Transfusion Indications: Update in 2019

Transcription

1 Transfusion Indications: Update in 2019 Yulia Lin, MD, FRCPC, CTBS Division Head, Transfusion Medicine, Sunnybrook HSC Associate Professor, Dept of Laboratory Medicine and Pathobiology, University of Toronto RCPA Pathology Update Friday, February

2 Disclosures Research: Novartis, Octapharma, Canadian Blood Services Consulting: Amgen, Pfizer

3 Objectives At the end of the presentation, attendees will: Describe the current guidelines and evidence base for red cell and platelet transfusion Identify gaps where questions remain unanswered List areas where transfusion has been shown to be harmful

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6 The TRICC Trial 838 ICU pts Transfuse 1 unit at a time and measure Hb Restrictive Hb < 70 g/l Liberal Hb < 100 g/l 30 d mortality 18.7% 23.3% P=0.11 In-hospital mortality 22.2% 28.1% P=0.05 RBC transfusion 2.6 units 5.6 units P<0.01 No RBC transfusion 33% 0% P<0.01 Hebert PC et al. NEJM 1999;340:409-17

7 The TRICC Trial 30 d mortality: 5.7% vs. 13.0%; P= d mortality: 8.7% vs. 16.1%; P=0.03

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9 FOCUS Trial Hip fracture surgery Age > 50 + cardiac disease or risk factors N=2016 pts Transfuse if symptomatic or if Hb < 80 g/l Transfuse if Hb < 100 g/l Outcomes 1 o : 60 day mortality or inability to walk independently 2 o : In-hospital outcomes, falls, fatigue, readmit to hospital, 60 day mortality Carson JL et al. NEJM 2011; 365:

10 FOCUS Trial Outcome Restrictive Liberal Difference, 95% CI Dead or unable to walk 34.7% 35.2% 0.5% (-3.7 to 4.7) Dead 6.6% 7.6% 1.0 (-1.9 to 4.0) No difference: in-hospital MI, CHF, stroke, infection, thrombotic events, return to OR, transfer to ICU Conclusion Reasonable to withhold transfusion in the absence of symptoms until Hb < 80 g/l even in elderly patients with CV disease or risk factors Carson JL et al. NEJM 2011; 365:

11 Villanueva et al. NEJM Jan 2013;368:11-21 Acute UGI Bleeding Excluded: massively bleeding or low risk of bleeding 921 pts with severe UGIB Restrictive Hb < 70 g/l Liberal Hb < 90 g/l portal pressures Mortality at 45 days 5% 9% P=0.02 Further bleeding 10% 16% P=0.01 Adverse events 40% 48% P=0.02 RBC transfusion 1.5 units 3.7 units P<0.001 Any RBC transfusion 49% 86% P<0.001

12 Villanueva et al. NEJM Jan 2013;368:11-21

13 26 trials 15,681 pts 30 day mortality OR 1.00 (0.86, 1.16) Carson et al. Am Heart Journal 2018;200:96-101

14 AABB RBC Guideline 2016 Transfusion not indicated until hemoglobin 70 g/l for hemodynamically stable hospitalized patients, including critically ill patients 80 g/l for patients undergoing orthopedic surgery, cardiac surgery or with preexisting cardiovascular disease 70 g/l likely comparable with 80 g/l (but data not available in all patient categories) Recommendations do not apply to acute coronary syndrome, severe thrombocytopenia (heme onc), and chronic transfusion dependent anemia Carson et al. JAMA 2016;316:

15 Acute Coronary Syndromes?

16 Anemia in Heart Disease Heart Disease Liberal strategy did not improve short-term mortality rates compared with restrictive (RR 0.94 [95% CI, 0.61 to 1.42]; 6 RCTs and 26 observational studies) American College of Physicians Restrictive RBC transfusion strategy (trigger Hb 70 to 80 g/l) in hospitalized pts with coronary heart disease Kansagara et al. Ann Intern Med 2013;159:746-57, Qaseem et al. Ann Intern Med 2013;159:770-9

17 RCTs in Symptomatic CAD CRIT Pilot Trial in Acute MI 45 pts with Acute MI Hb < 80 g/l vs. < 100g/L Randomization favoured restrictive Restrictive did better Larger studies underway REALITY: 630 pts acute MI MINT: 3500 pts acute MI MINT Pilot Trial 110 pts with ACS or stable angina for cath Hb < 80 g/l vs. < 100g/L Randomization favoured liberal (younger, more stable CAD for cath) Liberal did better Cooper et al. Am J Cardiol 2011;108: Carson et al. AHJ 2013;165:964-71

