Methaemoglobinaemia is a condition that can be caused by nitrates, including amyl nitrite.

Further Reading:

Methaemoglobinaemia is a condition where haemoglobin is oxidised from Fe2+ to Fe3+. This process is normally regulated by NADH methaemoglobin reductase, which transfers electrons from NADH to methaemoglobin, converting it back to haemoglobin. In healthy individuals, methaemoglobin levels are typically less than 1% of total haemoglobin. However, an increase in methaemoglobin can lead to tissue hypoxia as Fe3+ cannot bind oxygen effectively.

Methaemoglobinaemia can be congenital or acquired. Congenital causes include haemoglobin chain variants (HbM, HbH) and NADH methaemoglobin reductase deficiency. Acquired causes can be due to exposure to certain drugs or chemicals, such as sulphonamides, local anaesthetics (especially prilocaine), nitrates, chloroquine, dapsone, primaquine, and phenytoin. Aniline dyes are also known to cause methaemoglobinaemia.

Clinical features of methaemoglobinaemia include slate grey cyanosis (blue to grey skin coloration), chocolate blood or chocolate cyanosis (brown color of blood), dyspnoea, low SpO2 on pulse oximetry (which often does not improve with supplemental oxygen), and normal PaO2 on arterial blood gas (ABG) but low SaO2. Patients may tolerate hypoxia better than expected. Severe cases can present with acidosis, arrhythmias, seizures, and coma.

Diagnosis of methaemoglobinaemia is made by directly measuring the level of methaemoglobin using a co-oximeter, which is present in most modern blood gas analysers. Other investigations, such as a full blood count (FBC), electrocardiogram (ECG), chest X-ray (CXR), and beta-human chorionic gonadotropin (bHCG) levels (in pregnancy), may be done to assess the extent of the condition and rule out other contributing factors.

Active treatment is required if the methaemoglobin level is above 30% or if it is below 30% but the patient is symptomatic or shows evidence of tissue hypoxia. Treatment involves maintaining the airway and delivering high-flow oxygen, removing the causative agents, treating toxidromes and consider giving IV dextrose 5%.

Chronic myeloid leukaemia (CML) is a type of blood disorder that arises from an abnormal pluripotent haemopoietic stem cell. The majority of CML cases, more than 80%, are caused by a cytogenetic abnormality called the Philadelphia chromosome. This abnormality occurs when there is a reciprocal translocation between the long arms of chromosomes 9 and 22.

CML typically develops slowly over a period of several years, known as the chronic stage. During this stage, patients usually do not experience any symptoms, and it is often discovered incidentally through routine blood tests. Around 90% of CML cases are diagnosed during this stage. In the bone marrow, less than 10% of the white cells are immature blasts.

Symptoms start to appear when the CML cells begin to expand, which is known as the accelerated stage. Approximately 10% of cases are diagnosed during this stage. Between 10 and 30% of the blood cells in the bone marrow are blasts at this point. Common clinical features during this stage include tiredness, fatigue, fever, night sweats, abdominal distension, left upper quadrant pain (splenic infarction), splenomegaly (enlarged spleen), hepatomegaly (enlarged liver), easy bruising, gout (due to rapid cell turnover), and hyperviscosity (which can lead to complications like stroke, priapism, etc.).

In some cases, a small number of patients may present with a blast crisis, also known as the blast stage. During this stage, more than 30% of the blood cells in the bone marrow are immature blast cells. Patients in this stage are generally very ill, experiencing severe constitutional symptoms such as fever, weight loss, and bone pain, as well as infections and bleeding tendencies.

Laboratory findings in CML include a significantly elevated white cell count (often greater than 100 x 109/l), a left shift with an increased number of immature leukocytes, mild to moderate normochromic, normocytic anaemia, variable platelet counts (low, normal, or elevated), presence of the Philadelphia chromosome in more than 80% of cases, and elevated levels of serum uric acid and alkaline phosphatase.

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).

Glanzmann’s thrombasthenia is an uncommon condition affecting platelets, where they have a deficiency or abnormality in glycoprotein IIb/IIIa. This disorder leads to platelet dysfunction and can result in various complications.

Acute lymphoblastic leukaemia (ALL) is the most common type of leukaemia that occurs in childhood, typically affecting children between the ages of 2 and 5 years. The symptoms of ALL can vary, but many children initially experience an acute illness that may resemble a common cold or viral infection. Other signs of ALL include general weakness and fatigue, as well as muscle, joint, and bone pain. Additionally, children with ALL may have anaemia, unexplained bruising and petechiae, swelling (oedema), enlarged lymph nodes (lymphadenopathy), and an enlarged liver and spleen (hepatosplenomegaly).

