Irradiated blood products are utilized because they have been stripped of T-lymphocytes, which can trigger severe reactions and even death if recognized as foreign agents by the host. This special requirement is particularly necessary for patients who are vulnerable to TA-GvHD, such as those with immune deficiencies or Hodgkin’s lymphoma. On the other hand, CMV negative blood products are used to minimize the risk of CMV transmission in neonates or immunocompromised individuals. In some cases, washed blood products may be ordered for patients who experience recurrent severe allergic transfusion reactions or urticarial reactions that are not prevented by pre-transfusion antihistamine and corticosteroid administration. It is important to note that the depletion of B-lymphocytes is not a primary reason for using irradiated blood products, and there is no evidence that irradiation reduces the risk of TA-GvHD by depleting eosinophil count.

CMV Negative and Irradiated Blood Products

Blood products that are CMV negative and irradiated are used in specific situations to prevent certain complications. CMV is a virus that is transmitted through leucocytes, but as most blood products are now leucocyte depleted, CMV negative products are not often needed. However, in situations where CMV transmission is a concern, such as in granulocyte transfusions, intra-uterine transfusions, neonates up to 28 days post expected date of delivery, bone marrow/stem cell transplants, immunocompromised patients, and those with/previous Hodgkin lymphoma, CMV negative blood products are used.

On the other hand, irradiated blood products are depleted of T-lymphocytes and are used to prevent transfusion-associated graft versus host disease (TA-GVHD) caused by engraftment of viable donor T lymphocytes. Irradiated blood products are used in situations such as granulocyte transfusions, intra-uterine transfusions, neonates up to 28 days post expected date of delivery, bone marrow/stem cell transplants, and in patients who have received chemotherapy or have congenital immunodeficiencies.

In summary, CMV negative and irradiated blood products are used in specific situations to prevent complications related to CMV transmission and TA-GVHD. The use of these blood products is determined based on the patient’s medical history and condition.

Bleeding time is typically unaffected by haemophilia as it is a disorder of secondary haemostasis and does not impact platelets. However, APTT is likely to be prolonged due to a deficiency in factor VIII, which is reduced in haemophilia A. The disruption of the coagulation cascade is a result of this factor VIII deficiency. In cases of severe haemophilia A with significant blood loss, haemoglobin levels may be low.

Haemophilia is a genetic disorder that affects blood coagulation and is inherited in an X-linked recessive manner. It is possible for up to 30% of patients to have no family history of the condition. Haemophilia A is caused by a deficiency of factor VIII, while haemophilia B, also known as Christmas disease, is caused by a lack of factor IX.

The symptoms of haemophilia include haemoarthroses, haematomas, and prolonged bleeding after surgery or trauma. Blood tests can reveal a prolonged APTT, while the bleeding time, thrombin time, and prothrombin time are normal. However, up to 10-15% of patients with haemophilia A may develop antibodies to factor VIII treatment.

Overall, haemophilia is a serious condition that can cause significant bleeding and other complications. It is important for individuals with haemophilia to receive appropriate medical care and treatment to manage their symptoms and prevent further complications.

The superior mesenteric lymph nodes are responsible for draining the duodenum, which is the second section of the gastrointestinal system. This lymphatic drainage is important for staging gastrointestinal cancers, and is similar to the blood supply of the gut. While the coeliac lymph nodes drain the first part of the gastrointestinal system, the inferior mesenteric lymph nodes drain the third part, and the internal iliac lymph nodes drain the lower part of the rectum and some of the anal canal. The para-aortic lymph nodes are not involved in the drainage of the gastrointestinal system, but instead drain the genito-urinary system. It is important to understand the correct lymphatic drainage patterns for accurate cancer staging.

Lymphatic drainage is the process by which lymphatic vessels carry lymph, a clear fluid containing white blood cells, away from tissues and organs and towards lymph nodes. The lymphatic vessels that drain the skin and follow venous drainage are called superficial lymphatic vessels, while those that drain internal organs and structures follow the arteries and are called deep lymphatic vessels. These vessels eventually lead to lymph nodes, which filter and remove harmful substances from the lymph before it is returned to the bloodstream.

The lymphatic system is divided into two main ducts: the right lymphatic duct and the thoracic duct. The right lymphatic duct drains the right side of the head and right arm, while the thoracic duct drains everything else. Both ducts eventually drain into the venous system.

