Anaemia

1. Anaemia Managing anaemia in patients with cancer

2. A collaborative approach to managing anaemia: Assessment Nurse • Assess signs, symptoms and risk • Request laboratory tests • Evaluate underlying cause of anaemia • Educate patient and family Patient • Report symptoms • Take a proactive role in own health • Nutrition and hydration • Maintain daily living activities NCCN (cancer and CT-induced anemia), 2017; Joseph-Williams, 2014;Ault and Jones, 2009; Davidson, 2007; Hurter and Bush, 2006

3. Challenges in anaemia management Multifactorial aetiology complicates diagnosis Under-management • Lack of awareness of: • Target values for Hb • Trigger values for treatments Failure to recognise fatigue as a significant symptom NCCN (cancer and CT-induced anemia), 2017; Hurter and Bush, 2006

4. ESMO guidelines for ESAs in patients with chemotherapy-induced anaemia • Indication: • Treatment of symptomatic chemotherapy-induced anaemia in patients with non-myeloid malignancies. • Target: • Maintain Hb levels around 12 g/dL in patients receiving chemotherapy. • Treatment Guidelines: • Prior to ESA treatment: evaluate anaemia and correct underlying cause if possible. • Hb should not exceed 12 g/dL. ESA doses should be adapted or discontinued accordingly. • ESAs are not deemed beneficial if: Hb increse is <1-2 g/dL from baseline or RBC transfusion need is not reduced by week 6-8 of treatment Aim: Improve QOL andprevent RBC transfusion NCCN (cancer and CT-induced anemia), 2017; Tonia, 2012; Schrijvers, 2010

5. ESMO guidelines for ESAs in patients with chemotherapy-induced anaemia Evaluate the cause of anaemia If possible, correct cause of anaemia prior to ESA treatment Iron deficiency Nutritional status Bleeding Renal impairment Inflammation Haemolysis Schrijvers, 2010

6. Iron Folic acid Vitamin B12 Vitamin C Protein supplements Nutritional supplements for correcting anaemia due to deficiencies Choice based on underlying cause of anaemia • Route of administration determined by: • Severity of the deficiency • Status of the individual • ESMO guidelines recommend regular iron status monitoring • IV iron can provide greater Hb increments than oral iron • A tool to evaluate of nutritional deficits has been developed Maccio, 2014; Aapro, 2012; Schrijvers, 2010; Henry, 2007; Okuyama, 2005; Goddard, 2000

7. Iron deficiency (ID) evaluation and management: NCCN guideline Assess iron status:TSAT, serum ferritin, serum iron Absolute ID(SF <30 ng/mL AND TSAT <20%) Functional ID (SF 30-500 ng/mL AND TSAT <50%) Maybe functional ID (SF 500-800 ng/mL AND TSAT <50%) No ID (SF >800 ng/mL OR TSAT ≥50%) IV or oral iron IV iron with ESA No iron needed OR IV iron for selected patients No iron needed • Hb ↑ after 4 wks: •  Periodic evaluation of TSAT and SF • No Hb ↑ after 4 wks: •  Follow pathway for functional ID • Points to consider with IV iron: • IV iron has superior efficacy and should be considered for supplementation, oral iron is less effective • Test doses are required for low-molecular weight iron dextran but not for iron sucrose, ferric gluconate or ferric carboxymaltose • Patients with an active infection should not receive IV iron ID=iron deficiency, IV=intravenousSF = serum ferritin, TSAT=transferrin saturation. NCCN (cancer and CT-induced anemia), 2017

8. Iron Overload • Iron overload can be a consequence of repeated RBC transfusion • Patients with MDS who are transfusion-dependent often present with iron overload • Iron overload can cause tissue damage in: • Liver, heart and endocrineorgans • Iron overload is managed with oral iron chelators • Deferoxamine has been the treatment of choice for the last 40 years • Effectiveness of deferasirox in patients with MDS was not evaluated in randomized controlled clinical trials (up to April 2014) • IV iron given according to indication is not associated with iron overload • Stop iron treatment if ferritin exceeds 1000 ng/mL or transferrin saturation (TSAT) exceeds 50% • Early symptoms of ironoverload include: • Vomiting • Diarrhoea • Hypotension • Tachycardia NCCN (cancer and CT-induced anemia), 2017; Meerpohl, 2014; Schrijvers, 2011; Ault and Jones, 2009

