Haem Flashcards
Q: How is APTT, PT, and Bleeding Time altered in Hemophilia?
A: Hemophilia: APTT is increased, PT is normal, and Bleeding Time is normal.
Q: What is the result of APTT, PT, and Bleeding Time in von Willebrand’s disease?
A: von Willebrand’s disease: APTT is increased, PT is normal, and Bleeding Time is increased.
Q: How does Vitamin K deficiency affect blood clotting tests?
A: Vitamin K deficiency: APTT is increased, PT is increased, and Bleeding Time is normal.
Q: What is the cause of Acute Intermittent Porphyria (AIP)?
A: AIP is caused by a defect in porphobilinogen deaminase, an enzyme involved in the biosynthesis of haem.
Q: What is the result of the defect in porphobilinogen deaminase in AIP?
A: The defect leads to the toxic accumulation of delta-aminolaevulinic acid and porphobilinogen.
Q: What are the classical symptoms of Acute Intermittent Porphyria (AIP)?
Abdominal symptoms: Abdominal pain, vomiting
Neurological symptoms: Motor neuropathy
Psychiatric symptoms: E.g., depression
Other common signs: Hypertension and tachycardia
Q: How can Acute Intermittent Porphyria (AIP) be diagnosed?
Urine turns deep red on standing
Raised urinary porphobilinogen (elevated between attacks and more during acute attacks)
Assay of red cells for porphobilinogen deaminase
Raised serum levels of delta-aminolaevulinic acid and porphobilinogen
Q: What is the management approach for Acute Intermittent Porphyria (AIP)?
Avoiding triggers
Acute attacks:
IV haematin or haem arginate
IV glucose (if haematin/haem arginate is not immediately available)
Q: What is the most common form of acute leukaemia in adults?
A: Acute Myeloid Leukaemia (AML) is the more common form of acute leukaemia in adults.
Q: What are the typical features of Acute Myeloid Leukaemia (AML)?
Anaemia: Pallor, lethargy, weakness
Neutropenia: High white cell count but low functioning neutrophil levels, leading to frequent infections
Thrombocytopenia: Bleeding
Splenomegaly
Bone pain
Q: What are the poor prognostic features of Acute Myeloid Leukaemia (AML)?
Age > 60 years
20% blasts after the first course of chemotherapy
Cytogenetic abnormalities: Deletions of chromosomes 5 or 7
Q: What is the specific association for Acute Promyelocytic Leukaemia (M3)?
A: Acute Promyelocytic Leukaemia (M3) is associated with the t(15;17) translocation and fusion of PML and RAR-alpha genes.
Q: At what age does Acute Promyelocytic Leukaemia (M3) typically present?
A: It typically presents in younger patients, with an average age of 25 years.
Q: What are the characteristic features of Acute Promyelocytic Leukaemia (M3)?
Auer rods (seen with myeloperoxidase stain)
DIC or thrombocytopenia often at presentation
Good prognosis
Q: What is Antiphospholipid Syndrome?
A: Antiphospholipid Syndrome is an acquired disorder characterized by a predisposition to both venous and arterial thromboses, recurrent fetal loss, and thrombocytopenia.
Q: What pregnancy complications are associated with Antiphospholipid Syndrome?
Recurrent miscarriage
Intrauterine growth restriction (IUGR)
Pre-eclampsia
Placental abruption
Pre-term delivery
Venous thromboembolism
Q: What is the management for Antiphospholipid Syndrome in pregnancy?
Low-dose aspirin should be started once pregnancy is confirmed on urine testing
Low molecular weight heparin should be started once a fetal heart is seen on ultrasound, typically discontinued at 34 weeks gestation
These interventions increase the live birth rate seven-fold
Q: What is Aplastic Anaemia characterized by?
A: Aplastic anaemia is characterized by pancytopenia and a hypoplastic bone marrow.
Q: What are the typical features of Aplastic Anaemia?
Normochromic, normocytic anaemia
Leukopenia (with lymphocytes relatively spared)
Thrombocytopenia
May present as acute lymphoblastic or myeloid leukaemia
A minority of patients may later develop paroxysmal nocturnal haemoglobinuria or myelodysplasia
Q: What are the causes of Aplastic Anaemia?
Idiopathic
Congenital: Fanconi anaemia, dyskeratosis congenita
Drugs: Cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold
Toxins: Benzene
Infections: Parvovirus, hepatitis
Radiation
Q: What are the two types of Autoimmune Haemolytic Anaemia (AIHA)?
A: AIHA can be divided into ‘warm’ and ‘cold’ types, based on the temperature at which the antibodies cause haemolysis.
Q: What is the most common cause of Autoimmune Haemolytic Anaemia (AIHA)?
A: AIHA is most commonly idiopathic but can also be secondary to a lymphoproliferative disorder, infection, or drugs.
Q: What are the general features of haemolytic anaemia?
Anaemia
Reticulocytosis
Low haptoglobin
Raised lactate dehydrogenase (LDH) and indirect bilirubin
Blood film showing spherocytes and reticulocytes
Q: What is a specific feature of Autoimmune Haemolytic Anaemia (AIHA) on investigations?
A: A positive direct antiglobulin test (Coombs’ test) is a specific feature of AIHA.
Q: What characterizes Warm AIHA?
The antibody (usually IgG) causes haemolysis best at body temperature.
Haemolysis tends to occur in extravascular sites, such as the spleen.
It is the most common type of AIHA.
Q: What are the causes of Warm AIHA?
Idiopathic
Autoimmune disease: E.g., systemic lupus erythematosus
Neoplasia: E.g., lymphoma, chronic lymphocytic leukaemia
Drugs: E.g., methyldopa
Q: What is the management for Warm AIHA?
Treatment of any underlying disorder
First-line treatment: Steroids (+/- rituximab)
Q: What characterizes Cold AIHA?
The antibody (usually IgM) causes haemolysis best at 4°C.
Haemolysis is mediated by complement and is more commonly intravascular.
Features may include Raynaud’s symptoms and acrocyanosis.
Patients tend to respond less well to steroids.
Q: What are the causes of Cold AIHA?
Neoplasia: E.g., lymphoma
Infections: E.g., mycoplasma, EBV
Q: Can systemic lupus erythematosus (SLE) be associated with Autoimmune Haemolytic Anaemia?
A: Yes, SLE can rarely be associated with a mixed-type autoimmune haemolytic anaemia.
Q: What is the underlying cause of Beta-Thalassaemia Major?
A: Beta-Thalassaemia Major is caused by the absence of beta globulin chains, located on chromosome 11.
Q: What is the pattern of hemoglobin in Beta-Thalassaemia Major?
HbA is absent
HbA2 and HbF are raised
Q: What is the primary management for Beta-Thalassaemia Major?
A: The primary management involves repeated transfusions.
Q: What is a major complication of repeated transfusions in Beta-Thalassaemia Major?
A: Repeated transfusions lead to iron overload, which can result in organ failure.
Q: How is iron overload managed in Beta-Thalassaemia Major?
A: Iron chelation therapy (e.g., desferrioxamine) is important to prevent organ failure from iron overload.
Q: What is Beta-Thalassaemia Trait?
A: Beta-Thalassaemia Trait is an autosomal recessive condition characterized by a mild hypochromic, microcytic anaemia, usually without symptoms.
Q: What type of anaemia is seen in Beta-Thalassaemia Trait?
A: Beta-Thalassaemia Trait presents with mild hypochromic, microcytic anaemia.
Q: What is the hemoglobin pattern in Beta-Thalassaemia Trait?
A: HbA2 is raised (> 3.5%) in Beta-Thalassaemia Trait.
Q: What condition(s) are associated with Target Cells?
Sickle-cell/thalassaemia
Iron-deficiency anaemia
Hyposplenism
Liver disease
Q: What blood cell abnormality is associated with Myelofibrosis?
A: ‘Tear-drop’ poikilocytes are associated with Myelofibrosis.
Q: What conditions are associated with Spherocytes?
Hereditary spherocytosis
Autoimmune hemolytic anaemia
Q: What conditions are associated with Basophilic Stippling?
Lead poisoning
Thalassaemia
Sideroblastic anaemia
Myelodysplasia
Q: What is associated with Howell-Jolly Bodies?
A: Howell-Jolly bodies are associated with hyposplenism.
Q: What conditions are associated with Heinz Bodies?
G6PD deficiency
Alpha-thalassaemia
Q: What conditions are associated with Schistocytes (‘helmet cells’)?
