Aplastic anaemia is a rare and potentially life-threatening condition where the bone marrow fails to produce enough blood cells. This results in a decrease in the number of red blood cells, white blood cells, and platelets in the body, a condition known as pancytopenia. The main cause of aplastic anaemia is damage to the bone marrow and the stem cells that reside there. This damage can be caused by various factors such as autoimmune disorders, certain medications like sulphonamide antibiotics and phenytoin, viral infections like EBV and parvovirus, chemotherapy, radiotherapy, or inherited conditions like Fanconi anaemia. Patients with aplastic anaemia typically experience symptoms such as anaemia, recurrent infections due to a low white blood cell count, and an increased tendency to bleed due to low platelet levels.

Anaemia can be categorized based on the size of red blood cells. Microcytic anaemia, characterized by a mean corpuscular volume (MCV) of less than 80 fl, can be caused by various factors such as iron deficiency, thalassaemia, anaemia of chronic disease (which can also be normocytic), sideroblastic anaemia (which can also be normocytic), lead poisoning, and aluminium toxicity (although this is now rare and mainly affects haemodialysis patients).

On the other hand, normocytic anaemia, with an MCV ranging from 80 to 100 fl, can be attributed to conditions like haemolysis, acute haemorrhage, bone marrow failure, anaemia of chronic disease (which can also be microcytic), mixed iron and folate deficiency, pregnancy, chronic renal failure, and sickle-cell disease.

Lastly, macrocytic anaemia, characterized by an MCV greater than 100 fl, can be caused by factors such as B12 deficiency, folate deficiency, hypothyroidism, reticulocytosis, liver disease, alcohol abuse, myeloproliferative disease, myelodysplastic disease, and certain drugs like methotrexate, hydroxyurea, and azathioprine.

It is important to understand the different causes of anaemia based on red cell size as this knowledge can aid in the diagnosis and management of this condition.

The CHA2DS2-VASc score is a tool used to predict the likelihood of future stroke in individuals with atrial fibrillation (AF). It is scored on a scale of 0-9, with higher scores indicating a higher risk of stroke. If a male has a score of 1 or more, or if a female has a score of 2 or more, it is recommended to start anticoagulation therapy to prevent future strokes. However, it is important to assess the risk of bleeding before initiating anticoagulation using the HAS-BLED score. The HAS-BLED score does not evaluate the risk of stroke, but rather the risk of bleeding. QRISK3, on the other hand, is a tool used to estimate the risk of cardiovascular disease over a 10-year period and is primarily used to determine the benefits of starting lipid lowering drugs. It is the preferred tool recommended by NICE over the Framingham risk score.

Further Reading:

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting around 5% of patients over the age of 70-75 years and 10% of patients aged 80-85 years. While AF can cause palpitations and inefficient cardiac function, the most important aspect of managing patients with AF is reducing the increased risk of stroke.

AF can be classified as first detected episode, paroxysmal, persistent, or permanent. First detected episode refers to the initial occurrence of AF, regardless of symptoms or duration. Paroxysmal AF occurs when a patient has 2 or more self-terminating episodes lasting less than 7 days. Persistent AF refers to episodes lasting more than 7 days that do not self-terminate. Permanent AF is continuous atrial fibrillation that cannot be cardioverted or if attempts to do so are deemed inappropriate. The treatment goals for permanent AF are rate control and anticoagulation if appropriate.

Symptoms of AF include palpitations, dyspnea, and chest pain. The most common sign is an irregularly irregular pulse. An electrocardiogram (ECG) is essential for diagnosing AF, as other conditions can also cause an irregular pulse.

Managing patients with AF involves two key parts: rate/rhythm control and reducing stroke risk. Rate control involves slowing down the irregular pulse to avoid negative effects on cardiac function. This is typically achieved using beta-blockers or rate-limiting calcium channel blockers. If one drug is not effective, combination therapy may be used. Rhythm control aims to restore and maintain normal sinus rhythm through pharmacological or electrical cardioversion. However, the majority of patients are managed with a rate control strategy.

Reducing stroke risk in patients with AF is crucial. Risk stratifying tools, such as the CHA2DS2-VASc score, are used to determine the most appropriate anticoagulation strategy. Anticoagulation is recommended for patients with a score of 2 or more. Clinicians can choose between warfarin and novel oral anticoagulants (NOACs) for anticoagulation.

Before starting anticoagulation, the patient’s bleeding risk should be assessed using tools like the HAS-BLED score or the ORBIT tool. These tools evaluate factors such as hypertension, abnormal renal or liver function, history of bleeding, age, and use of drugs that predispose to bleeding.

Von Willebrand disease (vWD) is a common hereditary coagulation disorder that affects approximately 1 in 100 individuals. It occurs due to a deficiency in Von Willebrand factor (vWF), which plays a crucial role in blood clotting. vWF not only binds to factor VIII to protect it from rapid breakdown, but it is also necessary for proper platelet adhesion. When vWF is lacking, both factor VIII levels and platelet function are affected, leading to prolonged APTT and bleeding time. However, the platelet count and thrombin time remain unaffected.

