A nodule is a solid, well circumscribed, raised area that lies in or under the skin and measures greater than 0.5 cm in diameter. They are usually painless.A vesicle is a visible collection of fluid measuring less than 0.5 cm in diameter. A macule is a flat, well circumscribed area of discoloured skin less than 1 cm in diameter with no changes in the thickness or texture of the skin.A papule is a solid, well circumscribed, skin elevation measuring less than 0.5 cm in diameter.A plaque is a palpable skin lesion that is elevated and measures >1cm in diameter

Examples of type II reactions include: Incompatible blood transfusionsHaemolytic disease of the newbornAutoimmune haemolytic anaemiasGoodpasture’s syndromeRheumatic heart diseaseBullous pemphigoid

This patient has Nephrotic Syndrome confirmed by the presence of 1. Heavy proteinuria (greater than 3-3.5 g/24 hours)2. Hypoalbuminemia (serum albumin < 25 g/L)3. Generalised oedema (often with periorbital involvement)4. Severe hyperlipidaemia (total cholesterol is often > 10 mmol/L). Focal Segmental Glomerulosclerosis will be the most likely answer as it is the most common cause of Nephrotic Syndrome in African American adults. Minimal change disease is the most common cause of nephrotic syndrome in children. Membranous glomerulonephritis is the most common cause of Nephrotic Syndrome in Caucasian adults. In IgA nephropathy, patients will complain of cola-coloured urine. Mesangiocapillary glomerulonephritis presents with features of Nephritic Syndrome.

Fat-soluble vitamin K is obtained from green vegetables and bacterial synthesis in the gut. Deficiency may present in the newborn (haemorrhagic disease of the newborn) or in later life. Deficiency may be caused by an inadequate diet, malabsorption or inhibition of vitamin K by drugs such as warfarin. The activity of factors II, VII, IX and X are vitamin K dependent as well as that of protein C and protein S. Both PT and APTT are prolonged.

Innate, or non-specific, immunity is the immune system we are born with.There are three aspects of innate immunity:1. Anatomical barriers, such as:The cough reflexEnzymes in tears and skin oilsMucus – which traps bacteria and small particlesSkinStomach acid2. Humoral barriers, such as:The complement systemInterleukin-13. Cellular barriers, such as:NeutrophilsMacrophagesDendritic cellsNatural killer cellsAntibody production is part of the specific, or inducible immune response. T-lymphocytesare responsible for the cell mediated immune response which is part of specific, or inducible immunity.

Following neuronal injury, as seen in traumatic brain injury, the axon undergoes anterograde degeneration. Degradation starts from the cell body (proximally) and progresses distally. The axon becomes fragmented and degenerates. The brain shows no reactive changes to injury is incorrect. Following major injury such as stroke, the brain undergoes a process of liquefactive degeneration, which leaves cystic spaces within the brain.Axonal regeneration does not occur to any significant extent within the central nervous system unlike what is seen in the peripheral nervous system. Astrocytes undergo reactive gliosis, leaving behind a firm translucent tissue around sites of damage.

Features include:- severe anaemia (becoming apparent at 3 – 6 months when the switch from gamma-chain to beta-chain production takes place)- failure to thrive- hepatosplenomegaly (due to excessive red cell destruction, extramedullary haemopoiesis and later due to transfusion related iron overload)- expansion of bones (due to marrow hyperplasia, resulting in bossing of the skull and cortical thinning with tendency to fracture)- increased susceptibility to infections (due to anaemia, iron overload, transfusion and splenectomy)- osteoporosis- hyperbilirubinaemia and gallstones- hyperuricaemia and gout- other features of haemolytic anaemia- liver damage and other features of iron overload

Compression of the thecal sac causes metastatic Spinal Cord Compression (MSCC) due to a Metastatic tumour and its components. It can cause symptoms of limb weakness, sensory disturbances and back pain depending on the extent and level of Compression. The most common source of a tumour causing MSCC is a prostate carcinoma that metastasized to the spinal cord via the vertebral venous plexus.

About 20% of patients that suffer an anaphylactic reaction suffer a biphasic response 4-6 hours after the initial response (sometimes up to 72 hours after).

CREST syndrome is usually associated with anti-centromere antibodies.Primary biliary cirrhosis is associated with anti-mitochondrial antibodies.Sjogren’s syndrome is associated with anti-Ro and anti-La antibodies.Polymyositis is associated with anti-Jo1 antibodies.Anti-double stranded DNA antibodies are highly characteristic of systemic lupus erythematosus (SLE). They are a group of anti-nuclear antibodies (ANA) that target double stranded DNA and are implicated in the pathogenesis of lupus nephritis.

