroviral therapy.
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8
Q

Name some AIDS defining clinical manifestations of HIV with a CD4 count of 200-500/mm3?

A
  • Herpes Simplex -> Chronic Ulcers.
  • Pulmonary Tuberculosis Reactivation -> Haemoptysis, night sweats, weight loss.
  • Kaposi sarcoma -> Vascular proliferation of the skin.
  • Invasive cervical cancer -> increased risk of HPV infection.
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9
Q

Name some AIDS defining clinical manifestations of HIV with a CD4 count of 100-200/mm3?

A
  • Pneumocystis pneumonia -> most common cause of death.
  • Cryptosporidiosis -> red cyst visible visible during staining.
  • Histoplasmosis pneumonia -> disseminated or extrapulmonary
  • JC Virus infection -> confusion, loss of co-ordination, weakness, seizures.
  • HIV encephalopathy -> HIV associated dementia (memory problems and cognitive impairment)
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10
Q

Name some AIDS defining clinical manifestations of HIV with a CD4 count of 50-100/mm3?

A
  • Toxoplasmosis -> fever, lymphadenopathy, seizures. Parasite spread by cat faeces.
  • Oesophagitis (candida, HSV, CMV) -> odynophagia.
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11
Q

Name some AIDS defining clinical manifestations of HIV with a CD4 count of <50 /mm3?

A
  • CMV retinitis/coilitis -> visual loss/diarrhoea
  • Cryptococcal meningitis -> fever, headache, meningism
  • Mycobacterium avium complex -> cough, fever, abdominal pain, lymphadenopathy.
  • CNS lymphoma -> increased risk of EBV associated primary CNS lympoma.
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12
Q

What are some other non-AIDS defining opportunist infections?

A
  • Aspergillosis -> respiratory fungal infection
  • Hairy leucoplakia -> white hairy patch on the side of the tongue
  • Shingles -> blistering rash caused by herpes zoster.
  • Oral candidiasis -> white spots in the mouth
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13
Q

What are some complications of HIV infection and HIV therapy?

A
  • Opportunistic infections e.g. AIDS-defining illness
  • Drug side effects
  • Immune reconstitution inflammatory syndrome (IRIS):as the immune system begins to recover with ART, T cells mount an aggressive immune response against previously acquired infections, thus causing a paradoxical worsening of symptoms
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14
Q

What is the management for patients with HIV?

A
  • All patients with HIV, regardless of CD4 count, should commence antiretroviral therapy (ART): aimed atmaximally suppressingthe HIV virus,stopping the progressionof HIV disease andpreventing onward transmissionof HIV.Treatment aims to achieve a normal CD4 count and undetectable viral load. ‘Undetectable = Untransmittable’ (U=U)
  • 2 nucleoside reverse-transcriptase inhibitors (NRTI)and
  • Athird agent:usually a protease inhibitor, integrase inhibitor, or non-nucleoside reverse-transcriptase inhibitor (NNRTI)
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15
Q

What is AML?

A
  • Acute Myeloid Leukaemia involves the uncontrolled proliferation of myeloblasts.
  • The most common acute leukaemia in adults >75 years old.
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16
Q

What is the pathology behind acute promyelocytic leukaemia (M3)?

A
  • A t(15;17)translocation involves the fusion of retinoic acid receptor (RAR) with promyelocytic protein (PML), blocking maturation of myeloblasts causing promyelocyte accumulation
  • Abnormal promyelocytes release granules which can cause thrombocytopaenia and disseminated intravascular coagulation(DIC)
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17
Q

What is the pathology behind acute monocytic leukaemia (M5)?

A
  • Characterised by monoblast accumulation and usually lack Auer rods
  • Results in gum infiltration
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18
Q

What are some risk factors for AML?

A
  • Increasing age
  • Myelodysplastic syndromes
  • Myeloproliferative neoplasm
  • Down syndrome
  • Previous chemotherapy / radiation exposure
  • Benzene exposure
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19
Q

What are the signs of AML?

A
  • Pallor
  • Lymphadenopathy
  • Hepatosplenomegaly
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20
Q

What are the symptoms of AML?

A
  • Fatigue
  • Loss of appetite
  • Weight loss
  • Fever
  • Bruising and mucosal bleeding: due to thrombocytopaenia
  • Recurrent infections: due to leukopaenia
  • Pain and tenderness in the bones can occur when there’s increased cell production which causes the bone marrow to expand.
  • Abdominal fullness: due to hepatosplenomegaly
  • Localised pain in lymph nodes: due to lymphadenopathy
  • Gingival swelling: swollen gums seen in acute monocytic leukaemia
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21
Q

What are the primary investigations for AML?

A
  • FBC:leukocytosis, thrombocytopaenia and anaemia with a low reticulocyte count. Neutropenia may be present.
  • Blood film:high proportion of blast cells seen. Myeloblasts are usually seen as large cells with nuclei containing fine chromatin and prominent nucleoli, with Auer rods
  • Clotting screen:DIC
  • Bone marrow aspirate and biopsy:≥20% myeloblasts isdiagnostic
  • Cytogenetic and molecular studies:identify specific translocations, e.g. t(15;17) RAR-PML.
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22
Q

What other investigations should be considered for AML?

A
  • Lactate dehydrogenase (LDH): often raised in leukaemia but is not specific to leukaemia.
  • Lumbar puncture may be used if there is central nervous system involvement.
  • Lymph node biopsy can be used to assess lymph node involvement or investigate for lymphoma.
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23
Q

What are some differential diagnoses for AML?

A
  • Differentials for bleeding and bruising:
    • Meningococcal septicaemia
    • Vasculitis
    • Henoch-Schonlein Purpura (HSP)
    • Idiopathic Thrombocytopenia Purpura (ITP)
    • Non-accidental injury
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24
Q

What is the aim of management in leukaemia?

A

The aim of treatment is to induce clinical and haematological remission (< 5% blast cells)

