Transfusion Medicine Update KEMC Nov 5, 2014

Transcription

1 Transfusion Medicine Update KEMC Nov 5, 2014 Allison Collins MD FRCPC Ontario Regional Blood Coordinating Network Physician Clinical Project Coordinator

2 Disclosure I have no conflict of interest with this event because I have no affiliations, sponsorships, honoraria, monetary support or conflict of interest from any commercial source.

3 Objectives 1. Review the indications for transfusion of red cells, plasma, and prothrombin complex concentrate. 2. Review safe ordering practices for transfusion of blood components. 3. Review selected serious hazards of transfusion.

4 Case 1 A 55 year old man with peptic ulcer disease presents to the Emergency Department with upper GI bleeding. He is alert. BP 100/60 mmhg, pulse 90/min, Hb 85 g/l Would you transfuse red cells?

5 NEJM October 9, 2014 Why do they say this?

6 Randomised Trials of RBC Transfusion Trial (year) TRICC (1999) TRACS (2010) FOCUS (2011) UGIB (2013) TRISS (2014) N Res Hb/Hct Lib Hb/Hct Result d mortality same d mortality and serious morbidity same d mortality same d mortality in Res group d mortality same RBC use 54% 58% 65% 59% 50%

7 Randomised Trials of RBC Transfusion Trial (year) TRICC (1999) TRACS (2010) FOCUS (2011) UGIB (2013) TRISS (2014) N Res Hb/Hct Lib Hb/Hct Result d mortality same d mortality and serious morbidity same d mortality same d mortality in Res group d mortality same RBC use 54% 58% 65% 59% 50%

8 Acute UGI Bleeds - survival at 45 days % survival 70 g/l 90 g/l days Villanueva. NEJM 2013;368:11 KEMC

9 Acute UGI Bleeds - survival at 45 days

10 Acute UGI Bleeds: Other Results Outcome Restrictive (%) Liberal (%) P value Re-bleeding 45 (10) 71 (16) 0.01 Days in Hospital 9.6 +/ / TACO* 2 (< 1) 16 (4) *Transfusion-associated circulatory overload better in restrictive group Villanueva. NEJM 2013;368:11-21 KEMC

11 KEMC

12 Guidelines for RBC Transfusion 1. Adhere to a restrictive strategy in hospitalised stable patients (Hb g/l) 2. Consider transfusion in hospitalised patients with pre-existing cardiovascular disease if symptomatic or Hb 80 g/l, otherwise use a restrictive strategy 3. Cannot recommend against restrictive or liberal strategy in stable hospitalised patients with acute coronary syndrome 4. Transfusion decisions should be based on symptoms as well as Hb Carson. Ann Int Med 2012;157:49 KEMC

13 Case 1 A 55 year old man with peptic ulcer disease presents to the emergency department with upper GI bleeding. He is alert. BP 100/60, pulse 90, Hb 85 Would you transfuse red cells? Patient evaluation and Threshold Hb 70 g/l

14 RBC Transfusion in Acute Coronary Syndrome no large RCTs in ACS patients 2 pilot RCTs in ACS patients with conflicting results: Trial N R vs L threshold Cooper (2011) 1 outcome Result P 45 Hct.24 vs.30 Death/ MI/ CHF at 30d R 13% L 38%.046 Carson (2013) 110 Hb 80 vs 100 Death/ MI/ unscheduled revascularisation at 30d R 26% L 11%.049 (.076) Cooper. Am J Cardiol 2011;108:1108 Carson. Am Heart J 2013;165:964

15 RBC Transfusion in Acute Coronary Syndrome All other studies are retrospective, subject to confounding, and show conflicting results A recent very large retrospective study of 34,937 AMI patients at 57 US hospitals showed: Only 9% of patients could be matched for pretransfusion characteristics (n = 3108) Is this 9% generalizable to all AMI patients? 25% underwent coronary angiography, 10% underwent PCI, CKD rate 3x that in the unmatched population, avg. nadir Hb < 90 g/l In this 9%, transfused patients with Hb < 90 g/l had higher in-hospital mortality Salisbury. J Am Coll Cardiol 2014;64(8):811 Yeh. J Am Coll Cardiol 2014;64(8):820

16 RBC Transfusion in Acute Coronary Syndrome Salisbury. J Am Coll Cardiol 2014;64(8):811

17 Choosing Wisely Campaign 1. Don t transfuse more units of blood than absolutely necessary. 2. Don t transfuse red blood cells for iron deficiency without hemodynamic instability. 3. Don t routinely use blood products to reverse warfarin. 4. Don t perform serial blood counts on clinically stable patients. 5. Don t transfuse O negative blood except to O negative patients and in emergencies for women of child bearing potential with unknown blood group. Callum. Transfusion; September

