There is a lifelong susceptibility to increased risk of infection from a variety of organisms in patients with hyposplenism, especially in children under 5 years and those with sickle cell anaemia. Patients are most susceptible is to the encapsulated bacteria Streptococcus pneumoniae, Haemophilus influenzae type B and Neisseria meningitidis. Streptococcus pneumoniae is particular concerning as it can cause rapid and fulminant disease, which can be fatal. Malaria and animal bites that become infected also tend to be more severe.

Granulomatous inflammation is typically seen when an infective agent with a digestion-resistance capsule (e.g. Mycobacterium tuberculosis) or a piece of inert foreign material (such as suture or glass) is introduced into the tissue. A transient acute inflammatory response occurs and when this is ineffective in eradicating the stimulus, chronic inflammation occurs.

Tuberculosis is the prototype of the granulomatous diseases, but sarcoidosis, cat-scratch disease, lymphogranuloma inguinale, leprosy, brucellosis, syphilis, some mycotic infections, berylliosis, reactions of irritant lipids, and some autoimmune diseases are also included

A diagnosis of Haemophilia is supported in this patient by the family history and the presence of hemarthrosis-both characteristics of Haemophilia. Haemophilia A is caused by Factor VIII deficiency, leading to impaired coagulation. This disease typically presents after six months when the child starts crawling.

Von Willebrand disease presents with nosebleeds and hematomas. Idiopathic thrombocytopenic purpura presents with bruises that resemble a rash.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency presents with haemolytic anaemia induced by specific drugs or foods.

Factor V Leiden mutation causes blood clotting rather than bleeding.

The causes of AKI can be divided into pre-renal, intrinsic renal and post-renal causes. Majority of AKI developing in the community is due to a pre-renal causes (90% of cases).

Pre-renal causes: Haemorrhage, severe vomiting or diarrhoea, burns, cardiac failure, liver cirrhosis, nephrotic syndrome, hypotension, severe cardiac failure, NSAIDs, COX-2 inhibitors, ACE inhibitors or ARBs, Abdominal aortic aneurysm, renal artery stenosis, hepatorenal syndrome,

Intrinsic (renal) causes:
Eclampsia, glomerulonephritis, thrombosis, haemolytic-uraemic syndrome, acute tubular necrosis (ATN), acute interstitial nephritis, drugs ( NSAIDs), infection or autoimmune diseases, vasculitis, polyarteritis nodosa, thrombotic microangiopathy, cholesterol emboli, renal vein thrombosis, malignant hypertension

Post-renal causes: Renal stones, Blood clot, Papillary necrosis, Urethral stricture, Prostatic hypertrophy or malignancy, Bladder tumour, Radiation fibrosis, Pelvic malignancy, Retroperitoneal fibrosis

CLL (chronic lymphocytic leukaemia) is the most common type of chronic lymphoid leukaemia, with a peak incidence between the ages of 60 and 80. It is the most common type of leukaemia in Europe and the United States, but it is less common elsewhere.

The CLL tumour cell is a mature B-cell with low immunoglobulin surface expression (IgM or IgD). The average age at diagnosis is 72 years, with only 15% of cases occurring before the age of 50.

The male-to-female ratio is about 2:1. Over 80% of cases are identified by the results of a routine blood test, which is usually performed for another reason.

Lymphocytic anaemia, thrombocytopenia, and normochromic normocytic anaemia are common laboratory findings. Aspiration of bone marrow reveals up to 95% lymphocytic replacement of normal marrow elements.

Glanzmann’s thromboasthenia is a rare platelet disorder in which platelets contain defective or low levels of glycoprotein IIb/IIIa.

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.

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.

Laboratory findings typically show (although this varies depending on VWD type):
Abnormal PFA-100 test
Low factor VIII levels (if low a factor VIII/VWF binding assay is performed)
Prolonged APTT (or normal)
Normal PT
Low VWF levels
Defective platelet aggregation
Normal platelet count

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).

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.

Myelodysplastic syndromes are a group of clonal haematopoietic disorders which are characterised by anaemia, leukopenia and thrombocytopenia.

Patients will complain of fatigue, symptoms of thrombocytopenia such as nosebleeds and easy bleeding and a history of repeated infections due to low white blood cells (especially Neutrophils).

In Chronic lymphocytic leukaemia production of hematopoietic cells goes on for a longer time.

Folate and B12 deficiency would result in hypersegmented neutrophils and a raised MCV.

Iron deficiency anaemia would not cause neutropenia or thrombocytopenia.

Gout and pseudogout are both characterised by crystal deposition in the affected joints. The deposition of urate crystals causes gout, while calcium pyrophosphate crystals cause pseudogout. The crystals can be distinguished microscopically because urate crystals are negatively birefringent needle-shaped crystals, whilst calcium pyrophosphate crystals are positively birefringent brick-shaped crystals.

