Group AB donors are the universal donors of FFP. This is because they produce neither anti-A nor anti-B antigens in their plasma and are, therefore, compatible with all ABO groups.

The aforementioned patient’s blood group is B meaning, thereby, she naturally produces anti-A antigens in her plasma and would need to receive plasma that does not have anti-B antigens in it. Hence, she can only receive FFP from donors of group B or AB. Moreover, as she is of childbearing age, she must receive RhD negative blood in order to avoid problems with future pregnancies if her foetus would be RhD positive.

The principal mechanism of action of taxanes (e.g. docetaxel) is the prevention of microtubule disassembly.

Other aforementioned options are ruled out because:

1. Doxorubicin: stabilizes DNA topoisomerase II complex and inhibits DNA and RNA synthesis.

2. Vincristine, vinblastine: inhibits formation of microtubules.

3. Cisplatin: causes cross-linking in DNA.

Involvement of lymph nodes on both sides of the diaphragm accompanied by night sweats would be staged as IIIB according to the Ann Arbor staging system for Hodgkin lymphoma (HL).

HL is a malignant proliferation of lymphocytes characterised by the presence of distinctive giant cells known as Reed-Sternberg cells. It has a bimodal age distribution being most common in the third and seventh decades of life.

Staging of HL is done according to the Ann Arbor staging system:
Stage
I: Single lymph node region (I) or one extra lymphatic site (IE)

II: Two or more lymph node regions on same side of the diaphragm (II) or local extra lymphatic extension plus one or more lymph node regions on same side of the diaphragm (IIE)

III: Lymph node regions on both sides of the diaphragm (III) which may be accompanied by local extra lymphatic extension (IIIE)

IV: Diffuse involvement of one or more extra lymphatic organs or sites

Suffix
A: No B symptoms

B: Presence of at least one of the following: unexplained weight loss >10% baseline during 6 months before staging; recurrent unexplained fever >38°C; recurrent night sweats—poor prognosis.

St John’s wort interferes with warfarin by increasing its breakdown and decreasing its effectiveness. This leads to the need for adjustment in the dose of warfarin and careful attention to monitoring if the patient decides to continue with the drug. Ideally, an alternative antidepressant should also be considered.

The patient is on stage IV according to the Ann Arbor staging system for Hodgkin lymphoma (HL). The disease has spread beyond the lymph nodes into the liver (involvement of extra lymphatic organ).

HL is a malignant proliferation of lymphocytes characterised by the presence of distinctive giant cells known as Reed-Sternberg cells. It has a bimodal age distribution being most common in the third and seventh decades of life.

Staging of HL is done according to the Ann Arbor staging system:
Stage
I: Single lymph node region (I) or one extra lymphatic site (IE)

II: Two or more lymph node regions on same side of the diaphragm (II) or local extra lymphatic extension plus one or more lymph node regions on same side of the diaphragm (IIE)

III: Lymph node regions on both sides of the diaphragm (III) which may be accompanied by local extra lymphatic extension (IIIE)

IV: Diffuse involvement of one or more extra lymphatic organs or sites

Suffix
A: No B symptoms

B: Presence of at least one of the following: unexplained weight loss >10% baseline during 6 months before staging; recurrent unexplained fever >38°C; recurrent night sweats

Normal pO2 but decreased oxygen saturation is characteristic of methemoglobinemia.

Methemoglobinemia is a rare condition in which the haemoglobin iron is in oxidized or ferric state (Fe3+) and cannot reversibly bind oxygen. Normally, the conversion of ferrous form of iron (Fe2+) to its ferric form (Fe3+) is regulated by NADH methaemoglobin reductase, which results in the reduction of methaemoglobin to haemoglobin. Disruption in the enzyme leads to increased methaemoglobin in the blood. There is tissue hypoxia as Fe3+ cannot bind oxygen, and hence the oxygen-haemoglobin dissociation curve is shifted to the left.

Methemoglobinemia can occur due to congenital or acquired causes. Congenital causes include haemoglobin variants such as HbM and HbH, and deficiency of NADH methaemoglobin reductase. Acquired causes are drugs (e.g. sulphonamides, nitrates, dapsone, sodium nitroprusside, and primaquine) and chemicals (such as aniline dyes).

The features of methemoglobinemia are cyanosis, dyspnoea, anxiety, headache, severe acidosis, arrhythmias, seizures, and loss of consciousness. Patients have normal pO2 but oxygen saturation is decreased. Moreover, presence of chocolate-brown coloured arterial blood (colour does not change with addition of O2) and brown urine also point towards the diagnosis of methemoglobinemia.