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25
How would you treat AML?
- Chemotherapy: combination of  cytarabine  and an  anthracycline, such as daunorubicin - All-trans retinoic acid (ATRA; tretinoin) is added in acute promyelocytic leukaemia (APML). ATRA binds RAR on promyelocytic cells and causes the blasts to mature into neutrophils, which eventually go on to die. - Patients who are high risk may receive  stem cell transplantation for consolidation.
26
What are some complications of AML chemotherapy?
- Myelosuppression and neutropenic sepsis. - Tumour lysis syndrome. - Infections due to immunodeficiency - Neurotoxicity - Infertility - Secondary malignancy - Cardiotoxicity
27
What are some complications due to AML itself?
- Myelosuppression and neutropenic sepsis. - Disseminated intravascular coagulation (DIC) - Extramedullary involvement
28
What is the standard age of a patient who is diagnosed with AML?
AML is generally a disease of older people and is uncommon before the age of 45.
29
What is ALL?
Acute Lymphoblastic Leukemia involves the uncontrolled proliferation of lymphoblasts, most commonly of the B cell lineage.
30
What is the standard age of a patient who is diagnosed with ALL?
- ALL is the most common childhood malignancy → 75% of cases occur before 6 years old. - Bimodial age distribution → one peak at 4-5 years old and a second peak after the age of 50.
31
What are the 4 different types of B cell ALL?
- Pro B ALL - Common ALL - Precursor ALL - Mature B-ALL
32
What are the 3 different types of T cell ALL?
- Pro-T ALL - Intermediate-T ALL - Mature-T ALL
33
What are some risk factors for ALL?
- Previous chemotherapy - Radiation exposure - Down syndrome: 20-fold increased risk - Benzene exposure: painters, petroleum, rubber manufacturers - Family history: there is some evidence of genetic predisposition
34
What are the signs of ALL?
- Lymphadenopathy - Hepatosplenomegaly - Pallor - Flow murmur: due to anaemia - Parotid infilitration - Thymus enlargement in T-ALL: mass or growth in the mediastinum - Testicular swelling: due to testicular involvement - CNS involvement: e.g. meningism and cranial nerve palsies
35
What are the symptoms of ALL?
- Fatigue - Loss of appetite - Weight loss - Easy bruising, prolonged bleeding and mucosal bleeding: due to thrombocytopaenia - Recurrent infections: due to neutropoenia - Bone pain: due to bone marrow infiltration - Fever - Failure to thrive (children) - Abdominal fullness: due to hepatosplenomegaly - Localised pain in lymph nodes: due to lymphadenopathy
36
What are the primary investigations of ALL?
- FBC: lymphocytosis, thrombocytopenia and normocytic anaemia with a low reticulocyte count - Blood film: lymphoblasts - relatively small cells with coarse chromatin, which are clumped together and have small nucleoli. They have very little cytoplasm, which has glycogen granules. - Bone marrow aspiration and trephine biopsy: ≥ 20% lymphoblasts is diagnostic - Immunophenotyping - Cytogenetic and molecular studies: can identify specific translocations, e.g. t(12;21) or t(9;22)
37
What other investigations can be done for ALL?
- Lactate dehydrogenase (LDH) often raised in leukaemia but is not specific to leukaemia. - Chest X-ray: may be used to identify a mediastinal mass, e.g. thymus mass - Lumbar puncture: may be indicated to identify CNS involvement - Lymph node biopsy can be used to assess lymph node involvement or investigate for lymphoma. - CT, MRI and PET scans can be used for staging and assessing for lymphoma and other tumours.
38
What are some differential diagnoses for ALL?
- Differential diagnosis for bleeding and bruising: - Meningococcal septicaemia - Vasculitis - Henoch-Schonlein Purpura (HSP) - Idiopathic Thrombocytopenia Purpura (ITP) - Non-accidental injury
39
What is the first line pre-phase treatment for ALL?
- 5 - 7 days of treatment shortly after diagnosis - Treat with corticosteroids, with or without an additional chemotherapy agent
40
What is the first line induction treatment for ALL?
- 4 - 8 week therapy, e.g. corticosteroids, vincristine  or  doxorubicin (chemotherapy) - Imatinib can be used in addition if Philadelphia chromosome-positive - Intrathecal therapy (administration into CSF) can be used if there is CNS involvement - The aim of treatment is to induce remission, defined as < 5% blast cells in bone marrow
41
What is the first line consolidation therapy for ALL?
- Up to 1 year of high-dose chemotherapy, which is started  after  complete remission - The aim of treatment is to eliminate clinically undetectable residual leukaemia, hence preventing relapse
42
What is the first line maintenance therapy for ALL?
- 2 years  of  mercaptopurine  and  methotrexate  therapy - The aim of treatment is to eliminate minimal residual disease (leukemic cells not present on microscopy but cell surface markers still present)
43
What is the second line treatment for ALL?
Bone marrow transplantation: may be used as consolidation therapy in people at high risk of relapse, or for treating relapse when it occurs
44
What are some complications of ALL due to the chemotherapy?
- Myelosuppression and neutropenic sepsis. - Tumour lysis syndrome. - Infections due to immunodeficiency - Neurotoxicity - Infertility - Secondary malignancy - Cardiotoxicity - Stunted growth and development in children
45
What are some complications of ALL due to the disease iteself?
- Myelosuppression and neutropenic sepsis - Infertility - Extramedullary involvement: CNS, testicular, and renal involvement
46
What is CML?
Chronic Myeloid Leukemia (CML) involves the uncontrolled proliferation of partially mature myeloid cells, in particular granulocytes, within the bone marrow of the blood.
47
What is the standard age of a patient who is diagnosed with CML?
CML is generally considered a condition of the elderly, with a peak age of diagnosis between 65 and 74 years old.
48
What is the chronic phase of CML?
- Lasts may years and may be asymptomatic, or with non-specific symptoms such as fever, weight loss, and splenomegaly. - Characterised by < 10% blast cells.
49
What is the accelerated phase of CML?
It is further progression of the disease and characterised by 10-19% blast cells and > 20% basophils.
50
What is the blast crisis phase of CML?
- Terminal phase and mimics acute leukaemia. - Subtype: myeloid blast crisis (2/3) or lymphoid blast crisis (1/3). - > 20% blasts cells.
51
What are the risk factors of CML?
- Being male - Radiation exposure
52
What are the signs of CML?
- Hepatosplenomegaly - Abdominal tenderness - Pallor - Pyrexia
53
What investigations should be done for CML?
- FBC: leukocytosis, granulocytosis, anaemia with a reduced reticulocyte count, and reduced leukocyte ALP may be seen. Thrombocytosis is found in 30% of patients. - Blood film: an increase in all stages of maturing granulocytes. Precise findings depend on the disease phase (e.g. blast transformation) - Bone marrow biopsy: myeloblast infiltration in the bone marrow - Cytogenetic and molecular studies: Philadelphia chromosome t(9;22)(q34;q11) - Lactate dehydrogenase (LDH) often raised in leukaemia but is not specific to leukaemia.
54
What are the symptoms of CML?
- Fatigue - Weight loss - Fever - Night sweats - Shortness of breath - Easy bruising and bleeding, e.g. epistaxis: due to thrombocytopenia - Recurrent infections: due to leukopenia - Bone pain: due to marrow expansion - Abdominal fullness: due to hepatosplenomegaly
55
What are the differential diagnoses of CML?
- Differential diagnosis of bleeding and bruising: - Meningococcal septicaemia - Vasculitis - Henoch-Schonlein Purpura (HSP) - Idiopathic Thrombocytopenia Purpura (ITP) - Non-accidental injury
56
What is the management for CML in the chronic or accelerated phase?
- Tyrosine kinase inhibitor: imatinib is generally considered first-line - Hydroxyurea may be used prior to confirmation of the BCR–ABL1 fusion, following which patients are then switched to a tyrosine kinase inhibitor! - Tyrosine kinase inhibitor  may be combined with  interferon-alpha  if required - High dose induction  chemotherapy  and  allogeneic  stem cell transplantation  if the above fails
57
What is the management for CML in the blast phase?