In patients with ALL, a complete blood count typically reveals certain characteristics. These include anaemia, which can be either normocytic or macrocytic. Approximately 50% of patients with ALL have a low white blood cell count (leukopaenia), with a white cell count below 4 x 109/l. On the other hand, around 60% of patients have a high white blood cell count (leukocytosis), with a white cell count exceeding 10 x 109/l. In about 25% of cases, there is an extreme elevation in white blood cell count (hyperleukocytosis), with a count surpassing 50 x 109/l. Additionally, patients with ALL often have a low platelet count (thrombocytopaenia).

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.

If a patient’s INR reading is above 5, it is necessary to take action. In this case, the patient’s INR is between 5 and 8, but there is no evidence of bleeding. According to the provided table, it is recommended to temporarily stop 1-2 doses of warfarin and closely monitor the INR. While it may be optional to switch antibiotics, it is not a crucial step in this situation.

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 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.

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 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.

The beta thalassaemias are a group of blood disorders that occur when there is an abnormality in the production of the globin chains. These disorders are inherited in an autosomal recessive manner. In individuals with beta thalassaemia trait, there is a slight decrease in the production of beta-globin chains. This condition is most commonly found in people of Mediterranean and Asian descent.

The presentation of beta thalassaemia trait is characterized by a mild form of microcytic hypochromic anaemia. This type of anaemia can be challenging to differentiate from iron deficiency anaemia. However, it can be distinguished from iron deficiency anaemia by the presence of normal iron levels. Another useful marker for diagnosing beta thalassaemia trait is an elevated HbA2 level. A value greater than 3.5% is considered diagnostic for this condition.

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

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

Methaemoglobinaemia is a condition characterized by various symptoms such as headache, anxiety, acidosis, arrhythmia, seizure activity, reduced consciousness or coma. One notable feature is the presence of brown or chocolate coloured blood. It is important to note that the patient is taking chloroquine, which is a known trigger for methaemoglobinaemia. Additionally, despite the condition, the patient’s arterial blood gas analysis shows a normal partial pressure of oxygen.

Further Reading:

Methaemoglobinaemia is a condition where haemoglobin is oxidised from Fe2+ to Fe3+. This process is normally regulated by NADH methaemoglobin reductase, which transfers electrons from NADH to methaemoglobin, converting it back to haemoglobin. In healthy individuals, methaemoglobin levels are typically less than 1% of total haemoglobin. However, an increase in methaemoglobin can lead to tissue hypoxia as Fe3+ cannot bind oxygen effectively.

Methaemoglobinaemia can be congenital or acquired. Congenital causes include haemoglobin chain variants (HbM, HbH) and NADH methaemoglobin reductase deficiency. Acquired causes can be due to exposure to certain drugs or chemicals, such as sulphonamides, local anaesthetics (especially prilocaine), nitrates, chloroquine, dapsone, primaquine, and phenytoin. Aniline dyes are also known to cause methaemoglobinaemia.

Clinical features of methaemoglobinaemia include slate grey cyanosis (blue to grey skin coloration), chocolate blood or chocolate cyanosis (brown color of blood), dyspnoea, low SpO2 on pulse oximetry (which often does not improve with supplemental oxygen), and normal PaO2 on arterial blood gas (ABG) but low SaO2. Patients may tolerate hypoxia better than expected. Severe cases can present with acidosis, arrhythmias, seizures, and coma.

Diagnosis of methaemoglobinaemia is made by directly measuring the level of methaemoglobin using a co-oximeter, which is present in most modern blood gas analysers. Other investigations, such as a full blood count (FBC), electrocardiogram (ECG), chest X-ray (CXR), and beta-human chorionic gonadotropin (bHCG) levels (in pregnancy), may be done to assess the extent of the condition and rule out other contributing factors.

Active treatment is required if the methaemoglobin level is above 30% or if it is below 30% but the patient is symptomatic or shows evidence of tissue hypoxia. Treatment involves maintaining the airway and delivering high-flow oxygen, removing the causative agents, treating toxidromes and consider giving IV dextrose 5%.

Sickle-cell disease is a blood disorder that is inherited in an autosomal recessive manner. It is characterized by the production of abnormal red blood cells that have a sickle shape. These abnormal cells are triggered by various factors such as low oxygen levels, dehydration, stress, and infection. The disease is caused by a specific mutation in the beta-globin chain of hemoglobin, resulting in the substitution of glutamic acid with valine at the sixth position. The gene responsible for this mutation is located on chromosome 11.

On the other hand, sickle-cell trait refers to the carrier state of the disease. Individuals with sickle-cell trait have one normal allele and one abnormal allele. Both alleles are co-dominant, meaning that both normal and abnormal hemoglobin are produced. As a result, individuals with sickle-cell trait do not experience the same severity of symptoms as those with sickle-cell disease.

