Transfusion of Children Undergoing Treatment for Cancer

1. Transfusion of Children Undergoing Treatment for Cancer Dr. Prasanna N Kumar Head of Department of Pathology

2. PRIMUM NON NOCERE - FIRST DO NO HARM Patient’s safety – top priority Decision to transfuse – like any other therapeutic decision – risks, benefits, alternatives

3. Annual global blood collection – 81.2 million units 55% collected in countries with a high HDI with 18% of the world population 45% of the global blood supply from medium and low HDI countries with 78% of the world population WHO. Blood Transfusion Service Global database on blood safety (2004). Geneva, WHO/BTS, Essential health Technologies

4. BLOOD USAGE IN RESOURCE LIMITED COUNTRIES • Transfusion recipient population in economically restricted countries versusdeveloped countries • Majority of transfusions for basic, usually urgent or life-threatening conditions vs support of tertiary care needs • Pediatric transfusions – dominate • Children, pregnant women, thalassaemics, haemoglobinopathies, nutritional anaemias, malaria

5. CHILDREN WITH CANCER - NEED FOR TRANSFUSION May be predicted from the expected myelotoxicity of the chemotherapy/ radiotherapy regimen. ↑transfusion requirements may increase in patients with: • Bone marrow involvement by neoplastic process • Severe malnutrition at diagnosis or during therapy • Presence of sepsis and DIC • Acute haemorrhage

6. BLOOD COMPONENTS • 80% of collected blood used as whole blood – widens gap between supply and demand • Inappropriate transfusion practices – lack of guidelines – additional stress India – 20% WB fractionated by 222 blood banks

7. WHOLE • BLOOD • PACKED RED • CELLS

8. RBCs - SELECTING A PRODUCT • Minimize donor exposures • Split bags – PEDIPAKS Minimizes patient exposure to multiple donors, transfer bags • Available in O positive & O negative

9. INADEQUATE INVENTORY – TRANSFUSION POLICIES Use compatible blood groups, packed cells • Group O Rh negative uncrossmatched • Group O, Rh positive uncrossmatched • ABO type specific uncrossmatched • ABO type specific crossmatched • Use only O Rh negative if patient sensitized to D antigen/ females < 45 years • Massive volumes of blood – switch to Rh positive • Conserve group O blood

10. RED CELL TRANSFUSIONS IN CHILDEN • More stringent guidelines- normal Hb levels < in adults + • better ability to compensate for lower Hb/HCT • More conservative triggers – TTI + shortage English M et al Lancet 2002;359:494-495

11. TRANSFUSION TRIGGERS IN PAEDIATRIC HAEMATO-ONCOLOGY • Pediatric Blood & Cancer, VOLUME 44, Issue 2, • pages 114–116, February 2005 Blood transfusions in children with cancer and hematologic disorders: Why, when, and how? • George R. Buchanan MD Research Article Transfusion management strategies: A survey of practicing pediatric hematology/oncology specialists† Edward C.C. Wong MD1,*, Evelio Perez-Albuerne MD, PhD2, Jeffrey A. Moscow MD3, Naomi L.C. Luban MD4 Pediatric Blood & Cancer Volume 44, Issue 2, pages 119–127, February 2005

12. SUGGESTED RED CELL TRIGGERS IN PAEDIATRIC HAEMATO-ONCOLOGY • Stable patients on chemotherapy -7g/dl • Neutropenic fever, tachycardia, tachypnea, hypotension– 8g/dl • Intensive RBC support when patient is started on CT/RT - (need↑as intensity of therapy increases) • Repeated transfusions – leukocyte depleted red cells • To ↑ Hb by 2.5-3 gm/dL. transfuse 10cc/kg • Correction of anemia vs risk of bleeding

13. FRESH FROZEN PLASMA • DIC/significant coagulopathy (PT, PTT > 1.5 X normal) + significant risk of bleeding • Urgent anticoagulant reversal • Do not use FFP to correct prolonged coag. values in the absence of bleeding • Dose - 10 - 15 ml /kg, one unit ↑ coagulation factors by about 3 % • Group AB or compatible with recipient's ABO red cell antigens

14. PLATELETS • Stored at 22 C wıth agitation, NEVER REFRIGERATE • ABO identical/compatible plts. for paediatric • transfusions • Volume reductıonfor non- identical/ıncompatible • platelets SDP RDP

15. SUGGESTED PLATELET PROPHYLACTIC TRIGGERS • Asymptomatic, non-bleeding pts. wıth thrombocytopenıa due to marrow failure - <10 x109/L • Major surgıcal procedures – <50 x109/L • Minorsurgery, liverbiopsy, transbronchialbiopsy, dental extraction - <50 x109/L • Severemucositis, anticoagulant therapy, infection with fever >38 C <25x109/L • APL induction, extremehyperleucocytoses <50x109 /L Do not transfuse to patients with immune-mediatedplatelet destruction INCTR Supportive Care handbook