Basophils are only occasionally seen in normal peripheral blood comprising < 1% of circulating white cells. However, they are the largest type of granulocyte. They have many dark cytoplasmic granules which overlie the nucleus and contain heparin and histamine. They have immunoglobulin E (IgE) attachment sites and their degranulation is associated with histamine release. Basophils are very similar in both appearance and function to mast cells.

Non-Hodgkin’s lymphoma (NHL) refers to a group of lymphoproliferative malignancies (about 85% of B-cell and 15% of T or NK (natural killer) cell origin) with different behavioural patterns and treatment responses. This group of malignancies encompasses all types of lymphoma without Reed-Sternberg cells being present. The Reed-Sternberg cell is classically seen in Hodgkin’s lymphoma.NHL is five times as common as Hodgkin’s lymphoma. The peak incidence of NHL is in the 50-70 years age group, it affects men and women equally, but affects the Caucasian population more commonly than black and Asian ethnic groups.The following are recognised risk factors for NHL:Chromosomal translocations and molecular rearrangementsEpstein-Barr virus infectionHuman T-cell leukaemia virus type-1 (HTLV-1)Hepatitis CCongenital and acquired immunodeficiency statesAutoimmune disorders, e.g. Sjogren’s syndrome and Hashimoto’s thyroiditisThe most common clinical features at presentation are:Lymphadenopathy (typically asymmetrical and painless)Weight lossFatigueNight sweatsHepatosplenomegalyFor clinical purposes, NHL is divided into three groups: indolent, high-grade, and lymphoblastic.Indolent (low-grade) NHL:The cells are relatively matureDisease follows an indolent course without treatmentOften acceptable to follow a ‘watch and wait’ strategyLocal radiotherapy often effectiveRelatively good prognosis with median survival of 10 yearsHigh-grade NHL:Cells are immatureDisease progresses rapidly without treatmentSignificant number of patients can be cured with intensive combination chemotherapy regimensApproximately 40% cure rateLymphoblastic NHL:Cells are very immature and have a propensity to involve the CNSTreatment and progression are similar to that of acute lymphoblastic leukaemia (ALL)

C-reactive protein(CRP) is synthesized in the liver in response to increased interleukin-6 (IL-6) secretion by macrophages and T-cells. Some conditions that cause CRP levels to a rise include: bacterial infection, fungal infection, severe trauma, autoimmune disease, Organ tissue necrosis, malignancy and surgery.It is useful in the clinical setting as a marker of inflammatory activity and can be used to monitor infections. CRP levels start to rise 4-6 hours after an inflammatory trigger and reaches peak levels at 36-50 hours.In the absence of a disease process, the normal plasma concentration is less than 5 mg/l.CRP is useful for monitoring inflammatory conditions (e.g. rheumatoid arthritis and malignancy), can be used as a prognostic marker in acute pancreatitis, and serial measurement can be used to recognize the onset of nosocomial infections in the intensive care settling.

DIC is characterised by a widespread inappropriate intravascular deposition of fibrin with consumption of coagulation factors and platelets. This may occur as a consequence of many disorders that release procoagulant material into the circulation or cause widespread endothelial damage or platelet aggregation. Increased activity of thrombin in the circulation overwhelms its normal rate of removal by natural anticoagulants. In addition to causing increased deposition of fibrin in the microcirculation and widespread platelet aggregation to the vessels, intravascular thrombin formation interferes with fibrin polymerisation. Intense fibrinolysis is stimulated by thrombi on vascular walls and the release of fibrin degradation products again interferes with fibrin polymerisation. The combined action of thrombin and plasmin causes depletion of fibrinogen and all coagulation factors, compounded by thrombocytopaenia caused by platelet consumption.

A type IV hypersensitivity reaction occurred in this patient. Allergic contact dermatitis is an inflammatory skin reaction occurring in response to an external stimulus, acting either as an allergen or an irritant, caused by a type IV or delayed hypersensitivity reaction. They usually take several days to develop.