Hb S is the most common type of abnormal haemoglobin and the basis of sickle cell trait and sickle cell anaemia. It differs from normal adult haemoglobin (called haemoglobin A—Hb A) only by a single amino acid substitution due to point mutation—a valine replacing a glutamine in the sixth position of the beta chain of globin. Hb S molecules polymerize in hypoxic and acidic environments, imparting a sickle shape to the RBCs. Hb S molecules are less negatively charged than Hb A (due to the loss of glutamine) and have a lower affinity for oxygen (right shift of the oxygen-dissociation curve).

An MRI whole spine should be performed in a patient suspected of spinal metastasis which can occur before developing metastatic spinal cord compression. This patient has renal cell carcinoma, which readily metastasises to the bones and also has progressive back pain. He, therefore, needs urgent imaging of his spine before any neurological compromise develops. MRI whole spine is preferable because patients with spinal metastasis often have metastases at multiple levels within the spine. Plain radiographs and CT scans should not be performed as they have a lower sensitivity for revealing lesions and cannot exclude cord compression.

In general, imaging should be performed within one week if symptoms suspicious of spinal metastasis without neurological symptoms are present. If there are symptoms suggestive of malignant spinal cord compression, then imaging should be done within 24 hours.

The signs and symptoms of spinal metastases include:
1. Unrelenting lumbar back pain
2. Thoracic or cervical back pain
3. Pain associated with tenderness and worsens with sneezing, coughing, or straining
4. Nocturnal pain

Transfusion-related acute lung injury (TRALI) is a serious complication of blood transfusion characterised by the acute onset of non-cardiogenic pulmonary oedema following transfusion of blood products.

TRALI is a more severe manifestation of the febrile non-haemolytic group of transfusion reactions and usually occur in patients who have had multiple previous transfusions. TRALI is related to leucocyte antibodies which are present in the plasma of the blood donor. Multiparous women are the highest-risk donors for TRALI.

For management, leucocyte-depleted blood is now used for transfusion and this is associated with a reduced risk of this type of transfusion reaction.

The most common type of Hodgkin’s lymphoma (HL) is nodular sclerosing.

HL is a malignant proliferation of lymphocytes characterised by the presence of distinctive giant cells known as Reed-Sternberg cells. It has a bimodal age distribution being most common in the third and seventh decades of life.

According to the histological classification, there are four types of HL:

1. Nodular sclerosing: most common (around 70%), more common in women, associated with lacunar cells, good prognosis

2. Mixed cellularity: Around 20%, associated with a large number of Reed-Sternberg cells, good prognosis

3. Lymphocyte-predominant: Around 5%, Reed-Sternberg cells with nuclei surrounded by a clear space found, best prognosis

4. Lymphocyte-depleted: rare, worst prognosis

The major delayed problem with radiotherapy is the development of secondary cancers. This risk begins to appear ten years after therapy.

All of the aforementioned listed tumours, except brain tumours, can metastasise to lungs and produce the typical CXR picture consisting of hilar lymphadenopathy with either diffuse multinodular shadows resembling miliary disease or multiple large well-defined masses (canon balls). Occasionally, cavitation or calcification may also be seen.

Most brain tumours, however, do not metastasise. Some, derived form neural elements, do so but in these cases, intraparenchymal metastases generally precede distant haematogenous spread.

Red cell aplasia is commonly associated with thymomas.

Thymoma is the most common tumour of the anterior mediastinum and is usually detected between the sixth and seventh decades of life. It is associated with myasthenia gravis (30–40% of patients), red cell aplasia, and dermatomyositis. Compression of airway and cardiac tamponade are the common causes of death in thymoma.

Monoclonal gammopathy of undetermined significance (MGUS)—also known as benign paraproteinemia and monoclonal gammopathy—is a pre-malignant condition not necessarily leading to its malignant form—multiple myeloma. MGUS causes increase of a serum monoclonal protein (M protein). It is not associated with ostealgia or increased risk of infections. It is often mistaken for multiple myeloma, differing from the latter in, no immunosuppression, anaemia, hypercalcaemia, lytic bone lesions, or renal failure; normal levels of beta-2 microglobulin; and stable lower levels of paraproteinemia.

Diagnosis of multiple myeloma (MM) is based on the confirmation of (a) one major criterion and one minor criterion or (b) three minor criteria in an individual who has signs or symptoms of multiple myeloma.