While some individuals with vWD may not experience any symptoms and are diagnosed incidentally during a clotting profile check, others may present with easy bruising, nosebleeds (epistaxis), and heavy menstrual bleeding (menorrhagia). In severe cases, more significant bleeding and joint bleeding (haemarthrosis) can occur.

For mild cases of von Willebrand disease, bleeding can be managed with desmopressin. This medication works by stimulating the release of vWF stored in the Weibel-Palade bodies, which are storage granules found in the endothelial cells lining the blood vessels and heart. By increasing the patient’s own levels of vWF, desmopressin helps improve clotting. In more severe cases, replacement therapy is necessary. This involves infusing cryoprecipitate or Factor VIII concentrate to provide the missing vWF. Replacement therapy is particularly recommended for patients with severe von Willebrand’s disease who are undergoing moderate or major surgical procedures.

Myelodysplastic syndromes are a group of disorders affecting the haemopoietic stem cell, leading to ineffective production of myeloid blood cells. These conditions typically manifest between the ages of 60 and 75 and are more prevalent in men than women.

The clinical features of myelodysplastic syndromes include tiredness due to anaemia (the most common presentation), easy bruising, and a tendency to bleed. Laboratory findings often reveal anaemia (usually macrocytic or normocytic), neutropenia, thrombocytopenia, and abnormal cell morphology with oddly shaped macrocytes.

Chronic lymphocytic leukaemia (CLL) is the most common form of adult leukaemia, primarily affecting B-lymphocytes. It often presents asymptomatically in patients who undergo routine blood tests revealing elevated white cell counts and lymphocytosis. Men over the age of 50 account for over 75% of CLL cases. Blood films typically show a predominance of mature-looking lymphocytes and smear cells.

Iron deficiency anaemia is characterized by hypochromic microcytic anaemia and a reduced red blood cell count. Peripheral blood smears in iron deficiency anaemia may exhibit poikilocytosis (varying shapes) and anisocytosis (varying sizes). Pencil cells are also observed in this condition.

Vitamin B12 and folate deficiency can also cause macrocytic anaemia. However, the severity of anaemia and macrocytosis would generally need to be much more pronounced to result in neutropenia and thrombocytopenia. Therefore, a myelodysplastic syndrome is more likely in such cases.

Blood transfusion is a potentially life-saving treatment that can provide great clinical benefits. However, it also carries several risks and potential problems. These include immunological complications, administration errors, infections, immune dilution, and transfusion errors. While there have been improvements in safety procedures and efforts to minimize the use of transfusion, errors and serious adverse reactions still occur and often go unreported.

One rare complication of blood transfusion is transfusion-associated graft-vs-host disease (TA-GVHD). This condition typically presents with fever, rash, and diarrhea 1-4 weeks after the transfusion. Laboratory findings may show pancytopenia and abnormalities in liver function. Unlike GVHD after marrow transplantation, TA-GVHD leads to severe marrow aplasia with a mortality rate exceeding 90%. Unfortunately, there are currently no effective treatments available for this condition, and survival is rare, with death usually occurring within 1-3 weeks of the first symptoms.

During a blood transfusion, viable T lymphocytes from the donor are transfused into the recipient’s body. In TA-GVHD, these lymphocytes engraft and react against the recipient’s tissues. However, the recipient is unable to reject the donor lymphocytes due to factors such as immunodeficiency, severe immunosuppression, or shared HLA antigens. Supportive management is the only option for TA-GVHD.

The following summarizes the main complications and reactions that can occur during a blood transfusion:

Complication Features Management
Febrile transfusion reaction
– Presents with a 1-degree rise in temperature from baseline, along with chills and malaise.
– Most common reaction, occurring in 1 out of 8 transfusions.
– Usually caused by cytokines from leukocytes in transfused red cell or platelet components.
– Supportive management, with the use of paracetamol for symptom relief.

Acute haemolytic reaction
– Symptoms include fever, chills, pain at the transfusion site, nausea, vomiting, and dark urine.
– Often accompanied by a feeling of ‘impending doom’.
– Most serious type of reaction, often due to ABO incompatibility caused by administration errors.
– Immediate action required: stop the transfusion, administer IV fluids, and consider diuretics if necessary.

Delayed haemolytic reaction
– Typically occurs 4-8 days after a blood transfusion.
– Symptoms include fever, anemia and/or hyperbilirubinemia

Anaemia can be categorized based on the size of red blood cells. Microcytic anaemia, characterized by a mean corpuscular volume (MCV) of less than 80 fl, can be caused by various factors such as iron deficiency, thalassaemia, anaemia of chronic disease (which can also be normocytic), sideroblastic anaemia (which can also be normocytic), lead poisoning, and aluminium toxicity (although this is now rare and mainly affects haemodialysis patients).

On the other hand, normocytic anaemia, with an MCV ranging from 80 to 100 fl, can be attributed to conditions like haemolysis, acute haemorrhage, bone marrow failure, anaemia of chronic disease (which can also be microcytic), mixed iron and folate deficiency, pregnancy, chronic renal failure, and sickle-cell disease.