- Tyrosine kinase inhibitor  plus  high dose induction  chemotherapy, followed by stem cell transplantation - Patients may have pancytopaenia requiring blood and platelet transfusion - If remission is not achieved through the above measures, death is imminent
58
What are the complications of CML secondary to chemotherapy?
- Myelosuppression and neutropenic sepsis. Management will require broad-spectrum antibiotics, such as tazocin, and isolation. - Gout - Tumour lysis syndrome - Infections due to immunodeficiency - Neurotoxicity - Infertility - Secondary malignancy - Cardiotoxicity
59
What are the complications of CML due to the disease itself?
- Myelosuppression and neutropaenic sepsis: lymphoblasts invade the bone marrow, disrupting function. - Predisposition to infection - Blast crisis: conversion to acute leukaemia and seen in the terminal phase of CML. May result in pancytopaenia
60
What is CLL?
Chronic Lymphocytic Leukemia (CLL) describes the neoplastic proliferation of mature B lympocytes.
61
What is the standard age of a patient who is diagnosed with CLL?
- Usually affects adults over 55 years old.
62
What are the risk factors for CLL?
- Age → median age of diagnosis is 70. - Family history. - Males are twice as likely to get it.
63
What are the signs of CLL?
- Lymphadenopathy - Hepatosplenomegaly: neoplastic cells invade the liver and spleen - Pallor
64
What are the symptoms for CLL?
- Fatigue - Loss of appetite - Weight loss - Fever - Easy bruising and bleeding: due to thrombocytopaenia - Recurrent infections: due to hypogammaglobulinaemia - Abdominal fullness: due to hepatosplenomegaly - Localised pain at lymph nodes: due to lymphadenopathy
65
What are the primary investigations for CLL?
- FBC: lymphocytosis - Thrombocytopaenia and anaemia may also be seen as leukaemic cells infiltrate the bone marrow - Blood film: increased number of premature lymphocytes and smudge cells (immature B cells that have broken during the smear). - Immunophenotype: CD5, CD19, CD20, CD23 - Immunoglobulins: hypogammaglobulinemia - Genetic analysis: identify chromosomal deletions, e.g. del 17p, which helps guide treatment
66
What other investigations can be done for CLL?
- Bone marrow biopsy: increased number of mature lymphocytes and few immature cells. Not necessary for a diagnosis - Lymph node biopsy: conduct if lymphadenopathy is present - Chest x-ray may show infection or mediastinal lymphadenopathy - CT, MRI and PET scans can be used for staging and assessing for lymphoma and other tumours - Coombs’ test: also known as the direct antiglobulin test (DAT). Conducted if an autoimmune haemolytic anaemia is suspected - Lactate dehydrogenase (LDH) often raised in leukaemia but is not specific to leukaemia
67
What are the differential diagnoses for CLL?
- Differential diagnosis of bleeding and bruising: - Meningococcal septicaemia - Vasculitis - Henoch-Schonlein Purpura (HSP) - Idiopathic Thrombocytopenia Purpura (ITP) - Non-accidental injury
68
What is the management for CLL during the early stages of disease?
- Monitor: blood counts and clinical examinations carried out every 3-12 months - Evidence shows chemotherapy in early-stage disease does not confer a survival advantage
69
What is the management for CLL during the active/advanced stage of disease?
- FCR: fludarabine, cyclophosphamide and rituximab are used in patients with good performance status - Chlorambucil and rituximab: used in patients with poor performance status - Other chemotherapeutic agents: tyrosine kinase inhibitors, such as ibrutinib, are considered in those with del(17p) - Allogenic stem cell transplant: considered in a specific subset of patients with a good performance status
70
What are the complications of CLL due to chemotherapy?
- Myelosuppression and neutropenic sepsis - Gout - Tumour lysis syndrome - Infections due to immunodeficiency - Neurotoxicity - Infertility - Secondary malignancy - Cardiotoxicity
71
What are the complications of CLL due to the disease itself?
- Hypogammaglobulinemia - Autoimmune haemolytic anaemia - Richter transformation
72
What is multiple myeloma?
- Myeloma describes the malignant monoclonal proliferation of plasma cells in the bone marrow, resulting in the production of various types of monoclonal proteins, most commonly immunoglobulins (usually IgG and IgA) and free light chains. - Multiple myeloma is where the myeloma affects multiple areas of the body.
73
What are the risk factors for multiple myeloma?
- Increasing age: the incidence rises steeply from around age 65 to 69 - Monoclonal gammopathy of uncertain significance (MGUS) - Smouldering myeloma - Family history - Male - Black African ethnicity - Radiation exposure
74
What are the signs of multiple myeloma?
- Pallor: due to anaemia - Signs due to amyloidosis: - Macroglossia - Carpal tunnel syndrome: Tinel’s and Phalen’s sign positive - Peripheral neuropathy
75
What are the symptoms of multiple myeloma?
- Related to hypercalcaemia: - Bones: bony pain with back pain being common - Stones: renal stones and renal colic - Abdominal groans: abdominal pain and constipation - Thrones: urinary frequency - Psychiatric overtones: confusion, depression, psychosis - Related to anaemia: - Fatigue - Related to thrombocytopaenia: - Bleeding and bruising - Related to a reduction in normal immunoglobulins: - Recurrent infections
76
What are the investigations for multiple myeloma?
- Urine electrophoresis: Bence-Jones proteins, which are immunoglobulin (monoclonal) light chains - Serum electrophoresis: paraprotein band, or ‘M’ spike (usually IgG or IgA) - Bone marrow aspirate and trephine biopsy: ≥ 10% plasma cell infiltration. - FBC and blood film: anaemia due to disrupted erythropoiesis. - U&Es: renal failure - Bone profile: hypercalcaemia and raised ALP - Beta-2-microglobulin: a higher concentration is associated with poorer prognosis - Imaging: conducted to ascertain bone marrow infiltrative lesions - MRI (first line), CT (second line) - Skeletal survey - X-Rays - raindrop skull
77
What is the diagnostic criteria for multiple myeloma?
Bone marrow plasma cells ≥ 10% (or biopsy-proven bony / extramedullary plasmacytoma) AND a myeloma-defining event: - bone marrow plasma cells >60% - >1 focal lesion on MRI - involved:uninvolved serum free light chain ratio >100. OR Evidence of end-organ damage CRAB mnemonic.
78
What is the CRAB mnemonic?
Used for end-organ damage. C - HyperCalcemia R - Renal insufficiency A - Anaemia B - Bone lesions
79
What are the differential diagnoses for multiple myeloma?
- MGUS - Smouldering myeloma - Solitary plastocytoma - Amyloidosis
80
What is the induction therapy management for multiple myeloma?
- Patients with good performance status and < 70 years: bortezomib and dexamethasone +/- thalidomide, followed by stem cell transplantation. This is followed by maintenance therapy - Patients with poor performance status and > 70 years: bortezomib, prednisolone, and melphalan (an alkylating agent)
81
What is the monitoring management for multiple myeloma?
- Repeat blood tests, including serum and urine electrophoresis, every 2-3 months - Bortezomib monotherapy is recommended first-line following a first relapse - Certain patients may be suitable for a second autologous stem cell transplant, if required
82
What other management can be given for multiple myeloma?
- Bisphosphonates: zoledronate is first-line and started on all patients to protect against bone disease - Radiotherapy: to bone lesions can improve bone pain - Orthopaedic surgery: can stabilise bones or treat fractures - Cement augmentation: involves injecting cement into vertebral fractures or lesions and can improve spine stability and pain - Anaemia may require transfusion of RBCs and erythropoietin - Venous thromboembolism prophylaxis: with aspirin or low molecular weight heparin whilst on certain chemotherapy regimes
83
What are some complications of multiple myeloma?
- Myelosuppression and neutropenic sepsis - Recurrent infections - Pancytopenia - Fatigue - AL amyloidosis - Plasmacytoma - Pathological fracture - Renal failure - Hyperviscosity - Chronic pain
84
What is PCV?
Polycythaemia Vera (PCV) is a myeloproliferative disorder characterised by neoplasia of mature myeloid cells, in particular those involved in the red cell lineage, within the bone marrow.
85
What is the JAK2 +ve criteria for PCV?
