The patient has acute promyelocytic leukaemia (APML) with associated disseminated intravascular coagulation (DIC). Although the platelet count is high, platelet function is ineffective.

Patients may present, as in this case, with severe bleeding, and the most appropriate emergency treatment would be administration of fresh frozen plasma (FFP).

This is a classical picture of graft versus host disease (GVHD) following bone marrow transplant. Acute GVHD occurs in the first 100 days post transplant with chronic GVHD occurring 100-300 days after transplant. GVHD is graded according to the Seattle system, and each organ involved is scored (skin, liver, and gut).

The standard initial treatment in the acute setting is high-dose methylprednisolone started immediately. If there is no response, a more intensive immunosuppressive agent such as alemtuzumab or antilymphocyte globulin is needed.

Generally, underlying causes of confusion need to be looked for and treated as appropriate, for example, hypercalcaemia, infection, urinary retention, and medication. If specific treatments fail, the following may be tried:

1. First choice: haloperidol
2. Other options: chlorpromazine, levomepromazine

In the terminal phase of the illness, agitation or restlessness is best treated with midazolam.

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.

In patients with factor V Leiden, inactivation of the active factor V (a clotting factor) by active protein C occurs 10x more slowly than normal. Therefore, this condition is also called activated protein C resistance.

Factor V Leiden is the most commonly inherited thrombophilia, being present in around 5% of the UK’s population. It occurs due to gain-of-function mutation in the Factor V Leiden protein.

Out of the aforementioned markers, low corrected calcium is the only biochemistry result consistent with the diagnosis. All of the other markers are elevated in TLS.

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. As phosphate precipitates calcium, the serum concentration of calcium becomes low. 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. Rasburicase is a recombinant version of urate oxidase which is an enzyme that metabolizes uric acid to allantoin. Allantoin is much more water soluble than uric acid and is therefore more easily excreted by the kidneys. 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

Aplastic crisis is characterized by a rapid fall in hemoglobin levels associated with few or no reticulocytes, indicating a failure of the bone marrow to respond to increased cell turnover. Folate deficiency can occur in the setting of chronic hemolytic anemia in some patients unless supplemental folate is taken. Parvovirus (B19) has been associated with bone marrow suppression and subsequent aplastic crisis; other viral infections or severe bacterial infections may also suppress the bone marrow. Treatment of aplastic crisis may be necessary when the hematocrit level becomes dangerously low. Packed red blood cells are given to support an adequate hematocrit until bone marrow suppression is resolved, folate is repleted, and the reticulocyte count improves.

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.

Exposure to aniline dyes is a risk factor for transitional cell carcinoma. Aniline dyes are used in dyestuffs and pigment manufacturing.

The other aforementioned options are ruled out because:
1. Feed production may expose to aflatoxin (hepatocellular carcinoma).

2. Being a military personnel may expose to mustard gas (lung cancer).

3. Rubber industry may expose to nitrosamines (oesophageal and gastric cancer).

4. Refrigerant production before 1974 may expose to vinyl chloride (hepatic angiosarcoma).

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.

Hypogammaglobulinemia is a complication of chronic lymphocytic leukaemia (CLL) that leads to recurrent infections.

CLL is a type of cancer caused by monoclonal proliferation of well-differentiated lymphocytes, typically B cells (99%). Onset of the disease is usually asymptomatic and later constitutes anorexia, weight loss, bleeding, and recurrent infections. Lymphadenopathy is more marked in CLL than in chronic myelogenous leukaemia (CML).

Investigations to diagnose CLL include blood film and immunophenotyping. Smudge cells (also known as smear cells) seen on the blood film point towards CLL. Complications of the disease include hypogammaglobulinemia leading to recurrent infections, autoimmune haemolytic anaemia in 10-15% of the patients, and transformation to high-grade lymphoma (Richter’s transformation).

Many of the symptoms favour blast cells: the patient’s young age; a reoccurring sore throat caused by neutropenia and abnormal lymphoblasts; pale conjunctiva due to reduced production of red blood cells (this is because the marrow has been occupied by blast cells). There are no risk factors present for aplastic anaemia, and congenital aplastic anaemia would present itself earlier in life. A bone marrow aspiration would be needed to confirm the diagnosis.

The patient has paroxysmal nocturnal haemoglobinuria (PNH) complicated by acute hepatic vein thrombosis (Budd-Chiari syndrome).

PNH is an acquired clonal disorder of haematopoietic stem cells, characterised by variable combination of intravascular haemolysis, thrombosis, and bone marrow failure. Diagnosis is made by flow cytometric evaluation of blood, which confirms the CD55 and CD59 deficiencies and deficiency of expression of other GPI-linked proteins. This test is replacing older complement-based assays such as the Ham test and sucrose lysis test.

Signs and symptoms of haemolytic uremic syndrome can include bloody diarrhoea, low urine output, nausea, vomiting, abdominal pain and general fatigue. Increased values of urea and creatinine are also typical.

This is a case of Vit. B12 or folic acid deficiency. The anaemia with angular stomatitis is highly suggestive of Vit. B12 or folate deficiency. The absence of koilonychia excludes Iron deficiency anaemia.

A grossly elevated APTT may be caused by heparin therapy, haemophilia, or antiphospholipid syndrome. A normal factor VIIIc activity, however, points towards the diagnosis of haemophilia B, which is the deficiency of factor IX in the blood.