Lastly, macrocytic anaemia, characterized by an MCV greater than 100 fl, can be caused by factors such as B12 deficiency, folate deficiency, hypothyroidism, reticulocytosis, liver disease, alcohol abuse, myeloproliferative disease, myelodysplastic disease, and certain drugs like methotrexate, hydroxyurea, and azathioprine.

It is important to understand the different causes of anaemia based on red cell size as this knowledge can aid in the diagnosis and management of this condition.

Immunoglobulin light chains that are present in the urine are commonly known as Bence-Jones proteins (BJP). These proteins are primarily observed in individuals with multiple myeloma, although they can occasionally be detected in Waldenström macroglobulinemia, although this is a rare occurrence. It is important to note that BJP in the urine is not observed in the other conditions mentioned in this question.

The current recommendations from NICE for managing warfarin in the presence of bleeding or an abnormal INR are as follows:

In cases of major active bleeding, regardless of the INR level, the first step is to stop administering warfarin. Next, 5 mg of vitamin K (phytomenadione) should be given intravenously. Additionally, dried prothrombin complex concentrate, which contains factors II, VII, IX, and X, should be administered. If dried prothrombin complex is not available, fresh frozen plasma can be given at a dose of 15 ml/kg.

If the INR is greater than 8.0 and there is minor bleeding, warfarin should be stopped. Slow injection of 1-3 mg of vitamin K can be given, and this dose can be repeated after 24 hours if the INR remains high. Warfarin can be restarted once the INR is less than 5.0.

If the INR is greater than 8.0 with no bleeding, warfarin should be stopped. Oral administration of 1-5 mg of vitamin K can be given, and this dose can be repeated after 24 hours if the INR remains high. Warfarin can be restarted once the INR is less than 5.0.

If the INR is between 5.0-8.0 with minor bleeding, warfarin should be stopped. Slow injection of 1-3 mg of vitamin K can be given, and warfarin can be restarted once the INR is less than 5.0.

If the INR is between 5.0-8.0 with no bleeding, one or two doses of warfarin should be withheld, and the subsequent maintenance dose should be reduced.

For more information, please refer to the NICE Clinical Knowledge Summary on the management of warfarin therapy and the BNF guidance on the use of phytomenadione.

Blood transfusion is a crucial treatment that can save lives, but it also comes with various risks and potential problems. These include immunological complications, administration errors, infections, and immune dilution. While there has been an improvement in safety procedures and a reduction in transfusion use, errors and serious adverse reactions still occur and often go unreported.

Mild allergic reactions during blood transfusion are relatively common and typically occur within a few minutes of starting the transfusion. These reactions happen when patients have antibodies that react with foreign plasma proteins in the transfused blood components. Symptoms of mild allergic reactions include urticaria, Pruritus, and hives.

Anaphylaxis, on the other hand, is much rarer and occurs when an individual has previously been sensitized to an allergen present in the blood. When re-exposed to the allergen, the body releases IgE or IgG antibodies, leading to severe symptoms such as bronchospasm, laryngospasm, abdominal pain, nausea, vomiting, hypotension, shock, and loss of consciousness. Anaphylaxis can be fatal.

Mild allergic reactions can be managed by slowing down the transfusion rate and administering antihistamines. If there is no progression after 30 minutes, the transfusion may continue. Patients who have experienced repeated allergic reactions to transfusion should be given pre-treatment with chlorpheniramine. In cases of anaphylaxis, the transfusion should be stopped immediately, and the patient should receive oxygen, adrenaline, corticosteroids, and antihistamines following the ALS protocol.

The table below summarizes the main transfusion reactions and complications, along with their features and management:

Complication | Features | Management
Febrile transfusion reaction | 1 degree rise in temperature, chills, malaise | Supportive care, paracetamol
Acute haemolytic reaction | Fever, chills, pain at transfusion site, nausea, vomiting, dark urine | STOP THE TRANSFUSION, administer IV fluids, diuretics if necessary
Delayed haemolytic reaction | Fever, anaemia, jaundice, haemoglobinuria | Monitor anaemia and renal function, treat as required
Allergic reaction | Urticaria, Pruritus, hives | Symptomatic treatment with ant

Haemophilia is a collection of genetic disorders that are inherited and lead to impaired blood clotting. Haemophilia A specifically occurs when there is a deficiency of factor VIII and is typically passed down as a recessive trait on the X chromosome.

The initial signs of haemophilia A usually appear around 6 months of age when infants start crawling, although it can manifest later. Bleeding can occur either spontaneously or as a result of trauma. One key indicator of haemophilia is bleeding into muscles and joints, known as haemarthrosis. While gastrointestinal and cerebral bleeding can also happen, they are less common occurrences.

Based on the symptoms described, the most likely diagnosis from the given options would be Haemophilia A, especially when there is a combination of haemarthrosis and an older brother with the same disorder.