- Raised haematocrit (>0.52 in men, >0.48 in women) OR raised red cell mass (>25% above predicted) - Mutation in JAK2
86
What are the risk factors for PCV?
- Age > 40 years - Family history - Slightly more common in men
87
What are the signs of PCV?
- Splenomegaly: because the excess red blood cells buildup in the spleen, which usually helps with removing excess cells. - Conjunctival plethora (excessive redness to the conjunctiva in the eyes) - Plethoric appearance - Palmar erythema - Hypertension
88
What are the symptoms of PCV?
- Fatigue - Dizziness - Headache - Blurred vision - Increased sweating - Facial flushing - Pruritus: characteristically exacerbated by hot water, such as after a bath. This is due to the increased number of basophils and mast cells which contain histamine. - Erythromelalgia: pain, redness and swelling especially in the hands and feet
89
What are the primary investigations for PCV?
- FBC - U&Es - LFTs - ABG - Ferratin - Erythropoietin - JAK2 V617F mutation - Bone marrow biopsy
90
What are some investigations to consider if a patient is JAK2 negative for PCV?
- Red cell mass - Abdominal ultrasound - If EPO is normal or low: JAK2 exon 12 analysis and bone marrow biopsy - If EPO is high: further imaging (e.g. CT head and neck) to exclude a rare tumour - ESR - Leukocyte ALP
91
What is the management for PCV?
- Venesection (first line) - Hydroxycarbamide (hydroxyurea):  the  first-line  cytoreductive  agent - Aspirin - Ruxolitinib (JAK2 inhibitor) - Radioactive phosphorus-32 - less commonly used - Modifiable risk factors management
92
What are the complications of PCV?
- Thrombosis - Haemorrhage - Gout / Kidney stones - Leukaemia - Myelofibrosis
93
What is lymphoma?
Lymphoma is an uncontrolled myeloproliferative disorder of B cells, which can be subdivided into Hodgkin and Non-Hodgkin Lymphoma.
94
What is the difference between Hodgkin and non-Hodgkin lymphoma?
The difference is the presence of Reed-Sternberg cells in Hodgkin Lymphoma.
95
How does lymphoma differ from leukaemia?
Lymphoma differs from leukaemia in that neoplastic cells predominantly involve the lymph nodes and extra-nodal sites, unlike leukaemia which predominantly involves the bone marrow and blood.
96
What are the risk factors for Hodgkin lymphoma?
- Bimodal age distribution: 15-35 years and > 60 years - EBV infection: mixed cellularity subtype - HIV infection: lymphocyte-deplete subtype - Autoimmune conditions such as rheumatoid arthritis and sarcoidosis - Family history - Gender - Male > Female
97
What are the signs of Hodgkin lymphoma?
- Lymphadenopathy (may be cervical, axillary, or inguinal) - Painless - Hard - Rubbery - Fixed - Contiguous spread (to nearby nodes) unlike in NHL - Splenomegaly: rarer compared to NHL
98
What are the symptoms of Hodgkin lymphoma?
- B symptoms: occur in around 30% of cases - Fever - Weight loss - Night sweats - Pel-Ebstein fever: an intermittent fever every few weeks - Alcohol-induced lymph node pain - Pruritus - Dyspnoea: due to mediastinal lymphadenopathy
99
What are the investigations for suspected Hodgkin lymphoma?
- FBC - LDH - Ultrasound of lymph nodes - Excisional lymph node biopsy - Staging imaging (CXR, CT, PET) - Immunophenotyping
100
What is the management for Hodgkin lymphoma?
- Depends on stage, severity, age etc - Chemotherapy - Radiotherapy: usually administered after completing a number of cycles of chemotherapy - Rituximab: monoclonal antibody targets CD20 on lymphocytes and is used in CD20+ lymphoma, i.e. nodular lymphocyte-predominant HL (atypical). It is often used alongside chemotherapy and/or radiotherapy
101
What are some complications for Hodgkin lymphoma?
- Myelosuppression and neutropenic sepsis - Tumour lysis syndrome - Impaired immunity
102
What are the risk factors for non-Hodgkin lymphoma?
- Age: >50 years - Male - Family history - Infection: HIV, HTLV-1, EBV, H. pylori, Hep B and C - Autoimmunity: Hashimoto's thyroiditis and Sjogren’s syndrome are implicated in marginal zone lymphoma - Immunodeficiency: HIV as well as hereditary immunodeficiency syndromes, e.g. Wiskott-Aldrich syndrome - Exposure to pesticides and a specific chemical called trichloroethylene used in several industrial processes
103
What are the signs of non-Hodgkin lymphoma?
- Lymphadenopathy - Painless - Hard - Rubbery - Fixed - Non-contiguous spread unlike in HL - Splenomegaly: more common in NHL compared to HL - Extra-nodal disease: bone marrow, thyroid, salivary gland, GI tract, CNS
104
What are the symptoms of non-Hodgkin lymphoma?
- B symptoms: - Fever - Weight loss - Night sweats - Related to extra-nodal involvement: - GI tract: bowel obstruction - Bone marrow: fatigue, easy bruising, or recurrent infections - Spinal cord: weakness and a loss of sensation - usually in the legs
105
What are the primary investigations for non-Hodgkin lymphoma?
- FBC - Blood film - LDH and Uric acid - Ultrasound of lymph nodes - Excisional lymph node biopsy - Skin biopsy - Bone marrow biopsy
106
What other investigations should be considered for non-Hodgkin lymphoma?
- Staging imaging (CT, PET) - Genetic testing - Immunophenotyping
107
What is the management for non-Hodgkin lymphoma?
- Chemotherapy e.g. RCHOP, R-CVP, RCODOX-M - Radiotherapy - Rituximab: monoclonal antibody targets CD20 on lymphocytes and is used in CD20+ lymphoma - Stem cell transplant - Antibiotics, if any infection e.g. H.pylori eradication in gastric MALToma
108
What are the complications of non-Hodgkin lymphoma?
- Myelosuppression and neutropenic sepsis - Tumour lysis syndrome - Impaired immunity
109
What staging system is used for both Hodgkin and non-Hodgkin lymphoma?
The Ann Arbor staging system: Stage 1 - Involvement of a single lymph node region. Stage 2 - Involvement of two or more lymph node regions on the same side of the diaphragm. Stage 3 - Involvement of lymph node regions or structures on both sides of the diaphragm. Stage 4 - Diffuse involvement of one or more extra-lymphatic organs.
110
Define anti-phospholipid syndrome?
Antiphospholipid syndrome is the association of antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibody, and/or anti-beta2-glycoprotein I) with a variety of clinical features characterised by thromboses (arterial and venous) and pregnancy-related morbidity.
111
What are the risk factors for anti-phospholipid syndrome?
- More common in females than males - Often associated with SLE (20-30% of cases) - Age
112
What are the clinical manifestations for anti-phospholipid syndrome?
- Thrombosis - Miscarriage - Livedo-reticularis - Thrombocytopenia - Ischaemic stroke, TIA, MI - arteries - Deep vein thrombosis, Budd-chiari syndrome - veins - Valvular heart disease, migraines, epilepsy
113
What are the investigations for anti-phospholipid syndrome?
- Anticardiolipin test: detects IgG or IgM antibodies. - Lupus anticoagulant test - Anti-B2-glycoprotein I test - A persistently positive test in one or more of these tests, more than 12 weeks apart, with some of the clinical symptoms.
114
What is the management for anti-phopholipid syndrome?
- Long term warfarin to minimise thrombosis - Pregnant women: - Oral aspirin and SC heparin early on in pregnancy - Reduces chance of miscarriage but pre-eclampsia and poor fetal growth remain common - Prophylaxis: - Aspirin or Clopidogrel for people with aPL, especially those with a high IgG aPL (antiphospholipid antibody)
115
What is glandular fever?
Glandular fever (also known as infectious mononucleosis) is an infection most commonly caused by the Epstein-Barr virus (EBV), which is a human herpes virus.
116
What are the risk factors for glandular fever?
Teenagers and young adults
117
What are the symptoms of glandular fever?
- Sore throat - Fever - Anorexia - Malaise - Palatal petechiae
118
What are the signs of glandular fever?
- Lymphadenopathy - Splenomegaly - Hepatomegaly - Jaundice
119
What are the investigations for glandular fever?
- Blood film: Lymphocytosis - Heterophile antibody tests: detect non-EVB heterophile antibodies - Serology: IgM to EVB viral capsid antigen in acute infection. IgG if there is a past infection. - Reverse transcriptase viral PCR. - Consider checking LFTs
120
What are the differential diagnoses for glandular fever?