18 Transfusion Thresholds Today Patient s signs and symptoms PLUS: Hb 70 g/l for stable in-patients Hb 80 g/l for patients with cardiac risk factors but without cardiac symptoms Hb 90 g/l for patients with acute coronary syndromes (no large RCT evidence yet) Cardiac symptoms: dyspnea, syncope, chest pain, tachycardia not fatigue alone

19 Ontario RBC Audit hospitals, 1345 RBC units, 17% ordered in ED

20 Ontario RBC Audit hospitals, 1345 RBC units, 17% ordered in ED

21 Risks of Transfusion RISK OF EVENT EVENT 1 in 100 Hives 1 in 300 Fever 1 in 700 TACO 1 in 7,000 Delayed hemolysis 1 in 12,000 TRALI 1 in 10,000 Symptomatic bacterial sepsis, per pool of platelets. 1 in 40,000 Getting the wrong (ABO) blood type, per unit of red cells 1 in 40,000 Anaphylaxis 1 in 60,000 Death from bacterial sepsis, per pool of platelets 1 in Hepatitis B virus infection, per unit of component 1,700,000 1 in 250,000 Symptomatic bacterial sepsis per unit of red blood cells 1 in 500,000 Death from bacterial sepsis, per unit of red blood cells < 1 in 1,000,000 1 in 6,700,000 1 in 8,000,000 West Nile virus infection Hepatitis C virus infection TACO TRALI SEPSIS WRONG BLOOD ANAPHYLAXIS Human Immunodeficiency Virus (HIV) infection Most common causes of death from transfusion Bloody Easy 3 ; 2011 Vox Sang 2012;103:83 Blood 2012;119:1757 Slide credit Y. Lin

22 ONTARIO TRANSFUSION TRANSMITTED INJURIES SURVEILLANCE SYSTEM 5 year report Total 662 Ontario TTISS Coordinating Office to publish a 5 year report for Ontario ATEs July Below is preliminary data (draft only) for the types of ATEs occurring from 2008 to KEMC

23 Transfusion-associated Circulatory Overload Within 6 hours of transfusion: 1. Acute respiratory distress 2. Tachycardia 3. Increased blood pressure 4. Acute or worsening pulmonary edema 5. Evidence of positive fluid balance Mortality rate 5-15% Single most common cause of transfusion-related death in the UK (SHOT report 2013) Incidence as high as 1:68 (under-reported) Narick. Transfusion 2012;52:160 23

24 TACO Patients at risk Older patients (>70 yrs) Renal insufficiency Cardiac dysfunction Positive fluid balance crackles, JVP, peripheral edema Infusion of large volumes Faster infusion rates 1. Consider pretransfusion furosemide in atrisk patients 2. Specify the infusion rate (max 4 hrs) Lieberman. Transfusion Medicine Reviews 2013;27:206 24

25 Order the Infusion Rate Bedside Audit 2011 infusion rate was specified in fewer than 50% of transfusion orders Infusion rate is a significant factor in TACO 25

26 Patients with chronic iron deficiency without hemodynamic instability (even with low Hb levels) should be given oral and/or IV iron 26

27 I know all of this! My patient needs blood! How quickly can I get Red Cells? How quickly? What you get Comment 5-10 min Type O un-crossmatched min Group specific un-crossmatched 45 min Group specific crossmatched 90 min Maybe hrs/days Group specific Antigen neg in pt with RBC Ab crossmatched 0.5% will have RBC antibody Serious hemolysis is rare O Rh(D) neg to women < 45 yrs Wait for group specific if you can As above Rh(D) neg to women < 45 yrs Wait for crossmatched if you can No RBC antibody detected Crossmatch compatible RBC RBC antibody detected Antigen-neg RBC must be found Do not withhold a critically necessary transfusion; serious hemolysis is rare Communicate with the Blood Bank

28 Case 2 A 70 year old 70 kg man with cirrhosis requires paracentesis. Labs: Hb 125 g/l, PLT 80 x 10 9 /L, INR 1.9 Which of the following should he receive before the paracentesis? 1. No frozen plasma 2. 2 units frozen plasma 3. 3 units frozen plasma 4. 4 units frozen plasma 5. 5 units frozen plasma

29 Plasma Consent required Needs to be ABO compatible Needs to be thawed (20-30 minutes) Dose is 15 ml/kg 3-4 units for an adult 1 unit = 250 ml Each dose increases coagulation factor levels by 20% Lin. Transfusion 2012;52:

30 Indications for Plasma Transfusion Treatment Bleeding patient with coagulopathy liver disease, DIC, massive transfusion and no other options (drugs, PCC, factor concentrates) Plasma exchange in Thrombotic Thrombocytopenic Purpura Prophylaxis Prevent bleeding in patients with coagulopathy before invasive procedures with INR > 2 or lumbar puncture with INR > 1.5 Poor evidence for use before invasive procedures with mild to moderate elevations of INR ( ) Platelet count is also a factor, usually want Plt 50 Guidelines vary because of lack of evidence (only 1 RCT) Tavares. Transfusion 2011;51:754. Segal. Trans fusion 2005;45:

31 Does elevated INR/PTT predict bleeding in the setting of a procedure? An RCT 81 critical care pts INR with planned: central venous line insertion percutaneous tracheostomy chest tube placement abscess drainage But 263 eligible 182 non-participants 40 received FP 12 ml/kg INR corrected to < 1.5 in 54% 41 no FP 81 randomised Incidence of bleeding and lung injury scores same at 24 hrs Müller. Transfusion May 2014 epub ahead of print 9 June 2014 KEMC

32 Will plasma infusion correct a high INR? 100 % 60 ml/kg = 4 L plasma Coag factor level 50 % 30 % 15 ml/kg FFP zone of normal hemostasis zone of anticoagulation INR KEMC 2014 Slide credit J. Callum 32

33 Effect of FP with mild elevation of INR (121 patients with INR ) Change in INR Fails to correct the INR in 99% of patients Abdel-Wahab. Transfusion 2006;46:

34 Bleeding risk differences: Normal vs. Abnormal Coagulation Test Results Study designs are not strong Segal. Transfusion 2005;45:

35 Ontario Audit of Plasma Orders in 2013: Pre-transfusion INR Results (n=303) 29% PRHC: 27% INR > plasma orders had no pre-transfusion INR KEMC

36 Ontario Audit of Plasma Orders in 2013: Dose of plasma ordered (n=303) 40-50% of orders are for 2 U. 2U is dose for 33 kg (73 lb) pt KEMC

37 PRHC Audit Data Dose of plasma ordered (n = 77) 61% of orders were for 2U (58% in provincial audit)

38 Risks of Transfusion RISK OF EVENT EVENT 1 in 100 Hives 1 in 300 Fever 1 in 700 TACO 1 in 7,000 Delayed hemolysis 1 in 12,000 TRALI 1 in 10,000 Symptomatic bacterial sepsis, per pool of platelets. 1 in 40,000 Getting the wrong (ABO) blood type, per unit of red cells 1 in 40,000 Anaphylaxis 1 in 60,000 Death from bacterial sepsis, per pool of platelets 1 in Hepatitis B virus infection, per unit of component 1,700,000 1 in 250,000 Symptomatic bacterial sepsis per unit of red blood cells 1 in 500,000 Death from bacterial sepsis, per unit of red blood cells < 1 in 1,000,000 1 in 6,700,000 1 in 8,000,000 West Nile virus infection Hepatitis C virus infection TACO TRALI SEPSIS WRONG BLOOD ANAPHYLAXIS Human Immunodeficiency Virus (HIV) infection Most common causes of death from transfusion Bloody Easy 3 ; 2011 Vox Sang 2012;103:83 Blood 2012;119:1757 Slide credit Y. Lin

39 TRALI Fatalities: FDA

40 TRALI: Definition Sudden onset of acute lung injury occurring 1-2 hours post transfusion, may be delayed up to 6 hours Hypoxemia: PaO 2 /FiO 2 300, SpO 2 < 90% on room air dyspnea, fever, hypotension CXR shows bilateral interstitial and alveolar infiltrates No other cause for ALI, no TACO

41 TRALI: Management Supportive care, including mechanical ventilation Usually resolves in hours Report to the Blood Bank Other patients may be affected a donor unit is divided into RBC, plasma and platelets Recipient and donor testing at CBS may be necessary, arrange with the Blood Bank

42 Case 2 A 70 year old 70 kg man with cirrhosis requires paracentesis. Labs: Hb 125 g/l, PLT 80 x 10 9 /L, INR 1.9 Which of the following should he receive before the paracentesis? 1. No frozen plasma 2. 2 units frozen plasma 3. 3 units frozen plasma 4. 4 units frozen plasma 5. 5 units frozen plasma

43 Case 3 An 80 year old presents with intracranial hemorrhage. She is taking warfarin for atrial fibrillation. INR is 3.5. How should she be treated? 1.Vitamin K PO and plasma 2.Vitamin K PO and PCC 3.Vitamin K IV and plasma 4.Vitamin K IV and PCC 5.PCC