Haemophilia is an X-linked recessive disorder of coagulation. Up to 30% of patients have no family history of the condition. Haemophilia A is due to the deficiency of clotting factor VIII and is more common than haemophilia B, accounting for 90% of the cases. In haemophilia B (Christmas disease), there is a deficiency of clotting factor IX.

Characteristic features of haemophilia include hemarthrosis, haematomas, and prolonged bleeding following trauma or surgery. Coagulation profile of a haemophiliac person shows prolonged bleeding time, activated partial thromboplastin time (APTT), thrombin time (TT), but a normal prothrombin time (PT).

Tumour marker CA 15-3 is mostly associated with breast cancer.

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)

The patient seems to be conscious about his decision, which should be respected. According to Mental Capacity Act 2005, a person who makes an unwise decision should not be treated as unable to make a decision.

The risk factors for bladder cancer are:

1. Smoking
2. Exposure to aniline dyes in the printing and textile industry
3. Exposure to rubber manufacturing
4. Cyclophosphamides
5. Schistosomiasis.

Multiple myeloma presents with bone pain usually in the back or at the level of the ribs. Pathological fractures are common. The patient usually experiences fatigue, paleness, weakness, dyspnoea and gastro-intestinal complaints such as nausea and constipation. Characteristic for this case is the presence of many plasma cells in the peripheral blood smear.

Lymphomas are a type of cancer that arises from lymphocytes. There are two main types of lymphoma:
1. Hodgkin lymphomas, which are characterized by the presence of Reed-Sternberg cells, and
2. Non-Hodgkin lymphomas (NHLs), which comprise all other types of lymphoma. NHLs are further classified according to the cell type, i.e., B cells, T cells, and natural killer (NK) cells, and tumour grade.
Low-grade tumours originate from mature cells that have a slow growth rate and an indolent clinical course. The most common low-grade B-cell lymphoma is follicular lymphoma, while the most common low-grade T-cell lymphomas are the cutaneous T-cell lymphomas such as mycosis fungoides. High-grade tumours, on the other hand, have a rapid growth rate and an aggressive clinical course. Certain subtypes of NHL are more common in children and young adults, such as Burkitt lymphoma.
There is a variety of treatment options, depending on the type of lymphoma. Generally, treatment involves a combination of chemotherapy and radiation therapy. Limited disease low-grade tumours and high-grade NHL are treated with a curative approach. Advanced, low-grade tumours are treated with a palliative approach in symptomatic patients.

Individuals with thalassemia major usually develop symptoms within the first two years of life. These infants may fail to thrive and often have difficulty feeding, tire easily and suffer from severe anemia.

The infants may also suffer from diarrhea, irritability, recurrent episodes of fever, and other intestinal problems. These children have trouble gaining weight and growing at the rate expected for their age. Other complications include enlarged spleen, heart and liver and misshapen bones.

In many cases, the symptoms are severe enough to warrant regular blood transfusion to replenish the blood with healthy red blood cells. However, these regular transfusions can lead to a build up of iron in the blood that can damage the heart, liver and endocrine system and chelation therapy may be needed to remove this iron from the body.

Individuals with beta thalassemia trait usually have evidence of microcytosis and increased levels of hemoglobin A2. Hemoglobin F is sometimes elevated as well. Individuals with alpha thalassemia trait usually have evidence of microcytosis and normal levels of hemoglobin A2 and F.

In thalassemia major, the hemoglobin (Hb) level is usually less than 7 g/dl; the mean corpuscolar volume (MCV) less than 70 fl and the mean corpuscolar Hb (MCH) is over 20 pg.

In thalassemia intermedia, the hemoglobin level is between 7 and 10 g/dl; the MCV between 50 and 80 fl and MCH between 16 and 24 pg.

Thalassemia minor is characterized by a reduced MCV and MCH and an increased haemoglobin A2 level.

The patient could respond well to palliative radiotherapy. This course of action is likely to shrink the cancer and will, therefore, reduce the pain felt. Analgesics should then be used to control the symptoms.

Good prognosis of chronic lymphocytic leukaemia (CLL) is associated with deletion of the long arm of chromosome 13 (del 13q). This is the most common abnormality, seen in around 50% of all CLL patients. Poor prognosis of the disease is related to deletion of part of the short arm of chromosome 17 (del 17p). This is seen in around 5-10% of the patients suffering from CLL.

Poor prognostic factors of CLL include:
1. Male sex
2. Age >70 years
3. Lymphocyte count >50
4. Prolymphocytes comprising more than 10% of blood lymphocytes
5. Lymphocyte doubling time <12 months
6. Raised LDH
7. CD38 expression positive

The results of the blood exam are suggestive of aplastic anaemia which might be secondary to carbamazepine use. The use of antiepileptic’s, in particular carbamazepine and valproate, is associated with a nine fold increased risk of aplastic anaemia.

Acute lymphoblastic leukaemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, frequent infections with fever as well as anaemia with thrombocytopenia. As an acute leukaemia, ALL progresses rapidly and is typically fatal within weeks or months if left untreated. The patient’s age also favours the diagnosis of ALL as it occurs most commonly in children, particularly those between the ages of two and five.

An increase in the patient’s haemoglobin tells us that the patient might be having an increased number of red blood cells. Smoking causes raised carboxyhaemoglobin levels and thus hypoxemia. Hypoxemia will increase the erythropoietin levels in the blood.

Poor prognostic factors for breast cancer include:
1. Young age (<40 years)
2. Premenopausal at the time of diagnosis
3. Increased tumour size
4. High-grade tumour
5. Oestrogen and progesterone receptor-negative tumour
6. Positive lymph node status