Different areas of the body have specific primary lymph node drainage sites. For example, the superficial inguinal lymph nodes drain the anal canal below the pectinate line, perineum, skin of the thigh, penis, scrotum, and vagina. The deep inguinal lymph nodes drain the glans penis, while the para-aortic lymph nodes drain the testes, ovaries, kidney, and adrenal gland. The axillary lymph nodes drain the lateral breast and upper limb, while the internal iliac lymph nodes drain the anal canal above the pectinate line, lower part of the rectum, and pelvic structures including the cervix and inferior part of the uterus. The superior mesenteric lymph nodes drain the duodenum and jejunum, while the inferior mesenteric lymph nodes drain the descending colon, sigmoid colon, and upper part of the rectum. Finally, the coeliac lymph nodes drain the stomach.

G6PD deficiency is a genetic disorder that affects the production of glucose-6-phosphate dehydrogenase, which is necessary for the production of NADPH. NADPH is essential for maintaining glutathione, which helps prevent oxidative damage by neutralizing free radicals. Patients with G6PD deficiency have low levels of glutathione, making them more susceptible to oxidative stress and resulting in the destruction of red blood cells. This destruction leads to an enlarged spleen and jaundice, as bilirubin is released during the breakdown of hemoglobin. The patient’s Mediterranean descent and family history of the disease suggest G6PD deficiency, which was confirmed by a G6PD enzyme assay. The presence of Heinz bodies on blood film is also characteristic of the disease. The suggestion of an autosomal dominant defect of red cells is incorrect, as this is the pathophysiology for hereditary spherocytosis, which has different clinical features and would be seen on blood film.

Understanding G6PD Deficiency

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

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

The patient’s CT scan showed lymphadenopathy in the superficial inguinal lymph nodes, which is expected as the infection is located in the perineum. The deep inguinal lymph nodes, which drain the glans penis and clitoris, are not the primary site for perineal drainage. The medial group of external iliac lymph nodes drain the urinary bladder, membranous aspect of the urethra, cervix, and upper part of the vagina, while the internal iliac lymph nodes drain the anal canal above the pectinate line, the lower part of the rectum, the cervix, and the inferior uterus. If there were retained products of conception in the uterus causing an infection or a type 4 perineal tear involving a substantial portion of the rectum, lymphadenopathy of the internal iliac lymph nodes may be seen on the CT scan. The para-aortic lymph nodes drain the ovaries, but this is not relevant to the patient’s case as there is no indication of an ovarian pathology.

Lymphatic drainage is the process by which lymphatic vessels carry lymph, a clear fluid containing white blood cells, away from tissues and organs and towards lymph nodes. The lymphatic vessels that drain the skin and follow venous drainage are called superficial lymphatic vessels, while those that drain internal organs and structures follow the arteries and are called deep lymphatic vessels. These vessels eventually lead to lymph nodes, which filter and remove harmful substances from the lymph before it is returned to the bloodstream.

The lymphatic system is divided into two main ducts: the right lymphatic duct and the thoracic duct. The right lymphatic duct drains the right side of the head and right arm, while the thoracic duct drains everything else. Both ducts eventually drain into the venous system.

Different areas of the body have specific primary lymph node drainage sites. For example, the superficial inguinal lymph nodes drain the anal canal below the pectinate line, perineum, skin of the thigh, penis, scrotum, and vagina. The deep inguinal lymph nodes drain the glans penis, while the para-aortic lymph nodes drain the testes, ovaries, kidney, and adrenal gland. The axillary lymph nodes drain the lateral breast and upper limb, while the internal iliac lymph nodes drain the anal canal above the pectinate line, lower part of the rectum, and pelvic structures including the cervix and inferior part of the uterus. The superior mesenteric lymph nodes drain the duodenum and jejunum, while the inferior mesenteric lymph nodes drain the descending colon, sigmoid colon, and upper part of the rectum. Finally, the coeliac lymph nodes drain the stomach.

Hodgkin’s disease is characterized by the presence of Reed Sternberg cells, while sarcoid is associated with the presence of all other cell types.