44 Prothrombin Complex Concentrate (Beriplex or Octaplex ) Available in Canada since 2008

45 PCC Plasma Plasma all the clotting factors PCC II, VII, IX, X only (plus Proteins C and S, heparin) Consent required 45

46 Indications for PCC INR > 1.5 AND: Urgent (< 6 hours) warfarin reversal Life- or limb-threatening bleeding surgery required within 6 hours Urgent (< 6 hours) correction of Vit K deficiency For non-urgent reversal use oral or IV Vit K alone PCC is a warfarin antidote Effective half life of PCC is 6 hrs so give 10 mg IV Vit K at the same time, to prevent rebound bleeding Ageno. Chest 2012;141(2)(Suppl):e44S 46

47 PCC is Not Indicated for Non-urgent warfarin reversal Correcting an elevated INR in a non-bleeding patient Coagulopathy associated with liver dysfunction Massive transfusion 47

48 Administration of PCC Dose PCC INR < 3.0 INR INR > ml (1000 IU) 80 ml (2000 IU) 120 ml (3000 IU) INR-based or INR- and weight-based dosing With 10 mg Vit K IV If major bleeding and INR unknown use 4 vials (= 80 ml = 2000 IU FIX) Measure INR immediately following the infusion, and 6 h post infusion 48

49 Updated PCC Dosing Recommendations May

50 Contraindications for PCC and Warning Contraindicated in: patients with heparin-induced thrombocytopenia (HIT) Recent history of MI, DIC, thrombosis A meta-analysis of 27 studies (1032 patients) showed 1.8% incidence of thromboembolic events t½ of prothrombin (FII) is long (50-80 hrs), with potential for accumulation after multiple doses National Advisory Committee on Blood and Blood Products Dentali. Thrombosis and Hemostasis 2011;106(3):429 Franchini. Blood Transfusion 2010;8:149 50

51 Case 3 An 80 year old presents with intracranial hemorrhage. She is taking warfarin for atrial fibrillation. INR is 3.5. How should she be treated? 1.Vitamin K PO and plasma 2.Vitamin K PO and PCC 3.Vitamin K IV and plasma 4.Vitamin K IV and PCC 5.PCC

52 Massive Transfusion Def: 10U RBC in 24 hrs, 3-4U in 1 hr Pre-established protocols are better: Team leader, communication procedures Rapid DI, laboratory response tranexamic acid, blood product delivery The ideal ratio of RBC:FP:PLT is unknown the PROPPR Trial will be published soon

53 PROPPR Trial (Pragmatic Randomized Optimal Platelet and Plasma Ratios) 12 Level 1 Trauma Centers (SHSC in Canada), 680 patients randomized within 26 min each, using EFIC regulations Co-primary endpoints: mortality at 24 hr and 30d Secondary endpoints: # vent-free, ICU-free and hospital-free days etc. Cooler 1 Cooler 2 Group 1 PLT X X 1:1:1 Plasma XXXXXX XXXXXX RBC XXXXXX XXXXXX Group 2 PLT X 1:1:2 Plasma XXX XXX RBC XXXXXX XXXXXX Baraniuk. Injury 2014;45:1287

54 Massive Transfusion in a Blood Shortage Emergency framework for rationing of blood for massively bleeding patients during a red phase of a blood shortage Working group on emergency disposition of blood during a red phase blood shortage The bad news: Emergency Physicians may need to triage patients according to the National Plan The good news: This probably will not occur frequently

55 general exclusion criteria competing patients? is there enough? specific exclusion criteria supplemental inclusion criteria re-assess q24h/q10u

56 National Emergency Blood Management Committee Exercise November provinces participated in a mock exercise of a red phase red cell shortage To determine how much RBC use could be deferred To determine how many massively bleeding patients would have to be triaged to transfusion vs. no transfusion Preliminary results here, not yet published

57 National Emergency Blood Management Committee Exercise November units RBC to 321 patients over the 4 days of the exercise Could RBC use by 7% by cancelling all elective surgery Could RBC use by 35% by adhering to a 70 g/l threshold for RBC transfusion Only 7 patients would have needed triage to RBC vs no RBC

58 CME Resources e-learning with CME credit, books, apps All free of charge

59 Summary 1. Informed consent is required before transfusion of any blood product. 2. Use restrictive transfusion thresholds for RBC, and order 1 unit at a time. 3. Specify the product, dose and infusion rate in all orders. 4. Don t transfuse plasma if the INR is The correct plasma dose is 15 ml/kg, or 3-4 units in an adult. 6. Use PCC for urgent warfarin reversal.

60 Questions? Thank you to the PRHC Emergency Medicine Department Chiefs : Vince Arcieri Al Rogers Steve Baxter Jim McGorman Tom Miller Nancy White