18 Hematology inpatients?

19 Survey says. Hoeks et al. Vox Sang 2018;113:152-9 Pine et al. Transfusion 2017;57:289-95

20 Inpatients Acute Leukemia Feasibility Trial Excluded: ACS, known active blood loss with hemodynamic instability Low Hb < 70 g/l 89 pts with acute leukemia 2:1 High Hb < 80 g/l Mean Hb pre (g/l) Mean Hb post (g/l) RBC units, median (IQR) 8 (6-11) 10 (8-12) P=0.01 Fatigue (NCI score out of 10) P=NS Bleeding 32% 37% P=NS DeZern AE et al. Transfusion 2016;56:1760-7

21 Transfusion in SCT (TRIST) 300 adult patients undergoing autologous or allogeneic HSCT Hemoglobin trigger 70 vs. 90 g/l Results Mean pre-transfusion hb difference 13.7 (± 9.8) g/l RBC units transfused in the restrictive-strategy group vs. the liberal-strategy group [2(2-6) vs. 4(2-6), p=0.10] No difference in QOL (FACT-BMT) or any clinical outcomes Tay et al. Blood 2016;128:1032. ASH 2016: Abstract #1032.

22 Survey says. Hoeks et al. Vox Sang 2018;113:152-9

23 Single vs. Multiple Units? Systematic review: 7 pre- and post- intervention studies single unit decreased RBC use by 10-41% Why single unit? Restrictive vs. Liberal OR 1.0 Most studies have used single unit at a time Potential TACO reduction strategy Shih et al. Transfusion 2018;58:

24 Chronic transfusion dependent anemia?

25 Transfusion in MDS Ongoing feasibility trial of 30 pts in Toronto/Hamilton Feasibility trial of 38 pts in the UK/Aus/NZ Intervention: maintain hb g/l vs g/l Pre-tx Hb 80 vs. 97 g/l Total # of units 92 vs. 192 Exploratory analysis: QOL favoured liberal group Buckstein et al. ENHANCE Study. NCT Stanworth et al. Blood 2018;132:527. ASH 2018: Abstract #527

26 Controversies for Restrictive vs. Liberal? Cardiac Surgery & Mortality Age

27 Cardiac Surgery: TITRe2 (UK) 2003 non-emergency cardiac surgery pts - POSTOP Transfuse 1 unit at a time and measure Hb Restrictive Hb < 75 g/l Liberal Hb < 90 g/l Infection/ischemic event at 3mo 35.1% 33.0% P=0.30 Secondary: death at 3mo 4.2% 2.6% P=0.045 Postop complication 35.7% 34.2% RBC transfusion 53% 92% P<0.01 Murphy et al. NEJM 2015;372:

28 TITRe2 Increased mortality at 3 months is this real? Randomized postop: 25.7% transfused pre-rct Mortality at 30 days: 2.6% restrictive vs. 1.9% liberal Causes of death did not suggest cause and effect Severe nonadherence 9.7% restrictive vs. 6.2% liberal Murphy et al. NEJM 2015;372:

29 Cardiac Surgery: TRICS III 5092 moderate to high risk cardiac surgery pts Transfuse 1 unit at a time and measure Hb Restrictive Hb < 75 g/l Liberal < 95 in OR/ICU < 85 ward Death, MI, stroke, dialysis (28 d) 11.4% 12.5% OR 0.90 ( ) Mortality (28 d) 3.0% 3.6% OR 0.85 ( ) RBC transfusion 52% 73% OR 0.41 ( ) RBC units, median (IQR) 2 (1,4) 3 (2,5) OR 0.85 ( ) Mazer et al. NEJM 2017;377:

30 TRICS III 6 month Followup Primary composite outcome: death, MI, stroke, dialysis Restrictive 17.4% vs. Liberal 17.1% (P= non-inferiority) Mortality 6.2% vs. 6.4% No difference in secondary outcomes: ED visit, readmission, coronary revascularization Mazer et al. NEJM 2018;379:

31 Long term outcomes after anemia Retrospective cohort study pts with hospitalizations from As RBC transfusion, moderate anemia at d/c over time Roubinian et al. Ann Intern Med 2018 Dec 18 Epub ahead of print

32 Long term outcomes after anemia Despite moderate anemia, rehospitalization/mortality over time Roubinian et al. Ann Intern Med 2018 Dec 18 Epub ahead of print

33 Transfusion Strategies in Older adults? Systematic review: patients 65 yrs = 3 RCTs (N=590 pts) Added 6 studies with mean age 64 yrs (N=5,780 pts) Results: restrictive vs. liberal 30 d mortality: RR 1.36 ( ) Composite cardiac complications: RR 1.62 ( ) Myocardial infarction: RR 1.50 ( ) Infection: no difference Simon et al. Lancet Haematology 2017;4:e465-74

34 Transfusion Strategies in Older adults? Missing 11 trials with mean or median age 65 yrs: if data included, then no longer significant TRICS III 6 mo primary composite outcome (mean age 72 yrs) Murphy et al. Lancet Haematology 2017;4:e453-54

