The image depicts bone marrow failure caused by acute myeloid leukemia, which occurs when abnormal white blood cells accumulate in the bone marrow, replacing normal blood cells. This type of leukemia is more common in individuals over the age of 45, whereas acute lymphoblastic leukemia is mostly seen in children. Unlike lymphoma, which typically presents with enlarged lymph nodes, acute myeloid leukemia can lead to bone marrow failure. Von Willebrand’s disease may cause severe cases of epistaxis and bleeding gums, but abnormalities in blood test results are rare.

Acute myeloid leukaemia is a prevalent form of acute leukaemia in adults that can occur as a primary disease or as a result of a myeloproliferative disorder. The condition is characterized by bone marrow failure, which can lead to anaemia, neutropenia, thrombocytopenia, splenomegaly, and bone pain. Poor prognostic features include being over 60 years old, having more than 20% blasts after the first course of chemotherapy, and deletions of chromosome 5 or 7.

Acute promyelocytic leukaemia M3 is a subtype of acute myeloid leukaemia that is associated with t(15;17) and the fusion of PML and RAR-alpha genes. This type of leukaemia typically presents at a younger age than other types of AML, with an average age of 25 years old. Auer rods, which are visible with myeloperoxidase stain, are often present, and patients may experience DIC or thrombocytopenia at presentation. However, the prognosis for acute promyelocytic leukaemia M3 is generally good.

The French-American-British (FAB) classification system categorizes acute myeloid leukaemia into seven subtypes based on the degree of maturation of the cells: MO (undifferentiated), M1 (without maturation), M2 (with granulocytic maturation), M3 (acute promyelocytic), M4 (granulocytic and monocytic maturation), M5 (monocytic), M6 (erythroleukaemia), and M7 (megakaryoblastic).

If a patient is taking aminosalicylates, they may experience various haematological adverse effects, including agranulocytosis. Therefore, it is crucial to conduct a full blood count promptly if the patient presents with symptoms such as fever, sore throat, fatigue, or bleeding gums.

While C-reactive protein may be a part of the overall management plan, it is not the most critical initial investigation and is unlikely to alter the management plan.

Although the monospot test for glandular fever may be useful if glandular fever is suspected, it is not the primary investigation that needs to be conducted urgently.

Similarly, while a throat swab may be necessary as part of the overall management plan, it is not the most crucial initial investigation that needs to be performed urgently.

Aminosalicylate Drugs for Inflammatory Bowel Disease

Aminosalicylate drugs are commonly used to treat inflammatory bowel disease (IBD). These drugs work by releasing 5-aminosalicyclic acid (5-ASA) in the colon, which acts as an anti-inflammatory agent. The exact mechanism of action is not fully understood, but it is believed that 5-ASA may inhibit prostaglandin synthesis.

Sulphasalazine is a combination of sulphapyridine and 5-ASA. However, many of the side effects associated with this drug are due to the sulphapyridine component, such as rashes, oligospermia, headache, Heinz body anaemia, megaloblastic anaemia, and lung fibrosis. Mesalazine is a delayed release form of 5-ASA that avoids the sulphapyridine side effects seen in patients taking sulphasalazine. However, it is still associated with side effects such as gastrointestinal upset, headache, agranulocytosis, pancreatitis, and interstitial nephritis.

Olsalazine is another aminosalicylate drug that consists of two molecules of 5-ASA linked by a diazo bond, which is broken down by colonic bacteria. It is important to note that aminosalicylates are associated with a variety of haematological adverse effects, including agranulocytosis. Therefore, a full blood count is a key investigation in an unwell patient taking these drugs. Pancreatitis is also more common in patients taking mesalazine compared to sulfasalazine.

Monitoring Response to Vitamin B12 Treatment in Pernicious Anaemia

Pernicious anaemia is a condition caused by vitamin B12 deficiency, which can lead to a range of symptoms including fatigue, weakness, and neurological problems. Treatment involves intramuscular injections of hydroxocobalamin, with the frequency and duration of treatment depending on the severity of the deficiency.

To monitor the response to treatment, several indicators can be measured. A rise in the reticulocyte count and haemoglobin level within 7-10 days indicates a positive effect. The mean cell volume (MCV) may initially increase due to the increased reticulocyte count, but should return to normal within 25-78 days. Intrinsic factor antibodies may remain present despite treatment. Measuring cobalamin levels is not always necessary, but can be done 1-2 months after starting treatment if there is no response.

Overall, monitoring these indicators can help confirm a diagnosis of pernicious anaemia and ensure that treatment is effective in addressing the deficiency.