A history of stroke and poor nutritional status points towards a nutritional deficiency as the most likely cause of her symptoms. The examination would differentiate between Vitamin B12 and Folic acid deficiency as in the former. The patient has a beefy red tongue and symptoms indicating peripheral nervous system involvement or subacute combined spinal cord degeneration. The patient may also have a lemon-yellow skin colour, loss of proprioception and vibratory sense and oral ulceration. Investigations in B12 deficiency can reveal the following:1. Macrocytic anaemia2. Neutropoenia3. Thrombocytopaenia4. Blood film: anisocytosis, poikilocytosis5. Low serum B126. Raised serum bilirubin (haemolysis)7. Intrinsic factor antibodies8. Positive Schilling test

Anaphylaxis transfusion reaction occurs when an individual has previously been sensitized to an allergen present in the blood and, on re-exposure, releases IgE or IgG antibodies. Patients with anaphylaxis usually develop laryngospasm, bronchospasm, abdominal pain, nausea, vomiting, hypotension, shock, and loss of consciousness. The transfusion should be stopped immediately and the patient should be treated with adrenaline, oxygen, corticosteroids, and antihistamines.

Delayed haemolytic transfusion reactions (DHTRs) commonly occurs 4-8 days after blood transfusion, but can occur up to a month after. Signs and symptoms include jaundice, fever, an inadequate rise in PCV, reticulocytosis, a positive antibody screen and a positive Direct Antiglobulin Test (Coombs test). DHTRs usually have a benign course and require no treatment but sometimes, life-threatening haemolysis with severe anaemia and renal failure can occur so haemoglobin levels and renal function should be monitored.Acute haemolytic reaction aka immediate haemolytic transfusion reaction presents with fever, chills, pain at transfusion site, nausea, vomiting, dark urine and feeling of ‘impending doom’. Often, it occurs due to ABO incompatibility.Febrile transfusion reaction presents with a 1 degree rise in temperature from baseline during transfusion. Patient may have chills and malaise. It is the most common transfusion reaction (1 in 8 transfusions) and is usually caused by cytokines released from leukocytes in transfused red cell or platelet components.Transfusion-associated circulatory overload (TACO) presents as acute or worsening respiratory distress within 6 hours of transfusion of a large volume of blood. It is common in patients with diminished cardiac reserve or chronic anaemia. Elderly patients, infants and severely anaemic patients are particularly susceptible. Clinical features of TACO include: Acute respiratory distress, Tachycardia, Hypertension, Acute/worsening pulmonary oedema on chest X-ray. The BNP is usually raised to at least 1.5 times the pre-transfusion baseline.Graft versus host disease(GVHD) is an immune mediated condition that arises from a complex interaction between donor and recipients adaptive immunity. It presents as dermatitis, hepatitis and enteritis developing within 100 days after stem cell or bone marrow transplant.

Aspirin irreversibly inhibits cyclooxygenase and blocks the platelet production of thromboxane A2 (TXA2), thus inhibiting platelet aggregation.

A total neutrophil count of greater than 7.5 x 109/L is called neutrophilia. Typhoid fever usually causes leukopenia or neutropenia. Both localised and generalised bacterial infections can cause neutrophilia. Metabolic disorders such as – gout- eclampsia- uraemia can also cause neutrophilia. Acute neutrophilia, in which immature neutrophils can be seen, is referred to as a left shift and can be seen in conditions such as appendicitis.

Bacterial infections are common in the following situations:Platelet transfusions are associated with a higher risk of bacterial infection (as platelets are stored at room temperature)Immersion in a water bath thawed previously frozen components.Components of red blood cells that have been stored for several weeksGram-positive and Gram-negative bacteria have both been linked to transfusion-transmitted bacterial infection, but Gram-negative bacteria are linked to a higher rate of morbidity and mortality.Yersinia enterocolitica is the most common bacterial organism linked to transfusion-transmitted bacterial infection. This organism can multiply at low temperatures while also utilising iron as a nutrient. As a result, it’s well-suited to proliferating in blood banks.The following are some of the most common clinical signs and symptoms of a bacterial infection transmitted through a blood transfusion. These symptoms usually appear shortly after the transfusion begins:Fever is very high.Rigours and chillsVomiting and nauseaTachycardiaHypotensionCollapse of the circulatory systemIf a bacterial infection from a transfusion is suspected, the transfusion should be stopped right away. Blood cultures and a Gram stain should be requested, as well as broad-spectrum antibiotics. In addition, the blood pack should be returned to the blood bank for an urgent culture and Gram-stain.