9. Erythropoiesis-stimulating agent (ESA*) therapy: ESMO guidelines Indication: Chemotherapy-induced anaemia (non-myeloid malignancies) Non-haematological malignancies Haematological malignancies Treated with chemotherapy and Hb level ≤10 g/dL Not treated with chemotherapy Treated with curative intent Myelodysplastic syndrome Bone marrow transplantation Consider ESA treatment to increase Hb-levels ESA treatment not indicated ESAs should be used with caution ESAs may be used ±G-CSFoff-label indication ESAs may be used after allogenic stem cell transplantation Dosing and dose titration in patients with no suspicion of functional iron deficiency (ferritin >100 ng/mL and TFS saturation <20%) ESMO Clinical Practice Guidelines: treatment of anaemia in cancer patients, 2010

10. Recombinant ESA formulations* in oncology *Marketing company, trade name, availability and dosing schedules may vary – refer to country SmPC for details ESAs should not be used outside licensed indication

11. Ensuring the safety of ESAs • ESAs should not be used outside of licensed indication • Previous studies raised concerns about the safety of ESAs1,2,3 • Current ESA risk status • Increased risk of mortality, thrombotic events and shortened time to tumour progression are stated in current NCCN guidelines and confirmed by a systematic Cochrane review5,8 • Biosimilars are not the same as the original branded drug and are not the same as generics6,7 1Henke, 2003; 2Leyland-Jones, 2005; 3Wright, 2007; 4Seidenfeld, 2006; 5NCCN (cancer and CT-induced anemia), 2017; 6Kuhlmann and Covic, 2006; 7Schellekens, 2004; 8Tonia, 2012

12. Treatment ofanaemia in myelodysplasticsyndromes (MDS) Iron overload should be monitored an treated with iron chelation therapy accordingly ESA treatment for transfusion dependent patients with serum EPO <500 mU/mL Anaemia (Hb<10 g/dL) observed in up to 90% of patients 90% of patients require RBC transfusion Fenaux, 2014; Kurtin, 2012; Shah, 2012; Kurtin, 2005

13. Indicationforredbloodcell (RBC) transfusion Asymptomaticwithout significant comorbidities Periodic re-evaluation Observe High risk (Hb decline after therapy) Or Asymptomatic with comorbidities (e.g. cardiac disease, chronic pulmonary disease, cerebral vascular disease) Cancer- related anaemia Consider RBC transfusion per guidelines Symptomatic (e.g. sustained tachycardia, tachypnea, dyspnea during exertion, chest pain, severe fatigue, lighheadedness, syncope) RBC transfusion per guidelines NCCN (cancer and CT-induced anemia), 2017;Prescot, 2016;Tonia, 2012; Schrijvers, 2011

14. A collaborative approach to managing anaemia: blood transfusions • Know transfusion protocols and report reactions at a national level • Educate patient about benefits and risks of transfusion • Monitor regularly – evaluate patient’s response Nurse Patient • Report symptoms DeYoung Sullivan, 2015; Cheung, 2014; Mickle and Reinke, 2006

15. Problems associated with Red Blood Cell Transfusions • Immunological complications • Red cell alloantibodies, transfusion reactions • HLA antibodies • Supply and availability • Transfusion errors • Transfusion-transmitted diseases • Viral • Bacterial • Possibly prion • Currently unknown/unidentified pathogens Delaney, 2016; Schrijvers, 2011

16. Patient identification and compatibility check prior to RBC transfusion • Human errors are still the biggest risk of an adverse event occurring during blood transfusions. • The most crucial steps in prevention of incompatible transfusions patient identification and compatibility check: • Patient identification: Surname, initials, date of birth, gender, patient identification number • Compatibility check: Component blood group • Checks should be performed visually and in writing by two individuals (unless supported by electronic systems), at bedside prior to transfusion • The patient should be asked to identify him/herself by name and date of birth NICE 2015