Major criteria:
1. >30% plasma cells on bone marrow biopsy
2. Monoclonal band of paraprotein on electrophoresis: >35g/L for IgG, 20g/L for IgA, or >1g of light chains excreted in the urine per day

Minor criteria:
1. 10–30% plasma cells on bone marrow biopsy
2. Abnormal monoclonal band but levels less than listed above
3. Lytic bone lesions observed radiographically
4. Immunosuppression

Hypersegmented neutrophils in the peripheral blood film is suggestive of megaloblastic changes in bone marrow.

Superior vena cava (SVC) obstruction is an oncological emergency caused by compression of the SVC and is most commonly associated with lung cancer.

Some causes of the condition include:
1. Common malignancies: non small cell lung cancer, lymphoma
2. Other malignancies: metastatic seminoma, Kaposi’s sarcoma, breast cancer
3. Aortic aneurysm
4. Mediastinal fibrosis

Clinical features of SVC obstruction include:
1. Dyspnoea: most common
2. Swelling of the face, neck, and arms: conjunctival and periorbital oedema may be seen
3. Headache: often worse in the morning
4. Visual disturbances
5. Pulseless jugular venous distension

Management options are:
1. General: dexamethasone, balloon venoplasty, stenting
2. Small cell lung cancer: chemotherapy and radiotherapy
3. Non small cell lung cancer: radiotherapy

Haemophilia B (Christmas disease), is the deficiency of clotting factor IX and is inherited in an X-linked recessive pattern. The factor IX level dictates the disease severity and established arthropathy is usually seen in those with severe disease.

The aforementioned patient’s history and presentation is consistent with the development of hemarthrosis. Joint aspiration is not recommended. The treatment, therefore, should be intravenous replacement of the deficient clotting factor with plasma-derived factor IX concentrate.

The other listed options are ruled out because:
1. Joint aspiration is not preferred over the administration of clotting factor as the first step of management.
2. DDAVP (desmopressin) can increase factor VIII levels transiently in those with mild haemophilia A and is useful prior to minor surgical procedures in such patients.
3. Cryoprecipitate is rich in fibrinogen, factor VIII, and von Willebrand factor and is used in the treatment of haemophilia A.

The prognosis of breast cancer depends chiefly on the extent of nodal metastases.

The breast cancer TNM staging system is the most common way that doctors use to stage breast cancer. TNM stands for Tumour, Node, Metastasis. The results are combined to determine the stage of cancer for each person. There are five stages: stage 0 (zero), which is non-invasive ductal carcinoma in situ (DCIS), and stages I through IV (1 through 4), which are used for invasive breast cancer.

Staging can be clinical or pathological. Clinical staging is based on the results of tests done before surgery, which may include physical examinations, mammogram, ultrasound, and MRI scans. Pathologic staging is based on what is found during surgery to remove breast tissue and lymph nodes. In general, pathological staging provides the most information to determine a patient’s prognosis.

This is a typical picture of acute chest syndrome (ACS). According to the British Committee for Standards in Haematology (BCSH), ACS is defined as ‘an acute illness characterised by fever and/or respiratory symptoms, accompanied by a new pulmonary infiltrate on chest X-ray’. ACS occurs in sequestration crisis, which is one of the four main types of crises occurring in sickle cell disease.

The fundamentals of initial management are as follows:
1. Oxygen therapy to maintain saturation >95%
2. Intravenous fluids to ensure euvolemia
3. Adequate pain relief
4. Incentive spirometry in all patients presenting with rib or chest pain
5. Antibiotics with cover for atypical organisms
6. Bronchodilators if asthma co-exists with acute chest syndrome, or if there is an evidence of acute bronchospasm on auscultation
7. Early consultation with the critical care team and haematology department

A senior haematologist then makes a decision as to whether a simple or exchange transfusion is necessary in order to achieve a target Hb of 10.0–11.0g/dL in either instance.

Sickle Cell Crises:
Sickle cell anaemia is characterised by periods of good health with intervening crises:
1. Sequestration crisis: acute chest syndrome (i.e. fever, dyspnoea, chest/rib pain, low pO2, and pulmonary infiltrates)

2. Thrombotic (painful or vaso-occlusive) crisis: precipitated by infection, dehydration, and deoxygenation

3. Aplastic crisis: sudden fall in haemoglobin without marked reticulocytosis, usually occurring secondary to parvovirus infection

4. Haemolytic crisis: fall in haemoglobin secondary to haemolysis, rare type of sickle cell crises

The patient has Meigs syndrome. Meigs syndrome is defined as a triad of benign ovarian tumour with ascites and pleural effusion that resolves after resection of the tumour. Ovarian fibromas constitute the majority of the benign tumours seen in Meigs syndrome.

