Paroxysmal Nocturnal Haemoglobinuria: A Clonal Defect of Red Cells

Paroxysmal nocturnal haemoglobinuria (PNH) is a condition where red blood cells have an increased susceptibility to lysis by complement due to an acquired clonal defect. This disorder typically presents in young adults and is often associated with other stem cell disorders, such as aplastic anaemia. The classic symptom of PNH is the intermittent passage of bloody urine, which tends to occur more frequently at night for unknown reasons. Diagnosis is often made through investigation of anaemia, pancytopenia, or recurrent thrombotic episodes, which are likely caused by complement-induced platelet aggregation. Flow cytometry can confirm the diagnosis by demonstrating a lack of erythrocyte membrane proteins CD59 and decay accelerating factor (DAF).

Overall, PNH is a rare but serious condition that can lead to significant complications if left untreated. Early diagnosis and management are crucial for improving outcomes and preventing further damage to the body.

Managing DIC in a Patient with Septic Shock: Evaluating Treatment Options

When managing a patient with disseminated intravascular coagulation (DIC), it is important to consider the underlying condition causing the DIC. In the case of a patient with septic shock secondary to a urinary tract infection, the sepsis 6 protocol should be initiated alongside pre-emptive management for potential blood loss.

While a blood cross-match is sensible, emergency blood products such as platelets are unwarranted in the absence of acute bleeding. Activated protein C, previously recommended for DIC management, has been removed from guidelines due to increased bleeding risk without overall mortality benefit.

Anticoagulation with low molecular weight heparin is unnecessary at this time, especially when given with blood products, which are pro-coagulant. Tranexamic acid and platelet transfusions are only warranted in the presence of severe active bleeding.

Prophylactic dose unfractionated heparin may be a good management strategy in the presence of both thrombotic complications and increased bleeding risk, but should be given at a treatment dose if deemed necessary. Ultimately, managing the underlying septic shock is the best way to manage DIC in this patient.

Common Medications and Their Uses

Thrombocytosis and Hydroxyurea
Thrombocytosis is a condition characterized by an elevated platelet count, which can lead to bleeding or thrombosis. Primary or essential thrombocytosis is a myeloproliferative disorder that results in overproduction of platelets by the bone marrow. Hydroxyurea is the first-line treatment for essential thrombocytosis, as it inhibits an enzyme involved in DNA synthesis and reduces the rate of platelet production.

Interferon Gamma for Immunomodulation
Interferon gamma is an immunomodulatory medication used to reduce the frequency of infections in patients with chronic granulomatous disease and severe malignant osteopetrosis. It is administered by subcutaneous injection.

Cromoglycate for Inflammation
Sodium cromoglycate is a synthetic non-steroidal anti-inflammatory drug used in the treatment of asthma, allergic rhinitis, and various food allergies.

Interferon β for Multiple Sclerosis
Interferon β is a cytokine used in the treatment of relapsing-remitting multiple sclerosis. It is administered subcutaneously.

Ranitidine for Acid Reduction
Ranitidine is a H2 (histamine) receptor blocker that inhibits the production of acid in the stomach. It can be used in the treatment of gastro-oesophageal reflux disease, peptic ulcer disease, and gastritis.

Hormone Levels and Menopausal Status

Follicle-stimulating hormone (FSH) levels that are greater than 30 IU/l, repeated over a period of four to eight weeks, are typically indicative of menopause. It is important to ensure that FSH is tested when the patient is not on contraception, although this is not relevant in the current scenario. While oestrogen and progesterone levels decrease after menopause, their assay is less reliable in determining menopausal status compared to FSH levels. Beta-HCG levels are elevated during pregnancy and trophoblastic disease, while prolactin levels increase in response to certain drug therapies and the presence of a pituitary tumour.

Venous Thromboembolism Prophylaxis for Long-Haul Flights

When it comes to preventing venous thromboembolism (VTE) during long-haul flights, the approach varies depending on the patient’s risk level. For low-risk patients without history of VTE, cardiac disease, major illness, or recent surgery, NICE recommends avoiding long periods of immobility by taking an aisle seat, performing ankle exercises, and wearing loose-fitting clothing. It’s also important to stay hydrated and avoid alcohol.

Moderate to high-risk patients, on the other hand, may benefit from compression stockings, especially if they have a history of VTE, cardiac disease, varicose veins, or are pregnant or postpartum. High-risk patients with thrombophilia, cancer, or recent surgery requiring general anesthesia should also consider compression stockings.

While some sources recommend a single dose of aspirin for VTE prophylaxis during long-haul flights, current NICE guidelines do not recommend this approach. Instead, patients should focus on staying mobile, wearing compression stockings if necessary, and staying hydrated.

Leukapheresis and Other Treatment Options for Chronic Myeloid Leukaemia with High White Blood Cell Count and Ischaemic Stroke

Chronic myeloid leukaemia can cause an extremely high white blood cell count, leading to hyperviscosity of the blood and an increased risk of ischaemic events such as stroke. While anticoagulation medications are important, they do not address the underlying issue of the high cell count. Leukapheresis is a procedure that can reduce the white cell volume by 30-60%, making it a crucial emergency treatment option. Other treatments, such as hydroxyurea and imatinib, can also be used to control disease burden. Imatinib is a tyrosine kinase inhibitor that is effective in treating chronic myeloid leukaemia with the Philadelphia chromosome translocation. Aspirin and heparin have limited roles in this scenario. While aspirin is recommended for long-term therapy after an ischaemic stroke, it does not address the hypercoagulable state caused by the high white blood cell count. Heparin is not used in the treatment of ischaemic strokes. Overall, leukapheresis should be the first step in emergency management for chronic myeloid leukaemia with a high white blood cell count and ischaemic stroke.

Preparation of Plasma Derivatives

The preparation of plasma derivatives, such as factor VIII, involves pooling several thousand plasma donations, typically 20,000 or 5,000 kg of plasma at a time. To avoid the risk of vCJD, pooled plasma has been sourced from outside the UK since 1999. The process includes several chemical steps, including ethanol extraction, chromatography, and viral inactivation, resulting in a freeze-dried product. These products have a long shelf life of several months to years.

Comparison of DIC, von Willebrand’s Disease, Liver Failure, Haemophilia, and Heparin Administration

Disseminated intravascular coagulopathy (DIC) is a serious complication of severe sepsis that can lead to multiorgan failure and widespread bleeding. It is characterized by high prothrombin time and the use of fibrinogen for widespread clot formation, resulting in high levels of D-dimer due to intense fibrinolytic activity. DIC is a paradoxical state in which the patient is prone to clotting but also to bleeding.

Von Willebrand’s disease is an inherited disorder of coagulation that is usually autosomal dominant. There is insufficient information to suggest that the patient in this case has von Willebrand’s disease.

Liver failure could result in excessive bleeding due to disruption of liver synthetic function, but there is no other information to support liver failure in this case. Signs of hepatic encephalopathy or jaundice would also be expected.

Haemophilia is an X-linked recessive disorder of coagulation that is characterized by prolonged activated partial thromboplastin time (APTT) and normal prothrombin time.

There is no information to suggest that heparin has been administered, and the bleeding time and platelet count would be normal.

Storage Guidelines for Blood Products

Blood products such as fresh frozen plasma, red cells, and platelets have specific storage guidelines to ensure their safety and efficacy. Fresh frozen plasma can be stored for up to 36 months at a temperature of −25°C. On the other hand, red cells are stored at a temperature of 4°C for a maximum of 35 days, while platelets are stored at a temperature of 22°C for up to 5 days on a platelet shaker/agitator.

These guidelines are important to follow to maintain the quality of blood products and prevent any adverse reactions in patients who receive them. It is crucial to store blood products at the appropriate temperature and for the recommended duration to ensure their effectiveness when used in transfusions. Healthcare professionals should be aware of these guidelines and ensure that they are followed to provide safe and effective blood transfusions to patients.

Smouldering myeloma is a stage between monoclonal gammopathy of unknown significance (MGUS) and myeloma. To diagnose this condition, the patient must have a monoclonal protein in the serum of at least 30 g/l and monoclonal plasma cells of at least 10% in bone marrow or tissue biopsy, but no evidence of end-organ damage. Patients with smouldering myeloma should be closely monitored as they are at high risk of developing symptomatic myeloma.

Multiple myeloma is a malignant neoplasm where there is clonal proliferation of plasma cells in the bone marrow, leading to the secretion of a monoclonal antibody and light immunoglobulin chains that cause organ damage. Patients with multiple myeloma present with various symptoms, including lethargy, bone pain, pathological fractures, renal impairment, amyloidosis, and pancytopenia due to marrow infiltration. To diagnose multiple myeloma, the patient must have a monoclonal antibody in serum and/or urine, clonal plasma cells of at least 10% on bone marrow biopsy, and evidence of end-organ damage.

MGUS is a condition where low levels of paraprotein are detected in the blood, but they are not causing clinically significant symptoms or end-organ damage. To diagnose MGUS, the patient must have a monoclonal protein in the serum of less than or equal to 30 g/l, monoclonal plasma cells of less than or equal to 10% in bone marrow or tissue biopsy, and no evidence of end-organ damage.

Non-secretory myeloma is a rare variant of multiple myeloma where the bone marrow findings and end-organ damage are similar to myeloma, but there is no detectable monoclonal protein in the serum or urine. This makes it difficult to diagnose.

Plasma cell leukemia is a rare and aggressive form of multiple myeloma characterized by high levels of plasma cells circulating in the peripheral blood. It can occur as a primary condition or a secondary leukaemic transformation of multiple myeloma.