Clinical Manifestations of Henoch-Schönlein Purpura

Henoch-Schönlein Purpura (HSP) is a type of vasculitis that affects small blood vessels in the body. Its clinical manifestations include subcutaneous oedema of the feet, hands, scalp, and ears, as well as scrotal oedema. Pitting oedema up to the knees may indicate cardiac failure or nephrotic syndrome. Gastrointestinal bleeding may lead to bloody stools, while haematuria and proteinuria may occur. Abdominal pain, intussusception, and arthritis are also common features. Petechiae, purpura, and papules are commonly present in the thighs and buttocks. Notably, thrombocytopenia, haemolysis, and splenomegaly are absent, and clotting is normal. Understanding the clinical manifestations of HSP is crucial for its timely diagnosis and management.

If there is no bleeding and the INR falls between 5.0-8.0, it is recommended by the BNF to hold back 1-2 doses of warfarin and decrease the following maintenance dose.

Managing High INR Levels in Patients Taking Warfarin

When a patient taking warfarin experiences high INR levels, the management approach depends on the severity of the situation. In cases of major bleeding, warfarin should be stopped immediately and intravenous vitamin K should be administered along with prothrombin complex concentrate or fresh frozen plasma if available. For minor bleeding, warfarin should also be stopped and a lower dose of intravenous vitamin K (1-3 mg) should be given. If the INR remains high after 24 hours, another dose of vitamin K can be administered. Warfarin can be restarted once the INR drops below 5.0.

In cases where there is no bleeding but the INR is above 8.0, warfarin should be stopped and vitamin K (1-5mg) can be given orally using the intravenous preparation. If the INR remains high after 24 hours, another dose of vitamin K can be given. Warfarin can be restarted once the INR drops below 5.0.

If the INR is between 5.0-8.0 and there is minor bleeding, warfarin should be stopped and a lower dose of intravenous vitamin K (1-3 mg) should be given. Warfarin can be restarted once the INR drops below 5.0. If there is no bleeding, warfarin can be withheld for 1 or 2 doses and the subsequent maintenance dose can be reduced.

It is important to note that in cases of intracranial hemorrhage, prothrombin complex concentrate should be considered instead of fresh frozen plasma as it can take time to defrost. These guidelines are based on the recommendations of the British Committee for Standards in Haematology and the British National Formulary.

Lower gastrointestinal tract investigation should be conducted on any patient in this age group who has an unexplained microcytic anaemia to rule out the possibility of colorectal cancer.

Colorectal cancer referral guidelines were updated by NICE in 2015. Patients who are 40 years or older with unexplained weight loss and abdominal pain, those who are 50 years or older with unexplained rectal bleeding, and those who are 60 years or older with iron deficiency anaemia or a change in bowel habit should be referred urgently to colorectal services for investigation. Additionally, patients with positive results for occult blood in their faeces should also be referred urgently.

An urgent referral should be considered if there is a rectal or abdominal mass, an unexplained anal mass or anal ulceration, or if patients under 50 years old have rectal bleeding and any of the following unexplained symptoms or findings: abdominal pain, change in bowel habit, weight loss, or iron deficiency anaemia.

The NHS offers a national screening programme for colorectal cancer every two years to all men and women aged 60 to 74 years in England and 50 to 74 years in Scotland. Patients aged over 74 years may request screening. Eligible patients are sent Faecal Immunochemical Test (FIT) tests through the post. FIT is a type of faecal occult blood test that uses antibodies to detect and quantify the amount of human blood in a single stool sample. Patients with abnormal results are offered a colonoscopy.

The FIT test is also recommended for patients with new symptoms who do not meet the 2-week criteria listed above. For example, patients who are 50 years or older with unexplained abdominal pain or weight loss, those under 60 years old with changes in their bowel habit or iron deficiency anaemia, and those who are 60 years or older who have anaemia even in the absence of iron deficiency.

Von Willebrand’s disease is the most probable diagnosis due to the presence of a petechial skin rash, along with a slightly increased APTT and decreased factor VIII activity.

Understanding Von Willebrand’s Disease

Von Willebrand’s disease is a genetic bleeding disorder that is inherited in an autosomal dominant or recessive manner. It is the most common inherited bleeding disorder, and it behaves like a platelet disorder. Patients with this condition often experience epistaxis and menorrhagia, while haemoarthroses and muscle haematomas are rare.