- Other viral infections - Other causes of sore throat - e.g. strep throat - Other causes of lymphadenopathy - e.g. lymphoma or solid metastatic tumour.
121
What is the management for glandular fever?
- Hospitalise if patient has: Stridor, Difficulty swallowing or dehydrated, and if there is suspect of potentially serious complication. - If not: Advise on the use of paracetamol or ibuprofen to relieve pain and fever symptoms.
122
Define tumour lysis syndrome?
A life threatening metabolic derangement that occurs when malignant cells breakdown resulting in neuro-, cardio-, and renal-complications.
123
What are the risk factors for tumour lysis syndrome?
- High tumour burden - High grade disease - Pre-existing renal impairment - Increasing age - Drugs which increase uric acid formation e.g. Alcohol
124
What are the clinical manifestations of tumour lysis syndrome?
- Nausea without vomiting - Lack of appetite - Fatigue - Dark tea-like urine - Numbness, Seizures, hallucinations - Muscles cramps and spasms - Palpitations
125
How is tumour lysis syndrome diagnosed?
Laboratory diagnosis of tumor lysis syndrome is based on having two or more abnormal lab values including hyperuricemia, hyperkalemia, hyperphosphatemia, and/or secondary hypocalcemia occurring within 3 days prior to or up to 7 days after the initiation of cytotoxic therapy for malignancy
126
What is the management for a low risk patient with tumour lysis syndrome?
Careful attention to monitoring and measurement of fluid status, labs results.
127
What is the management for a intermediate risk patient with tumour lysis syndrome?
7 days of allopurinol prophylaxis with increase hydration post initiation of treatment until risk of tumour lysis syndrome resolved (grade 2C).
128
What is the management for a high risk patient with tumour lysis syndrome?
These patients should be aggressively treated with vigorous hydration and should also be offered prophylaxis with rasburicase (grade 1B).
129
How would you treat hyperkalaemia?
Intravenous calcium gluconate.
130
How would you treat hyperphosphatemia?
Aggressive IV fluid resuscitations with maintenance of high urine output.
131
How would you treat hypocalcaemia?
Will correct without specific intervention as phosphate levels normalise.
132
How would you treat hyperuricemia?
May be addressed pharmacologically such as: xanthine oxidase inhibitors and uricosurics.
133
What is haemophilia?
- Haemophilia A and haemophilia B are inherited severe bleeding disorders. - It almost exclusively affects males due to it being an X-linked recessive disorder. - It can be either inherited or acquired.
134
What are the clinical manifestations of haemophilia?
- Abnormal bleeding: - Gums - Gastrointestinal tract - Urinary tract causing haematuria - Retroperitoneal space - Intracranial - Following procedures - Excessive bleeding - Ecchymosis: easy bruising - Spontaneous haemorrhage - Haematomas: collections of blood outside the blood vessels - Haemoarthrosis: bleeding into joint
135
What investigations should be performed for haemophilia?
- Diagnosis is based on bleeding scores, coagulation factor assays and genetic testing. - Platelets count: usually normal - Prothrombin time: tests the extrinsic and common pathway and so is normal - Activated partial thromboplastin time: tests the intrinsic and common pathways, usually prolonged
136
What are the differential diagnoses for haemophilia?
- Von Willebrand Disease: can present similarly to haemophilia - Platelet dysfunction
137
What is the management for haemophilia?
- Avoid contact sports and medicines that promote bleeding e.g. aspirin - IV infusion of deficient clotting factor (either prophylactic or in response to bleeding) - Complication: if patients initially had very low levels of the clotting factor, the immune system might mount an attack against the IV clotting factors, potentially leading to anaphylaxis - Desmopressin: to stimulate the release of von Willebrand Factor - Antifibrinolytics e.g. tranexamic acid
138
What are some complications of haemophilia?
- Bleeds into the brain are a dangerous complication: can cause a stroke or increased intracranial pressure - Hemarthrosis: can cause problems with joints
139
Define thrombocytopenia?
Thrombocytopenia describes a low platelet count. The normal platelet count is between 150 to 450 x 109/L.
140
What are the differential diagnoses for thrombocytopenia?
- Platelet concentration can fall as a result of large volume transfusions of platelet-free products - Pseudo-thrombocytopenia: clotting of platelet factors can falsely make platelet count appear low - Haemophilia A and haemophilia B - Von Willebrand Disease
141
Define ITP?
- ITP is a condition where antibodies are created against platelets. This causes an immune response against platelets, resulting in the destruction of platelets and a low platelet count. - Also known as autoimmune thrombocytopenic purpura, idiopathic thrombocytopenic purpura and primary thrombocytopenic purpura.
142
What is the difference between primary ITP and secondary ITP?
- Primary ITP: when ITP occurs by itself - Secondary ITP: triggered by another condition e.g. hepatitis C, HIV, or lupus
143
What are the clinical manifestations of ITP?
- Most of the time ITP is asymptomatic, but in severe cases it can present with: - Petechiae - Purpura (red or purple spots on the skin caused by bleeding underneath skin) - Easy bruising - Epistaxis (nose bleed) - Menorrhagia (heavy menstruation) - Gum bleeding - Major haemorrhage is rare - Splenomegaly is rare
144
What are the investigations for ITP?
- FBC diagnoses thrombocytopenia. - Blood film - mean platelet volume increased - Platelet autoantibodies in 70% of cases - Bone marrow biopsy
145
What is the management for secondary ITP?
- Treat the underlying cause.
146
What is the management for primary ITP?
- Prednisolone (steroids) - IV immunoglobulins (IgG) - Rituximab (a monoclonal antibody against B cells) - Immunosuppression (oral azathioprine) - Platelet transfusion - Additional measures such as carefully controlling blood pressure and suppressing menstrual periods are also important.
147
How should a patient with ITP be monitored?
The platelet count needs to be monitored and the patient needs education about concerning signs of bleeding such as persistent headaches and melaena and when to seek help.
148
What is TTP?
Thrombotic Thrombocytopenia Purpura, TTP, is a condition where tiny blood clots develop throughout the small vessels of the body using up platelets and causing thrombocytopenia, bleeding under the skin and other systemic issues. It affect the small vessels so it is described as a microangiopathy.
149
What are the clinical manifestations of TTP?
- Patients classically develop five symptoms: - Thrombocytopenia - Microangiopathic hemolytic anaemia - Fatigue - Fever - Renal insufficiency: which can cause haematuria and decreased urine output; and neurologic symptoms like headache and confusion. Can also present with: - Purpura - Epistaxis - Easy bruising - Headache - Abdominal pain - GI bleeding
150
What are the investigations for TTP?
- FBC: thrombocytopenia and normocytic normochromic anaemia - Blood film: schistocytes (fragmented red blood cells) - Unconjugated bilirubin: raised - Lactate dehydrogenase: raised - Haptoglobin levels: decreased, because haptoglobin binds to free haemoglobin in the circulation - U&E - Creatinine levels: may be elevated if there is kidney damage
151
What is the management for TTP?
- Plasma exchange: gets rid of the patient’s plasma along with all of the large von Willebrand factor multimers, and replaces it with new plasma - Steroids - IV methylprednisolone - Rituximab (a monoclonal antibody against B cells). - Folic acid
152
Define haemolytic uremic syndrome?
Haemolytic uremic syndrome (HUS) consists of a triad of: microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury (AKI).
153
What are the risk factors of haemolytic uremic syndrome?
- Age: most commonly < 5 years but can occur at any age, even in adults - Exposure to Escherichia coli (STEC) 0157:H7: particularly due to ingestion of undercooked meat; responsible for 90% of cases in children - Primary ‘atypical’ HUS: complement dysregulation associated with familial syndromes - Secondary ‘typical’ HUS: E. coli 0157:H7, pneumococcal infection, HIV, and other rare causes such as SLE, drugs (e.g. cyclosporin) and cancer
