Haematology 3

oelomar's version from 2016-03-31 19:00


Question Answer
What are autoimmune haemolytic anaemias (AIHAs)?AIHAs are acquired disorders resulting from increased red cell destruction due to red cell autoantibodies. These anaemias are characterised by the presence of a positive direct antiglobulin (Coombs) test, which detects the autoantibody on the surface of the patient’s red cells.
Autoimmune haemolytic anaemias can be divided into “warm” and “cold” types. What is the difference between them?This depends on whether the antibody attaches better to the red cells at body temperature (37°C) or at lower temperatures. In warm AIHA, IgG antibodies predominate. In cold AIHA, the antibodies are IgM.
How do warm autoimmune haemolytic anaemias present?They can present as a short episode of anaemia and jaundice but they often remit and relapse and may progress to an intermittent chronic pattern. The spleen is often palpable.
What will a blood film show in people with warm autoimmune haemolytic anaemia?Spherocytes.
What are the causes of warm autoimmune haemolytic anaemia?About half are idiopathic. However, they may be associated with lymphoid malignancies, or diseases including rheumatoid arthritis and systemic lupus erythematosus.
How is warm autoimmune haemolytic anaemia treated?Corticosteroids are effective in inducing a remission in most patients. Splenectomy may be necessary if there is no response to steroids or if the remission is not maintained when the dose of prednisolone is reduced. Blood transfusion may be necessary if there is severe anaemia.


Question Answer
What is cold agglutinin disease?Cold agglutinin disease is an autoimmune disease characterised by the presence of high concentrations of circulating antibodies, usually IgM, directed against red blood cells. It is a form of autoimmune haemolytic anaemia, specifically one in which antibodies only bind red blood cells at low body temperatures, typically 28-31°C. After exposure to cold, the patient develops an acrocyanosis (bluish or purple colouring of the hands and feet) similar to Raynaud’s as a result of red cell autoagglutination.
How is cold agglutinin disease diagnosed?Direct antiglobulin (Coombs) test is positive with complement (C3d) alone.
How is cold agglutinin disease treated?Patients should avoid exposure to cold. Treatment with rituximab has been successful in some cases. Blood transfusion may be necessary.
What is paroxysmal cold haemoglobinuria (PCH)?A disease characterised by the sudden presence of haemoglobin in the urine typically after exposure to cold temperatures. It is associated with common childhood infections.
What is haemolytic disease of the newborn?A condition that develops in the foetus when the IgG molecules produced by the mother pass through the placenta, some of which may attack the foetus’ RBCs. When the mother is Rh-negative and the father is Rh-positive, the foetus can inherit the Rh factor from the father. This makes the foetus Rh-positive too. A mother who is Rh-negative may develop antibodies to an Rh-positive baby. If a small amount of the baby’s blood mixes with the mother’s blood, which often happens in such situations, the mother’s body may respond as if it were allergic to the baby. The mother’s body may make antibodies to the Rh antigens in the baby’s blood. This means the mother has become sensitised and her antibodies may cross the placenta and attack the baby’s blood. Such an attack breaks down the foetus’ RBCs, creating anaemia.
Is haemolytic disease of the newborn fatal?The foetus can develop reticulocytosis and anaemia. This foetal disease ranges from mild to very severe, and foetal death from heart failure (hydrops foetalis) can occur.
What is paroxysmal nocturnal haemoglobinuria?Paroxysmal nocturnal haemoglobinuria, is a rare, acquired, life-threatening disease of the blood characterised by destruction of red blood cells by the complement system.
What are the clinical features of paroxysmal nocturnal haemoglobinuria?The major clinical signs are intravascular haemolysis, venous thrombosis (not fully understood why) and haemoglobinuria. Haemolysis may be precipitated by infection, iron therapy or surgery. Characteristically only the urine voided at night and in the morning on waking is dark in colour. Urinary iron loss may be sufficient to cause iron deficiency. Some patients present insidiously with signs of anaemia and recurrent abdominal pains. Venous thrombotic episodes are very common in unusual places and severe thromboses may occur, for example in hepatic, mesenteric, or cerebral veins.
How is paroxysmal nocturnal haemoglobinuria treated?PNH is a chronic disorder requiring supportive measures such as blood transfusions. Leucocyte-depleted blood should be used. Treatment is with eculizumab, a monoclonal antibody that prevents the cleavage of C5. Long-term anticoagulation may be necessary for patients with recurrent thrombotic episodes. In patients with bone marrow failure, bone marrow transplantation may be carried out.
Does paroxysmal nocturnal haemoglobinuria have any potential serious complications?PNH may transform into aplastic anaemia or acute leukaemia, but it may remain stable for many years and even disappear.