Intravascular haemolysis
Mechanical heart valve
Disseminated intravascular coagulation (DIC)
Q: What condition is associated with ‘Pencil’ Poikilocytes?
A: ‘Pencil’ poikilocytes are associated with Iron deficiency anaemia.
Q: What conditions are associated with Burr Cells (echinocytes)?
Uraemia
Pyruvate kinase deficiency
Q: What is associated with Acanthocytes?
A: Acanthocytes are associated with abetalipoproteinaemia.
Q: What blood film abnormality is seen in Megaloblastic anaemia?
A: Hypersegmented neutrophils are seen in megaloblastic anaemia.
Q: What are the main categories of blood product transfusion complications?
Immunological: Acute haemolytic, non-haemolytic febrile, allergic/anaphylaxis
Infective
Transfusion-related acute lung injury (TRALI)
Transfusion-associated circulatory overload (TACO)
Other: Hyperkalaemia, iron overload, clotting
Q: What causes a Non-haemolytic febrile reaction during a blood transfusion?
A: It is thought to be caused by antibodies reacting with white cell fragments in the blood product and cytokines that have leaked during storage.
Q: What are the symptoms and management of a Non-haemolytic febrile reaction?
Symptoms: Fever, chills
Management: Slow or stop the transfusion, give paracetamol, and monitor the patient.
Q: What causes a Minor allergic reaction during blood transfusion, and how is it managed?
Cause: Thought to be caused by foreign plasma proteins.
Symptoms: Pruritus, urticaria.
Management: Temporarily stop the transfusion, give antihistamine, and monitor.
Q: What is an Anaphylaxis reaction during a blood transfusion, and how should it be managed?
Cause: Can occur in patients with IgA deficiency who have anti-IgA antibodies.
Symptoms: Hypotension, dyspnoea, wheezing, angioedema.
Management: Stop the transfusion, administer IM adrenaline, ABC support, oxygen, fluids.
Q: What is an Acute haemolytic reaction and how is it managed?
Cause: ABO-incompatible blood (secondary to human error).
Symptoms: Fever, abdominal pain, hypotension.
Management: Stop the transfusion, confirm diagnosis, check identity of patient, send blood for direct Coombs’ test, supportive care, fluid resuscitation.
Q: What is Transfusion-associated circulatory overload (TACO) and how is it managed?
Cause: Excessive transfusion rate or pre-existing heart failure.
Symptoms: Pulmonary oedema, hypertension.
Management: Slow or stop the transfusion, consider IV loop diuretic (e.g., furosemide), and oxygen.
Q: What is Transfusion-related acute lung injury (TRALI) and how is it managed?
Cause: Non-cardiogenic pulmonary oedema secondary to neutrophil activation by substances in donated blood.
Symptoms: Hypoxia, pulmonary infiltrates on chest x-ray, fever, hypotension.
Management: Stop the transfusion, provide oxygen and supportive care.
Q: What are the infective risks associated with Red Blood Cells (RBCs) and Platelets?
RBCs: Primarily at risk for transmitting viral agents like HIV, HBV, and HCV.
Platelets: Stored at room temperature, increasing the risk of bacterial contamination (e.g., Staphylococcus epidermidis, Bacillus cereus), potentially leading to sepsis.
Q: How are blood transfusion complications like Acute haemolytic reaction and Non-haemolytic febrile reaction differentiated?
Acute haemolytic reaction: Caused by ABO-incompatible blood, presents quickly with fever, abdominal pain, hypotension.
Non-haemolytic febrile reaction: Thought to be caused by white cell fragments and cytokines, presents with fever and chills.
Q: What is the cause of Cytomegalovirus (CMV) transmission in blood products?
A: CMV is transmitted through leucocytes in blood products.
Q: What is the purpose of irradiated blood products?
A: Irradiated blood products are depleted of T-lymphocytes and are used to avoid transfusion-associated graft versus host disease (TA-GVHD) caused by the engraftment of viable donor T lymphocytes.
Q: At what temperature should red blood cells be stored prior to infusion?
A: Red blood cells should be stored at 4°C prior to infusion.
Q: How long is a unit of red blood cells usually transfused over in a non-urgent scenario?
A: In a non-urgent scenario, a unit of red blood cells is usually transfused over 90-120 minutes.
Q: What are the two major forms of Burkitt’s lymphoma?
Endemic (African) form, typically involving the maxilla or mandible.
Sporadic form, with abdominal (e.g., ileo-caecal) tumours being the most common, and more common in patients with HIV.
Q: What genetic abnormality is associated with Burkitt’s lymphoma?
A: Burkitt’s lymphoma is associated with the c-myc gene translocation, usually t(8:14).
Q: What virus is strongly implicated in the development of the African form of Burkitt’s lymphoma?
A: The Epstein-Barr virus (EBV) is strongly implicated in the development of the African form of Burkitt’s lymphoma, and to a lesser extent in the sporadic form.
Q: What is the characteristic microscopy finding in Burkitt’s lymphoma?
A: The characteristic microscopy finding is a ‘starry sky’ appearance, with lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells.
Q: What is the primary treatment for Burkitt’s lymphoma?
A: The primary treatment for Burkitt’s lymphoma is chemotherapy, which usually produces a rapid response.
Q: What complication can occur due to the rapid response to chemotherapy in Burkitt’s lymphoma, and how is it managed?
A: Tumour lysis syndrome can occur due to the rapid response to chemotherapy. Rasburicase, a recombinant version of urate oxidase, is often given before chemotherapy to reduce the risk of tumour lysis syndrome.
Q: What are the complications of tumour lysis syndrome?
Hyperkalaemia
Hyperphosphataemia
Hypocalcaemia
Hyperuricaemia
Acute renal failure
Q: What are some common complications of Chronic Lymphocytic Leukaemia (CLL)?
Anaemia
Hypogammaglobulinaemia leading to recurrent infections
Warm autoimmune haemolytic anaemia (10-15% of patients)
Transformation to high-grade lymphoma (Richter’s transformation)
Q: What is Richter’s transformation in Chronic Lymphocytic Leukaemia (CLL)?
A: Richter’s transformation occurs when leukaemia cells enter the lymph node and transform into a high-grade, fast-growing non-Hodgkin’s lymphoma. Patients often become unwell very suddenly.
Q: What are some symptoms that indicate Richter’s transformation in CLL?
Lymph node swelling
Fever without infection
Weight loss
Night sweats
Nausea
Abdominal pain
Q: What is the cause of Chronic Lymphocytic Leukaemia (CLL)?
A: CLL is caused by a monoclonal proliferation of well-differentiated lymphocytes, which are almost always B-cells (99%). It is the most common form of leukaemia seen in adults.
Q: What are common features of Chronic Lymphocytic Leukaemia (CLL)?
Often none: may be detected by incidental lymphocytosis
Constitutional symptoms: anorexia, weight loss
Bleeding and infections
More marked lymphadenopathy compared to chronic myeloid leukaemia (CML)
Q: What are common findings on a full blood count in Chronic Lymphocytic Leukaemia (CLL)?
Lymphocytosis
Anaemia (may be due to bone marrow replacement or autoimmune haemolytic anaemia)
Thrombocytopenia (due to bone marrow replacement or immune thrombocytopenia)
Q: What is seen on the blood film in Chronic Lymphocytic Leukaemia (CLL)?
A: The blood film in CLL typically shows smudge cells (also known as smear cells), which are fragile B-cells that are damaged during the preparation of the blood sample.
Q: What is the key investigation for Chronic Lymphocytic Leukaemia (CLL)?
A: Immunophenotyping is the key investigation. Most cases can be identified using a panel of antibodies specific for CD5, CD19, CD20, and CD23.
Q: What genetic abnormality is present in more than 95% of patients with Chronic Myeloid Leukaemia (CML)?
A: The Philadelphia chromosome, a translocation between the long arms of chromosomes 9 and 22 (t(9:22)(q34; q11)), resulting in the fusion of the ABL proto-oncogene from chromosome 9 and the BCR gene from chromosome 22, creating the BCR-ABL fusion gene.
Q: What does the BCR-ABL fusion gene produce?
A: The BCR-ABL fusion gene produces a fusion protein with excess tyrosine kinase activity, which is associated with CML.
Q: What are common symptoms of Chronic Myeloid Leukaemia (CML)?
Anaemia (leading to lethargy)
Weight loss and sweating
Splenomegaly (may cause abdominal discomfort)
Increase in granulocytes at different stages of maturation
Thrombocytosis
Decreased leukocyte alkaline phosphatase
Q: What is blast transformation in Chronic Myeloid Leukaemia (CML)?