35 RBC Guidelines Hb < 90 g/l Hb < 80 g/l Hb < 70 g/l Hb < 60 g/l Clear signs and symptoms of impaired tissue oxygen delivery (including acute coronary syndrome) Cardiac disease, elderly (possibly lower?) Likely appropriate although younger patients may tolerate even lower hemoglobins (i.e. Hb < 60 g/l)

36 Platelets

37 ICTMG Guidelines Prophylactic transfusion at < 10 x 10 9 /L Low dose (1.41 x /m 2 ) as hemostatically effective as higher dose but requires more frequent platelet transfusion Whole blood derived can be used interchangeably with apheresis platelets ABO compatible platelet to improve platelet increment and decrease rates of refractoriness Nahirniak et al. Transfusion Med Reviews 2015;29:3-13

38 Platelet Transfusion in Heme Malignancy 396 pts with hematologic malignancy and plt < 10 x 10 9 /L Randomized *Fever was not indication to transfuse Therapeutic transfusion N = 199 Prophylactic transfusion N = o Outcome: # of platelet transfusions 2 o Outcome: bleeding, # of RBC units, side effects, survival Wandt et al. Lancet 2012;380:

39 Wandt et al. Lancet 2012;380:

40 Platelet Transfusion in Heme Malignancy (TOPPS Study) 600 pts with hematologic malignancy and plt < 10 x 10 9 /L (70% autosct) Randomized No Prophylaxis N = 301 Prophylactic transfusion N = o Outcome: WHO grade 2,3,4 bleed at 30 days Noninferiority Stanworth et al. NEJM May 2013;368:

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42 Prophylactic platelet transfusion at < 10 x 10 9 /L Patients receiving therapy for hematologic malignancies Allogeneic stem cell transplantation Therapeutic platelet transfusion Autologous SCT: similar rates of bleeding with decreased platelet usage when patients transfused at first sign of bleeding rather than prophylactically (experienced centers) Chronic stable severe thrombocytopenia (MDS, aplastic anemia) not receiving active treatment Schiffer et al. JCO 2018;36:283-99

43 PATH Study Platelet transfusion in autologous SCT Intervention: Prophylactic tranexamic acid 1 g po TID Control: Prophylactic platelet transfusion < 10 x 10 9 /L Outcome: Feasibility Sample Size: 100 pts Tay et al. NCT Accessed 9 Feb 2019

44 AABB Guidelines 1. Prophylactic transfusion < 10 x 10 9 /L (strong) 2. Central venous catheter < 20 x 10 9 /L (weak) 3. Diagnostic lumbar puncture < 50 x 10 9 /L (weak) 4. Major elective non-neuraxial surgery < 50 x 10 9 /L (weak) 5. Cardiopulmonary bypass + bleeding transfuse (weak) 6. Antiplatelet therapy + ICH no recommendation Kaufman et al. Ann Int Med 2015;162:205-13

45 PATCH Study 190 pts within 6h of spontaneous ICH on antiplatelet therapy (ASA) Randomized to platelet transfusion vs. no platelets + standard care Results: Death or dependence at 3 mo OR 2.05 (95% CI ) Serious adverse event: 42% vs. 29% (ICH related) Death during hospital stay: 24% vs. 17% Platelet transfusion seems INFERIOR to standard care alone Baharoglu et al, Lancet 2016;387:

46 GI bleeding Retrospective case-control study (N=408) GI bleeding pts on antiplatelet agents and plt > 100,000/µL Zakko et al, Clin Gastroenterol Hepatol 2017;15:46-52

47 Why harmful? Platelet transfusions for bleeding with antiplatelet therapy - Pro-thrombotic (activated during storage) - In ICH: lead to cerebral ischemia in areas around ICH - Pro-inflammatory: enhance vascular permeability - Pro-volume: increase BP and disrupt thrombosis - Even if not ultimately harmful, it is unlikely to be beneficial Baharoglu et al, Lancet 2016;387: Zakko et al, Clin Gastroenterol Hepatol 2017;15:46-52

48 Platelet Guidelines Any plt count Plt < 100 x 10 9 /L Plt < 50 x 10 9 /L Plt < 20 x 10 9 /L Plt < 10 x 10 9 /L Severe bleeding with platelet dysfunction (post CPB) Bleeding in sanctuary sites (CNS, eye) To prevent bleeding in sanctuary sites Massive bleeding Major bleeding/surgery Minor procedures: CVC line, thoracentesis, paracentesis Prophylactic hypoproliferative thrombocytopenia

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50 Summary Gaps: outpatient hematology patients, elderly? Potentially harmful: GI bleeding,?antiplatelets (ICH, GI bleeding)