Chronic inflammation can occur as a result of acute inflammation or as a primary process. There are three main processes that can lead to chronic inflammation: persisting infection with certain organisms, prolonged exposure to non-biodegradable substances, and autoimmune conditions involving antibodies formed against host antigens. Acute inflammation involves changes to existing vascular structure and increased permeability of endothelial cells, as well as infiltration of neutrophils. In contrast, chronic inflammation is characterized by angiogenesis and the predominance of macrophages, plasma cells, and lymphocytes. The process may resolve with suppuration, complete resolution, abscess formation, or progression to chronic inflammation. Healing by fibrosis is the main result of chronic inflammation. Granulomas, which consist of a microscopic aggregation of macrophages, are pathognomonic of chronic inflammation and can be found in conditions such as colonic Crohn’s disease. Growth factors released by activated macrophages, such as interferon and fibroblast growth factor, may have systemic features resulting in systemic symptoms and signs in individuals with long-standing chronic inflammation.

A helpful mnemonic for remembering transfusion reactions is Got a bad unit. Each letter represents a potential complication:

G – Graft vs. Host disease
O – Overload
T – Thrombocytopenia
A – Alloimmunization
B – Blood pressure unstable
A – Acute hemolytic reaction
D – Delayed hemolytic reaction
U – Urticaria
N – Neutrophilia
I – Infection
T – Transfusion-associated lung injury

Graft vs. Host disease occurs when the patient’s own lymphocytes are similar to the donor’s lymphocytes, causing severe complications. Thrombocytopenia may occur a few days after transfusion and may resolve on its own. Patients with IGA antibodies require IgA deficient blood transfusions.

Blood product transfusion complications can be categorized into immunological, infective, and other complications. Immunological complications include acute haemolytic reactions, non-haemolytic febrile reactions, and allergic/anaphylaxis reactions. Infective complications may arise due to transmission of vCJD, although measures have been taken to minimize this risk. Other complications include transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), hyperkalaemia, iron overload, and clotting.

Non-haemolytic febrile reactions are thought to be caused by antibodies reacting with white cell fragments in the blood product and cytokines that have leaked from the blood cell during storage. These reactions may occur in 1-2% of red cell transfusions and 10-30% of platelet transfusions. Minor allergic reactions may also occur due to foreign plasma proteins, while anaphylaxis may be caused by patients with IgA deficiency who have anti-IgA antibodies.

Acute haemolytic transfusion reaction is a serious complication that results from a mismatch of blood group (ABO) which causes massive intravascular haemolysis. Symptoms begin minutes after the transfusion is started and include a fever, abdominal and chest pain, agitation, and hypotension. Treatment should include immediate transfusion termination, generous fluid resuscitation with saline solution, and informing the lab. Complications include disseminated intravascular coagulation and renal failure.

TRALI is a rare but potentially fatal complication of blood transfusion that is characterized by the development of hypoxaemia/acute respiratory distress syndrome within 6 hours of transfusion. On the other hand, TACO is a relatively common reaction due to fluid overload resulting in pulmonary oedema. As well as features of pulmonary oedema, the patient may also be hypertensive, a key difference from patients with TRALI.

Anaphylactic blood transfusion reactions are known to be associated with IgA deficiency, which increases the risk of such reactions. Classic symptoms include sudden onset shortness of breath, angioedema, and wheeze, and require immediate treatment with intramuscular adrenaline, followed by IV hydrocortisone and chlorphenamine to prevent a secondary reaction. Other conditions such as adult polycystic kidney disease, HIV infection, and liver cirrhosis are not known to be associated with anaphylactic blood transfusion reactions.

Blood product transfusion complications can be categorized into immunological, infective, and other complications. Immunological complications include acute haemolytic reactions, non-haemolytic febrile reactions, and allergic/anaphylaxis reactions. Infective complications may arise due to transmission of vCJD, although measures have been taken to minimize this risk. Other complications include transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), hyperkalaemia, iron overload, and clotting.

Non-haemolytic febrile reactions are thought to be caused by antibodies reacting with white cell fragments in the blood product and cytokines that have leaked from the blood cell during storage. These reactions may occur in 1-2% of red cell transfusions and 10-30% of platelet transfusions. Minor allergic reactions may also occur due to foreign plasma proteins, while anaphylaxis may be caused by patients with IgA deficiency who have anti-IgA antibodies.