Idiopathic thrombocytopenic purpura (ITP) is a condition where the immune system causes a decrease in platelet count. Antibodies target the glycoprotein IIb-IIIa or Ib complex. Acute ITP is more prevalent in children and affects both sexes equally. Chronic ITP, on the other hand, is more common in young to middle-aged women. Unlike haemophilia, ITP typically presents with symptoms such as nosebleeds, oral bleeding, purpura, or petechiae, rather than haemarthrosis. Additionally, ITP is not an inherited disorder.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited disorder that follows an X-linked recessive pattern. It is characterized by a defect in the G6PD enzyme, which plays a crucial role in red blood cell metabolism. Most individuals with G6PD deficiency do not experience symptoms. However, haemolytic crisis can occur in response to factors like illness (especially infection and diabetic ketoacidosis), certain medications (such as specific antibiotics, antimalarials, sulphonamides, and aspirin), or certain foods (notably fava beans).

Von Willebrand disease (vWD) is the most common hereditary coagulation disorder, affecting approximately 1 in 100 individuals. It arises from a deficiency in Von Willebrand factor (vWF), which leads to reduced levels of factor VIII. vWF is responsible for protecting factor VIII from rapid breakdown in the blood and is also necessary for platelet adhesion.

Transfusion-related lung injury (TRALI) is responsible for about one-third of all transfusion-related deaths, making it the leading cause. On the other hand, transfusion-associated circulatory overload (TACO) accounts for approximately 20% of these fatalities, making it the second leading cause. TACO occurs when a large volume of blood is rapidly infused, particularly in patients with limited cardiac reserve or chronic anemia. Elderly individuals, infants, and severely anemic patients are especially vulnerable to this reaction.

The typical signs of TACO include acute respiratory distress, rapid heart rate, high blood pressure, the appearance of acute or worsening pulmonary edema on a chest X-ray, and evidence of excessive fluid accumulation. In many cases, simply reducing the transfusion rate, positioning the patient upright, and administering diuretics will be sufficient to manage the condition. However, in more severe cases, it is necessary to halt the transfusion and consider non-invasive ventilation.

Transfusion-related acute lung injury (TRALI) is defined as new acute lung injury (ALI) that occurs during or within six hours of transfusion, not explained by another ALI risk factor. Transfusion of part of one unit of any blood product can cause TRALI.

Protamine sulphate is a potent base that forms a stable salt complex with heparin, an acidic substance. This complex is inactive and is used to counteract the effects of heparin. Additionally, protamine sulphate can be used to reverse the effects of LMWHs, although it is not as effective, providing only about two-thirds of the relative effect.

Apart from its ability to neutralize heparin, protamine sulphate also possesses a weak intrinsic anticoagulant effect. This is believed to be due to its inhibition of the formation and activity of thromboplastin.

To administer protamine sulphate, it is slowly injected intravenously. The dosage should be adjusted based on the amount of heparin to be neutralized, the time elapsed since heparin administration, and the aPTT. For every 100 IU of heparin, 1 mg of protamine is required for neutralization. However, the maximum adult dose within a 10-minute period should not exceed 50 mg.

It is important to note that protamine sulphate has additional effects on the body. It acts as a depressant on the heart muscle and may lead to bradycardia and hypotension. These effects are caused by complement activation and the release of leukotrienes.

Reed-Sternberg cells are distinctive large cells that are typically observed in Hodgkin lymphoma. These cells are often found to have two nuclei or a nucleus with two lobes. Additionally, they possess noticeable nucleoli that resemble eosinophilic inclusion-like structures, giving them an appearance similar to that of an owl’s eye.

All individuals diagnosed with chronic lymphocytic leukaemia (CLL) experience some level of weakened immune system, although for many, it is not severe enough to have a significant impact on their health. Infections are the leading cause of death for 25-50% of CLL patients, with respiratory tract, skin, and urinary tract bacterial infections being the most prevalent. The primary factor contributing to the weakened immune system in CLL patients is hypogammaglobulinaemia, which is present in approximately 85% of all individuals with this condition.

Febrile transfusion reactions, also known as non-haemolytic transfusion reactions, occur when there is an unexpected increase in body temperature (≥ 38ºC or ≥ 1ºC above the baseline, if the baseline is ≥ 37ºC) during or shortly after a blood transfusion. This temperature rise is usually the only symptom, although sometimes it may be accompanied by chills.

Febrile transfusion reactions are the most common type of transfusion reaction, happening in approximately 1 out of every 8 transfusions.

The main cause of febrile transfusion reactions is believed to be the accumulation of cytokines during the storage of blood components, particularly in platelet units. Cytokines are substances released by white blood cells, and the risk of symptoms can be reduced by removing these cells before storage.

In addition to cytokine accumulation, febrile transfusion reactions can also be triggered by recipient antibodies that have been produced as a result of previous transfusions or pregnancies. These antibodies react to specific antigens, such as human leukocyte antigen (HLA), found on the donor’s lymphocytes, granulocytes, or platelets.

Treatment for febrile transfusion reactions is mainly supportive. Other potential causes of fever should be ruled out, and antipyretic medications like paracetamol can be used to reduce the fever. If another cause is suspected, the transfusion should be temporarily stopped, but it can be resumed at a slower rate once other potential causes of fever have been ruled out.

