Haematology 5

oelomar's version from 2016-03-31 19:11


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Name some different types of blood transfusion therapy and what they can be used to treat.Packed RBCs (can be used in severe anaemia and acute blood loss); platelets (stop bleeding in thrombocytopenia and platelet defects); fresh frozen plasma (increases coagulation factor levels by about 20% - can be used in disseminated intravascular coagulation, cirrhosis, and warfarin over-anticoagulation); cryoprecipitate (a frozen blood product prepared from plasma – it contains fibrinogen, factor VIII, and factor XIII, and can be used in treating coagulation factor deficiencies involving fibrinogen and factor VIII).
Name some risks of blood transfusions.Infection transmission (unlikely), transfusion reactions, iron overload, hypocalcaemia, hyperkalaemia.


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What is factor V Leiden and what are its implications?This is a mutant form of factor V. In this disorder, the Leiden variant of factor V cannot be inactivated by the anticoagulant activated protein C. As such, this results in a tendency to thrombosis. Factor V Leiden is found in 3– 5% of healthy individuals in the western world and in about 20-30% of patients with venous thrombosis.
What is the “prothrombin mutation” and what are its implications?A genetic variant that approximately doubles or triples the risk of forming blood clots in the veins. About 2 to 3% of Caucasians carry the variant, and it confers a 2- to 3-fold higher risk of VTE (venous thromboembolism).
What are the causes of antithrombin deficiency?This deficiency can be inherited as an autosomal dominant trait. It can also be acquired following trauma, with major surgery and with the contraceptive pill. Low levels are also seen in severe proteinuria.
Does heparin help in the treatment of antithrombin deficiency?Not much, because the action of heparin requires antithrombin.
Protein C and protein S deficiencies, both of which are rare inherited disorders, are associated with increased incidence of arterial thrombotic disease as opposed to venous thromboembolism. True or false?False. No association with arterial thrombotic disease has been found.
Homozygous protein C or S deficiency causes neonatal purpura fulminans, which is fatal without immediate replacement therapy. What is neonatal purpura fulminans?Purpura fulminans is an acute, often fatal, thrombotic disorder which manifests as blood spots, bruising and discolouration of the skin resulting from coagulation in small blood vessels within the skin, and rapidly leads to skin necrosis and disseminated intravascular coagulation.
In patients with protein C and protein S deficiency, what should one be very careful of regarding warfarin administration?There is an increased risk of haemorrhagic skin necrosis.


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What is hyperhomocystenaemia and what are its implications?This is a medical condition characterised by an abnormally high level of homocysteine in the blood. When elevated, this amino acid is associated with both arterial thrombosis and venous thromboembolism.
How can hyperhomocystenaemia be managed?Folate, B12, and B6 supplementation are often helpful in reducing levels of homocysteine.
What are the symptoms of acute leukaemia’s?Patients with acute leukaemia present with symptoms reflecting inadequate haematopoiesis secondary to leukaemic cell infiltration of the bone marrow, including: anaemia – shortness of breath on effort, excessive tiredness, weakness; leukopenia – recurrent infections; thrombocytopenia – bleeding and bruising; marrow infiltration – bone pain.
What will a blood film show in acute leukaemia’s?In acute lymphoblastic leukaemia, a blood film will show lymphoblasts (pre-B or pre-T). In acute myeloid leukaemia, a blood film will show myeloblasts.
What age range is most likely to be affected by acute lymphoblastic leukaemia?<15 years.
What age range is most likely to be affected by acute myeloid leukaemia?Median age at presentation is around 65 years.
What age range is most likely to be affected by chronic myeloid leukaemia?30-60 years.
What age range is most likely to be affected by chronic lymphocytic leukaemia?>60 years.
How are acute leukaemia’s treated?Avoidance of symptoms of anaemia – repeated transfusion. Prevention or control of bleeding. Treatment of infection prophylactically and therapeutically. Treatment of neutropenia with granulocyte-colony stimulating factor (G-CSF). Control of hyperuricaemia with hydration, prophylactic allopurinol and occasionally rasburicase.
Name some complications of acute leukaemia’s.Tumour lysis syndrome, hyperviscosity (WBC thrombi may form in the brain, lung, and heart), disseminated intravascular coagulation.


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Tumour lysis syndrome is a complication that can occur during the treatment of cancer, most commonly after the treatment of lymphomas and leukaemias. What is tumour lysis syndrome?A group of metabolic abnormalities characterised by hyperkalaemia, hyperphosphataemia, hypocalcaemia, hyperuricaemia, and higher than normal levels of blood urea nitrogen.
What is acute myeloid leukaemia?A cancer of the myeloid line (i.e. arising from bone marrow) of blood cells, characterised by the rapid growth of abnormal WBCs that accumulate in the bone marrow and interfere with the production of normal blood cells.
What are auer rods and what relevance do they have in acute myeloid leukaemia?Auer rods are clumps of granular material that form elongated needles seen in the cytoplasm of leukaemic blasts. Auer rods are diagnostic of acute myeloid leukaemia.
How is acute myeloid leukaemia treated?Those at “low risk” are treated with moderately intensive combination chemotherapy. Usually daunorubicin and cytarabine. Those at “high risk” may only be treated with curative intent if an HLA-identified sibling is available for stem cell transplantation.
What are the features of daunorubicin toxicity?Cardiotoxicity; myelosuppression; alopecia (hair loss).
What are the features of cytarabine toxicity?Leukopenia; thrombocytopenia; megaloblastic anaemia.