A: Blast transformation in CML refers to the progression of the disease to a more aggressive phase, typically either Acute Myeloid Leukaemia (AML) in 80% of cases or Acute Lymphoblastic Leukaemia (ALL) in 20%.
Q: What is the first-line treatment for Chronic Myeloid Leukaemia (CML)?
A: Imatinib, a tyrosine kinase inhibitor targeting the BCR-ABL defect, is now considered first-line treatment for CML.
Q: What other treatments may be used for Chronic Myeloid Leukaemia (CML)?
Hydroxyurea
Interferon-alpha
Allogenic bone marrow transplant
Q: What is Cryoglobulinaemia?
A: Cryoglobulinaemia is a condition characterized by the reversible precipitation of immunoglobulins at 4°C, which dissolve when warmed to 37°C.
Q: How many types of Cryoglobulinaemia are there, and what are they?
Type I: Monoclonal (IgG or IgM)
Type II: Mixed monoclonal and polyclonal (usually with rheumatoid factor)
Type III: Polyclonal (usually with rheumatoid factor)
Q: What are the possible clinical features of Cryoglobulinaemia?
Raynaud’s phenomenon (only seen in Type I)
Cutaneous vascular purpura
Distal ulceration
Arthralgia
Renal involvement, such as diffuse glomerulonephritis
Q: What investigations are commonly associated with Cryoglobulinaemia?
Low complement (especially C4)
High ESR (erythrocyte sedimentation rate)
Q: What is the management for Cryoglobulinaemia?
Treatment of the underlying condition (e.g., hepatitis C)
Immunosuppression
Plasmapheresis
Q: What are the mechanisms of action for Dabigatran, Rivaroxaban, Apixaban, and Edoxaban?
Dabigatran: Direct thrombin inhibitor.
Rivaroxaban, Apixaban, and Edoxaban: Direct factor Xa inhibitors.
Q: What are the reversal agents for DOACs?
Dabigatran: Reversed by Idarucizumab.
Rivaroxaban and Apixaban: Reversed by Andexanet alfa.
Edoxaban: No authorised reversal agent; Andexanet alfa has been studied.
Q: What happens during Disseminated Intravascular Coagulation (DIC)?
A: In DIC, there is dysregulation of coagulation and fibrinolysis, leading to widespread clotting and bleeding. Coagulation factors are activated excessively, leading to clot formation, while fibrinolysis is also activated, resulting in clot breakdown and bleeding.
Q: What is the critical mediator of DIC?
A: Tissue Factor (TF) is the critical mediator of DIC. It is released from damaged vascular tissue and binds with coagulation factors to activate the extrinsic and intrinsic coagulation pathways.
Q: What are common causes of DIC?
Sepsis
Trauma
Obstetric complications (e.g., amniotic fluid embolism, HELLP syndrome)
Malignancy
Q: What are typical diagnostic findings in DIC?
↓ Platelets
↓ Fibrinogen
↑ Prothrombin Time (PT)
↑ Activated Partial Thromboplastin Time (APTT)
↑ Fibrinogen degradation products
Schistocytes (microangiopathic hemolytic anemia)
Q: How does the blood picture in DIC compare to other disorders?
DIC:
Prolonged PT, APTT, and Bleeding Time.
Low Platelet Count.
Warfarin administration:
Prolonged PT, normal APTT and Platelet count.
Aspirin administration:
Normal PT, APTT, but Prolonged Bleeding Time.
Heparin:
Often normal PT, prolonged APTT, normal Platelet count.
Q: What is Factor V Leiden?
A: Factor V Leiden is the most common inherited thrombophilia, caused by a gain-of-function mutation in the Factor V protein, resulting in resistance to inactivation by activated protein C.
Q: What is the effect of the Factor V Leiden mutation?
A: The mutation makes activated Factor V inactivated 10 times more slowly by activated protein C, which increases the risk of venous thrombosis.
Q: What type of inheritance pattern does Fanconi Anaemia follow?
A: Fanconi Anaemia is inherited in an autosomal recessive pattern.
Q: What are some haematological features of Fanconi Anaemia?
Aplastic anaemia
Increased risk of acute myeloid leukaemia (AML)
Q: What are the neurological features of Fanconi Anaemia?
A: Fanconi Anaemia can involve neurological features, but they are less specific. Further detailed features would depend on individual cases.
Q: What skeletal abnormalities are commonly seen in Fanconi Anaemia?
Short stature
Thumb/radius abnormalities
Cafe-au-lait spots
Q: What is the inheritance pattern of G6PD deficiency?
A: G6PD deficiency is inherited in an X-linked recessive fashion.
Q: What is the pathophysiology behind G6PD deficiency?
A: G6PD deficiency leads to a reduction in NADPH, which is required to convert oxidized glutathione to its reduced form, thus impairing the ability of red blood cells to protect themselves from oxidative damage, resulting in increased red cell susceptibility to oxidative stress.
Q: What are the typical clinical features of G6PD deficiency?
Neonatal jaundice
Intravascular haemolysis
Gallstones
Splenomegaly
Heinz bodies on blood films, with possible bite and blister cells
Q: How is G6PD deficiency diagnosed?
A: G6PD deficiency is diagnosed by measuring G6PD enzyme activity. However, levels should be checked around 3 months after an acute hemolysis episode, as severely reduced G6PD activity in RBCs may result in a false negative.
Q: What are some drugs that can precipitate hemolysis in patients with G6PD deficiency?
Anti-malarials (e.g., primaquine)
Ciprofloxacin
Sulph- group drugs (e.g., sulphonamides, sulfasalazine, sulfonylureas)
Q: How does G6PD deficiency compare to hereditary spherocytosis?
Q: What are the three conditions required for the diagnosis of GVHD, known as the Billingham criteria?
The transplanted tissue contains immunologically functioning cells.
The recipient and donor are immunologically different.
The recipient is immunocompromised.
Q: What are the principal risk factors for GVHD?
Poorly matched donor and recipient (especially HLA mismatch).
Type of conditioning used prior to transplantation.
Gender disparity between donor and recipient.
Graft source (bone marrow/peripheral blood is associated with higher risk than umbilical cord blood).
Q: What is the definition of acute GVHD in terms of onset and common organ involvement?
A: Acute GVHD: Onset is within 100 days of transplantation. It usually affects the skin (>80%), liver (50%), and gastrointestinal tract (50%).
Q: What are some common clinical signs and symptoms of acute GVHD?
Painful maculopapular rash (neck, palms, and soles)
Erythroderma or toxic epidermal necrolysis-like syndrome
Jaundice
Watery or bloody diarrhea
Persistent nausea and vomiting
Culture-negative fever
Q: What is the characteristic feature of chronic GVHD in terms of timing and organ involvement?
A: Chronic GVHD typically occurs after 100 days following transplantation, with more varied clinical presentations, often affecting the skin, eyes, gastrointestinal tract, and lungs.
Q: What are some clinical features of chronic GVHD?
Skin: Poikiloderma, scleroderma, vitiligo, lichen planus.
Eye: Keratoconjunctivitis sicca, corneal ulcers, scleritis.
GI: Dysphagia, odynophagia, oral ulceration, ileus.
Lung: Obstructive or restrictive lung disease.
Q: What are some investigations that can aid in the diagnosis of GVHD?
Liver Function Tests (LFTs) may show cholestatic jaundice.
Hepatitis screen and ultrasound to exclude other causes.
Abdominal imaging: May reveal air-fluid levels and small bowel thickening (“ribbon sign”).
Lung function testing.
Biopsy of affected tissue if needed for confirmation.
Q: What is the mainstay treatment for acute GVHD?
A: Intravenous steroids are the mainstay of treatment for severe acute GVHD, with extended courses of steroids often required.
Q: What is the t(9;22) translocation and what is its significance?
t(9;22) is the Philadelphia chromosome translocation.
It is present in >95% of patients with Chronic Myelogenous Leukemia (CML).
It results in the fusion of the BCR gene on chromosome 22 and the ABL gene on chromosome 9, creating the BCR-ABL fusion gene.
This fusion gene encodes a tyrosine kinase with excessive activity, contributing to the leukemogenesis.
It is a poor prognostic indicator in Acute Lymphoblastic Leukemia (ALL).
Q: What is the t(15;17) translocation and which condition is it associated with?
t(15;17) is associated with Acute Promyelocytic Leukemia (M3).
It results in the fusion of the PML and RAR-alpha genes.
This fusion is important in the pathogenesis of the disease.