Von Willebrand disease (vWD) is a common hereditary coagulation disorder that affects approximately 1 in 100 individuals. It occurs due to a deficiency in Von Willebrand factor (vWF), which plays a crucial role in blood clotting. vWF not only binds to factor VIII to protect it from rapid breakdown, but it is also necessary for proper platelet adhesion. When vWF is lacking, both factor VIII levels and platelet function are affected, leading to prolonged APTT and bleeding time. However, the platelet count and thrombin time remain unaffected.

While some individuals with vWD may not experience any symptoms and are diagnosed incidentally during a clotting profile check, others may present with easy bruising, nosebleeds (epistaxis), and heavy menstrual bleeding (menorrhagia). In severe cases, more significant bleeding and joint bleeding (haemarthrosis) can occur.

For mild cases of von Willebrand disease, bleeding can be managed with desmopressin. This medication works by stimulating the release of vWF stored in the Weibel-Palade bodies, which are storage granules found in the endothelial cells lining the blood vessels and heart. By increasing the patient’s own levels of vWF, desmopressin helps improve clotting. In more severe cases, replacement therapy is necessary. This involves infusing cryoprecipitate or Factor VIII concentrate to provide the missing vWF. Replacement therapy is particularly recommended for patients with severe von Willebrand’s disease who are undergoing moderate or major surgical procedures.

The most frequently encountered virus transmitted through blood transfusion is parvovirus B19. This particular occurrence happens in roughly 1 out of every 10,000 transfusions.

On the other hand, the transmission of other viruses is extremely uncommon. The likelihood of contracting Hepatitis B through a blood transfusion is estimated to be around 1 in 100,000 to 200,000. Similarly, the chances of acquiring Hepatitis C or HIV through a blood transfusion are even rarer, with the odds being approximately 1 in 1 million for both viruses.

The current recommendations from NICE for managing warfarin in the presence of bleeding or an abnormal INR are as follows:

In cases of major active bleeding, regardless of the INR level, the first step is to stop administering warfarin. Next, 5 mg of vitamin K (phytomenadione) should be given intravenously. Additionally, dried prothrombin complex concentrate, which contains factors II, VII, IX, and X, should be administered. If dried prothrombin complex is not available, fresh frozen plasma can be given at a dose of 15 ml/kg.

If the INR is greater than 8.0 and there is minor bleeding, warfarin should be stopped. Slow injection of 1-3 mg of vitamin K can be given, and this dose can be repeated after 24 hours if the INR remains high. Warfarin can be restarted once the INR is less than 5.0.

If the INR is greater than 8.0 with no bleeding, warfarin should be stopped. Oral administration of 1-5 mg of vitamin K can be given, and this dose can be repeated after 24 hours if the INR remains high. Warfarin can be restarted once the INR is less than 5.0.

If the INR is between 5.0-8.0 with minor bleeding, warfarin should be stopped. Slow injection of 1-3 mg of vitamin K can be given, and warfarin can be restarted once the INR is less than 5.0.

If the INR is between 5.0-8.0 with no bleeding, one or two doses of warfarin should be withheld, and the subsequent maintenance dose should be reduced.

For more information, please refer to the NICE Clinical Knowledge Summary on the management of warfarin therapy and the BNF guidance on the use of phytomenadione.

Blood transfusion is a crucial medical treatment that can save lives, but it also comes with various risks and potential problems. These include immunological complications, administration errors, infections, and immune dilution. While there have been improvements in safety procedures and a reduction in transfusion usage, errors and adverse reactions still occur.

One serious complication is acute haemolytic transfusion reactions, which happen when incompatible red cells are transfused and react with the patient’s own antibodies. This usually occurs due to human error, such as mislabelling sample tubes or request forms. Symptoms of this reaction include a feeling of impending doom, fever, chills, pain and warmth at the transfusion site, nausea, vomiting, and back, joint, and chest pain. Immediate action should be taken to stop the transfusion, replace the donor blood with normal saline or another suitable crystalloid, and check the blood to confirm the intended recipient. IV diuretics may be administered to increase renal blood flow, and urine output should be maintained.

Another common complication is febrile transfusion reaction, which presents with a 1-degree rise in temperature from baseline, along with chills and malaise. This reaction is usually caused by cytokines from leukocytes in the transfused blood components. Supportive treatment is typically sufficient, and paracetamol can be helpful.

Allergic reactions can also occur, usually due to foreign plasma proteins or anti-IgA. These reactions often present with urticaria, pruritus, and hives, and in severe cases, laryngeal edema or bronchospasm may occur. Symptomatic treatment with antihistamines is usually enough, and there is usually no need to stop the transfusion. However, if anaphylaxis occurs, the transfusion should be stopped, and the patient should be administered adrenaline and treated according to the ALS protocol.

Transfusion-related acute lung injury (TRALI) is a severe complication characterized by non-cardiogenic pulmonary edema within 6 hours of transfusion. It is associated with antibodies in the donor blood reacting with recipient leukocyte antigens. This is the most common cause of death related to transfusion reactions. Treatment involves stopping the transfusion, administering oxygen, and providing aggressive respiratory support in approximately 75% of patients. Diuretic usage should be avoided.