Mitochondrial diseases are a group of disorders caused by dysfunctional mitochondria. Most cases are maternally inherited, as we inherit our mitochondrial DNA from our mothers only, although mutations in nuclear DNA cause some cases.Examples of Mitochondrial Diseases include:1. Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS)2. Mitochondrial epilepsy with ragged red fibres (MERRF)3. Leber’s hereditary optic neuropathy (LHON)4. Diabetes mellitus and deafness (DAD)5. Neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP)6. Leigh syndrome (subacute sclerosing encephalopathy). Red-green colour blindness and G6PD deficiency have an X-linked recessive pattern of inheritance. Tay-Sachs Disease and spinal muscular atrophy have an autosomal recessive pattern of inheritance.

Newborn babies have a higher concentration of red blood cells with shorter lifespan leading to higher bilirubin levels than in adults. This condition is short-lived and harmless but with potential serious causes that need to be assessed for if present. The most obvious physical sign of jaundice is a yellow discolouration of the sclera, skin and mucous membranes. At a bilirubin level of 35 μmol/L or higher, the eye is affected. The bilirubin level will need to be higher than 255 μmol/L for the feet and extremities to be affected.

Blood loss from the gastrointestinal (GI) tract is the most common cause of iron deficiency anaemia in adult men and postmenopausal women.

Febrile transfusion reactions presents with an unexpected temperature rise (≥ 38ºC or ≥ 1ºC above baseline, if baseline ≥ 37ºC) during or shortly after transfusion. It is usually an isolated finding and the fever is accompanied by chills and malaise occasionally.Allergic reaction is commonly caused by foreign plasma proteins but may be due to anti-IgA. Allergic type reactions usually present with urticaria, pruritus, hives. Associations include laryngeal oedema or bronchospasm.Acute haemolytic reaction aka immediate haemolytic transfusion reaction presents with fever, chills, pain at transfusion site, nausea, vomiting, dark urine and feeling of ‘impending doom’. Often, it occurs due to ABO incompatibility.Transfusion-associated circulatory overload (TACO) presents as acute or worsening respiratory distress within 6 hours of transfusion of a large volume of blood. It is common in patients with diminished cardiac reserve or chronic anaemia. Elderly patients, infants and severely anaemic patients are particularly susceptible. Clinical features of TACO include: Acute respiratory distress, Tachycardia, Hypertension, Acute/worsening pulmonary oedema on chest X-ray. The BNP is usually raised to at least 1.5 times the pre-transfusion baseline.Transfusion-related lung injury (TRALI) is a form of acute respiratory distress caused by the donor plasma containing antibodies against the patient’s leukocytes. It is defined as hypoxia and bilateral pulmonary oedema that occurs within 6 hours of a transfusion in the absence of other causes of acute lung injury. Clinical features include Breathlessness, cough, frothy sputum, hypertension or hypotension, hypoxia and fever. Chest X-ray shows multiple perihilar nodules with infiltration of the lower lung fields.

AKI is diagnosed based on an acutely rising serum creatinine and/or reduction in urine output.

AKI can often be non-oliguric.

AKI is present if any one or more of the following criteria is met:

• A rise in serum creatinine of ≥26 micromol/L (≥0.3 mg/dL) within 48 hours
• A rise in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the past 7 days (in practice you can use the lowest value from the past 3 months as the baseline for the patient)
• Urine volume <0.5 ml/kg/hour for at least 6 hours.

Mast cells play a central role in the response to allergen challenges. The activation of mast cells results in both an early and a delayed phase of inflammation. Mast cells have been implicated in both physiologic and pathogenic processes. Mast cells are important in defence against some bacteria and viruses and contribute to defence against parasites. They are key effector cells in both innate and acquired immunity and are capable of inducing and amplifying both types of responses. Specifically, mast cells are capable of detecting microbial products through surface pattern recognition receptors, and they are involved in the recruitment of other leukocytes, containment of bacterial infections, and tissue repair.

ALL affects children predominantly.The CNS is commonly involved in ALL.The Philadelphia chromosome is present in 25% of adult ALL and 5% of childhood ALL cases.The cure rate in children is approximately 80% in children and 50% in adults.ALL is classified into 3 groups using the French-American-British (FAB) classification:ALL-L1: small uniform cellsALL-L2: large varied cellsALL-L3: large varied cells with vacuoles.