Q: What is the significance of the t(8;14) translocation?
The t(8;14) translocation is seen in Burkitt’s lymphoma.
It involves the translocation of the MYC oncogene to an immunoglobulin gene.
This leads to the overexpression of MYC, contributing to tumorigenesis.
Q: What does the t(11;14) translocation indicate?
t(11;14) is seen in Mantle Cell Lymphoma.
It results in the deregulation of the Cyclin D1 (BCL-1) gene.
This leads to the overproduction of cyclin D1, which promotes cell cycle progression and contributes to malignancy.
Q: What is the t(14;18) translocation and its role in cancer?
The t(14;18) translocation is characteristic of Follicular Lymphoma.
It results in increased transcription of the BCL-2 gene.
This leads to the overexpression of BCL-2, an anti-apoptotic protein, which helps the lymphoma cells evade programmed cell death.
Q: Which virus is associated with Hodgkin’s lymphoma, Burkitt’s lymphoma, and nasopharyngeal carcinoma?
Epstein-Barr Virus (EBV) is associated with Hodgkin’s lymphoma, Burkitt’s lymphoma, and nasopharyngeal carcinoma.
Q: What condition is linked to HTLV-1 (Human T-lymphotropic virus type 1)?
HTLV-1 is linked to Adult T-cell Leukemia/Lymphoma.
Q: Which virus is associated with high-grade B-cell lymphoma?
HIV-1 is associated with high-grade B-cell lymphoma.
Q: Which bacterium is linked to gastric lymphoma (MALT)?
Helicobacter pylori is linked to gastric lymphoma, particularly MALT lymphoma.
Q: Which protozoan infection is associated with Burkitt’s lymphoma?
Malaria is associated with Burkitt’s lymphoma.
Q: What are the hereditary causes of haemolytic anaemia related to membrane defects?
Hereditary spherocytosis
Hereditary elliptocytosis
Q: What metabolic defect is associated with hereditary haemolytic anaemia?
G6PD deficiency (Glucose-6-phosphate dehydrogenase deficiency)
Q: What are the haemoglobinopathies that can cause hereditary haemolytic anaemia?
Sickle cell disease
Thalassaemia
Q: What are the autoimmune causes of Coombs-positive acquired haemolytic anaemia?
Warm antibody type
Cold antibody type
Q: What are the alloimmune causes of Coombs-positive acquired haemolytic anaemia?
Transfusion reaction
Haemolytic disease of the newborn
Q: Which drugs can cause Coombs-positive acquired haemolytic anaemia?
Methyldopa
Penicillin
Q: What is microangiopathic haemolytic anaemia (MAHA), and what are some causes?
TTP/HUS (Thrombotic thrombocytopenic purpura / Hemolytic uremic syndrome)
DIC (Disseminated intravascular coagulation)
Malignancy
Pre-eclampsia
Q: What is an acquired cause of Coombs-negative haemolytic anaemia related to mechanical heart valves?
Prosthetic heart valves
Q: What is paroxysmal nocturnal haemoglobinuria (PNH)?
Paroxysmal nocturnal haemoglobinuria (PNH) is a non-immune cause of Coombs-negative haemolytic anaemia due to a mutation in hematopoietic stem cells that causes red blood cell destruction.
Q: Which infection can cause Coombs-negative acquired haemolytic anaemia?
Malaria
Q: What happens during intravascular haemolysis?
Free haemoglobin is released, which binds to haptoglobin.
Once haptoglobin is saturated, the haemoglobin binds to albumin, forming methaemalbumin (detected by Schumm’s test).
Free haemoglobin is excreted in the urine as haemoglobinuria or haemosiderinuria.
Q: What are the causes of intravascular haemolysis?
Mismatched blood transfusion
G6PD deficiency (though with some extravascular component as well)
Red cell fragmentation (e.g., heart valves, TTP, DIC, HUS)
Paroxysmal nocturnal haemoglobinuria (PNH)
Cold autoimmune haemolytic anaemia
Q: What are the causes of extravascular haemolysis?
Haemoglobinopathies (e.g., sickle cell disease, thalassaemia)
Hereditary spherocytosis
Haemolytic disease of the newborn
Warm autoimmune haemolytic anaemia
Q: What is haemophilia?
An X-linked recessive disorder of coagulation.
Haemophilia A is due to a deficiency of Factor VIII.
Haemophilia B (Christmas disease) is caused by a lack of Factor IX.
Q: What are the common features of haemophilia?
Haemoarthroses (bleeding into joints)
Haematomas (bruising)
Prolonged bleeding after surgery or trauma
Q: What are the blood test findings in haemophilia?
Prolonged APTT (Activated Partial Thromboplastin Time)
Normal bleeding time, thrombin time, and prothrombin time
Q: What is hereditary angioedema (HAE)?
An autosomal dominant condition.
Caused by low levels of C1 esterase inhibitor (C1-INH) protein.
The mechanism behind attacks is the uncontrolled release of bradykinin, leading to tissue oedema.
Q: What are the investigation findings in hereditary angioedema (HAE)?
Low C1-INH levels during an attack.
Low C2 and C4 levels, even between attacks.
Serum C4 is the most reliable and widely used screening tool.
Q: What are the symptoms of hereditary angioedema (HAE)?
Painless, non-pruritic swelling of subcutaneous or submucosal tissues.
Painful macular rash may precede attacks.
Swelling may affect the upper airways, skin, or abdominal organs (can cause abdominal pain due to visceral oedema).
Urticaria is not usually a feature.
Q: How is hereditary angioedema (HAE) managed?
Acute management:
IV C1-inhibitor concentrate or fresh frozen plasma (FFP) if C1-inhibitor is unavailable.
HAE does not respond to adrenaline, antihistamines, or glucocorticoids.
Prophylaxis:
Anabolic steroid Danazol may help.
Q: What is hereditary spherocytosis (HS)?
Most common hereditary haemolytic anaemia in people of northern European descent.
Autosomal dominant defect of red blood cell cytoskeleton.
Spherocyte (sphere-shaped) red blood cells replace the normal biconcave disc shape.
Red blood cell survival is reduced due to destruction by the spleen.
Q: What are the symptoms of hereditary spherocytosis?
Failure to thrive.
Jaundice and gallstones.
Splenomegaly (enlarged spleen).
Aplastic crisis may be precipitated by parvovirus infection.
Degree of haemolysis is variable.
Elevated MCHC (mean corpuscular haemoglobin concentration).
Q: How is hereditary spherocytosis diagnosed?
Family history and clinical features are key.
Blood findings: spherocytes, raised MCHC, and increased reticulocytes.
Osmotic fragility test was once recommended but is now considered unreliable.
The EMA binding test is preferred for diagnosis.
For atypical presentations, electrophoresis of erythrocyte membranes may be used.
Q: How is hereditary spherocytosis managed?
Acute haemolytic crisis:
Treatment is supportive, with transfusion if needed.
Long-term management:
Folate replacement.
Splenectomy may be considered to improve red blood cell survival and reduce haemolysis.
Q: What is Hodgkin’s lymphoma?
A malignant proliferation of lymphocytes.
Characterized by the presence of Reed-Sternberg cells.
Has a bimodal age distribution, being most common in the third and seventh decades of life.
Q: What are the risk factors for Hodgkin’s lymphoma?
HIV.
Epstein-Barr virus (EBV).
Q: What are the features of Hodgkin’s lymphoma?
Lymphadenopathy (75%):
Most commonly in the neck (cervical/supraclavicular) > axillary > inguinal.
Usually painless, non-tender, and asymmetrical.
Alcohol-induced lymph node pain: Seen in < 10% of patients (characteristic).
Systemic symptoms (‘B symptoms’, 25%):
Weight loss.
Pruritus (itching).
Night sweats.
Fever (Pel-Ebstein).
Q: What are some other presentations of Hodgkin’s lymphoma?
Mediastinal mass:
May be symptomatic (e.g., cough) or found incidentally on chest X-ray.
Q: What are common investigations in Hodgkin’s lymphoma?
Blood tests:
Normocytic anaemia (may be multifactorial).
Eosinophilia (due to cytokine production like IL-5).
LDH raised.
Lymph node biopsy:
Reed-Sternberg cells (diagnostic).
These cells are large, multinucleated or bilobed with “owl’s eye” appearance.
Q: What is the main imaging technique used for staging Hodgkin’s lymphoma?
Positron emission tomography/computed tomography (PET/CT) is the mainstay for imaging.
Q: What is the Ann-Arbor staging system for Hodgkin’s lymphoma?