Anaemia of chronic disease is a type of anaemia that can occur in various chronic conditions, such as rheumatoid arthritis, systemic lupus erythematosus, tuberculosis, malignancy, malnutrition, hypothyroidism, hypopituitarism, chronic kidney disease, and chronic liver disease. The underlying mechanisms of this type of anaemia are complex and not fully understood, with multiple contributing factors involved. One important mediator in inflammatory diseases like rheumatoid arthritis is interleukin-6 (IL-6). Increased levels of IL-6 lead to the production of hepcidin, a hormone that regulates iron balance. Hepcidin prevents the release of iron from the reticulo-endothelial system and affects other aspects of iron metabolism.

Anaemia of chronic disease typically presents as a normochromic, normocytic anaemia, although it can also be microcytic. It is characterized by reduced serum iron, reduced transferrin saturation, and reduced total iron-binding capacity (TIBC). However, the serum ferritin levels are usually normal or increased. Distinguishing anaemia of chronic disease from iron-deficiency anaemia can be challenging, but in iron-deficiency anaemia, the TIBC is typically elevated, and serum ferritin is usually low.

Blood transfusion is a crucial medical treatment that can save lives, but it also comes with various risks and potential problems. These include immunological complications, administration errors, infections, and immune dilution. While there have been improvements in safety procedures and a reduction in transfusion usage, errors and adverse reactions still occur.

One serious complication is acute haemolytic transfusion reactions, which happen when incompatible red cells are transfused and react with the patient’s own antibodies. This usually occurs due to human error, such as mislabelling sample tubes or request forms. Symptoms of this reaction include a feeling of impending doom, fever, chills, pain and warmth at the transfusion site, nausea, vomiting, and back, joint, and chest pain. Immediate action should be taken to stop the transfusion, replace the donor blood with normal saline or another suitable crystalloid, and check the blood to confirm the intended recipient. IV diuretics may be administered to increase renal blood flow, and urine output should be maintained.

Another common complication is febrile transfusion reaction, which presents with a 1-degree rise in temperature from baseline, along with chills and malaise. This reaction is usually caused by cytokines from leukocytes in the transfused blood components. Supportive treatment is typically sufficient, and paracetamol can be helpful.

Allergic reactions can also occur, usually due to foreign plasma proteins or anti-IgA. These reactions often present with urticaria, pruritus, and hives, and in severe cases, laryngeal edema or bronchospasm may occur. Symptomatic treatment with antihistamines is usually enough, and there is usually no need to stop the transfusion. However, if anaphylaxis occurs, the transfusion should be stopped, and the patient should be administered adrenaline and treated according to the ALS protocol.

Transfusion-related acute lung injury (TRALI) is a severe complication characterized by non-cardiogenic pulmonary edema within 6 hours of transfusion. It is associated with antibodies in the donor blood reacting with recipient leukocyte antigens. This is the most common cause of death related to transfusion reactions. Treatment involves stopping the transfusion, administering oxygen, and providing aggressive respiratory support in approximately 75% of patients. Diuretic usage should be avoided.

When the INR (International Normalized Ratio) is above 8 but there is no sign of bleeding, the usual approach is to stop administering warfarin and instead provide oral vitamin K. If the INR is below 8 and there is no evidence of bleeding, it is appropriate to discontinue warfarin. However, if there is evidence of bleeding or the INR exceeds 8, reversal agents are administered. In cases where the INR is greater than 8 without any bleeding, oral vitamin K is typically prescribed at a dosage of 1-5 mg.

Further Reading:

Management of High INR with Warfarin

Major Bleeding:
– Stop warfarin immediately.
– Administer intravenous vitamin K 5 mg.
– Administer 25-50 u/kg four-factor prothrombin complex concentrate.
– If prothrombin complex concentrate is not available, consider using fresh frozen plasma (FFP).
– Seek medical attention promptly.

INR > 8.0 with Minor Bleeding:
– Stop warfarin immediately.
– Administer intravenous vitamin K 1-3mg.
– Repeat vitamin K dose if INR remains high after 24 hours.
– Restart warfarin when INR is below 5.0.
– Seek medical advice if bleeding worsens or persists.

INR > 8.0 without Bleeding:
– Stop warfarin immediately.
– Administer oral vitamin K 1-5 mg using the intravenous preparation orally.
– Repeat vitamin K dose if INR remains high after 24 hours.
– Restart warfarin when INR is below 5.0.
– Seek medical advice if any symptoms or concerns arise.

INR 5.0-8.0 with Minor Bleeding:
– Stop warfarin immediately.
– Administer intravenous vitamin K 1-3mg.
– Restart warfarin when INR is below 5.0.
– Seek medical advice if bleeding worsens or persists.

INR 5.0-8.0 without Bleeding:
– Withhold 1 or 2 doses of warfarin.
– Reduce subsequent maintenance dose.
– Monitor INR closely and seek medical advice if any concerns arise.

Note: In cases of intracranial hemorrhage, prothrombin complex concentrate should be considered as it is faster acting than fresh frozen plasma (FFP).