Acute haemolytic transfusion reaction is a serious complication that results from a mismatch of blood group (ABO) which causes massive intravascular haemolysis. Symptoms begin minutes after the transfusion is started and include a fever, abdominal and chest pain, agitation, and hypotension. Treatment should include immediate transfusion termination, generous fluid resuscitation with saline solution, and informing the lab. Complications include disseminated intravascular coagulation and renal failure.

TRALI is a rare but potentially fatal complication of blood transfusion that is characterized by the development of hypoxaemia/acute respiratory distress syndrome within 6 hours of transfusion. On the other hand, TACO is a relatively common reaction due to fluid overload resulting in pulmonary oedema. As well as features of pulmonary oedema, the patient may also be hypertensive, a key difference from patients with TRALI.

Understanding Antithrombin III Deficiency

Antithrombin III deficiency is a genetic condition that affects approximately 1 in 3,000 people. It is inherited in an autosomal dominant manner. This condition occurs when the body does not produce enough antithrombin III, a protein that helps to prevent blood clots by inhibiting certain clotting factors. Some patients with this deficiency have a shortage of normal antithrombin III, while others produce abnormal antithrombin III.

People with antithrombin III deficiency are at an increased risk of developing recurrent venous thromboses, which are blood clots that form in the veins. While arterial thromboses can also occur, they are less common. To manage this condition, patients may need to take warfarin for the rest of their lives to prevent thromboembolic events. During pregnancy, heparin may be used instead. Antithrombin III concentrates may also be used during surgery or childbirth.

It is important to note that patients with antithrombin III deficiency have a degree of resistance to heparin, so anti-Xa levels should be monitored carefully to ensure adequate anticoagulation. Compared to other inherited thrombophilias, antithrombin III deficiency is less common but has a higher relative risk of venous thromboembolism. Understanding this condition and its management is crucial for those affected and their healthcare providers.

Haptoglobin is a liver-produced protein that binds to free haemoglobin in blood plasma, allowing the reticuloendothelial system to remove it. This consumption of haptoglobin reduces its detectable levels in the blood, making it a useful indicator of haemolysis.

If an individual has a functioning liver, conjugated bilirubin levels will increase in haemolysis. This is because the liver generates conjugated bilirubin from unconjugated bilirubin, which is produced from the porphyrin rings of haemoglobin. Conjugated bilirubin is more soluble in water and can be secreted through the kidneys.

Lactate dehydrogenase is an intracellular enzyme that is leaked from cells, including erythrocytes, which are broken down. Its levels increase due to cell breakdown, not only in haemolysis but also in cardiomyocyte damage due to infarction and lymphocyte turnover due to leukaemia.

Potassium is an intracellular ion that can increase in levels due to haemolysis and cell breakdown. This can lead to cardiac arrhythmias such as ventricular tachycardia and fibrillation.

Low platelets and a purpuric rash suggest that the likely form of intravascular haemolysis is a microangiopathic haemolytic anaemia (MAHA) such as thrombotic thrombocytopenic purpura (TTP) or haemolytic uraemic syndrome (HUS). These rare conditions result in the accumulation of intravascular thrombosis, leading to platelet and clotting factor consumption.

Understanding Haemolytic Anaemias by Site

Haemolytic anaemias can be classified by the site of haemolysis, either intravascular or extravascular. In intravascular haemolysis, free haemoglobin is released and binds to haptoglobin. As haptoglobin becomes saturated, haemoglobin binds to albumin forming methaemalbumin, which can be detected by Schumm’s test. Free haemoglobin is then excreted in the urine as haemoglobinuria and haemosiderinuria. Causes of intravascular haemolysis include mismatched blood transfusion, red cell fragmentation due to heart valves, TTP, DIC, HUS, paroxysmal nocturnal haemoglobinuria, and cold autoimmune haemolytic anaemia.

On the other hand, extravascular haemolysis occurs when red blood cells are destroyed by macrophages in the spleen or liver. This type of haemolysis is commonly seen in haemoglobinopathies such as sickle cell anaemia and thalassaemia, hereditary spherocytosis, haemolytic disease of the newborn, and warm autoimmune haemolytic anaemia.

It is important to understand the site of haemolysis in order to properly diagnose and treat haemolytic anaemias. While both intravascular and extravascular haemolysis can lead to anaemia, the underlying causes and treatment approaches may differ.