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What is acute promyelocytic leukaemia (APML)? Name a major cause of death in this condition.APML is a subtype of acute myeloid leukaemia in which there is an abnormal accumulation of immature granulocytes called promyelocytes. There is an almost invariable coagulopathy (DIC), which is a major cause of death.
How is acute promyelocytic leukaemia treated?APML is treated with all-trans-retinoic acid (ATRA) (vitamin A) combined with chemotherapy and, following successful remission induction, with maintenance ATRA. Allogeneic transplantation may be necessary either if the leukaemia is not eliminated at the molecular level, or following a second remission after recurrence. Arsenic trioxide, which induces apoptosis, is used with resistant or relapsed disease.
What is most common malignancy in childhood?Acute lymphoid leukaemia.
Acute lymphoid leukaemia is associated with Down’s syndrome and x-rays during pregnancy. True or false?True.
How is remission induced in acute lymphoid leukaemia?Remission induction is undertaken with; vincristine, dexamethasone, daunorubicin and asparaginase. In those patients with high-risk features, allogeneic transplantation is recommended upon achieving first complete remission.
Following a remission, what is the maintenance therapy in acute lymphoid leukaemia?Maintenance therapy typically comprises 2 years of treatment with methotrexate and mercaptopurine, vincristine, prednisolone.
What is the prognosis of acute lymphoid leukaemia?The prognosis of ALL in childhood is excellent: complete remission is achieved in almost all, with up to 80% being alive without recurrence at 5 years. Failure occurs most frequently in those with high blast count and t(9;22) translocation. The prognosis gets worse with advancing years. 30% overall patient cure.
How does asparaginase work and what are its main side-effects?It breaks down asparagine to aspartic acid, depriving neoplastic cells of it and leading to their death. Main side effects are hypersensitivity reactions.


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What is the Philadelphia chromosome and what relevance does it have in chronic myeloid leukaemia (CML)?The Philadelphia chromosome/translocation is a specific genetic abnormality in chromosome 22 of leukaemia cancer cells. 95% of people with CML have this abnormality.
What are the three phases in chronic myeloid leukaemia?Chronic phase (around 85% are in the chronic phase at time of diagnosis), accelerated phase (this develops from the chronic phase over the course of several years), and blast crisis (the final phase in the evolution of CML – it behaves like an acute leukaemia, with rapid progression and short survival).
What are the clinical features of chronic myeloid leukaemia?CML usually presents in the chronic phase and can be asymptomatic. Symptoms can include abdominal discomfort due to splenomegaly, often massive. Lymphadenopathy is uncommon, but when found suggests a blast crisis.
What is first-line treatment for chronic myeloid leukaemia?Imatinib (tyrosine kinase inhibitor).
What are the effects of imatinib toxicity?Fluid retention.
Can stem cell transplantation be used in the treatment of chronic myeloid leukaemia?Stem cell transplantation can cure most chronic phase CML patients. It is now only used in those with an inadequate response to imatinib or those that have disease progression on therapy.


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What is the most common leukaemia?Chronic lymphocytic leukaemia.
Monoclonal B-cell lymphocytosis (MBL) is a condition that resembles chronic lymphocytic leukaemia (CLL), but does not meet the criteria for CLL, and does not require treatment. What criterion must be met in order for the diagnosis of CLL to be made?B cells greater than 5 × 109/L.
What are the clinical features of chronic lymphoid leukaemia?The vast majority are asymptomatic and are identified as a chance finding on a blood count. There may be lymphadenopathy (which is more marked than CML) and hepatosplenomegaly, sometimes massive.
What are some of the complications of chronic lymphoid leukaemia?Hypogammaglobulinaemia leading to recurrent infections; warm autoimmune haemolytic anaemia in 10-15% of patients; transformation to high-grade lymphoma (Richter's transformation).
What is Richter’s syndrome?Also known as Richter's transformation, this is a transformation which occurs in about 5-10% of B cell chronic lymphocytic leukaemia and hairy cell leukaemia into a fast-growing diffuse large B cell lymphoma, a variety of non-Hodgkin lymphoma which is refractory to treatment and carries a bad prognosis.
In chronic lymphoid leukaemia, what should be considered regarding initiation of treatment?In CLL, the major consideration is when to treat, as 30% of patients will never require intervention. Treatment depends on the stage of the disease and the prognostic biomarkers.
How is chronic lymphoid leukaemia treated?First-line is rituximab in combination with fludarabine and cyclophosphamide. Allogeneic stem cell transplantation is the only curative therapy.