Blood transfusion is a crucial treatment that can save lives, but it also comes with various risks and potential problems. These include immunological complications, administration errors, infections, and immune dilution. While there has been an improvement in safety procedures and a reduction in transfusion use, errors and serious adverse reactions still occur and often go unreported.

Mild allergic reactions during blood transfusion are relatively common and typically occur within a few minutes of starting the transfusion. These reactions happen when patients have antibodies that react with foreign plasma proteins in the transfused blood components. Symptoms of mild allergic reactions include urticaria, Pruritus, and hives.

Anaphylaxis, on the other hand, is much rarer and occurs when an individual has previously been sensitized to an allergen present in the blood. When re-exposed to the allergen, the body releases IgE or IgG antibodies, leading to severe symptoms such as bronchospasm, laryngospasm, abdominal pain, nausea, vomiting, hypotension, shock, and loss of consciousness. Anaphylaxis can be fatal.

Mild allergic reactions can be managed by slowing down the transfusion rate and administering antihistamines. If there is no progression after 30 minutes, the transfusion may continue. Patients who have experienced repeated allergic reactions to transfusion should be given pre-treatment with chlorpheniramine. In cases of anaphylaxis, the transfusion should be stopped immediately, and the patient should receive oxygen, adrenaline, corticosteroids, and antihistamines following the ALS protocol.

The table below summarizes the main transfusion reactions and complications, along with their features and management:

Complication | Features | Management
Febrile transfusion reaction | 1 degree rise in temperature, chills, malaise | Supportive care, paracetamol
Acute haemolytic reaction | Fever, chills, pain at transfusion site, nausea, vomiting, dark urine | STOP THE TRANSFUSION, administer IV fluids, diuretics if necessary
Delayed haemolytic reaction | Fever, anaemia, jaundice, haemoglobinuria | Monitor anaemia and renal function, treat as required
Allergic reaction | Urticaria, Pruritus, hives | Symptomatic treatment with ant

HbAS is known as Sickle cell trait, while HbSS is the genotype for Sickle-cell disease. Sickle-shaped red blood cells have a shorter lifespan of 10-20 days compared to the normal red blood cells that live for 90-120 days. Cholelithiasis, a complication of sickle-cell disease, occurs due to excessive bilirubin production caused by the breakdown of red blood cells. The inheritance pattern of sickle-cell disease is autosomal recessive. The disease is caused by a point mutation in the beta-globin chain of hemoglobin, resulting in the substitution of glutamic acid with valine at the sixth position. Individuals with one normal hemoglobin gene and one sickle gene have the genotype HbAS, which is commonly referred to as Sickle Cell trait.

Blood transfusion is a potentially life-saving treatment that can provide great clinical benefits. However, it also carries several risks and potential problems. These include immunological complications, administration errors, infections, and immune dilution. While there has been an increased awareness of these risks and improved reporting systems, transfusion errors and serious adverse reactions still occur and may go unreported.

One specific transfusion reaction is transfusion-associated circulatory overload (TACO), which occurs when a large volume of blood is rapidly infused. It is the second leading cause of transfusion-related deaths, accounting for about 20% of fatalities. TACO is more likely to occur in patients with diminished cardiac reserve or chronic anemia, particularly in the elderly, infants, and severely anemic patients.

The typical clinical features of TACO include acute respiratory distress, tachycardia, hypertension, acute or worsening pulmonary edema on chest X-ray, and evidence of positive fluid balance. The B-type natriuretic peptide (BNP) can be a useful diagnostic tool for TACO, with levels usually elevated to at least 1.5 times the pre-transfusion baseline.

In many cases, simply slowing the transfusion rate, placing the patient in an upright position, and administering diuretics can be sufficient for managing TACO. In more severe cases, the transfusion should be stopped, and non-invasive ventilation may be considered.

Blood transfusion is a potentially life-saving treatment that can provide great clinical benefits. However, it also carries several risks and potential problems. These include immunological complications, administration errors, infections, immune dilution, and transfusion errors. While there have been improvements in safety procedures and efforts to minimize the use of transfusion, errors and serious adverse reactions still occur and often go unreported.

One rare complication of blood transfusion is transfusion-associated graft-vs-host disease (TA-GVHD). This condition typically presents with fever, rash, and diarrhea 1-4 weeks after the transfusion. Laboratory findings may show pancytopenia and abnormalities in liver function. Unlike GVHD after marrow transplantation, TA-GVHD leads to severe marrow aplasia with a mortality rate exceeding 90%. Unfortunately, there are currently no effective treatments available for this condition, and survival is rare, with death usually occurring within 1-3 weeks of the first symptoms.

During a blood transfusion, viable T lymphocytes from the donor are transfused into the recipient’s body. In TA-GVHD, these lymphocytes engraft and react against the recipient’s tissues. However, the recipient is unable to reject the donor lymphocytes due to factors such as immunodeficiency, severe immunosuppression, or shared HLA antigens. Supportive management is the only option for TA-GVHD.