When both parents are carriers of the sickle-cell trait, there is a 50% chance that their child will also be an unaffected carrier, a 25% chance that the child will be unaffected, and a 25% chance that the child will develop sickle-cell disease. This is because the inheritance of the disease follows the principles of autosomal recessive inheritance.

In the blood tests, certain findings can support a diagnosis of glandular fever. One of these findings is lymphocytosis, which refers to an increased number of lymphocytes in the blood. Lymphocytes are a type of white blood cell that plays a crucial role in the immune response. In glandular fever, the Epstein-Barr virus (EBV) is the most common cause, and it primarily infects and activates lymphocytes, leading to their increased numbers in the blood.

On the other hand, neutropenia (a decreased number of neutrophils) and neutrophilia (an increased number of neutrophils) are not typically associated with glandular fever. Neutrophils are another type of white blood cell that helps fight off bacterial infections. In glandular fever, the primary involvement is with lymphocytes rather than neutrophils.

Monocytosis, which refers to an increased number of monocytes, can also be seen in glandular fever. Monocytes are another type of white blood cell that plays a role in the immune response. Their increased numbers can be a result of the immune system’s response to the Epstein-Barr virus.

Eosinophilia, an increased number of eosinophils, is not commonly associated with glandular fever. Eosinophils are white blood cells involved in allergic reactions and parasitic infections, and their elevation is more commonly seen in those conditions.

In summary, the presence of lymphocytosis and possibly monocytosis in the blood tests would support a diagnosis of glandular fever, while neutropenia, neutrophilia, and eosinophilia are less likely to be associated with this condition.

Further Reading:

Glandular fever, also known as infectious mononucleosis or mono, is a clinical syndrome characterized by symptoms such as sore throat, fever, and swollen lymph nodes. It is primarily caused by the Epstein-Barr virus (EBV), with other viruses and infections accounting for the remaining cases. Glandular fever is transmitted through infected saliva and primarily affects adolescents and young adults. The incubation period is 4-8 weeks.

The majority of EBV infections are asymptomatic, with over 95% of adults worldwide having evidence of prior infection. Clinical features of glandular fever include fever, sore throat, exudative tonsillitis, lymphadenopathy, and prodromal symptoms such as fatigue and headache. Splenomegaly (enlarged spleen) and hepatomegaly (enlarged liver) may also be present, and a non-pruritic macular rash can sometimes occur.

Glandular fever can lead to complications such as splenic rupture, which increases the risk of rupture in the spleen. Approximately 50% of splenic ruptures associated with glandular fever are spontaneous, while the other 50% follow trauma. Diagnosis of glandular fever involves various investigations, including viral serology for EBV, monospot test, and liver function tests. Additional serology tests may be conducted if EBV testing is negative.

Management of glandular fever involves supportive care and symptomatic relief with simple analgesia. Antiviral medication has not been shown to be beneficial. It is important to identify patients at risk of serious complications, such as airway obstruction, splenic rupture, and dehydration, and provide appropriate management. Patients can be advised to return to normal activities as soon as possible, avoiding heavy lifting and contact sports for the first month to reduce the risk of splenic rupture.

Rare but serious complications associated with glandular fever include hepatitis, upper airway obstruction, cardiac complications, renal complications, neurological complications, haematological complications, chronic fatigue, and an increased risk of lymphoproliferative cancers and multiple sclerosis.

Chronic myeloid leukaemia (CML) is a type of blood disorder that arises from an abnormal pluripotent haemopoietic stem cell. The majority of CML cases, more than 80%, are caused by a cytogenetic abnormality called the Philadelphia chromosome. This abnormality occurs when there is a reciprocal translocation between the long arms of chromosomes 9 and 22.

CML typically develops slowly over a period of several years, known as the chronic stage. During this stage, patients usually do not experience any symptoms, and it is often discovered incidentally through routine blood tests. Around 90% of CML cases are diagnosed during this stage. In the bone marrow, less than 10% of the white cells are immature blasts.

Symptoms start to appear when the CML cells begin to expand, which is known as the accelerated stage. Approximately 10% of cases are diagnosed during this stage. Between 10 and 30% of the blood cells in the bone marrow are blasts at this point. Common clinical features during this stage include tiredness, fatigue, fever, night sweats, abdominal distension, left upper quadrant pain (splenic infarction), splenomegaly (enlarged spleen), hepatomegaly (enlarged liver), easy bruising, gout (due to rapid cell turnover), and hyperviscosity (which can lead to complications like stroke, priapism, etc.).

In some cases, a small number of patients may present with a blast crisis, also known as the blast stage. During this stage, more than 30% of the blood cells in the bone marrow are immature blast cells. Patients in this stage are generally very ill, experiencing severe constitutional symptoms such as fever, weight loss, and bone pain, as well as infections and bleeding tendencies.