Stage I: Single lymph node involvement.
Stage II: 2 or more lymph nodes on the same side of the diaphragm.
Stage III: Lymph node involvement on both sides of the diaphragm.
Stage IV: Spread beyond lymph nodes to extranodal sites.
A/B:
A = No systemic symptoms.
B = Weight loss > 10%, fever > 38ºC, night sweats (indicates poor prognosis).
Q: What is the Lugano classification for Hodgkin’s lymphoma staging?
Stage I: Single lymph node region or extralymphatic organ (IE).
Stage II: Two or more lymph nodes on the same side of the diaphragm (II) or with localized extralymphatic involvement (IIE).
Stage III: Involvement on both sides of the diaphragm, possibly with extralymphatic or splenic involvement (IIIE, IIIS, or IIIE+S).
Stage IV: Diffuse or disseminated involvement of extranodal organs.
Additional designations:
A: No significant symptoms.
B: Presence of fever, night sweats, or weight loss.
E: Extranodal disease involvement.
S: Spleen involvement.
X: Bulky disease.
Q: What is the mainstay treatment for Hodgkin’s lymphoma?
Chemotherapy is the primary treatment.
ABVD (Doxorubicin, Bleomycin, Vinblastine, Dacarbazine) is considered the standard regimen.
BEACOPP (Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, Prednisone) is an alternative with higher remission rates but more toxicity.
Q: When is hematopoietic cell transplantation used in Hodgkin’s lymphoma?
It may be used for relapsed or refractory classic Hodgkin lymphoma.
Q: What are the complications of treatment for Hodgkin’s lymphoma?
Secondary malignancies (solid tumors like breast and lung cancer) are a risk due to the toxicity of treatment.
Despite this, most patients achieve long-term survival with modern therapy.
Q: What are some common causes of hyposplenism?
Splenectomy (surgical removal of the spleen)
Sickle-cell disease
Coeliac disease and dermatitis herpetiformis
Graves’ disease
Systemic lupus erythematosus (SLE)
Amyloid deposition
Q: What are characteristic features seen in hyposplenism on a blood film?
Howell-Jolly bodies (nuclear remnants in red blood cells)
Siderocytes (red blood cells containing iron granules)
Q: What are the common presenting symptoms of ITP in adults?
Incidental detection following routine blood tests.
Petechiae and purpura.
Bleeding, e.g., epistaxis.
Catastrophic bleeding (e.g., intracranial) is rare.
Q: What are the common investigations for ITP in adults?
Full blood count: isolated thrombocytopenia.
Blood film to assess platelet morphology.
Bone marrow examination is not routinely performed.
Antiplatelet antibody testing has poor sensitivity and does not affect management.
Q: What is the first-line treatment for ITP in adults?
Oral prednisolone (steroid therapy).
Pooled normal human immunoglobulin (IVIG) may be used in active bleeding or before urgent invasive procedures as it raises the platelet count faster than steroids.
Splenectomy is now less commonly used.
Q: What are the main causes of iron deficiency anaemia?
Excessive blood loss:
Menorrhagia (most common in pre-menopausal women).
Gastrointestinal bleeding (most common in men and post-menopausal women, always suspect colon cancer).
Inadequate dietary intake:
Lack of meat in the diet (especially in vegans/vegetarians).
Dark green leafy vegetables provide alternative iron sources.
Poor intestinal absorption:
Conditions like coeliac disease affect iron absorption.
Increased iron requirements:
Children during rapid growth.
Pregnant women (due to fetal demands and dilutional effect of increased plasma volume).
Q: What are the common features of iron deficiency anaemia?
Fatigue
Shortness of breath on exertion
Palpitations
Pallor
Nail changes: Koilonychia (spoon-shaped nails)
Hair loss
Atrophic glossitis
Post-cricoid webs
Angular stomatitis
Q: What investigations are used for iron deficiency anaemia?
History: Diet, medication, menstrual history, weight loss, change in bowel habit.
Full blood count (FBC): Hypochromic microcytic anaemia.
Serum ferritin: Likely low (but raised in inflammation).
Total iron-binding capacity (TIBC)/transferrin: High, indicating low iron stores.
Blood film: Anisopoikilocytosis, target cells, ‘pencil’ poikilocytes.
Endoscopy: For males and post-menopausal women with unexplained iron-deficiency anaemia (to rule out malignancy).
Q: What is the management of iron deficiency anaemia?
Identify and treat the underlying cause (important to rule out malignancy).
Oral ferrous sulfate: Continue for 3 months after correction to replenish iron stores.
Side effects: Nausea, abdominal pain, constipation, diarrhea.
Iron-rich diet: Includes dark-green leafy vegetables, meat, and iron-fortified bread.
IDA vs anaemia of chronic disease
Q: What is the main cause of immune thrombocytopenic purpura (ITP)?
A: It is an immune-mediated reduction in platelet count, with antibodies directed against the glycoprotein IIb-IIIa or Ib-V-IX complex.
Q: What is the typical treatment for ITP?
A: First-line treatment includes oral prednisolone. If ineffective, IV immunoglobulins or splenectomy may be considered.
Q: What is the purpose of bone marrow aspiration in ITP?
A: Bone marrow aspiration shows megakaryocytes, indicating platelet production. It should be done before starting steroids to rule out conditions like leukaemia.
Q: When is splenectomy considered in ITP management?
A: Splenectomy is considered if platelets remain <30 x 10^9/L after 3 months of steroid therapy.
Q: What are the key signs of ITP?
A: Common signs include petechiae, purpura, and bleeding (e.g., epistaxis). Severe bleeding is rare.
Q: What tests are used to diagnose ITP?
A: Tests include checking for antiplatelet autoantibodies (IgG) and bone marrow aspiration to confirm megakaryocyte presence.
Q: What does a decrease in haptoglobin indicate?
A: A decrease in haptoglobin is associated with intravascular haemolysis as it binds to free haemoglobin.
Q: What are the common features of lead poisoning?
A: Common features include abdominal pain, peripheral neuropathy (mainly motor), neuropsychiatric features, fatigue, constipation, and blue lines on gum margin (seen in 20% of adult patients, rare in children).
Q: What is the diagnostic investigation for lead poisoning?
A: The blood lead level is used for diagnosis; levels greater than 10 mcg/dl are considered significant. Additional tests include full blood count (showing microcytic anaemia) and a blood film showing basophilic stippling and clover-leaf morphology.
Q: What red cell abnormalities are seen in the blood film of someone with lead poisoning?
A: Basophilic stippling and clover-leaf morphology are seen on the blood film.
Q: How is lead poisoning managed?
A: Chelating agents are used for management, including dimercaptosuccinic acid (DMSA), D-penicillamine, EDTA, and dimercaprol.
Q: What is macrocytic anaemia?
A: Macrocytic anaemia is a condition where the red blood cells are larger than normal, typically due to impaired DNA synthesis, and is divided into megaloblastic and normoblastic causes.
Q: What are megaloblastic causes of macrocytic anaemia?
A: Megaloblastic causes include vitamin B12 deficiency, folate deficiency, and methotrexate use.
Q: What are normoblastic causes of macrocytic anaemia?
A: Normoblastic causes include alcohol, liver disease, hypothyroidism, pregnancy, reticulocytosis, myelodysplasia, and certain drugs (e.g., cytotoxics).
Q: What is Methaemoglobinaemia?
A: Methaemoglobinaemia occurs when haemoglobin is oxidised from Fe²⁺ to Fe³⁺, which prevents it from binding oxygen, leading to tissue hypoxia and a left-shifted oxygen dissociation curve.
Q: What are the congenital causes of methaemoglobinaemia?
A: Congenital causes include haemoglobin chain variants (HbM, HbH) and NADH methaemoglobin reductase deficiency.
Q: What are the acquired causes of methaemoglobinaemia?
A: Acquired causes include drugs (e.g., sulphonamides, nitrates, dapsone, sodium nitroprusside, primaquine) and chemicals (e.g., aniline dyes).
Q: What are the features of methaemoglobinaemia?
A: Features include “chocolate” cyanosis, dyspnoea, anxiety, headache, and in severe cases, acidosis, arrhythmias, seizures, and coma. There is normal pO₂ but decreased oxygen saturation.
Q: What is the management for methaemoglobinaemia?
A: Management includes ascorbic acid for NADH methaemoglobinaemia reductase deficiency and IV methylthioninium chloride (methylene blue) for acquired cases.
Q: What are the causes of microcytic anaemia?