The following summarizes the main complications and reactions that can occur during a blood transfusion:

Complication Features Management
Febrile transfusion reaction
– Presents with a 1-degree rise in temperature from baseline, along with chills and malaise.
– Most common reaction, occurring in 1 out of 8 transfusions.
– Usually caused by cytokines from leukocytes in transfused red cell or platelet components.
– Supportive management, with the use of paracetamol for symptom relief.

Acute haemolytic reaction
– Symptoms include fever, chills, pain at the transfusion site, nausea, vomiting, and dark urine.
– Often accompanied by a feeling of ‘impending doom’.
– Most serious type of reaction, often due to ABO incompatibility caused by administration errors.
– Immediate action required: stop the transfusion, administer IV fluids, and consider diuretics if necessary.

Delayed haemolytic reaction
– Typically occurs 4-8 days after a blood transfusion.
– Symptoms include fever, anemia and/or hyperbilirubinemia

Blood transfusion is a crucial medical treatment that can save lives, but it also comes with various risks and potential problems. These include immunological complications, administration errors, infections, and immune dilution. While there have been improvements in safety procedures and a reduction in transfusion use, errors and adverse reactions still occur. One common adverse reaction is febrile transfusion reactions, which present as an unexpected rise in temperature during or after transfusion. This can be caused by cytokine accumulation or recipient antibodies reacting to donor antigens. Treatment for febrile transfusion reactions is supportive, and other potential causes should be ruled out.

Another serious complication is acute haemolytic reaction, which is often caused by ABO incompatibility due to administration errors. This reaction requires the transfusion to be stopped and IV fluids to be administered. Delayed haemolytic reactions can occur several days after a transfusion and may require monitoring and treatment for anaemia and renal function. Allergic reactions, TRALI (Transfusion Related Acute Lung Injury), TACO (Transfusion Associated Circulatory Overload), and GVHD (Graft-vs-Host Disease) are other potential complications that require specific management approaches.

In summary, blood transfusion carries risks and potential complications, but efforts have been made to improve safety procedures. It is important to be aware of these complications and to promptly address any adverse reactions that may occur during or after a transfusion.

Anaemia can be categorized based on the size of red blood cells. Microcytic anaemia, characterized by a mean corpuscular volume (MCV) of less than 80 fl, can be caused by various factors such as iron deficiency, thalassaemia, anaemia of chronic disease (which can also be normocytic), sideroblastic anaemia (which can also be normocytic), lead poisoning, and aluminium toxicity (although this is now rare and mainly affects haemodialysis patients).

On the other hand, normocytic anaemia, with an MCV ranging from 80 to 100 fl, can be attributed to conditions like haemolysis, acute haemorrhage, bone marrow failure, anaemia of chronic disease (which can also be microcytic), mixed iron and folate deficiency, pregnancy, chronic renal failure, and sickle-cell disease.

Lastly, macrocytic anaemia, characterized by an MCV greater than 100 fl, can be caused by factors such as B12 deficiency, folate deficiency, hypothyroidism, reticulocytosis, liver disease, alcohol abuse, myeloproliferative disease, myelodysplastic disease, and certain drugs like methotrexate, hydroxyurea, and azathioprine.

It is important to understand the different causes of anaemia based on red cell size as this knowledge can aid in the diagnosis and management of this condition.

Macrolide antibiotics, such as clarithromycin and erythromycin, are widely known to prolong the International Normalized Ratio (INR). Several drugs can increase the potency of warfarin, and the macrolides, along with ciprofloxacin and metronidazole, are the antibiotics that have the most significant impact on enhancing the effect of warfarin.

Further Reading:

Management of High INR with Warfarin

Major Bleeding:
– Stop warfarin immediately.
– Administer intravenous vitamin K 5 mg.
– Administer 25-50 u/kg four-factor prothrombin complex concentrate.
– If prothrombin complex concentrate is not available, consider using fresh frozen plasma (FFP).
– Seek medical attention promptly.

INR > 8.0 with Minor Bleeding:
– Stop warfarin immediately.
– Administer intravenous vitamin K 1-3mg.
– Repeat vitamin K dose if INR remains high after 24 hours.
– Restart warfarin when INR is below 5.0.
– Seek medical advice if bleeding worsens or persists.

INR > 8.0 without Bleeding:
– Stop warfarin immediately.
– Administer oral vitamin K 1-5 mg using the intravenous preparation orally.
– Repeat vitamin K dose if INR remains high after 24 hours.
– Restart warfarin when INR is below 5.0.
– Seek medical advice if any symptoms or concerns arise.

INR 5.0-8.0 with Minor Bleeding:
– Stop warfarin immediately.
– Administer intravenous vitamin K 1-3mg.
– Restart warfarin when INR is below 5.0.
– Seek medical advice if bleeding worsens or persists.

INR 5.0-8.0 without Bleeding:
– Withhold 1 or 2 doses of warfarin.
– Reduce subsequent maintenance dose.
– Monitor INR closely and seek medical advice if any concerns arise.

Note: In cases of intracranial hemorrhage, prothrombin complex concentrate should be considered as it is faster acting than fresh frozen plasma (FFP).