The disease is caused by a deficiency or abnormality in von Willebrand factor, a large glycoprotein that promotes platelet adhesion to damaged endothelium and serves as a carrier molecule for factor VIII. There are three types of von Willebrand’s disease: type 1, which involves a partial reduction in vWF and accounts for 80% of cases; type 2, which is characterized by an abnormal form of vWF; and type 3, which involves a total lack of vWF and is inherited in an autosomal recessive manner.

To diagnose von Willebrand’s disease, doctors may perform a bleeding time test, measure APTT, and check factor VIII levels. Defective platelet aggregation with ristocetin is also a common finding. Treatment options include tranexamic acid for mild bleeding, desmopressin to raise levels of vWF, and factor VIII concentrate. The type of von Willebrand’s disease a patient has doesn’t necessarily correlate with their symptoms, but common themes include excessive mucocutaneous bleeding, bruising without trauma, and menorrhagia in females.

Patients with glucose-6-phosphate dehydrogenase deficiency may experience haemolysis as a result of taking ciprofloxacin.

Understanding G6PD Deficiency

G6PD deficiency is a common red blood cell enzyme defect that is inherited in an X-linked recessive fashion and is more prevalent in people from the Mediterranean and Africa. The deficiency can be triggered by many drugs, infections, and broad (fava) beans, leading to a crisis. G6PD is the first step in the pentose phosphate pathway, which converts glucose-6-phosphate to 6-phosphogluconolactone and results in the production of nicotinamide adenine dinucleotide phosphate (NADPH). NADPH is essential for converting oxidized glutathione back to its reduced form, which protects red blood cells from oxidative damage by oxidants such as superoxide anion (O2-) and hydrogen peroxide. Reduced G6PD activity leads to decreased reduced glutathione and increased red cell susceptibility to oxidative stress, resulting in neonatal jaundice, intravascular hemolysis, gallstones, splenomegaly, and the presence of Heinz bodies on blood films. Diagnosis is made by using a G6PD enzyme assay, and some drugs are known to cause hemolysis, while others are considered safe.

Compared to hereditary spherocytosis, G6PD deficiency is more common in males of African and Mediterranean descent and is characterized by neonatal jaundice, infection/drug-induced hemolysis, and gallstones. On the other hand, hereditary spherocytosis affects both males and females of Northern European descent and is associated with chronic symptoms, spherocytes on blood films, and the presence of erythrocyte membrane protein band 4.2 (EMA) binding.

Haemorrhagic cystitis can be caused by cyclophosphamide.

Cytotoxic agents are drugs that are used to kill cancer cells. There are several types of cytotoxic agents, each with their own mechanism of action and potential adverse effects. Alkylating agents, such as cyclophosphamide, work by causing cross-linking in DNA. However, they can also cause haemorrhagic cystitis, myelosuppression, and transitional cell carcinoma. Cytotoxic antibiotics, like bleomycin and anthracyclines, degrade preformed DNA and stabilize DNA-topoisomerase II complex, respectively. However, they can also cause lung fibrosis and cardiomyopathy. Antimetabolites, such as methotrexate and fluorouracil, inhibit dihydrofolate reductase and thymidylate synthesis, respectively. However, they can also cause myelosuppression, mucositis, and liver or lung fibrosis. Drugs that act on microtubules, like vincristine and docetaxel, inhibit the formation of microtubules and prevent microtubule depolymerisation & disassembly, respectively. However, they can also cause peripheral neuropathy, myelosuppression, and paralytic ileus. Topoisomerase inhibitors, like irinotecan, inhibit topoisomerase I, which prevents relaxation of supercoiled DNA. However, they can also cause myelosuppression. Other cytotoxic drugs, such as cisplatin and hydroxyurea, cause cross-linking in DNA and inhibit ribonucleotide reductase, respectively. However, they can also cause ototoxicity, peripheral neuropathy, hypomagnesaemia, and myelosuppression.

Diagnosis of Myeloma

Up to one-third of patients with myeloma may not show any abnormality in their serum immunoglobulin electrophoresis. In such cases, urine protein electrophoresis is the next appropriate step to confirm the diagnosis. The presence of monoclonal protein in serum often leads to an excess of free light chains in the urine, which can be detected through urine electrophoresis.

While bone scanning is not very effective in confirming myeloma, plain radiography can be used to evaluate the disease. A skeletal survey is the preferred option for disease evaluation. A trial of iron supplements should be avoided as it can delay the diagnosis of myeloma and lead to a poorer outlook. Endoscopy should only be considered after ruling out myeloma as the cause of anaemia.

In summary, a combination of serum and urine protein electrophoresis, plain radiography, and skeletal survey can help diagnose myeloma accurately.