17. Electronic patient identification systems for RBC Transfusion • Electronic patient identification systems such as barcode scanning were developed to: • reduce the potential for human errors • improve patient safety • optimize the efficiency of the transfusion process • Electronic systems prompt staff to carry out key steps in the process and electronically identifying the patient via the scanning of the patient’s identification bands and blood components • They also aim to ensure that the correct steps are followed in the correct order to reduce the possibility of human error occurring • Electronic patient identification systems are recommended by guidelines NICE 2015

18. Informing patients before and after RBC Transfusion • Prior to the transfusion, patients should be informed about: • Reason(s) for the transfusion • Associated benefits and risks • Overall transfusion process • Any available alternatives or means to reduce their need for transfusions • That they are no longer eligible to donate blood • That they are encouraged to ask questions • Following the transfusion, patients should be provided with a written communication explaining: • Details of any transfusions • Reasons for the transfusion • Any advers events • That they are no longer eligible to donate blood NICE 2015

19. Monitoring RBC Transfusion Information and vital parameters recording before, during and after blood transfusion In addition, the effect of transfusion may need to be measured following transfusion to determine whether additional transfusion may be required per unit of RBCs a increase in 0.5 – 0.6 mmol/L Hb is expected in adults NICE 2015

20. Symptoms of transfusion reactions • Monitoring for acute transfusion reactions: • Start transfusion slowly -> if no reaction, increase the speed • Stop immediately if any sign of transfusion reaction • Keep the IV line open and act according to local protocol • Haemolysis should be immediately excluded (or proven) in every case of an acute transfusion reaction • Symtpoms of delayed transfusion reactions are similar to those for acute reactions, but less severe • Symptoms of acute HTR: • Fever • Chills • Burning sensation at infusion site • Pain in chest/abdomen/back • Headache • Nausea • Vomiting • Tachycardia • Agitation • Hypotension • Urine color change Strobel E. 2008

21. Managing RBC TransfusionReactions • Haemolytic transfusion reactions (HRT) occurr in approximately 1:70’000 units and account for most transfusion-related deaths • Clinical consequences of incompatible transfusions may include: • Immunization of patient with alloantibodies bearing a potential risk for later transfusions or gravidities (may occur without symptoms) • Missing or short-lasting therapeutic effect of the transfusion (i.e. Hb rise) • Severe or life-threatening disorders, e.g. haemolytic transfusion reactions (HTR) • Severe acute HTRs are often caused by identification errors (identification of the patient or of the blood product Strobel E. 2008

22. Summary • Anaemia management starts with a proper assessment • Nutritionist, ESA’s, Iron and RBC can be considered • All options do have safety aspects NCCN (cancer and CT-induced anemia), 2017; Gilreath et al, 2014;Schrijvers et al, 2010

23. Test question 1 A: Blood loss, targeted therapy, nutritional deficiency B: Chemotherapy, obesity, hypertension C: Cachexia, radiotherapy, bone marrow infiltration D: Nausea/vomiting, chemotherapy, diarrhoea What are some of the causes of anemia?

24. Test question 1 A: Blood loss, targeted therapy, nutritional deficiency B: Chemotherapy, obesity, hypertension C: Cachexia, radiotherapy, bone marrow infiltration D: Nausea/vomiting, chemotherapy, diarrhoea What are some of the causes of anemia?

25. Test question 2 A: Dizziness, low skin temperature, tachycardia B: Fatigue, fever, loss of libido C: Urine loss, diarrhoea, peripheral neuropathy D: Pale skin, cardiac hypotrophy, paronychia Symptoms of anemia include?

26. Test question 2 A: Dizziness, low skin temperature, tachycardia B: Fatigue, fever, loss of libido C: Urine loss, diarrhoea, peripheral neuropathy D: Pale skin, cardiac hypotrophy, paronychia Symptoms of anemiainclude?

27. Test question 3 A: In patients with no iron overload B: In non haematological patients C: In haematological patients without chemotherapy treatment D: In specific indications ESA’scanbeusedonly:

28. Test question 3 A: In patients with no iron overload B: In non haematological patients C: In haematological patients without chemotherapy treatment D: In specific indications ESA’scanbeusedonly:

29. Test question 4 A: Liver B: Heart C: Endocrine organs D: All of the above Iron overloadcan cause tissuedamage in:

30. Test question 4 A: Liver B: Heart C: Endocrine organs D: All of the above Iron overloadcan cause tissuedamage in: