haem

• Any of the following features in a person aged 0-24 years should prompt a very urgent full blood count (within 48 hours) to investigate for leukaemia:

  • Pallor
  • Persistent fatigue
  • Unexplained fever
  • Unexplained persistent infections
  • Generalised lymphadenopathy
  • Persistent or unexplained bone pain
  • Unexplained bruising
  • Unexplained bleeding
• Steroids tend to cause a neutrophilia.
• Chronic lymphocytic leukaemia (CLL) is caused by a monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%). It is the most common form of leukaemia seen in adults.

  Investigations

  • full blood count:
  • lymphocytosis
  • anaemia
  • thrombocytopenia
  • blood film: smudge/ smear cells
  • immunophenotyping is the key investigation
  • most cases can be identified using a panel of antibodies specific for CD5, CD19, CD20 and CD23

  
• Multiple myeloma investigations

  Bloods

  • fbc: anaemia
  • peripheral blood film: rouleaux formation
  • urea and electrolytes: renal failure
  • bone profile: hypercalcaemia

  Protein electrophoresis

  • raised monoclonal IgA/IgG
  • in the urine, they are known as Bence Jones proteins

  Bone marrow aspiration

  • confirms the diagnosis if the plasma cells raised

  Imaging

  • skeletal survey for bone lesions
  • currently whole-body MRI
  • X-rays: 'rain-drop skull'. Note that a very similar, but subtly different finding is found in primary hyperparathyroidism - 'pepperpot skull'
• CML is characterized by anaemia, splenomegaly, and an increase in granulocytes at different stages of maturation, occasionally accompanied by thrombocytosis. The first-line management is imatinib.
• The Philadelphia chromosome is present in more than 95% of patients with chronic myeloid leukaemia (CML). It is due to a translocation between the long arm of chromosome 9 and 22.
• CML Management

  • imatinib is now considered first-line treatment
  • inhibitor of the tyrosine kinase associated with the BCR-ABL defect
  • very high response rate in chronic phase CML
  • hydroxyurea
  • interferon-alpha
  • allogenic bone marrow transplant
• TRALI is an acute lung injury following a blood transfusion and typically occurs within 6 hours of transfusion.
• Non-haemolytic febrile reaction 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

  
  

  Fever, chills

  Red cell transfusion (1-2%) Platelet transfusion (10-30%)

  
  

  Slow or stop the transfusion

  Paracetamol

  Monitor
• Minor allergic reactionThought to be caused by foreign plasma proteins

  Pruritus, urticaria

  Temporarily stop the transfusion

  AntihistamineMonitor
• Anaphylaxis can be caused by patients with IgA deficiency who have anti-IgA antibodies

  Hypotension, dyspnoea, wheezing, angioedema.

  Stop the transfusion IM adrenaline

  ABC support

  • oxygen
  • fluids
• Acute haemolytic reactionABO-incompatible blood e.g. secondary to human error

  Fever, abdominal pain, hypotension

  Stop transfusionConfirm diagnosis

  • check the identity of patient/name on blood product
  • send blood for direct Coombs test, repeat typing and cross-matching 

  Supportive care

  • fluid resuscitation
• Transfusion-associated circulatory overload (TACO) - Excessive rate of transfusion, pre-existing heart failure

  Pulmonary oedema, hypertension

  Slow or stop transfusion. Consider intravenous loop diuretic (e.g. furosemide) and oxygen
• Transfusion-related acute lung injury (TRALI) - Non-cardiogenic pulmonary oedema thought to be secondary to increased vascular permeability caused by host neutrophils that become activated by substances in donated blood

  Hypoxia, pulmonary infiltrates on chest x-ray, fever, hypotension

  Stop the transfusion. Oxygen and supportive care
• A lymph node biopsy with reed sternberg cells shows large multinucleate cells with prominent eosinophilic nucleoli
• Sarcoidosis would classically present with symmetrical lymphadenopathy 
• Hodgkin's lymphoma (HL) is a malignant proliferation of lymphocytes characterised by the presence of the Reed-Sternberg cell. It has a bimodal age distributions being most common in the third and seventh decadesRisk factors

  • HIV
  • Epstein-Barr virus

  Features

  • lymphadenopathy (75%)
  • neck (cervical/supraclavicular) > axillary > inguinal 
  • painless, non-tender, asymmetrical
  • alcohol-induced lymph node pain
  • systemic - 'B symptoms' (25%)
  • other possible presentations include a mediastinal mass
  • may be symptomatic (e.g. cough) or found incidentally on a chest x-ray
• Acute intermittent porphyria is a deficiency of an enzyme needed to synthesise haem. The build-up of haem precursors can cause acute attacks of severe abdominal pain (often accompanied by vomiting), hypertension and tachycardia. Severe cases result in psychiatric symptoms (anxiety, confusion, hallucinations) and neurological manifestations (seizures, muscle weakness and areflexia). Classically, urine fluoresces a bright red colour on standing. Nitrofurantoin commonly precipitates an acute attack e.g. when used to treat recurrent UTIs.
• TTP typically presents a pentad of neurological symptoms, renal dysfunction, fever, haemolytic anaemia and thrombocytopenia. These patients are likely to be jaundiced with evidence of bleeding into the skin/mucous membranes.
• AIP Management

  • avoiding triggers
  • acute attacks
  • IV haematin/haem arginate
  • IV glucose should be used if haematin/haem arginate is not immediately available
• Painless lymphadenopathy, constitutional symptoms (weight loss, lethargy, night sweats), hepatomegaly and testicular mass along with anaemia on blood tests is highly suggestive of lymphoma. The testicular mass is suggestive of extranodal disease which is more common in NHL than Hodgkin's lymphoma. The definitive diagnosis of lymphoma requires histological confirmation via excisional node biopsy.
• NHL Management

  • Management is dependent on the specific sub-type of non-Hodgkin's lymphoma and will typically take the form of watchful waiting, chemotherapy or radiotherapy. 
  • Rituximab is used in combination with conventional chemotherapy regimes (e.g. CHOP) for a variety of types of NHL
  • All patients will receive flu/pneumococcal vaccines
  • Patients with neutropenia may require antibiotic prophylaxis
• Von Willebrand's disease is the most common inherited bleeding disorder. The majority of cases are inherited in an autosomal dominantfashion* and characteristically behaves like a platelet disorder i.e. epistaxis and menorrhagia are common whilst haemoarthroses and muscle haematomas are rare
• VWD

  Investigation

  • prolonged bleeding time
  • APTT may be prolonged
  • factor VIII levels may be moderately reduced
  • defective platelet aggregation with ristocetin

  Management

  • tranexamic acid for mild bleeding
  • desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
  • factor VIII concentrate
• Aplastic crisis is is often precipitated by exposure to parvovirus B19.
• typical characteristics of thrombotic thrombocytic purpura (TTP):

  • Fever (T: 38ºC) 
  • Altered mental state (headache, confusion, excess tiredness, seizure)
  • Thrombocytopenia (platelets: 130 * 109/L)
  • Haemolytic anaemia (haemoglobin: 98 g/L)
  • Reduced renal function (creatinine: 126 µmol/L)
  • Hypertension (this does not form part of the pentad of symptoms but may be present)
• Causes of DIC

  • sepsis
  • trauma
  • obstetric complications e.g. aminiotic fluid embolism or hemolysis, elevated liver function tests, and low platelets (HELLP syndrome)
  • malignancy
• A typical DIC blood picture includes:

  • ↓ platelets
  • ↓ fibrinogen
  • ↑ PT & APTT
  • ↑ fibrinogen degradation products
  • schistocytes due to microangiopathic haemolytic anaemia
• Warfarin - Prolonged PT

  Aspirin - Prolonged bleeding time

  Heparin - Prolonged APTT, maybe PT

  DIC - Prolonged PT, APTT & bleeding , low platelet count
• Glucose-6-phosphate dehydrogenase deficiency is an X linked disorder affecting red cell enzymes. It results in a reduced ability of the red cells to respond to oxidative stress. Therefore, red cells have a shorter life span and are more susceptible to haemolysis, particularly in response to drugs (e.g. nitrofurantoin), infection, acidosis and certain dietary agents (e.g. fava beans). Red cell fragments, Heinz bodies and anaemia confirm a haemolytic anaemia.
• A blue line along the gum margin can occur in up to 20% patients with lead poisoning.
• A history of sudden onset hypotension, fever and dyspnoea is suggestive of ABO-incompatibility haemolytic transfusion reaction. Anti-A and anti-B antibodies are IgM-type antibodies which bind to red blood cells causing haemolysis in haemolytic transfusion reactions. 
• Bacterial contamination of blood products can result in a transfusion reaction, which typically develops over hours rather than minutes.
• Haemolytic transfusion reactions are usually the result of IgM type antibodies, rather than IgG binding to red blood cells.
• Sulfonylureas, such as gliclazide, can cause oxidative stress and precipitate an acute intravascular haemolytic episode in patients with G6PD deficiency. Primaquine, an anti-malarial, can also precipitate an acute haemolytic episode in G6PD deficiency.
• Tamoxifen is a selective estrogen receptor modulator used in the treatment of hormone receptor-positive breast cancer. It is known to increase the risk of venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, due to its estrogenic effects on the blood vessels.
• Bleeding post operatively, epistaxis and menorrhagia may indicate a diagnosis of vWD. Haemoarthroses are rare. The bleeding time is usually normal in haemophilia (X-linked) and vitamin K deficiency.
• The elderly, pregnancy, malignancy and autoimmune conditions are associated with acquired haemophilia. Prolonged APTT is key to the diagnosis. Management involves steroids.
• A combination of thromboembolism and bleeding in a young woman should raise the possibility of antiphospholipid syndrome. Other features may include foetal loss, venous and arterial thrombosis and thrombocytopenia. A Lupus anticoagulant may be present and the APTT is prolonged.
• Haemophilia - Increased APTT

  von Willebrand's disease - Increased APTT & bleeding time

  Vitamin K deficiency - Increased APTT & PT