Hodgkin’s lymphoma is a malignant tumour of the lymphatic system that is characterised histologically by the presence of Reed-Sternberg cells (multinucleated giant cells). The annual incidence of Hodgkin’s lymphoma in the UK is approximately 3 per 100,000 per year. The peak incidence is in young adults aged 20-35, and there is a slight male predominance.The following are recognised risk factors for Hodgkin’s lymphoma:Male genderAge 20-35Positive family historyEpstein-Barr virus infectionImmunosuppression including HIV infectionProlonged use of human growth hormoneMost patients present with an enlarged, but otherwise asymptomatic lymph node. The most commonly affected lymph nodes are in the supraclavicular and lower cervical areas. Other common clinical features include shortness of breath and chest discomfort secondary to mediastinal mass. Mediastinal masses are sometimes discovered as incidental findings on routine chest X-rays. Approximately 30% of patients with Hodgkin’s lymphoma develop splenomegaly.‘B’ symptoms occur in approximately 25% of patients. The ‘B’ symptoms of Hodgkin’s lymphoma are:Fever (>38ºC)Night sweatsWeight loss (>10% over 6 months)Pain after alcohol consumption is a pathognomonic sign of Hodgkin’s lymphoma, it is, however, not a ‘B’ symptom. It is rare though, only occurring in 2-3% of patients with Hodgkin’s lymphoma.The Ann Arbour clinical staging is as follows:Stage I: one involved lymph node groupStage II two involved lymph node groups on one side of the diaphragmStage III: lymph node groups involved on both sides of the diaphragmStage IV: Involvement of extra-nodal tissues, such as the liver or bone marrowDiagnosis is made by lymph node biopsy, which should be taken from a sufficiently large specimen or excisional biopsy, as opposed to a fine needle biopsy. The Reed-Sternberg cell is the most useful diagnostic feature. This is a giant cell with twin mirror-image nuclei and prominent ‘owl’s eye’ nucleoli.The Reed-Sternberg cell of Hodgkin’s LymphomaHistological typing depends upon the other cells within the diseased tissue. Nodular sclerosing is the most common type of Hodgkin’s lymphoma. Lymphocyte-depleted and lymphocyte-predominant are rare subtypes.The majority of cases can be successfully treated, and unlike many other malignancies even if the first-line treatment fails, a cure can often be achieved with second-line therapies. Stage 1 Hodgkin’s lymphoma is usually treated with radiotherapy alone, but more advanced stages require combination chemotherapy. In localised disease treated with irradiation, there is a 5-year survival rate of greater than 80%. In disseminated disease treated with chemotherapy, the 5-year survival falls to around 50%. Overall, a 5-year survival of >70% should be achieved.

Acute haemolytic transfusion reactions present with: Feeling of ‘impending doom’ as the earliest symptom, fever and chills, pain and warmth at transfusion site, nausea and vomiting, back, joint, and chest pain. Transfusion should be stopped immediately and IV fluid (usually normal saline) administered.Supportive measures and paracetamol can be given since patient has fever but it is not the immediate first step.

Multiple myeloma is a clonal abnormality affecting plasma cells in which there is an overproduction of functionless immunoglobulins. The most common patient complaint is bone pain, especially in the back and ribs. Anaemia and renal failure are common, along with hypercalcemia. Hypercalcemia may lead to an altered mental status, as in this case. Chronic lymphocytic leukaemia occurs due to the overproduction of lymphocytes, usually B cells. CLL may present with an asymptomatic elevation of B cells. Patients are generally more than 50 years old and present with non-specific fatigue and weight loss symptoms.There is no history of alcohol abuse in this case. Furthermore, patients with a history of alcohol abuse may have signs of liver failure, which are not present here. Metastatic prostate cancer would most often cause lower backache as it metastasises first to the lumbar spine via the vertebral venous plexus. A patient with Vitamin B12 deficiency would have anaemia, megaloblastic, hypersegmented neutrophils, and signs of peripheral neuropathy.

Anaphylaxis is an example of a type I hypersensitivity reaction. It is IgE mediated. It requires a prior exposure to the antigen. The initial exposure sensitizes the body to the antigen and a second exposure to that antigen leads to an anaphylactic reaction.Massive calcium influx into the cells leads to mast cell degranulation. The Immunoglobulin antigen complex binds to Fc receptors on the surface of mast cells. The result is mast cell degranulation and release of histamine, proteoglycans and serum proteases from cytoplasmic granules.