Laboratory findings in CML include a significantly elevated white cell count (often greater than 100 x 109/l), a left shift with an increased number of immature leukocytes, mild to moderate normochromic, normocytic anaemia, variable platelet counts (low, normal, or elevated), presence of the Philadelphia chromosome in more than 80% of cases, and elevated levels of serum uric acid and alkaline phosphatase.

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.

The majority of treatments provided to individuals with sickle cell disease are supportive measures that have limited impact on the underlying pathophysiology of the condition.

Currently, the only approved therapy that can modify the disease is Hydroxyurea. This medication is believed to function by increasing the levels of fetal hemoglobin, which in turn decreases the concentration of HbS within the cells and reduces the abnormal hemoglobin tendency to form polymers.

Hydroxyurea is currently authorized for use in adult patients who experience recurrent moderate-to-severe painful crises (at least three in the past 12 months). Its approval is specifically for reducing the frequency of these painful episodes and the need for blood transfusions.

Protamine sulphate is a potent base that forms a stable salt complex with heparin, an acidic substance. This complex renders heparin inactive, making protamine sulphate a useful tool for neutralizing 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.

It is important to note that protamine sulphate also possesses its own weak intrinsic anticoagulant effect. This effect is believed to stem from its ability to inhibit the formation and activity of thromboplastin.

When administering protamine sulphate, it is typically done through slow intravenous injection. The dosage should be adjusted based on the amount of heparin that needs to be neutralized, the time that has passed since heparin administration, and the aPTT (activated partial thromboplastin time). As a general guideline, 1 mg of protamine can neutralize 100 IU of heparin. However, it is crucial to adhere to a maximum adult dose of 50 mg within a 10-minute period.

It is worth mentioning that protamine sulphate can have some adverse effects. It acts as a myocardial depressant, potentially leading to bradycardia (slow heart rate) and hypotension (low blood pressure). These effects may arise due to complement activation and leukotriene release.

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.

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.

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.

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.

Transfusion transmitted bacterial infection is a rare complication that can occur during blood transfusion. It is more commonly associated with platelet transfusion, as platelets are stored at room temperature. Additionally, previously frozen components that are thawed using a water bath and red cell components stored for several weeks are also at a higher risk for bacterial infection.

Both Gram-positive and Gram-negative bacteria have been implicated in transfusion-transmitted bacterial infection, but Gram-negative bacteria are known to cause more severe illness and have higher rates of morbidity and mortality. Among the bacterial organisms, Yersinia enterocolitica is the most commonly associated with this type of infection. This particular organism is able to multiply at low temperatures and utilizes iron as a nutrient, making it well-suited for proliferation in blood stores.

The clinical features of transfusion-transmitted bacterial infection typically manifest shortly after the transfusion begins. These features include a high fever, chills and rigors, nausea and vomiting, tachycardia, hypotension, and even circulatory collapse.

If there is suspicion of a transfusion-transmitted bacterial infection, it is crucial to immediately stop the transfusion. Blood cultures and a Gram-stain should be requested to identify the specific bacteria causing the infection. Broad-spectrum antibiotics should be initiated promptly. Furthermore, the blood pack should be returned to the blood bank urgently for culture and Gram-stain analysis.

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 complete blood count findings indicate a severe case of iron deficiency anemia. The patient’s red blood cells are significantly reduced in number, and there is a noticeable hypochromic microcytic anemia. When examining the peripheral blood smear, variations in shape (poikilocytosis) and size (anisocytosis) can be observed, which are typical of iron deficiency anemia. Pencil cells are commonly seen in this condition. Additionally, it is common for iron deficiency anemia to be accompanied by thrombocytosis, an increase in platelet count.

Transfusion-associated circulatory overload (TACO) is a reaction that occurs when a large volume of blood is infused rapidly. It is the second leading cause of deaths related to transfusions, accounting for about 20% of all fatalities.

TACO typically happens in patients with limited cardiac reserve or chronic anemia who receive a fast blood transfusion. Elderly individuals, infants, and severely anemic patients are particularly vulnerable.

The common signs of TACO include acute respiratory distress, rapid heartbeat, high blood pressure, the appearance of acute or worsening fluid accumulation in the lungs on a chest X-ray, and evidence of excessive fluid retention.

The B-type natriuretic peptide (BNP) can be a helpful diagnostic tool for TACO. Usually, the BNP level is elevated to at least 1.5 times the baseline before the transfusion.

In many cases, simply slowing down the rate of transfusion, positioning the patient upright, and administering diuretics will be sufficient. In more severe cases, the transfusion should be stopped, and non-invasive ventilation may be considered.