Question Answer
What is meant by the term “myoproliferative disorder” ?Myeloproliferative disorders is the name for a group of conditions that cause blood cells -- platelets, white blood cells and red blood cells -- to grow abnormally in the bone marrow.
Give examples of myoproliferative disorders.Chronic myelogenous leukaemia, polycythaemia vera, essential thrombocythaemia, myelofibrosis.
What is polycythaemia?Polycythaemia is defined as an increase in haemoglobin, PCV (packed cell volume/haematocrit), and red cell count. It is divided into absolute erythrocytosis where there is a true increase in red cell volume, or relative erythrocytosis where the red cell volume is normal but there is a decrease in the plasma volume.
What is secondary polycythaemia?An increase in red cells in response to a stimulant e.g. an appropriate increase in red cells in response to anoxia, or an inappropriate increase associated with tumours, such as a renal carcinoma.
What is polycythaemia vera?Also known as primary polycythaemia, this is a clonal stem cell disorder in which excessive proliferation of marrow stem cells leads to an increase in red cells production, often accompanied by overproduction of neutrophils and platelets.
What are the clinical features of polycythaemia vera?May be asymptomatic. There may be non-specific symptoms of tiredness and depression. Pruritus, typically after a hot bath, is a classic symptom. Gouty arthritis due to increased cell turnover may be a feature, and peptic ulceration is also common. Patients may have a plethoric (flushed) appearance.
What are the major complications associated with polycythaemia vera?Thrombosis (and haemorrhage, according to Kumar & Clark).
How is polycythaemia vera diagnosed?Over 95% have acquired mutations of the gene Janus Kinase 2 (JAK2). As such, JAK2 mutation is diagnostic. A full blood count/film can also aid in diagnosis, and will show haemoglobin >18.5g/dl in men, >16.5g/dl in women, or other evidence of increased red cell volume, as well as raised neutrophils, basophils, and platelets in half of patients. The spleen in palpable in 70% and is useful in distinguishing polycythaemia vera from secondary polycythaemia (in which there is no splenomegaly).
How is polycythaemia vera managed?Venesection is often used as the sole treatment. Hydroxycarbamide is used frequently because of the ease of controlling thrombocytosis. Low dose aspirin with the above treatments is used for patients with recurrent thrombotic episodes. Anagrelide inhibits megakaryocyte differentiation and is useful for thrombolysis. Phosphorus-32 is only given to patients over 70 years because of the increased risk of transformation to acute leukaemia. Allopurinol is given to block uric acid production.
Polycythaemia is a high operative risk and should therefore be controlled before and surgery. True or false?True.
What is the prognosis of polycythaemia vera?30% develops into myelofibrosis, and 5% develops into acute myeloid leukaemia as part of the natural history of the disease.
What is the most common cause of secondary polycythaemia?Heavy smoking.
Like polycythaemia vera, secondary polycythaemia can develop into myelofibrosis and acute myeloid leukaemia. True or false?False. In secondary polycythaemia, complications due to myeloproliferative disease such as progression do not develop.


Question Answer
What is essential thrombocythaemia?A rare chronic blood disorder characterised by the overproduction of platelets by megakaryocytes in the bone marrow.
What do patients with essential thrombocythaemia present with?ET presents either symptomatically with thromboembolic problems, or less commonly bleeding problems, or incidentally.
How is essential thrombocythaemia diagnosed?Patients have elevated platelet counts. At diagnosis the platelet count will usually be >600 × 109/L. Diagnostically the JAK2 mutation tests are useful in that the gene is mutated in about 50% of all cases of ET.
Like polycythaemia vera, essential thrombocythaemia can develop into myelofibrosis and acute myeloid leukaemia. True or false?True, but it’s rare.
How is essential thrombocythaemia treated?Treatment is with hydroxyurea, anagrelide, or busulfan to control the platelet count to less than 400 × 109/L.
What is myelofibrosis?A rare bone marrow cancer in which the proliferation of an abnormal clone of haematopoietic stem cells in the bone marrow and other sites results in fibrosis, or the replacement of the marrow with scar tissue.


Question Answer
Give a typical blood film picture seen in hyposplenism.Target cells, howell-Jolly bodies, Pappenheimer bodies, siderotic granules, acanthocytes.
Give a typical blood film picture seen in iron deficiency anaemia.Target cells, “pencil” poikilocytes. If combined with B12/folate deficiency a 'dimorphic' film occurs with mixed microcytic and macrocytic cells.
Give a typical blood film picture seen in myelofibrosis.“Tear drop” poikilocytes.
Give a typical blood film picture seen in intravascular haemolysis.Schistocytes (severed/fragmented parts of RBCs).
Give a typical blood film picture seen in megaloblastic anaemia.Hypersegmented neutrophils.


Question Answer
What is prothrombin time and what is the normal range?Prothrombin time is a blood test that measures how long it takes blood to clot. It is an assay evaluating the extrinsic pathway of coagulation (factors I, II, V, VII, X) and is prolonged with abnormalities of these factors. A prothrombin time test can be used to check for bleeding problems. It is also used to check whether medicine to prevent blood clots is working. The normal range is 12-16 seconds.
What is INR and at what level should it be in absence of anticoagulation therapy?INR is a derived measure of prothrombin time, and as such, is also an assay for the evaluation of the extrinsic pathway. In absence of anticoagulation therapy, INR should be at 0.8-1.2.
What is the target range for INR in anticoagulant use?2-3.
The higher the intensity of the anticoagulation therapy, the higher the INR target. True or false?True.
What is activated partial thromboplastin time (APTT) and what is the normal range?An assay evaluating the intrinsic (factors I, II, V, VIII, IX, X, XI, XII) and common coagulation pathways, and is prolonged with deficiencies of one or more of these factors. The normal range is 30-50 seconds.
What is thrombin time (TT), what is the normal range, and when would it be prolonged?The thrombin time (TT), also known as the thrombin clotting time, is a blood test that measures the time it takes for a clot to form in the plasma of a blood sample containing anticoagulant, after an excess of thrombin has been added. The thrombin time is 12–14 seconds, and it is prolonged with fibrinogen deficiency, qualitative defects of fibrinogen (dysfibrinogenaemia) or inhibitors such as heparin.
What is the function of thrombin?Prothrombin (coagulation factor II) is proteolytically cleaved to form thrombin in the coagulation cascade, which ultimately results in the reduction of blood loss. Thrombin in turn acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin, as well as catalysing many other coagulation-related reactions.