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 weeks
Gram-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 chills
Vomiting and nausea
Tachycardia
Hypotension
Collapse of the circulatory system

If 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.

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.

Neutrophil polymorphs are the predominant type of white cells in an acute reaction. They pass between endothelial cell junctions to invade damaged tissue so that the effects of injury can be combated. Extravasation occurs with the movement of leukocytes out of the vessel lumen, and is achieved in five phases which are margination, ‘rolling’, adhesion, transmigration and chemotaxis.

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.

Neutrophils are the most numerous peripheral blood leukocytes, accounting for 50-70 percent of all circulating white cells. Neutrophils have a compact nucleus with two to five lobes and a pale cytoplasm with an irregular shape containing numerous fine pink-blue or grey-blue granules. The granules are classified as primary, which emerges during the promyelocyte stage, and secondary, which develop at the myelocyte stage and predominate in the mature nucleus.

The lifespan of neutrophils in the blood is only 6 – 10 hours. In response to tissue damage, cytokines and complement proteins, neutrophils migrate from the bloodstream to the site of insult within minutes, where they destroy pathogens by phagocytosis.

An exudate is an inflammatory fluid emanating from the intravascular space due to changes in the permeability of the surrounding microcirculation.

Some common causes of exudates are: pneumonia, empyema, lung cancer, breast cancer, cancer of the pleura, SLE, rheumatoid arthritis, pericarditis, subphrenic abscess, chylothorax.

Myxoedema, nephrotic syndrome, congestive cardiac failure, and liver cirrhosis all cause TRANSUDATE.

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.

Platelets are the first cells to be attracted to the wound site due to the release of the Von Willebrand factor from the damaged endothelium. Platelets, in turn, release cytokines such as platelet-derived growth factor, which will attract other inflammatory cells to the wound site.

Blood transfusion can be a life-saving treatment with significant clinical benefits, but it also comes with a number of risks and potential complications, including:
Immunological side effects
Errors in administration (episodes of ‘wrong blood’)
Viruses and Infections (bacterial, viral, possibly prion)
Immunodilution

A culture of better safety procedures as well as steps to reduce the use of transfusion has emerged as a result of growing awareness of avoidable risk and improved reporting systems. Transfusion errors, on the other hand, continue to occur, and some serious adverse reactions go unreported.

Transfusion-associated graft-vs-host disease (TA-GVHD) is a rare blood transfusion complication that causes fever, rash, and diarrhoea 1-4 weeks after the transfusion. Pancytopenia and liver function abnormalities are common laboratory findings.

TA-GVHD, unlike GVHD following allogeneic marrow transplantation, causes profound marrow aplasia with a mortality rate of >90%. Survival is uncommon, with death occurring within 1-3 weeks of the onset of symptoms.

Because of immunodeficiency, severe immunosuppression, or shared HLA antigens, viable T lymphocytes in blood components are transfused, engraft, and react against the recipient’s tissues, and the recipient is unable to reject the donor lymphocytes.
The following is a list of the most common transfusion reactions and complications:

1) Reaction to a febrile transfusion
The temperature rises by one degree from the baseline. Chills and malaise are also possible symptoms.
The most common response (1 in 8 transfusions).
Cytokines from leukocytes in transfused red cell or platelet components are usually to blame.
Only supportive. The use of paracetamol is beneficial.

2) Acute haemolytic reaction is a type of haemolytic reaction that occurs when the
Fever, chills, pain at the transfusion site, nausea, vomiting, and dark urine are all symptoms of a transfusion reaction.
Early on, many people report a sense of ‘impending doom.’
The most serious reaction. ABO incompatibility is frequently caused by a clerical error.
STOP THE TRANSFUSION OF INFORMATION. IV fluids should be given. It’s possible that diuretics will be required.

3) Haemolytic reaction that is delayed
It usually happens 4 to 8 days after a blood transfusion.
Fever, anaemia, jaundice, and haemoglobinuria are all symptoms that the patient has.
Positive Coombs test for direct antiglobulin.
Because of the low titre antibody, it is difficult to detect in a cross-match, and it is unable to cause lysis at the time of transfusion.
The majority of delayed haemolytic reactions are harmless and do not require treatment.
Anaemia and renal function should be monitored and treated as needed.

4) Reaction to allergens
Foreign plasma proteins are usually to blame, but anti-IgA could also be to blame.
Urticaria, pruritus, and hives are typical allergic reactions. It’s possible that it’s linked to laryngeal oedema or bronchospasm.
Anaphylaxis is a rare occurrence.
Antihistamines can be used to treat allergic reactions symptomatically. It is not necessary to stop transfusions.
If the patient develops anaphylaxis, the transfusion should be stopped and the patient should be given adrenaline and treated according to the ALS protocol.