154
What are the signs of haemolytic uremic syndrome?
- Dehydration - Capillary refill > 2s - Tachycardic/hypotensive - Mottled skin - Pyrexia - Pallor: due to anaemia
155
What are the symptoms of haemolytic uremic syndrome?
- Bloody diarrhoea - Fever - Abdominal pain - Vomiting - Reduced urine output - Due to RBC destruction: weakness, fatigue, lethargy, possibly jaundice - Due to thrombocytopenia: easy bruising and purpura (bleeding into skin)
156
What are the investigations for haemolytic uremic syndrome?
- Haemolysis screen: - FBC: anaemia, thrombocytopenia - Blood film: schistocytes due to microangiopathic haemolysis; fragmented - LDH: raised as haemolysis releases lactate dehydrogenase (LDH) - Haptoglobin: decreased as haptoglobin binds free haemoglobin - Liver function: haemoglobin is broken down to bilirubin - Urinalysis: microscopic haematuria and proteinuria - U&Es: raised creatinine and reduced eGFR (AKI), often with associated hyperkalaemia - Stool culture: E.coli 0157:H7 - PCR Shiga toxin
157
What is the supportive management for haemolytic uremic syndrome?
- IV fluids: re-pleating fluid losses is crucial - Red cell transfusion: indicated if significant anaemia or reduced haematocrit - Dialysis: indicated if there is refractory acidosis, hyperkalaemia, fluid overload or oliguria
158
What is the second line management for haemolytic uremic syndrome?
- Antibiotics: avoid in HUS due to E.coli 0157:H7 as they can exacerbate symptoms. - Plasma exchange - Eculizumab: a C5 inhibitor monoclonal antibody
159
What are the complications of haemolytic uremic syndrome?
- Neurological: encephalopathy, seizures, and strokes are seen in up to 25% of patients - Renal: there is a significant risk of renal failure, which may require dialysis
160
What is PT/INR?
- Prothrombin Time measures the extrinsic system (factor VII) as well as factors common to both the intrinsic and extrinsic systems (factors X, V, prothrombin and fibrinogen) - International Normalised Ratio (INR) is used for patients on anticoagulants - They measure overall clotting factor synthesis/consumption
161
What is APTT?
- The activated partial thromboplastin time is equivalent to the Kaolin cephalin clotting time - Is a measure of the activity of the intrinsic pathway of coagulation (VIII, IX, XI, XII). - The normal range is 30-45 seconds.
162
What is the Thrombin Time test?
- Tests how fast fibrinogen is converted to fibrin by thrombin - If the time is prolonged, it is caused by either a synthetic issue or a consumption time: - DIC - Liver failure - Malnutrition - Abnormal fibrinolysis
163
What the Bleeding Time test?
- Assesses overall platelet function and levels - Measure of how long it take a patient to stop bleeding from a wound - Platelet specific disorders increase BT - von Willebrand’s disease - ITP - DIC - Thrombocytopaenia
164
What is VWD?
Von Willebrand disease (VWD) is the most common inherited cause of abnormal bleeding. It is usually due to a reduced quantity or reduced quality of von Willebrand factor.
165
What are the risk factors of VWD?
Family history.
166
What are the clinical manifestations of VWD?
- Easy, prolonged or heavy bleeding e.g. - Bleeding gums with brushing - Nose bleeds (epistaxis) - Heavy menstrual bleeding (menorrhagia) - Heavy bleeding during surgical operations - Easy bruising - Severe cases: - Joint bleeding - Muscle bleeding - GI bleeding
167
What are the investigations for VWD?
- Diagnosis is based on a history of abnormal bleeding, family history, bleeding assessment tools and laboratory investigations. - Platelets count: usually normal except in type IIB - Prothrombin time: tests the extrinsic and common pathway and so is normal - Activated partial thromboplastin time: tests the intrinsic and common pathways, usually prolonged - Measurement of vWF antigen - FBC
168
What is the management for VWD?
- Management is required either in response to major bleeding or trauma (to stop bleeding) or in preparation for operations (to prevent bleeding): - Desmopressin: can be used to stimulates the release of VWF or tranexamic acid. - VWF can be infused - Factor VIII is often infused along with plasma-derived VWF - Combined oral contraceptives in women
169
What is DIC?
Disseminated intravascular coagulation (DIC) is an acquired syndrome characterised by activation of coagulation pathways, resulting in formation of intravascular thrombi and depletion of platelets and coagulation factors.
170
What are the clinical manifestations of DIC?
- Patient is often acutely ill and shocked - Bleeding may occur from the mouth, nose and venepuncture sites and there may be widespread ecchymoses - Confusion - Bruising - Thrombotic events occur as a result of vessel occlusion by fibrin and platelets - any organ may be involved but the skin, brain and kidneys are most affected
171
What are the investigations for DIC?
- Diagnosis can be suggested from history e.g severe sepsis, trauma or malignancy, clinical presentation and thrombocytopenia - Platelet count: low - Fibrinogen: low - D-dimer: breakdown product of fibrin, raised - Prothrombin time: prolonged - Partial thromboplastin time: prolonged
172
What is the management for DIC?
- Treat underlying cause - Supportive measures for complications - Replacement of platelets with transfusion - Fresh Frozen Plasma (FFP) to replace the coagulation factors - Cryoprecipitate to replace fibrinogen and some coagulation factors - Red cell transfusion in patients who are bleeding - Other e.g. ventilator support
173
What is HIT?
Heparin induced thrombocytopenia (HIT) involves the development of antibodies against platelets in response to exposure to heparin.
174
What are the clinical manifestations behind HIT?
- Some patients develop life-threatening thrombotic events, which are most often venous - causing deep vein thrombosis, pulmonary embolism, or cerebral venous sinus thrombosis or less often arterial - causing limb gangrene, stroke, or myocardial infarction. - Other patients simply have thrombocytopenia on a CBC.
175
What are the investigations for HIT?
- FBC: thrombocytopenia - Check for HIT antibodies
176
What is the management for HIT?
- Stop use of heparin - Start using an alternate anticoagulant
177
What are the generic signs of anaemia?
- Pale skin - Conjunctival pallor - Tachycardia - Bounding pulse - Raised respiratory rate - Postural hypotension - Shock
178
What anaemia would you associate koilonychia (spoon shaped nails) with?
Iron deficiency anaemia.
179
What anaemia would you associate angular cheilitis with?
Iron deficiency anaemia.
180
What anaemia would you associate atrophic glossitis with?
Iron deficiency anaemia.
181
What anaemia would you associate brittle hair and nails with?
Iron deficiency anaemia.
182
What anaemia would you associate jaundice with?
Haemolytic anaemia.
183
What anaemia would you associate bone deformities with?
Thalassaemia
184
What anaemia would you associate oedema, hypertension and excoriation with?
Can indicate chronic kidney disease.
185
What anaemia would you associate pica with?
Iron deficiency anaemia.
186
Give 4 examples of microcytic anaemias?
- Iron deficiency anaemia - Alpha thalassemia - Beta thalassemia - Sideroblastic anaemia
187
Give 5 examples of haemolytic normocytic anaemias?
- Sickle cell disease - Hereditary spherocytosis - G6PD deficiency - Autoimmune haemolytic - Malaria
188
Give 3 examples of non-haemolytic normocytic anaemias?
- Chronic kidney disease - Aplastic anaemia - Anaemia of chronic disease
189
Give 2 examples of megaloblastic macrocytic anaemias?
- B12 folate deficiency anaemia - Folate deficiency anaemia
190
What is iron deficiency anaemia?
- Anaemia (low Hb) caused by iron deficiency → low iron stores. - Most common anaemia worldwide.
191
What are some reasons for iron deficiency anaemia?
- Dietary insufficiency - Loss of iron - Heavy menstruation, gastric ulcer, colon cancer. - Inadequate iron store - Chron’s disease, coeliac disease, after gastric surgery. - Increased requirements - pregnancy, growing children, adolescents.
192
What are the risk factors for iron deficiency anaemia?
- Vegetarian or vegan diet. - H. pylori infection → bacteria uses iron. - Pregnancy. - Young children and adolescents. - IBD. - Coeliac disease. - Drugs → PPIs reduce stomach acid.
193
What are the signs of iron deficiency anaemia?
- Pallor - Conjunctival pallor - Glossitis - Koilonychia (spoon-shaped nails) - Angular cheilitis (stomatitis) - Post-cricoid webs (Plummer Vinson syndrome)
194
What are the symptoms of iron deficiency anaemia?
- Fatigue - Dyspnoea - Dizziness - Headache - Nausea - Bowel disturbance - Hairloss - Pica (abnormal cravings) - Possible exacerbation of cardiovascular co-morbidities causing angina, palpitations, and intermittent claudication.
195
What are the time primary investigations for iron deficiency anaemia?
- FBC → Low Hb, low MCV, Low MCHC. - Iron studies - Serum iron - Serum ferratin → low in anaemia. - Transferrin saturation → gives an indication of the total iron in the body. Decreased in anaemia. - Total iron binding capacity → can be used as a marker for how much transferrin is in the blood. Increased in anaemia.
196
What are some other investigations for iron deficiency anaemia?
- Oesophago-gastroduodenoscopy (OGD) and a colonoscopy to look for cancer of the gastrointestinal tract: for new iron deficiency in an adult without a clear underlying cause - Bone marrow biopsy: may be required if the cause is unclear
197
What is the management for iron deficiency anaemia?
- Treat the underlying cause. - Oral iron supplementation → Ferrous sulphate or ferrous fumarate. - Black stool, diarrhoea, abdominal discomfort, constipation, nausea, constipation. - IV iron → only if oral is impossible to administer or ineffective. - Blood transfusions may be needed in severe cases.
198
What is alpha thalassemia?
- Alpha-thalassemia is a genetic disorder where there is a deficiency in the production of alpha globin genes of haemoglobin. - An autosomal recessive disease.
199
What are the risk factors for alpha thalassemia?
Common in individuals of Asian or African descent → family history.
200
What are the signs of alpha thalassemia?
- Pallor - Jaundice → unconjugated bilirubin. - Chipmunk face → compensatory extramedullary hematopoiesis in the skull causes marrow expansion. - Hepatosplenomegaly - Failure to thrive
201
What are the symptoms of alpha thalassemia?
- Shortness of breath - Palpitations - Fatigue - Swollen abdomen → hepatosplenomegaly.
202
What are the investigations for alpha thalassemia?
- Hb electrophoresis is diagnostic and is gold standard. - Blood film - FBC - DNA testing
203
What is the management for alpha thalassemia?
- Patients with alpha thalassaemia trait don't require treatment. - Regular blood transfusions - Iron chelation -> deferoxamine - Folate supplementation - Stem cell transplantation is the only curative option for those with severe disease
204
What are some complications of alpha thalassemia?
- Heart failure - Hypersplenism - Aplastic crisis - Iron overload -> haemochromatosis - Gallstones
205
What is beta thalassemia?
- Beta thalassemia is a genetic disorder where there is deficiency in the production of the beta globin chains of haemoglobin. - It is a recessive autosomal condition.
206
What are the risk factors for beta thalassemia?
Most commonly seen in Mediterranean, African, and South East Asian populations → family history.
207
What are the signs of beta thalassemia?
Beta thalassemia minor is usually asymptomatic. Patients almost always present <2 years old. - Jaundice: due to unconjugated bilirubin - Pallor: due to anaemia - Hepatosplenomegaly - Chipmunk facies: enlarged forehead and cheekbones - Failure to thrive
208
What are the symptoms of beta thalassemia?
Beta thalassemia minor is usually asymptomatic. Patients almost always present <2 years old. - Shortness of breath - Palpitations - Fatigue - Swollen abdomen - Growth retardation
209
What are the investigations for beta thalassemia?
- Hb electrophoresis is diagnostic and is gold standard. - Blood film - FBC - Skull X-ray -> shows hair on end - DNA testing
210
What is the management for beta thalassemia?
- Patients with beta thalassaemia minor don't require treatment. - Regular blood transfusions - Iron chelation -> deferoxamine - Folate supplementation - Stem cell transplantation is the only curative option for those with severe disease
211
What are some complication of beta thalassemia?
- Heart failure - Hypersplenism - Aplastic crisis - Iron overload -> haemochromatosis - Gallstones
212
What is sideroblastic anaemia?
- Sideroblastic anaemia - Sidero - Iron - Blastic - Immature - Anaemia - decrease in the number of healthy red blood cells in the body - Impaired incorporation of iron to form heme in the red blood cells.
213
What are the clinical manifestations of sideroblastic anaemia?
- Weakness - Fatigue - SOB - Chest pain with exertion - Pale skin of the arms and hands - Hepatosplenomegaly
214
What are the investigations for sideroblastic anaemia?
- Diagnosis is based upon clinical judgement and lab findings from: - FBC - Peripheral blood smear - Iron studies
215
What is the management for sideroblastic anaemia?
- Treat underlying disease. - Pyridoxine, Thiamine, and Folic acid. - Repeated transfusions for severe anaemia. - Deferoxamine as an iron chelating agent.
216
What is sickle cell disease?
Sickle cell anaemia is a recessive mutation in the beta chain of haemoglobin, resulting in the sickling of red blood cells.
217
What are the risk factors for sickle cell disease?
- 8% of black people carry the sickle cell gene. - Family history → autosomal recessive pattern. - Triggers of sickling → dehydration, acidosis, infection, hypoxia. - Pregnancy can also worsen the disease.
218
What are the chronic symptoms of sickle cell disease?
- Pain - Related to anaemia: fatigue, dizziness, palpitations. - Related to haemolysis: jaundice and gallstones.
219
What are the acute symptoms of sickle cell disease during sequestration crisis?
- RBCs sickle in the spleen, causing pooling of blood and a rapid drop in Hb and platelets - Abdominal pain secondary to massive splenomegaly, possibly with hypovolaemic shock - Autosplenectomy: repeated episodes lead to splenic infarction, fibrosis, and atrophy.
220
What are the acute symptoms of sickle cell disease during aplastic crisis?
- Infection with parvovirus B19 causes bone marrow suppression - Sudden onset pallor, fatigue, and anaemia - Differentiated from sequestration as it usually causes anaemia with reduced reticulocyte count and no splenomegaly
221
What are the acute symptoms of sickle cell disease during haemolytic crisis?
Increased rate of intravascular and extravascular haemolysis; rare
222
What are the acute symptoms of sickle cell disease during vaso-occulisve crisis?
Painful, vaso-occlusive episodes occur as RBCs sickle in various organs - Dactylitis - Avascular necrosis - Osteomyelitis - Dyspnoea - Chest pain - Hypoxia - Pulmonary infiltrates on chest X-ray - Auto-splenectomy - Stroke - Renal papillary necrosis - Priapism
223
What are the acute symptoms of sickle cell disease during acute chest crisis?
- Fever and respiratory syndromes. - New infiltrates on chest X-ray.
224
What are the primary investigations for sickle cell disease?
- Newborn screening with Guthrie heel prick - FBC - Blood film (howell-jolly bodies) - Hb electrophoresis and solubility: diagnostic investigation
225
What are the investigations for an acute crisis in sickle cell disease?
- Urinary legionella/pneumococcal antigen - Sputum culture - ABG - FBC - U&Es - LFTs - G&S and crossmatch - Blood cultures - Serology - CXR for pulmonary infiltrates - Bone X-ray
226
What is the management for sickle cell disease?
- Precipitating factors should be avoided. - Folic acid - Acute attacks - IV fluids - Analgesia - Oxygen - Antibiotics - Blood transfusion - Exchange transfusion - Penile aspiration - Oral hydroxycarbamide to reduce frequency of acute crisis - Stem cell transplantation
227
What are some complications of sickle cell disease?
- Anaemia - Death - Sickle cell crises - Splenic infarct due to micro-vascular occlusion → increased risk of infection - Poor growth - Gallstones - Chronic renal failure - Retinal disease - Iron overload - Lung damage → hypoxia → fibrosis → pulmonary hypertension
228
What is hereditary spherocytosis?
- Hereditary spherocytosis (HS) is an inherited haemolytic anaemia due to an autosomal dominant mutation in the majority of cases (75%) - It can also be due to a autosomal recessive mutation.
