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Anaemia

Anaemia. An ‘ A – Z ’ of the causes, incidence, symptoms, risk factors and impact in patients with cancer. What is anaemia?. Deficiency in red blood cells. Low Hb levels Mild anaemia : 10.0 g/ dL to lower limit of normal Moderate anaemia : 8.0 to <10.0 g/ dL

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Anaemia

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  1. Anaemia An ‘A–Z’ of the causes, incidence, symptoms, risk factors and impact in patients with cancer

  2. What is anaemia? Deficiency in red blood cells Low Hb levels • Mild anaemia: 10.0 g/dL to lower limit of normal • Moderate anaemia: 8.0 to <10.0 g/dL • Severeanaemia: 6.5 to <8.0 g/dL • Life threatening anaemia: <6.5 g/dL A frequent haematological complication in cancer patients The sign of an underlying pathology For conversion of Hb g/dL to Hb mmol/L: Hb g/dL×0.6206 = Hb mmol/L (e.g. 10 g/dL = 6.21 mmol/L) NCCN (cancer and CT-induced anemia), 2017; Gilreath, 2014; Schrijvers, 2010

  3. Causes of anaemia in cancer patients • Blood loss • Bone marrow infiltration • Cytokine release(cancer-related anaemia, CRA) Disease-related • Chemotherapy • Radiotherapy • Targeted therapy Treatment-related • Other • Surgery • Nutritional deficiencies Gilreath, 2014; Barni, 2012; Schrijvers, 2010

  4. Types of cancer-related anaemia Cancer related anaemia (CRA) Chemotherapy-induced anaemia (CIA) Anaemia secondary to cancer (ASC) Chronic kidney disease (CKD) in cancer • Myelosuppressive chemotherapy • Chemotherapy-induced thrombocytopenia and blood loss • Production • Functional iron deficiency • Haematological malignancies (MDS) • Solid tumour marrow infiltration • Pure red-cell aplasia • Destruction • Haemolysis • Haemophagocytosis • Blood loss • Frequent phlebotomy • Mucocutaneous bleeding • Gastrointestinal bleeding • Primary CKD • Secondary to cancer or cancer treatment • Low erythropoietin production Gilreath, 2014

  5. Chemotherapy-induced anaemia (CIA) 89.5% ‘Delayed’ onset of anaemia after some CT cycles partly due to long half life of RBCs that circulated at start of CT Up to 89.5% of patients with solid tumours develop CIA NCCN (cancer and CT-induced anemia), 2017; Xu, 2014; Schrijvers, 2010

  6. Cancer-related anaemia (CRA) Tumour cells Activated immune system RBCs Macrophages AIS Erythrophagocytosis TNF Dyserythropoiesis IFN-IL-1TNF1-antitrypsin IL-1 IL-6 IL-1 , TNF Shortened survival Lactoferrin Hepcidin Suppressed erythroid progenitors Reduced EPO production Reduced available serum iron ANAEMIA AIS = anaemia-inducing substance; EPO = erythropoietin; IFN = interferon; IL-1 = interleukin-1; RBCs = red blood cells; TNF = tumour necrosis factor Rosa, 2017; Gaspar, 2015; Dicato, 2010; Nowrousian, 2008

  7. Myelodysplastic Syndromes • Myelodysplastic sydromes (MDSs) are a group of clonal myeloid malignancies characterised by: • Ineffective haematopoiesis • Progressive bone marrow failure • Variable risk of leukaemic transformation • Symptoms are often related to cytopenias (e.g. fatigue, infection, bleeding) • Prognosis is variable and depends on: • Numberand depth of cytopenias • Extent of cytogenetic abnormalities • Percentage of blast cells in the bone marrow • Choice of active treatmentisdependent on individual patient and disease characteristics • All MDS patients require supportive care and educational + QoL support from the oncology team Up to 90% of patients with MDS are affected by anaemia Cogle, 2015; Kurtin, 2012; Thomas, 2012; Kurtin, 2005

  8. Signs and symptoms of anaemia • General • Debilitating fatigue • Immune system • Impaired T cell and macrophage function • Central nervous system • Dizziness, vertigo • Depression • Mood changes • Headaches • Impaired cognitive function • Respiratory system • Dyspnoea • Shortness of breath • Cardiovascular system • Tachycardia, palpitations • Cardiac hypertrophy • Systolic ejection murmur • S3 (galloping heart rhythms) • Risk of cardiac failure • Gastrointestinal system • Anorexia • Nausea • Indigestion • Vascular system • Low skin temperature • Pale skin, mucous membranes, and conjunctivae • Genito-urinary • Menstrual irregularities • Loss of libido • Male impotence Hurter and Bush, 2007; Gillespie, 2002; Ludwig and Fritz, 1998

  9. Risk factors for anaemia • Patient and disease characteristics • Advanced age • Low pre-treatment haemoglobin • Comorbidities • Bleeding (comorbidity or at the tumour site) • Nutritional deficiencies (comorbidity or insufficient dietary intake) • Cancer-related coagulopathy • Type of malignancy (e.g. gynaecologic, lung) • Prior treatment • Transfusion in past 6 months • Myelosuppressive therapy • Radiotherapy to the skeleton • Current treatment • Duration and schedule of myelosuppressive therapy • Platinum-based chemotherapeutic agents • Type of targeted therapy NCCN (cancer and CT-induced anemia), 2017; Gilreath, 2014; Barni, 2012; Hurter and Bush, 2006

  10. Assessing anaemia: a comprehensive clinical assessment • Evaluate anaemia for possible cause as indicated: • First check • Reticulocyte count and MCV • Then consider • Haemorrhage • Haemolysis • Nutritional • Inherited • Renal dysfunction • Radiation-induced myelosuppression Treat as indicated Hb ≤11 g/dL or ≥2 g/dL below baseline • CBC with indices • Blood smear morphology No cause identified For conversion of Hb g/dL to Hb mmol/L: Hb g/dL×0.6206 = Hb mmol/L 11 g/dL = 6.83 mmol/L 2 g/dL = 1.24 mmol/L Evaluate risk and indication for transfusion NCCN (cancer and CT-induced anemia), 2017

  11. Common mistakes in assessing anaemia Assessment for anaemia more often reactive than proactive Acceptance of fatigue as side effect of cancer leads to lack of action Tendency to look at current Hb level in isolation, rather than tracking trends Hb level does not always correlate with patient symptoms Use your experience and educate the patient

  12. Anaemia reduces quality of life by causing fatigue Relationship with family and friends Patients reporting aspects of daily routine affected by fatigue* Physical well-being Ability to work Emotional well-being Rosti, 2017; Mouysset, 2016; Wanchai, 2010; Hurter and Bush, 2006; Gillespie, 2002

  13. Economic impact of anaemia Additional medical visits Increased treatment costs Reduced patient productivity • Almost double the hospital admissions & emergency visits • Use more healthcare resources • Require additional therapies • Need time off work due to fatigue Crathorne (health technology assessment), 2016; Deger, 2012; Tonia, 2012;Berndt, 2005a; Berndt, 2005b; Lyman, 2005

  14. Summary • Anaemia - sign of an underlying pathology: • Chemotherapy-induced anaemia • Cancer-related anaemia • Assessment of anaemia involves looking for signs, symptoms and risks • Anaemia impacts on survival, QoL and has economic costs NCCN (cancer and CT-induced anemia), 2017; Gilreath et al, 2014;Schrijvers et al, 2010

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