5) TRALI (Transfusion Related Acute Lung Injury)
Within 6 hours of transfusion, there was a sudden onset of non-cardiogenic pulmonary oedema.
It’s linked to the presence of antibodies to recipient leukocyte antigens in the donor blood.
The most common cause of death from transfusion reactions is this.
STOP THE TRANSFUSION OF INFORMATION. Oxygen should be given to the patient. Around 75% of patients will require aggressive respiratory support.
The use of diuretics should be avoided.

6) TACO (Transfusion Associated Circulatory Overload)
Acute or worsening respiratory distress within 6 hours of a large blood transfusion. Fluid overload and pulmonary and peripheral oedema can be seen. Rapid blood pressure rises are common. BNP is usually 1.5 times higher than it was before the transfusion. It is most common in the elderly and those who have chronic anaemia.

Blood transfusions should be given slowly, over the course of 3-4 hours.

Dietary iron may be in the form of haem or non-haem iron. Haem iron is degraded after absorption through the cell surface to release Fe2+. Most non-haem iron is in the form Fe3+, which is reduced at the luminal surface to the more soluble Fe2+, facilitated by hydrochloric acid in gastric secretions (and enhanced by ascorbic acid). Fe2+is taken across the enterocyte apical membrane by the divalent metal transporter (DMT1). In the enterocyte, Fe2+is then either stored in enterocyte epithelial cells as ferritin, or released into portal plasma via the molecule ferroportin at the basolateral membrane.

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.

The clinical and laboratory findings, in this case, support a diagnosis of polycythaemia vera. A plethoric appearance, lethargy, splenomegaly and itching are common in this disease. Patients may also have gouty arthritis, Budd-Chiari syndrome, erythromelalgia, stroke, myocardial infarction or DVT. The average age for diagnosis of Polycythaemia Vera is 65-74 years. It is a haematological malignancy in which there is overproduction of all three cell lines. Venesection is the treatment of choice as it would cause a decrease in the number of red blood cells within the body.

Erythropoietin is given in patients with chronic renal failure as they lack this hormone. Administration of erythropoietin in such patients causes stimulation of the bone marrow to produce red blood cells.

Desferrioxamine is a chelating agent for iron and is given to patients with iron overload due to repeated blood transfusions, e.g. in thalassemia patients.

Penicillamine is a chelating agent for Copper, given as treatment in Wilson’s disease.

Lymphoma is a cancer of the lymphatic system, which is part of the body’s germ-fighting network. They are a group of diseases that are caused by malignant lymphocytes. These malignant cells accumulate in lymph nodes and other lymphoid tissue, giving rise to the characteristic clinical feature of lymphadenopathy.
They can be subdivided into Hodgkin lymphoma (HL) which are characterised by the presence of Reed-Sternberg cells, and non-Hodgkin lymphoma (NHL).
Characteristics of HL include:
1. can present at any age but is rare in children and has a peak incidence in young adults,
2. almost 2:1 male predominance.
3. presents with painless, asymmetrical, firm and discrete enlargement of superficial lymph nodes.
4. cervical node involvement in 60-70% of cases,
5. axillary node involvement in 10-15%
6. inguinal node involvement in 6-12%.
7. modest splenomegaly during the course of the disease in 50% of patients
8. may occasionally have liver enlargement
9. bone marrow failure involvement is unusual in early disease.
Approximately 85% of patients are cured, but the prognosis depends on age, stage and histology.
Two well‐known but rare symptoms in HL are alcohol‐induced pain and pruritus.

Approximately one-third of patients who suffer DVT or PE have an identifiable heritable risk factor, although additional risk factors are usually present when they develop the thrombosis. The history of a spontaneous DVT in a close relative increases an individual’s risk of DVT even if no known genetic predisposition can be identified.

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.

Myocardial cells are unable to regenerate, they are unable to divide in response to tissue injury. The remain permanently in G0 and cannot progress to G1. If a segment of muscle dies, for example in myocardial infarction, this tissue will be replaced by scar tissue if the patient recovers. This scar tissue is non-contractile and therefore the remaining myocardium must work harder to maintain cardiac output. As a consequence the remaining undamaged myocardium undergoes compensatory hypertrophy without cell division.

The stages of wound healing are: haemostasis, inflammatory, proliferative and remodelling (maturation) phases in that order. The first stage in the healing process of a laceration is haemostasis. Haemostasis is the process of the wound being closed by clotting.

The inflammatory phase occurs just after and up to 48 hours after injury– Blood vessels dilate to allow white blood cells, antibodies, growth factors, enzymes and nutrients to reach the wounded area leading to the characteristic signs of inflammation seen.

Epithelialisation and angiogenesis are not phases of wound healing but occur during the proliferative phase. This ia after haemolysis and inflammation phases have occurred.

The maturation phase is the final phase and occurs when the wound has closed. It involves remodelling of collagen from type III to type I. Apoptosis remove unwanted cells, cellular activity reduces and the number of blood vessels in the wounded area regresses and decreases. This can continues for up to 1 year after injury.