Key elements of the maturation stage include collagen cross-linking, collagen remodelling, wound contraction, and repigmentation. The tensile strength of the wound is directly proportional to the amount of collagen present. Numerous types of collagen have been identified; types I and III predominate in the skin and aponeurotic layers. Initially, a triple helix (tropocollagen) is formed by three protein chains; two are identical alpha-1 protein chains, and the third is an alpha-2 protein.

Dipyridamole inhibits both the reuptake of adenosine and phosphodiesterase, preventing the degradation of cAMP and thus blocking the platelet aggregation response to ADP.

Megaloblastic anemia results from inhibition of DNA synthesis during red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the growth stage to the mitosis stage. This leads to continuing cell growth without division, which presents as macrocytosis, with an increase in mean corpuscular volume (MCV). The defect in red cell DNA synthesis is most often due to hypovitaminosis, specifically vitamin B12 deficiency or folate deficiency.Folate is an essential vitamin found in most foods, especially liver, green vegetables and yeast. The normal daily diet contains 200 – 250 μg, of which about 50% is absorbed. Daily adult requirements are about 100 μg. Absorption of folate is principally from the duodenum and jejunum. Stores of folate are normally only adequate for 4 months and so features of deficiency may be apparent after this time.

A serious complication in sickle cell disease (SCD) is the aplastic crisis. This may be caused by infection with Parvovirus B-19 (B19V). This virus causes fifth disease, a normally benign childhood disorder associated with fever, malaise, and a mild rash. This virus infects RBC progenitors in bone marrow, resulting in impaired cell division for a few days. Healthy people experience, at most, a slight drop in hematocrit, since the half-life of normal erythrocytes in the circulation is 40-60 days. In people with SCD, however, the RBC lifespan is greatly shortened (usually 10-20 days), and a very rapid drop in Hb occurs. The condition is self-limited, with bone marrow recovery occurring in 7-10 days, followed by brisk reticulocytosis.

Once muscle tissue is damaged, there will be healing via diffuse formation of fibrous tissue, especially due to the widespread ischemia. Callus formation takes place in the healing of bone, not muscle. Organised scar formation occurs when a lacerated wound is approximated by sutures so that primary intention wound healing can occur. Liquefaction degeneration occurs following ischemia in the brain. Volkmann’s ischemic contracture may occur, but it is not the primary type of healing that will take place but rather the effect of the fibrous scar formation.

Hepatitis A usually doesn’t pose a special risk to a pregnant woman or her baby. Maternal infection doesn’t result in birth defects, and a mother typically doesn’t transmit the infection to her baby. HAV is almost always transmitted by the faecal-oral route and is usually acquired through close personal contact or via contaminated food.When a woman has chickenpox in the first 20 weeks of pregnancy, there is a 1 in 50 chance for the baby to develop a set of birth defects. This is called the congenital varicella syndrome. It includes scars, defects of muscle and bone, malformed and paralyzed limbs, small head size, blindness, seizures, and intellectual disability.TORCH Syndrome refers to infection of a developing foetus or newborn by any of a group of infectious agents. “TORCH” is an acronym meaning (T)oxoplasmosis, (O)ther Agents, (R)ubella (also known as German Measles), (C)ytomegalovirus, and (H)erpes Simplex.Infection with any of these agents may cause a constellation of similar symptoms in affected newborns. These may include fever; difficulties feeding; small areas of bleeding under the skin, causing the appearance of small reddish or purplish spots; enlargement of the liver and spleen (hepatosplenomegaly); yellowish discoloration of the skin, whites of the eyes, and mucous membranes (jaundice); hearing impairment; abnormalities of the eyes; and other symptoms and findings.

Non-Hodgkin’s Lymphoma (NHL) causes neoplastic transformation of both B cell (85%) and T cell (15%) lines. The most common presentation is with enlarged, rubbery, painless lymph nodes. The patient may also have B symptoms which consist of night sweats, weight loss and fevers. Multiple myeloma most commonly presents with bone pain, especially in the back and ribs. The presence of Reed-Sternberg cells characterises Hodgkin’s lymphoma. Acute lymphoblastic leukaemia will present with features of anaemia, thrombocytopenia and leukopenia. The most common symptoms of chronic lymphocytic leukaemia are fatigue, night sweats and low-grade fever.The peak incidence of NHL is in the 50-70 years age group, it affects men and women equally, but affects the Caucasian population more commonly than black and Asian ethnic groups.The following are recognised risk factors for NHL:Chromosomal translocations and molecular rearrangementsEpstein-Barr virus infectionHuman T-cell leukaemia virus type-1 (HTLV-1)Hepatitis CCongenital and acquired immunodeficiency statesAutoimmune disorders, e.g. Sjogren’s syndrome and Hashimoto’s thyroiditis