229
What are the risk factors for hereditary spherocytosis?
- Northern European and North American descent → Family history.
230
What are the signs of hereditary spherocytosis?
- Splenomegaly - Pallor - Jaundice - Tachycardia - Flow murmur
231
What are the symptoms of hereditary spherocytosis?
- Fatigue - Dizziness - Palpitations - RUQ pain → due to gallstones - Neonatal jaundice (50%) - Failure to thrive
232
What is the diagnostic criteria for hereditary spherocytosis?
- No further test needed if (all three must be present): - Family history of HS - Typical features - Positive lab investigations (spherocytes, raised MCHC, increase in reticulocytes)
233
What are the primary investigations for hereditary spherocytosis?
- FBC - Blood film - LFTs - Coombs test will be negative - allows you to differentiate between hereditary spherocytosis and autoimmune haemolytic anaemia.
234
What other investigations can be performed for hereditary spherocytosis?
- EMA binding test - Cryohaemolysis tests - Gel electrophoresis test of choice for atypical cases - Osmotic fragility test
235
What is the management for hereditary spherocytosis?
- Phototherapy or exchange transfusion - Blood transfusion - Splenectomy in patients >6yo
236
What are the complications of hereditary spherocytosis?
- Episodes of haemolytic crisis - Aplastic crisis - Gallstones - Bone marrow expansion
237
What is G6PD deficiency?
- A defect found in the G6PHD enzyme normally found within all cells of the body. - It is an inherited X-linked recessive pattern → usually affects males.
238
What are the risk factors for G6PD deficiency?
- Middle eastern, Mediterranean, and African populations → family history. - Fava beans - Soy products - Red wine - Infections (viral hepatitis or pneumonia) - Metabolic acidosis - Certain medications (listed on another flashcard)
239
What medications are a risk factor for G6PD deficiency?
- Primaquine (an antimalarial) - Ciprofloxacin - Nitrofurantoin - Trimethoprim - Sulfonylureas (e.g gliclazide) - Sulfasalazine and other sulphonamide drugs
240
What are the signs for G6PD deficiency?
- Jaundice - Pallor - Splenomegaly - Dark tea-like coloured urine - Heinz bodies
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What are the symptoms of G6PD deficiency?
- SOB - Fatigue - Dizziness - Headaches - Palpitations
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What are the investigations for G6PD deficiency?
- Diagnosis → G6PD enzyme assay. - Gold standard → UV spectrophotometry. - FBC: low levels of RBC, high reticulocytes - Blood film: heinz bodies and bite cells - LDH: elevated - Bilirubin: elevated - Haptoglobin: low
243
What is the management for G6PD deficiency?
- Avoid trigger of haemolysis e.g. fava beans and certain medications - In certain cases, transfusions may be needed
244
What are the complications of G6PD deficiency?
- Can be protective against malaria (upside). - Gallstones due to jaundice - Kidney damage
245
What is autoimmune haemolytic anaemia?
- Increased RBC haemolysis due to an autoimmune response to antigens on the surface of RBCs. - Leads to decreases levels of RBCs in circulation.
246
What are the signs of autoimmune haemolytic anaemia?
- Splenomegaly - Increased reticulocyte count → compensatory for decreased RBCs count. - Lactate dehydrogenase levels increase → due to spilling out of haemolysed RBCs. - Black tea-like urine - Jaundice - Haemoglobinuria - Kidney failure
247
What are the symptoms of autoimmune haemolytic anaemia?
- Bounding heart rate - SOB - Multi-organ failure - Fatigue - Pallor - Oliguria
248
What are the diagnostic investigations for autoimmune haemolytic anaemia?
- Direct coombs test - Direct antigen test
249
What is the management for autoimmune haemolytic anaemia?
- Haemoglobin < 7 → transfusion. - If warm: - Steroids - Splenectomy to decrease the levels of phagocytosis - Immunosuppressive medications - If cold: no treatment is usually required. - If severe then plasmapheresis may be required to remove IgM antibodies.
250
What are some complications of autoimmune haemolytic anaemia?
- Gallstones - Jaundice due to kidney damage.
251
What is Malaria?
Malaria is a parasitic infection caused by the protozoa of the genus Plasmodium.
252
What 5 plasmodium genus can cause malaria?
- Plasmodium falciparum - Plasmodium vivax - Plasmodium malariae - Plasmodium ovale - Plasmodium knowlesi
253
What are the signs of malaria?
- Pallor - Jaundice - Hepatosplenomegaly
254
What are the symptoms of malaria?
- Fever, sweats and rigors (occurs in spikes) - Fatigue - Headaches - Myalgia - Vomiting - SOB - Cough
255
What are the investigations for suspected malaria?
- FBC - U&E - LFTs - Malaria blood film (thick and thin) - History -> travel history - CXR, lumbar puncture - PCR
256
What is the treatment for malaria?
- Chloroquine for non-falciparum malaria - Oral quinine sulphate for falciparum - Add IV quinine dihydrochloride for severe disease
257
What are some complications of complicated malaria?
- Cerebral malaria: altered mental status, seizures and coma - Bilious malaria: diarrhoea, vomiting, jaundice and liver failure - Acute kidney injury - Pulmonary oedema - Disseminated intravascular coagulopathy (DIC) - Severe haemolytic anaemia - Multi-organ failure and death
258
What is aplastic anaemia?
- Pancytopenia → all blood cell lines are decreased due to a stem cell disorder. - Anaemia, Leukopenia, and thrombocytopenia.
259
What are the clinical manifestations of aplastic anaemia?
- Pallor - Fatigue - Palpitations - Dizziness - Headaches - Chest pain and SOB; heart works harder to compensate for low RBC count. - Recurrent infections; due to leukopenia.
260
What are the investigations for aplastic anaemia?
- FBC - Erythropoietin: may be raised - Increased bleeding time - Bone marrow biopsy
261
What is the management for aplastic anaemia?
- Removal/ treatment of causes e.g. drugs or infections - Transfusions - Stem cell transplant - Immunosuppressive treatment
262
What is B12 deficiency anaemia?
- Anaemia caused by low levels of B12 deficiency. - A type of megaloblastic anaemia.
263
What are the risk factors for B12 deficiency anaemia?
- Vegan or vegetarian diet. - Age - Most commonly due to pernicious anaemia → common among Northern Europeans - Gender → Female. - Chron’s disease → malabsorption.
264
What are the clinical manifestations of B12 deficiency anaemia?
- Pallor - Signs of neurological deficit e.g. confusion, ataxia etc - SOB - Fatigue - Palpitations - Headaches - Glossitis - CNS involvement
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What are the primary investigations for B12 deficiency anaemia?
- FBC - Blood film - Haematinics - LDH - LFTs
266
What are some other investigations for B12 deficiency anaemia?
- Bone marrow aspirate - For underlying cause: - Schillings test - Serological assessment - Gastroscopy
267
What is the management for B12 deficiency anaemia?
- Treatment of the underlying cause of B12 deficiency. - B12 supplementation e.g. oral cyanocobalamin; intramuscular hydroxocobalamin
268
What is folate deficiency anaemia?
- Anaemia caused by folate deficiency (vitamin B9). - A type of macrocytic megaloblastic anaemia. - Most commonly seen in countries where poverty and by extension malnutrition is problematic.
269
What are the risk factors for folate deficiency anaemia?
- Children - Malnutrition (Poverty) - Pregnancy - Elderly - Alcoholic - Crohns disease - Coeliac disease
270
What are the clinical manifestations of folate deficiency anaemia?
- Pallor - Fatigue - Dyspnoea - Palpitations - Headache - Glossitis - Features of pancytopenia - Symptoms of underlying cause: coeliac and Chrohns
271
What are the investigations for folate deficiency anaemia?
- FBC - Blood film - Haematinics - Serum and red cell folate - low - GI investigation
272
What is the management for folate deficiency anaemia?
- Treat underlying cause e.g. stopping drugs or alcohol consumption - Folic acid supplements: always give alongside B12, because replacement of folic acid in the presence of vitamin B12 deficiency may cause significant neurological disease. - Folate 5mg PO OP for 3 months.

Phase 2a Sheffield Medicine (10 decks)

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