A: Iron-deficiency anaemia, thalassaemia, congenital sideroblastic anaemia, anaemia of chronic disease, lead poisoning.
Q: What condition should be considered in a patient with a normal haemoglobin level and microcytosis, especially if they are not at risk of thalassaemia?
A: Polycythaemia rubra vera, which may cause iron-deficiency secondary to bleeding.
Q: What should be urgently investigated in elderly patients with new onset microcytic anaemia?
A: Underlying malignancy.
Q: In which condition is microcytosis often disproportionate to the anaemia?
A: Beta-thalassaemia minor.
Q: What is monoclonal gammopathy of undetermined significance (MGUS)?
A: A common condition causing paraproteinaemia, often mistaken for myeloma, with around 10% of patients developing myeloma at 10 years and 50% at 15 years.
Q: What are the typical features of MGUS?
A: Usually asymptomatic, no bone pain or increased risk of infections, 10-30% of patients have demyelinating neuropathy.
Q: What are the differentiating features between MGUS and myeloma?
A: Normal immune function, normal beta-2 microglobulin levels, lower paraproteinaemia levels (e.g., < 30g/l IgG, < 20g/l IgA), stable paraproteinaemia, and no clinical features of myeloma (e.g., lytic lesions or renal disease).
Q: What is myelodysplastic syndrome (MDS)?
A: A heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, and a risk of progression to acute myeloid leukaemia (AML).
Q: What is the typical age group affected by myelodysplastic syndrome (MDS)?
A: MDS predominantly affects older adults, with a median age at diagnosis of 70-75 years.
Q: What are the common clinical features of myelodysplastic syndrome (MDS)?
A: Fatigue, weakness, pallor due to anaemia; recurrent infections due to neutropenia; easy bruising or bleeding due to thrombocytopenia; some patients may be asymptomatic.
Q: How is myelodysplastic syndrome (MDS) diagnosed?
A: Based on peripheral blood counts, bone marrow examination, and cytogenetic analysis, with bone marrow biopsy showing dysplastic changes and blasts, and cytogenetic analysis identifying chromosomal abnormalities.
Q: What are the treatment options for myelodysplastic syndrome (MDS)?
A: Supportive care (e.g., blood transfusions, growth factors), disease-modifying therapy (e.g., hypomethylating agents, lenalidomide), immunosuppressive therapy, and hematopoietic stem cell transplantation (the only potentially curative option).
Q: What is myelofibrosis?
A: A myeloproliferative disorder thought to be caused by hyperplasia of abnormal megakaryocytes, leading to the release of platelet-derived growth factor that stimulates fibroblasts.
Q: What does myelofibrosis result in regarding haematopoiesis?
A: Haematopoiesis develops in the liver and spleen.
Q: What are the common features of myelofibrosis?
A: Elderly person with symptoms of anaemia (e.g., fatigue), massive splenomegaly, and hypermetabolic symptoms (weight loss, night sweats).
Q: What are the laboratory findings in myelofibrosis?
A: Anaemia, high WBC and platelet count early in the disease, ‘tear-drop’ poikilocytes on blood film, unobtainable bone marrow biopsy (dry tap), high urate and LDH (reflecting increased cell turnover).
Q: What is the typical appearance of blood film in myelofibrosis?
A: ‘Tear-drop’ poikilocytes.
Q: Why might a bone marrow biopsy be unobtainable in myelofibrosis?
A: Due to a ‘dry tap,’ where a trephine biopsy is needed instead.
Q: What is multiple myeloma (MM)?
A: A haematological malignancy characterized by plasma cell proliferation, arising from genetic mutations during the differentiation of B-lymphocytes into plasma cells.
Q: What is the mnemonic for the features of multiple myeloma (MM)?
A: CRABBI: Calcium (hypercalcaemia), Renal (renal damage), Anaemia, Bleeding, Bones (bone lesions), Infection, and additional features like amyloidosis, carpal tunnel syndrome, neuropathy, and hyperviscosity.
Q: What causes hypercalcaemia in multiple myeloma?
A: Increased osteoclastic bone resorption due to local cytokines (e.g., IL-1, tumour necrosis factor) released by myeloma cells, and less common factors like impaired renal function and elevated PTH-rP.
Q: What are the renal complications of multiple myeloma?
A: Light chain deposition in renal tubules causing renal damage, dehydration, and increasing thirst, along with other causes like amyloidosis, nephrocalcinosis, and nephrolithiasis.
Q: How does multiple myeloma cause anaemia?
A: Bone marrow crowding suppresses erythropoiesis, leading to anaemia, which causes fatigue and pallor.
Q: What is the cause of bleeding in multiple myeloma?
A: Bone marrow crowding results in thrombocytopenia, increasing the risk of bleeding and bruising.
Q: What causes bone lesions in multiple myeloma?
A: Bone marrow infiltration by plasma cells and osteoclast overactivity, leading to lytic bone lesions, pain (especially in the back), and an increased risk of pathological fractures.
Q: How does multiple myeloma increase susceptibility to infection?
A: The reduction in normal immunoglobulin production increases susceptibility to infections.
Q: What is the appearance of a blood film in multiple myeloma?
A: Rouleaux formation.
Q: What are the key investigations for multiple myeloma?
A: Blood tests (e.g., full blood count, urea and electrolytes, bone profile), protein electrophoresis (raised monoclonal IgA/IgG in serum, Bence Jones proteins in urine), bone marrow aspiration, and imaging (e.g., skeletal survey, whole-body MRI, X-rays showing ‘rain-drop skull’).
Q: What are the diagnostic criteria for multiple myeloma?
A: Major criteria: plasmacytoma, 30% plasma cells in bone marrow, elevated M protein. Minor criteria: 10-30% plasma cells, minor elevations in M protein, osteolytic lesions, low antibody levels. One major and one minor or three minor criteria required for diagnosis.
Q: What are the viral causes of neutropaenia?
A: HIV, Epstein-Barr virus, hepatitis.
Q: What are the drug-related causes of neutropaenia?
A: Cytotoxic drugs, carbimazole, clozapine.
Q: What are the haematological causes of neutropaenia?
A: Myelodysplastic syndromes, aplastic anaemia.
Q: How can rheumatological conditions cause neutropaenia?
A: In systemic lupus erythematosus (via antineutrophil antibodies) and rheumatoid arthritis (e.g., hypersplenism in Felty’s syndrome).
What is neutropenic sepsis?
A common complication of cancer therapy, usually caused by chemotherapy.
Occurs 7-14 days after chemotherapy.
Defined as a neutrophil count of < 0.5 * 10^9 with a temperature > 38ºC or other signs of clinically significant sepsis.
What is the most common cause of neutropenic sepsis?
Coagulase-negative, Gram-positive bacteria, particularly Staphylococcus epidermidis.
Often associated with the use of indwelling lines in cancer patients.
What is the prophylaxis for neutropenic sepsis?
Fluoroquinolone should be offered if neutrophil count < 0.5 * 10^9 is anticipated due to cancer treatment.
What is the management for neutropenic sepsis?
Antibiotics must be started immediately, even before WBC results are available.
NICE recommends starting empirical therapy with piperacillin and tazobactam (Tazocin).
Vancomycin may be added if the patient has central venous access, though NICE does not support this.
Patients are risk-stratified to see if outpatient treatment is possible.
If still febrile after 48 hours, meropenem +/− vancomycin is commonly used.
If no response after 4-6 days, investigations for fungal infections are suggested (e.g., HRCT).
G-CSF may be considered in selected patients.
What is non-Hodgkin’s lymphoma?
Malignant proliferation of lymphocytes, affecting lymph nodes or other organs.
Classified as either B-cell or T-cell lymphoma and further categorized as high-grade or low-grade.
What are the risk factors for non-Hodgkin’s lymphoma?
Risk factors include age (elderly), ethnicity (Caucasians), history of viral infections (e.g., Epstein-Barr virus), family history, exposure to chemical agents (e.g., pesticides, solvents), history of chemotherapy or radiotherapy, immunodeficiency (e.g., HIV, diabetes, transplant), and autoimmune diseases (e.g., SLE, Sjogren’s, coeliac disease).
What are the clinical presentations of non-Hodgkin’s lymphoma?
Symptoms: painless lymphadenopathy, constitutional/B symptoms (fever, weight loss, night sweats, lethargy), and extranodal disease (gastric, bone marrow, lungs, skin, CNS).
Signs: weight loss, lymphadenopathy (cervical, axillary, inguinal), palpable abdominal mass, testicular mass, fever.
How can Hodgkin’s lymphoma be differentiated from non-Hodgkin’s lymphoma?
Hodgkin’s lymphoma may cause alcohol-induced pain in lymph nodes, has earlier ‘B’ symptoms, and less extranodal disease compared to non-Hodgkin’s lymphoma.
What investigations are used to diagnose non-Hodgkin’s lymphoma?
Excisional node biopsy (e.g., ‘starry sky’ in Burkitt’s lymphoma) (INVESTIGATION OF CHOICE)
, CT chest, abdomen, and pelvis for staging, HIV test, FBC (normocytic anaemia), ESR (prognostic), and LDH (cell turnover).
Other tests may include LFTs, PET-CT, bone marrow biopsy, or LP.
What is the Lugano staging for non-Hodgkin’s lymphoma?
Stage I: Single lymph node region or organ (IE).
Stage II: Multiple lymph node regions on the same side of the diaphragm or localized extralymphatic involvement (IIE).
Stage III: Involvement on both sides of the diaphragm (IIIE), with or without spleen involvement.
Stage IV: Diffuse or disseminated involvement of extralymphatic organs.
What are the additional staging designations in non-Hodgkin’s lymphoma?
A/B: ‘A’ indicates no symptoms, ‘B’ indicates fever, night sweats, or weight loss.
E: Extranodal disease.
S: Spleen involvement.
X: Bulky disease.
How is non-Hodgkin’s lymphoma managed?
Management includes watchful waiting, chemotherapy, or radiotherapy, depending on the subtype.
Rituximab is used with chemotherapy (e.g., CHOP).
Hepatitis B screening is required before Rituximab treatment.
Flu/pneumococcal vaccines and antibiotic prophylaxis are important for neutropenic patients.
What are the complications of non-Hodgkin’s lymphoma?
Complications include bone marrow infiltration (causing anaemia, neutropenia, thrombocytopenia), superior vena cava obstruction, metastasis, spinal cord compression, and chemotherapy side effects.
What is the prognosis of non-Hodgkin’s lymphoma?
Low-grade non-Hodgkin’s lymphoma has a better prognosis, while high-grade lymphoma has a worse prognosis but a higher cure rate.
What are the causes of normocytic anaemia?
Anaemia of chronic disease
Chronic kidney disease
Aplastic anaemia
Haemolytic anaemia
Acute blood loss
What is paroxysmal nocturnal haemoglobinuria (PNH)?
An acquired disorder leading to haemolysis, mainly intravascular, of haematological cells due to a lack of glycoprotein glycosyl-phosphatidylinositol (GPI), making cells more sensitive to complement. Patients are prone to venous thrombosis.
What are the features of paroxysmal nocturnal haemoglobinuria (PNH)?
Haemolytic anaemia
Pancytopaenia (red blood cells, white blood cells, platelets, or stem cells may be affected)
Haemoglobinuria (dark-coloured urine, especially in the morning)
Thrombosis (e.g. Budd-Chiari syndrome)
Aplastic anaemia in some cases
What is the diagnostic test for paroxysmal nocturnal haemoglobinuria (PNH)?
Flow cytometry of blood to detect low levels of CD59 and CD55. This has replaced Ham’s test as the gold standard.
What are the management options for paroxysmal nocturnal haemoglobinuria (PNH)?
Blood product replacement
Anticoagulation
Eculizumab (monoclonal antibody targeting terminal protein C5, showing promise in reducing intravascular haemolysis)
Stem cell transplantation
When should platelet transfusions be offered for active bleeding?
Platelet transfusions should be offered to patients with a platelet count of <30 x 10^9 with clinically significant bleeding (WHO bleeding grade 2, e.g., haematemesis, melaena, prolonged epistaxis).
What are the platelet transfusion thresholds for patients with severe bleeding or bleeding at critical sites?
Platelet transfusion thresholds are higher for patients with severe bleeding (WHO bleeding grades 3 & 4) or bleeding at critical sites (e.g., CNS). The threshold is <100 x 10^9.
What is the platelet transfusion threshold before an invasive procedure (prophylactic)?
For prophylactic transfusion before surgery/invasive procedures:
Aim for >50 x 10^9/L for most patients
50-75 x 10^9/L if there is a high risk of bleeding
100 x 10^9/L for surgery at critical sites
What is the platelet transfusion threshold if there is no active bleeding or planned invasive procedure?
The threshold is 10 x 10^9/L, except where platelet transfusion is contraindicated or alternative treatments are available.
What are the types of polycythaemia?
Polycythaemia can be relative, primary (polycythaemia rubra vera), or secondary.
What are the relative causes of polycythaemia?
Dehydration
Stress (e.g., Gaisbock syndrome)
What is the primary cause of polycythaemia?
Polycythaemia rubra vera
What are the secondary causes of polycythaemia?
COPD
High altitude
Obstructive sleep apnoea
Excessive erythropoietin due to conditions such as cerebellar haemangioma, hypernephroma, hepatoma, or uterine fibroids.
I.e hypoxia or inappropriately high EPO
How can you differentiate between true polycythaemia and relative polycythaemia?
Red cell mass studies are used. In true polycythaemia, the total red cell mass in males is >35 ml/kg and in females >32 ml/kg.
What is polycythaemia vera (PV)?
A myeloproliferative disorder caused by clonal proliferation of a marrow stem cell, leading to increased red cell volume, neutrophils, and platelets. It is associated with a JAK2 mutation in approximately 95% of cases.
What are the common features of polycythaemia vera?
Pruritus (typically after a hot bath)
Splenomegaly
Hypertension
Hyperviscosity
Arterial thrombosis
Venous thrombosis
Haemorrhage (due to abnormal platelet function)
Low ESR
What tests are recommended by the British Committee for Standards in Haematology (BCSH) for polycythaemia vera?
Full blood count/film (raised haematocrit, neutrophils, basophils, and platelets in half of patients)
JAK2 mutation testing
Serum ferritin
Renal and liver function tests
What additional tests may be suggested if JAK2 mutation is negative and no obvious secondary causes are present?
Red cell mass
Arterial oxygen saturation
Abdominal ultrasound
Serum erythropoietin level
Bone marrow aspirate and trephine
Cytogenetic analysis
Erythroid burst-forming unit (BFU-E) culture
What is the first-line treatment for polycythaemia vera?
Venesection, to keep the haemoglobin in the normal range.
What is the role of aspirin in the management of polycythaemia vera?
Aspirin reduces the risk of thrombotic events.
What chemotherapy agents may be used in the management of polycythaemia vera?
Hydroxyurea (with a slight increased risk of secondary leukaemia)
Phosphorus-32 therapy
What is post-thrombotic syndrome?
A clinical syndrome resulting from venous outflow obstruction and venous insufficiency, leading to chronic venous hypertension following deep vein thrombosis (DVT).
What are the common features of post-thrombotic syndrome?
Painful, heavy calves
Pruritus
Swelling
Varicose veins
Venous ulceration
What is the recommended treatment once post-thrombotic syndrome has developed?
Compression stockings and keeping the leg elevated.
Why is pregnancy considered a hypercoagulable state?
Pregnancy increases factors VII, VIII, X, and fibrinogen while decreasing protein S.
When do the majority of DVT/PE cases occur during pregnancy?
In the last trimester.
What causes sickle-cell anaemia?
Sickle-cell anaemia is an autosomal recessive condition caused by the synthesis of an abnormal haemoglobin chain, HbS.
Why is sickle-cell anaemia more common in people of African descent?
The heterozygous condition (HbAS) provides some protection against malaria.
When do symptoms of sickle-cell anaemia typically develop in homozygotes?
Symptoms generally develop at 4-6 months when HbSS molecules take over from fetal haemoglobin.
What is the difference between HbAA, HbAS, and HbSS?
HbAA: Normal haemoglobin;
HbAS: Sickle cell trait (heterozygous);
HbSS: Homozygous sickle cell disease.
How is sickle-cell anaemia definitively diagnosed?
Sickle-cell anaemia is definitively diagnosed by haemoglobin electrophoresis.
What is the first step in managing a sickle-cell anaemia crisis?
Provide analgesia (e.g. opiates), rehydrate, and administer oxygen.
When should antibiotics be considered in sickle-cell crisis management?
Consider antibiotics if there is evidence of infection.
When is blood transfusion indicated in sickle-cell anaemia crisis management?
Blood transfusion is indicated in a crisis, and exchange transfusion may be needed if neurological complications occur.
What is the role of hydroxyurea in sickle-cell anaemia?
Hydroxyurea increases HbF levels and is used prophylactically to prevent painful episodes.
How often should sickle-cell patients receive the pneumococcal polysaccharide vaccine?
Sickle-cell patients should receive the pneumococcal polysaccharide vaccine every 5 years.
What are the different types of sickle-cell crises?
Thrombotic (painful or vaso-occlusive), acute chest syndrome, anaemic, aplastic, sequestration, and infection.
What is acute chest syndrome in sickle-cell anaemia?
It is caused by vaso-occlusion in the pulmonary microvasculature, leading to lung parenchyma infarction. Symptoms include dyspnoea, chest pain, pulmonary infiltrates on chest x-ray, and low pO2.
What is the management of acute chest syndrome?
Pain relief, respiratory support (oxygen therapy), antibiotics (to treat infection), and transfusion (to improve oxygenation).
What is the most common cause of death in sickle-cell patients after childhood?
Acute chest syndrome.
What causes aplastic crises in sickle-cell anaemia?
Infection with parvovirus, leading to a sudden fall in haemoglobin and bone marrow suppression.
What is seen in the lab during aplastic crises?
A reduced reticulocyte count.
What causes sequestration crises in sickle-cell anaemia?
Sickle cells cause pooling of blood within organs, such as the spleen or lungs, which worsens anaemia.
What is seen in the lab during sequestration crises?
An increased reticulocyte count.
What are the general management strategies for sickle-cell crises?
Analgesia (e.g., opiates), rehydration, oxygen, antibiotics (if evidence of infection), and blood transfusion.
When is exchange transfusion indicated in sickle-cell crises?
In cases of acute vaso-occlusive crisis (e.g., stroke, acute chest syndrome, multiorgan failure, splenic sequestration crisis).
What is the underlying issue in sideroblastic anaemia?
Failure to completely form haem, leading to iron deposits in the mitochondria and ringed sideroblasts.
What are the key features in the investigations of sideroblastic anaemia?
Full blood count: Hypochromic microcytic anaemia (more so in congenital).
Iron studies: High ferritin, high iron, high transferrin saturation.
Blood film: Basophilic stippling of red blood cells.
Bone marrow: Prussian blue staining reveals ringed sideroblasts.
What is the management for sideroblastic anaemia?
Supportive treatment, address any underlying causes, and pyridoxine may help.
What are the causes of massive splenomegaly?
Myelofibrosis, chronic myeloid leukaemia, visceral leishmaniasis (kala-azar), malaria, Gaucher’s syndrome.
What is essential thrombocytosis?
A myeloproliferative disorder characterized by megakaryocyte proliferation and platelet overproduction, with a platelet count > 600 * 10^9/L. It may present with thrombosis, haemorrhage, and a burning sensation in the hands. A JAK2 mutation is found in around 50% of patients.
What is the management of essential thrombocytosis?
Hydroxyurea (hydroxycarbamide) to reduce platelet count, interferon-α in younger patients, and low-dose aspirin to reduce thrombotic risk.
What is the pathogenesis of thrombotic thrombocytopenic purpura (TTP)?
In TTP, abnormally large and sticky multimers of von Willebrand’s factor cause platelets to clump within vessels. A deficiency of ADAMTS13, a metalloprotease enzyme, prevents the breakdown of these large multimers.
What are the features of thrombotic thrombocytopenic purpura (TTP)?
TTP is rare, typically affecting adult females. Symptoms include fever, fluctuating neuro signs (due to microemboli), microangiopathic haemolytic anaemia, thrombocytopenia, and renal failure.
What are the causes of thrombotic thrombocytopenic purpura (TTP)?
Causes include post-infection (e.g., urinary or gastrointestinal infections), pregnancy, certain drugs (e.g., ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir), tumours, SLE, and HIV.
What are thymomas?
Thymomas are the most common tumour of the anterior mediastinum, typically detected between the sixth and seventh decades of life.
What conditions are thymomas associated with?
Thymomas are associated with myasthenia gravis (30-40% of patients with thymoma), red cell aplasia, dermatomyositis, and other conditions such as SLE and SIADH.
What is Tumour Lysis Syndrome (TLS)?
Tumour Lysis Syndrome is a potentially deadly condition that typically occurs after treatment for high-grade lymphomas and leukaemias, though it can also occur without chemotherapy, sometimes with steroid treatment alone. It results from the breakdown of tumour cells and the release of chemicals, leading to high potassium and phosphate levels with low calcium.
What are the main laboratory findings in Tumour Lysis Syndrome?
Elevated uric acid (>475umol/l or a 25% increase), potassium (>6 mmol/l or a 25% increase), and phosphate (>1.125mmol/l or a 25% increase), with a decreased calcium (<1.75mmol/l or a 25% decrease).
How can Tumour Lysis Syndrome be prevented?
Prevention includes IV fluids, and for high-risk patients, the use of allopurinol or rasburicase. Rasburicase is preferred for high-risk patients as it converts uric acid to a more water-soluble compound, allantoin.
What is the role of rasburicase and allopurinol in TLS?
Rasburicase is preferred in higher-risk patients as it metabolizes uric acid into allantoin, which is more easily excreted by the kidneys. Allopurinol is generally used for lower-risk patients. They should not be used together as they can reduce the effectiveness of rasburicase.
What are the typical features of Vitamin B12 deficiency?
Macrocytic anaemia, sore tongue and mouth, neurological symptoms (starting with dorsal column involvement such as joint position and vibration sense), distal paraesthesia, and neuropsychiatric symptoms like mood disturbances.
How is Vitamin B12 deficiency managed?
If no neurological involvement, 1 mg of IM hydroxocobalamin is given three times a week for 2 weeks, then once every 3 months. If there is concurrent folic acid deficiency, Vitamin B12 should be treated first to avoid precipitating subacute combined degeneration of the cord.
What are the types of Von Willebrand’s disease?
Type 1: Partial reduction in vWF (80% of cases)
Type 2: Abnormal form of vWF, with subtypes including 2A (defective platelet adhesion), 2B (pathological increase in vWF-platelet interaction), 2M (decreased vWF-platelet interaction), and 2N (abnormal binding of vWF to factor VIII).
Type 3: Total lack of vWF (autosomal recessive and the most severe form).
What are the typical features of Von Willebrand’s disease?
The disease behaves like a platelet disorder with common symptoms including epistaxis, menorrhagia, and rare occurrences of haemarthroses and muscle haematomas.
What investigations are used for diagnosing Von Willebrand’s disease?
Prolonged bleeding time, possible prolonged APTT, moderately reduced factor VIII levels, and defective platelet aggregation with ristocetin.
How is Von Willebrand’s disease managed?
Tranexamic acid for mild bleeding, desmopressin (DDAVP) to raise vWF levels by inducing release from endothelial cells, and factor VIII concentrate for more severe cases.
What is Waldenstrom’s macroglobulinaemia?
It is a lymphoplasmacytoid malignancy characterized by the secretion of a monoclonal IgM paraprotein.
What are the features of Waldenstrom’s macroglobulinaemia?
Systemic upset: weight loss, lethargy
Hyperviscosity syndrome: visual disturbance due to increased serum viscosity from the pentameric configuration of IgM
Hepatosplenomegaly
Lymphadenopathy
Cryoglobulinaemia: Raynaud’s phenomenon
What investigations are used to diagnose Waldenstrom’s macroglobulinaemia?
Monoclonal IgM paraproteinaemia
Bone marrow biopsy: diagnostic, showing infiltration of bone marrow with lymphoplasmacytoid lymphoma cells.
What is the management of Waldenstrom’s macroglobulinaemia?
Rituximab-based combination chemotherapy.
In DVT, if D dimer is positive but US is negative, they have been started on anticoags and DVT goes away, what should you do
Stop anticoags + repeat scan in 1 week
What effect does transfused red blood cells have on electrolyte levels
causes hyperkalaemia and hypocalcaemia
For patients who have IDA prior to a surgery and cant take oral iron, what should they take
IV iron, then repeat 1 week later
Difference between factor V leiden and antiphospholipid syndrome
factor V leiden only affects veins not arteries
Differentiating between AML and CML
Step given by my lecturer (simple yet helpful)
1. Look at lymphocytes
2. Look at WBC
3. Others hint (blast cell/ bands)
Example
1.Low Lymphocytes -> the answer should be AML or CML
2. WBC > 100 -> Chronic causes so Consider CML (rule out AML)
3. Presence of bands cell -> confirm CML
*blast -> Acute
*bands -> Chronic
When giving more than 1 unit of packed red cells, what must you also give
stat dose of furosemide between transfusions