Haemorrhage occurs into the fracture site from the ruptured vessels in the bone marrow and those supplying the periosteum immediately after fracture. This hematoma formation is the first phase of bone healing.The 4 stages of bone healing are:Haematoma at the fracture site (provides a framework for healing)Callus formationLamellar bone formationRemodelling

Features of intravascular haemolysis include:haemoglobinaemia, methaemalbuminaemia, haemoglobinuria (dark urine) and haemosiderinuria

Haemophilia A is the most common of the hereditary clotting factor deficiencies. The inheritance is sex-linked but up to one-third of patients have no family history and these cases result from recent mutation. The vast majority of cases are inherited in an X-linked recessive fashion, affecting males born to carrier mothers. Females born to affected fathers can also, rarely, be affected due to homozygosity for the gene, where there is marriage to close relatives. The defect is an absence or low level of plasma factor VIII. The APTT is prolonged but the PT is normal. Recurrent painful haemarthroses and muscle haematomas dominate the clinical course of severely affected patients and if inadequately treated, lead to progressive joint deformity and disability. Local pressure can cause entrapment neuropathy or ischaemic necrosis. Prolonged bleeding occurs after dental extractions or post-trauma. Spontaneous haematuria and gastrointestinal haemorrhage may occur. The clinical severity of the disease correlates inversely with the factor VIII level. Operative and post-traumatic haemorrhage are life-threatening both in severely and mildly affected patients.

Raised platelet levels have emerged as a cancer risk marker, according to a large population-based study published in 2017(link is external). According to the study, 12 percent of men and 6% of women with thrombocytosis were diagnosed with cancer within a year. These figures increased to 18% in men and 10% in women if a second platelet count was taken within 6 months of the first and showed an increased or stable elevated platelet count.The researchers discovered that thrombocytosis linked to cancer is most common in colorectal and lung cancers, and it is linked to a worse prognosis. Furthermore, one-third of the cancer patients in the study had no other symptoms that would have prompted an immediate cancer referral.The exact mechanism by which these cancers cause thrombocytosis is unknown, but one theory proposes the existence of pathogenic feedback loops between malignant cells and platelets, with a reciprocal interaction between tumour growth and metastasis, as well as thrombocytosis and platelet activation. Another hypothesis is that thrombocytosis occurs independently of cancer but aids in its spread and progression.The findings show that routinely testing for thrombocytosis could cut the time it takes to diagnose colorectal and lung cancer by at least two months. In the UK, this could result in around 5500 earlier cancer diagnoses per year.Because the positive predictive value of thrombocytosis in middle age for cancer (10%) is higher than the positive predictive value for a woman in her 50s presenting with a new breast lump (8.5%), this is clearly an important research paper that should be used to adjust future clinical practise. The current NICE guidelines predate these new research findings, so we’ll have to wait and see how they affect cancer referral guidelines in the UK.Because there are so many possible cancers associated with thrombocytosis, the treating clinician should take a thorough history and perform a thorough clinical examination if a patient is diagnosed with it. Further investigation and the most appropriate referral route should be aided by this information.It’s worth noting that the patients in the study had their blood tests done for a medical reason rather than as a random screening test.If there are no other symptoms to guide investigation and referral (one-third of the patients in the study had no other symptoms), keep in mind that the two most common cancers encountered were colorectal and lung cancer, so a chest X-ray and a faecal immunochemical test (FIT) for faecal blood may be reasonable initial investigations.

Anti-cyclic citrullinated peptide (anti-CCP) is an antibody present in 60-80% of rheumatoid arthritis patients. It is measured by enzyme-linked immunosorbent assay (ELISA). It may be present years before the onset of the disease and is associated with a more severe disease course.While most patients with anti-CCP antibodies are also positive for rheumatoid factor (RF), RF antibody is not specific for rheumatoid arthritis as it can occur in patients with other conditions such as infections and other autoimmune conditions.ESR, antinuclear antibodies(ANA) and Synovial fluid examination are not specific for rheumatoid arthritis.