16. PLATELET REFRACTORINESS - 1 • 5-10 ml/kg - ↑ platelet count by 50-100,000/cumm.- measure post-infusion ptl.counts 10’ – 1 hour after • Poor increment with atleast 2 ABO-compatible transfusions STORED FOR < 72 HOURS • Progressively diminishing clinical response • Causes – bleeding, fever, hypersplenism, DIC, heparin, amphotericin, antibodies to HLA, HPA

17. PLATELET REFRACTORINESS - 2STRATEGIES • Treatment of clinical causes • Transfuse ABO compatible platelets • Transfuse “fresh” platelets • Platelets from family donors • Small-dose frequent transfusions

18. PLATELET TRANSFUSIONS - CONCERNS • Transfusion thresholds – non-medical issues (eg: location of residence) • Orderingpractice for prophylactic transfusions – – high dose transfusions versuslowdose transfusions • Platelet dose– no effect on bleeding in patients with hypoproliferative thrombocytopenia • Possible increase in number of platelet transfusions N Engl J Med 2010;362:600-13

19. SPECIAL CONSIDERATIONS • LEUKODEPLETION IRRADIATION WASHED COMPONENTS VOLUME REDUCED COMPONENTS

20. TRANSFUSION OF BLOOD PRODUCTS IN PALLIATIVE CARE • Transfusion in advanced and life threatening disease – lead to difficult ethical and clinical situations Scenarios – • Continuation of transfusion which was part of supportive care for a patient for eg: with relapsed leukemia and no curative therapy available • Balance between benefits of transfusion vs potential harm/decisions of patient/family

21. SAFE TRANSFUSION THERAPY – VEIN TO VEIN SEQUENCE OF EVENTS Issue Recruit Screen donor Pre-transfusion testing Administer Collect & prepare Inf. diseases tests Medical decision to transfuse Monitor & evaluate PRODUCT PROCESS Adapted from Dzik WH. Emily Cooley lecture 2002 Transfusion 2003;43:1190-99

22. BLOOD DONORS • Nonremuneratedvolunteer blood donors – safest source of blood • Resource limited countries - funding, resources for mobile donor recruitment – limited • Forced reliance for blood on an “as-needed basis” on family/replacement donors • Paid donors who pose as surrogate family members

23. BLOOD DONOR RECRUITMENT • Donor deferral - frequent blood shortages - inhibits the full deployment of donor deferral procedures • Surrogate markers for HIV risk – age, demographic status – urban vs rural donors • Recruitment of rural donors – difficult, expensive, lower rate of potentially acceptable donors

24. SCREENING • Mandatory investigations • Investigations to be done as pernorms of the specific country malaria screening screening formicrofilaria bacterial contamination • Always diagnose malaria in any patient with fever post- RBC transfusion – most common parasitic infection

25. MALARIA Screening – thick and thin blood films – not sensitive enough – detect parasitaemia of > 300 – 5000/ml Parasitaemia of 10/ml can give rise to transfusion transmitted malaria Recipient chemoprophylaxis – controversial

26. PREVENTION OF TTI – SOME THOUGHTS • Cost-effectiveness of motivation of voluntary blood donors/use of replacement repeat donors • Prescreening donors - issues of counseling, stigmatisation+ use of blood bank as an entry point for HIV testing • Economics of prescreening Biologicals 38 (2010) 1 Biologicals 38 (2010) 65-67

27. TRANSFUSION – BASIC GUIDELINES CRITICAL POINTS IN TRANSFUSION Collection of patient samples – ID issues The medical decision to transfuse Bedside administration of blood components

28. THE DECISION TO TRANSFUSE Which component and how much? Need to transfuse incompatible blood PHYSICIAN’S RESPONSIBILITY FOR SAFE TRANSFUSION Need to transfuse uncrossmatched blood Inadvertent transfusion of incompatible blood TRANSFUSION REACTIONS, TTD

29. FOCAL POINT - 3THE TRANSFUSION • Rate of infusion of red cells ~ 4 hrs with BG set with 170 micron filter /platelets ~ 15 - 30 minutes/cryo 15 minutes • Ordinarily no need to warm blood - may be considered in elderly, neonates, massive transfusions • Strict patient monitoring

30. TRANSFUSION REACTIONS • Urticaria to acute hemolysis • Assume life-threatening till proved otherwise • Always be concerned about RECIPROCAL ERRORS

31. IN CONCLUSION • Blood transfusion: expensive business • Patients are at risk due to unsafe transfusions – unavoidable, avoidable • Unavoidable – window-period infections rare incompatibilities • Avoidable – wrong unit, wrongly used unit Multiple safeguards

32. Theory + technical skills SOPS Hospital transfusion committee Physician – one of the individuals responsible for QC in transfusion – immediate clinical intervention/ decisions/appropriate use of blood

33. “MYTHS OF TRANSFUSION” - REVISITED • Best strategy for blood system development • Organisational structure of blood services – centralised, regionalised, hospital-based, combination • Voluntary blood safety vs replacement donations • Post donation screening only – predonation lab testing with rapid diagnostic tests Biologicals 38 (2010) 1

34. RESOURCE LIMITED SETTINGS REQUIRE • simple and appropriate technology • innovative programmes Don’t let the perfect be the enemy of the good! Transfusion 2005;45