Tumour markers can be divided into:
1. Monoclonal antibodies
CA 125: Ovarian cancer, primary peritoneal cancer
CA 19-9: Pancreatic cancer
CA 15-3: Breast cancer

2. Tumour specific antigens
Prostate specific antigen (PSA): Prostatic carcinoma
Alpha-feto protein (AFP): Hepatocellular carcinoma, teratoma
Carcinoembryonic antigen (CEA): Colorectal cancer
S-100: Melanoma, schwannomas
Bombesin: Small cell lung carcinoma, gastric cancer

3. Enzymes
Alkaline phosphatase (ALP)
Neuron specific enolase (NSE)

4. Hormones
Calcitonin
Antidiuretic hormone (ADH)
Human chorionic gonadotropin (hCG)

Carcinoembryonic antigen (CEA) is a known tumour marker for colorectal cancer. It is not used diagnostically, but in patients with a known diagnosis of colorectal cancer associated with raised CEA levels, it can be used to monitor disease activity and help with the early identification of disease recurrence.

Tumour markers can be divided into:
1. Monoclonal antibodies
CA 125: Ovarian cancer, primary peritoneal cancer
CA 19-9: Pancreatic cancer
CA 15-3: Breast cancer

2. Tumour specific antigens
Prostate specific antigen (PSA): Prostatic carcinoma
Alpha-feto protein (AFP): Hepatocellular carcinoma, teratoma
Carcinoembryonic antigen (CEA): Colorectal cancer
S-100: Melanoma, schwannomas
Bombesin: Small cell lung carcinoma, gastric cancer

3. Enzymes
Alkaline phosphatase (ALP)
Neuron specific enolase (NSE)

4. Hormones
Calcitonin
Antidiuretic hormone (ADH)
Human chorionic gonadotropin (hCG)

Extra-nodal presentation is more common in non-Hodgkin lymphoma (NHL) than in Hodgkin lymphoma (HL). Bone marrow infiltration is more common in low-grade than in high-grade NHLs.

Low-grade NHL is predominantly a disease of older people. Most present with advanced disease, bone marrow infiltration being almost invariable. Anaemia, leucocytosis, and/or thrombocytopaenia in a patient are suggestive of bone marrow involvement. For definitive diagnosis, lymph node biopsy is sufficient.

The other aforementioned statements are ruled out because:
1. Renal impairment in NHL usually occurs as a consequence of ureteric obstruction secondary to intra-abdominal or pelvic lymph node enlargement.

2. Burkitt lymphoma is a high-grade NHL, which was first described in children in West Africa who presented with a jaw tumour, extra-nodal abdominal involvement, and ovarian tumours. It develops most often in children or young adults and is uncommon in older people.

3. High-grade lymphomas are potentially curable. They have a better prognosis and are responsive to chemotherapy unlike low-grade lymphomas, which are incurable with conventional therapy.

Lead poisoning is characterised by abdominal pain, fatigue, constipation, peripheral neuropathy (mainly motor), and blue lines on gum margin in 20% of the adult patients (very rare in children).

For diagnosis, the level of lead in blood is usually considered with levels greater than 10 mcg/dL being significant. Furthermore, the blood film shows microcytic anaemia and basophilic stippling of red blood cells. Urinary coproporphyrin is increased (urinary porphobilinogen and uroporphyrin levels are normal to slightly increased). Raised serum and urine levels of delta-aminolaevulinic acid may also be seen, making it sometimes difficult to differentiate from acute intermittent porphyria.

Patients with a VTE within the previous three months, patients with AF and previous stroke or TIA or multiple other risk factors, and patients with a mitral valve replacement should be considered for bridging therapy.

The most appropriate bridging therapy in this case would be low-molecular-weight heparin (LMWH), with the last dose given not less than 24 hours prior to the procedure. Warfarin should be discontinued 5 days prior to the procedure. If the INR is still above 3 on the day prior to the procedure, vitamin K should be administered.

Waldenström’s macroglobulinemia (also called lymphoplasmacytic lymphoma) is an uncommon type of non-Hodgkin lymphoma seen in older people. It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein. Its features include weight loss and lethargy; monoclonal IgM paraproteinemia; hyperviscosity syndrome leading to bilateral central retinal vein occlusion (CRVO) and hence, visual disturbances; hepatosplenomegaly and lymphadenopathy; and cryoglobulinemia. It is not, however, associated with bone pain.

The upper motor neurone signs in this patient point towards a diagnosis of spinal cord compression above the level of L1 and rules out cauda equina syndrome.

Spinal cord compression is an oncological emergency and affects up to 5% of cancer patients. Extradural compression accounts for the majority of cases, usually due to vertebral body metastases. One of the most common causes of spinal cord compression is osteoarthritis. It is also more commonly seen in patients with lung, breast, or prostate cancer.

Clinical features include:
1. Back pain: the earliest and most common symptom, may worsen on lying down or coughing
2. Lower limb weakness
3. Sensory changes: sensory loss and numbness
4. Neurological signs: depending on the level of the lesion.
Lesions above L1 usually result in upper motor neurone signs in the legs. Lesions below L1 usually cause lower motor neurone signs in the legs and perianal numbness. Tendon reflexes are increased below the level of the lesion and absent at the level of the lesion.

Management options are:
1. High-dose oral dexamethasone
2. Urgent MRI for consideration of radiotherapy or surgery

Cryoglobulinemia may be caused by paraprotein bands such as those seen in Waldenström’s macroglobulinemia and multiple myeloma (MM). Meltzer’s triad of arthralgia, weakness, and palpable purpura are common to all types of cryoglobulinemia—as are membranoproliferative glomerulonephritis and low C4 levels. Raynaud’s phenomenon, however, occurs only in type 1 cryoglobulinemia, and its presence can be helpful in ascertaining the underlying cause.

Cryoglobulinemia is a condition in which the blood contains large amounts of pathological cold-sensitive antibodies called cryoglobulins—proteins (mostly immunoglobulins themselves) that become insoluble at reduced temperatures. One-third of the cases are idiopathic.

There are three types of cryoglobulinemia:
1. Type I (25%):
Monoclonal—IgG or IgM
Associated with multiple myeloma (MM), Waldenström’s macroglobulinemia

2. Type II (25%):
Mixed monoclonal and polyclonal—usually with rheumatoid factor (RF)
Associated with hepatitis C, rheumatoid arthritis (RA), Sjogren’s syndrome

3. Type III (50%):
Polyclonal—usually with RF
Associated with rheumatoid arthritis, Sjogren’s syndrome

Investigation results for cryoglobulinemia show low complement (especially C4) and high ESR. Treatment options include immunosuppression and plasmapheresis.

Methemoglobinemia is a rare condition in which the haemoglobin iron is in oxidized or ferric state (Fe3+) and cannot reversibly bind oxygen. Normally, the conversion of ferrous form of iron (Fe2+) to its ferric form (Fe3+) is regulated by NADH methaemoglobin reductase, which results in the reduction of methaemoglobin to haemoglobin. Disruption in the enzyme leads to increased methaemoglobin in the blood. There is tissue hypoxia as Fe3+ cannot bind oxygen, and hence the oxygen-haemoglobin dissociation curve is shifted to the left.

Methemoglobinemia can occur due to congenital or acquired causes. Congenital causes include haemoglobin variants such as HbM and HbH, and deficiency of NADH methaemoglobin reductase. Acquired causes are drugs (e.g. sulphonamides, nitrates, dapsone, sodium nitroprusside, and primaquine) and chemicals (such as aniline dyes).

The features of methemoglobinemia are cyanosis, dyspnoea, anxiety, headache, severe acidosis, arrhythmias, seizures, and loss of consciousness. Patients have normal pO2 but oxygen saturation is decreased. Moreover, presence of chocolate-brown coloured arterial blood (colour does not change with addition of O2) and brown urine also point towards the diagnosis of methemoglobinemia.

Rasburicase is a recombinant version of urate oxidase which is an enzyme that metabolizes uric acid to allantoin.

TLS is a potentially fatal condition occurring as a complication during the treatment of high-grade lymphomas and leukaemias. It occurs from the simultaneous breakdown (lysis) of the tumour cells and subsequent release of chemicals into the bloodstream. This leads to hyperkalaemia and hyperphosphatemia in the presence of hyponatraemia. TLS can occur in the absence of chemotherapy, but it is usually triggered by the introduction of combination chemotherapy. Awareness of the condition is critical for its prophylactic management.

Patients at high risk of TLS should be given IV rasburicase or IV allopurinol immediately prior to and during the first few days of chemotherapy. Allantoin is much more water soluble than uric acid and is therefore more easily excreted by the kidneys. Patients in lower-risk groups should be given oral allopurinol during cycles of chemotherapy in an attempt to avoid the condition.

TLS is graded according to the Cairo-Bishop scoring system as:
1. Laboratory tumour lysis syndrome
2. Clinical tumour lysis syndrome