Chronic myeloid leukaemia (CML) is a clonal disorder of a pluripotent stem cell. The disease accounts for around 15% of leukaemias and may occur at any age. The diagnosis of CML is rarely difficult and is assisted by the characteristic presence of the Philadelphia (ph) chromosome. This disease occurs in either sex, most frequently between the ages of 40 and 60 years. In up to 50% of cases the diagnosis is made incidentally from a routine blood count. Leucocytosis is the main feature, with a complete spectrum of myeloid cells seen in the peripheral blood. The levels of neutrophils and myelocytes exceed those of blast cells and promyelocytes.Increased circulating basophils are a characteristic feature. Normochromic normocytic anaemia is usual. Platelet count may be increased (most frequently), normal or decreased. The clinical outlook is very good and 90% of patients can expect long-term control of disease.

Primary wound healing, or healing by first intention, occurs within hours of repairing a full-thickness surgical incision. This surgical insult results in the mortality of a minimal number of cellular constituents. Healing by first intention can occur when the wound edges are opposed, the wound is clean and uninfected and there is minimal loss of cells and tissue i.e. surgical incision wound. The wound margins are joined by fibrin deposition, which is subsequently replaced by collagen and covered by epidermal growth.

Polycythaemia vera (PCV), which is also referred to as polycythaemia rubra vera, is a clonal haematological malignancy in which the bone marrow produces too many red blood cells. It may also result in the overproduction of white blood cells and platelets. It is most commonly seen in the elderly and the mean age at diagnosis is 65-74 years.Patients can be completely asymptomatic and it is often discovered as an incidental finding on a routine blood count. Approximately 1/3 of patients present with symptoms due to thrombosis, of these 3/4 have arterial thrombosis and 1/4 venous thrombosis. Features include stroke, myocardial infarction, deep vein thrombosis and pulmonary embolism.The other clinical features of PCV include:Plethoric appearanceLethargy and tirednessSplenomegaly (common)Pruritis (in 40% – particularly after exposure to hot water)Headaches, dizziness and sweating (in 30%)Gouty arthritis (in 20%)Budd-Chiari syndrome (in 5-10%)Erythromyalgia (in 18.5 g/dl in men, 16.5 g/dl in womenElevated red cell mass > 25% above mean normal predicted valuePresence of JAK2 mutationMinor criteria:Bone marrow biopsy showing hypercellularity with prominent erythroid, granulocytic and megakaryocytic proliferationSerum erythropoietin level below normal rangeEndogenous erythroid colony formation in vitroThe main aim of treatment is to normalize the full blood count and prevent complications such as thrombosis. Venesection is the treatment of choice but hydroxyurea can also be used to help control thrombocytosis.

A total neutrophil count of less than 2 x 109/L is defined as neutropenia. It can be caused by the following:1. viral infections2. SLE3. RA4. hypersplenism5. chemo- and radiotherapy6. vitamin B12 and folate deficiency7. drug reactions

Anaemia is defined as a reduction in haemoglobin concentration below the normal range for the age and sex of the individual. Children tend to have lower haemoglobin than adults, and women tend to have lower haemoglobin than men. Anaemia may occur from an actual reduction in total circulating haemoglobin mass, or with an increase in plasma volume e.g. in pregnancy, causing a dilutional anaemia. After acute major blood loss, anaemia is not immediately apparent because total blood volume is reduced and it takes up to a day for plasma volume to be replaced and hence the degree of anaemia to become apparent. The initial clinical features in acute haemorrhage are therefore a result of reduction in blood volume rather than that of anaemia. When anaemia develops slowly, the associated symptoms are often very mild as the body has time to adapt to the fall in haemoglobin. This involves mechanisms such as an increase in red cell 2,3 -diphosphoglycerate (2,3 – DPG), which shifts the oxygen dissociation curve to the right, allowing enhanced delivery of O2 to the tissues, and an increase in stroke volume and heart rate.

Factor V Leiden gene mutation is the most common inherited cause of an increased risk of venous thrombosis. Activated protein C normally breaks down activated factor V and so should slow the clotting reaction and prolong the APTT, but a mutation in the factor V gene makes factor V less susceptible to cleavage by activated protein C, resulting in increased levels of activated factor V.Heterozygotes for factor V Leiden are at an approximately five- to eight- fold increased risk of venous thrombosis compared to the general population (but only 10% of carriers will develop thrombosis in their lifetime). Homozygotes have a 30 – 140-fold increased risk. The incidence of factor V Leiden in patients with venous thrombosis is approximately 20 – 40%. It does not increase the risk of arterial thrombosis.