Transfusion Medicine Reviews April 2009 batch

1. Transfusion Medicine ReviewsApril 2009 batch Plus “The difficult conversation”

2. “Transfusion medicine decisions are easy, it is the ordering physicians that are the most difficult thing about transfusion medicine.”

3. Conversation 1 • The technologist receives an order for 4 units of FFP for an INR 1.29 for a patient with an intracranial hemorrhage • You call Dr. Brain to explain why the patient will not benefit from the product • He cuts you off after the first few words about the clotting factors and the relationship with the INR and why FFP will not help him

4. Conversation 1 • “I need it to be normal – she is coning” • “The other neurosurgeons will think I am crazy for not giving FFP” • “She is going to die if we do not stop the bleeding” • “She is only 32 years old” The worried MD

5. Conservation 2 • Resident on ortho orders 2 units of blood for transfusion for an immediate post-op orthopedic case (total knee replacement) • The only hemoglobin is from 2 weeks ago in pre-admission (167 g/L) • The patient has a pacemaker set at 60 and he is at 80 bpm • MD transfusing because the BP is 100/50 and the patient has a ‘cardiac problem’ • Good urine output • Regional anesthesia + gabapentin • Refuses to do a pre-transfusion STAT hemoglobin

6. Conservation 2 • “Do you know who I am? – I am an orthopedic surgeon” • “You can not talk to me like this – I am an orthopedic surgeon” • “We can’t wait for a repeat hemoglobin – he has a ‘cardiac’ problem and is hypotensive The god-complex MD

7. Conversation 3 • Patient with ITP is taken to the OR for an ascending aorta repair • Pre-op platelet count is 146 one week before • Call from the OR from anesthesia they want 2 sets of platelets for management of bleeding • Patient is still ‘on-pump’

8. Conversation 3 • You ask them to do a platelet count pre- and post to see if this ITP patient responds to platelets at all • The anesthesiologist refuses – says he is too busy to do this • He hangs up on you The irrational MD

9. Conversation 4 • 28 year old MVA with massive out of control bleeding with thoracic and pelvic injuries • Hypothermic • Acidotic • Coagulopathic (INR 2.7) • Hypofibrinogenemic (0.8 g/L) • Anemic (57 g/L) • They want r7a now! (although they have not read any of the papers)

10. Conversation 4 • You try to explain that r7a is of questionable value with good baseline coagulation factors – probably completely useless at this point with this patient’s status • “Should we just let the patient bleed to death then??” The hard-to-refuse & no-time-to-talk MD

11. Fire-side chat • The most difficult conversations are with MDs you have never met face-to-face • The first few years – your whole goal should be to avoid difficult conflicts • You will have decades to improve transfusion practice • Inappropriate transfusions are common - half of plasma and a quarter of RBCs – they have been going unnoticed for a few decades – no rush • The most likely consequence of a difficult conversation = that MD will NEVER speak to you again

12. Fire-side chat • New staff MDs are the most difficult • They come with baggage • Often trained in the US – never questioned before • Don’t take it personally • Try to fall back asleep after – re-running the conversation over and over in your head is not useful • Give them an ‘easy out’ compromise to ‘save face’ • “Let’s try correcting the temperature, acidosis, coagulopathy and platelet count first” • “If that does not work, then I think you are right, let’s try r7a”

13. My approach • Prevention • Case related negotiation • Re-grouping after a nasty encounter • Email • Coffee • Medical literature • Rounds • Keep the lines of communication open

14. Prevention is the best medicine • You need to do the rounds circuit for all the subspecialties • The more they see you the more they will trust your judgment • Don’t expect trust without hard work • Academic detailing of any obliging MD • Can we meet for coffee next week? • I will look up some papers for you and bring them • Ask for input when developing protocols

15. Prevention • Send follow-up emails with key papers • Very appreciated • Prevents the next nasty conversation • Send out key papers to subspecialties by email spontaneously • Very effective • Get really good audit data for bigger problems – come to them with data • Then they may listen • Try to be really helpful when they come to you with problems or new initiatives

16. Prevention • Send out yearly transfusion data • Reaction statistics • Utilization figures • Audit results • They will save your email and connect back to you with any transfusion problems (you will get replies to this email for years) • Expedite consults from your high blood users • Speak at retreats for your different departments (including nursing conferences)

17. Really difficult residents • Ask their supervisor for a week rotation in blood bank for ‘extra help’ • Provide a binder of transfusion literature • Intensive training x 5 days • Don’t let them leave your hospital to go and terrorize some other transfusion medicine MD

18. Case based negotiation • I haven’t perfected this encounter • Not sure if you can • Pick your battles carefully – it may take 10 years for the MD to speak to you again if it goes badly • Take the tactic “this patient seems to be causing some problems – I just wanted to make sure we had everything covered in the blood bank” • Use first names – diffuses the situation and makes it friendly • Take them to the internet transfusion guidelines • They will trust you more if they see it in writing

19. Really dangerous transfusion decision that you can not avert • Resident • Easier – escalate to the staff MD • Staff MD to department chief • Not so easy • If it is clear they will never back down…”we never refuse blood even if it is outside the guidelines…we just put in a comment in the blood bank information system that we issued it outside of the guidelines and that you were aware. I am going to call the blood bank now. They will call you when the product is ready” • 90% of the time they do NOT take the product • ‘Easy out’ – they back down without you ‘knowing’

21. TMR April 2009 The three best articles from the final quarter of 2008

22. PLEX after infusion of RBC ‘rich’ stem cells RCT of granulocyte transfusions TT- Babesia 97-07 Blood transfusion and VTE DDAVP meta-analysis Freezed-dried plasma & MVA pigs PINT – longterm follow-up G-6DP blood for exchange transfusion ICU patients and CMV infection Interruptions in the OR during blood checks Strawberry lollipops for DSMO-induced nausea Review article on PCCs Uncrossmatched RBCs increase mortality The articles

24. PINT study thresholds

26. Methods • Patients were assessed using standard clinical tools for measurement of neurological development (measures of cerebral palsy, visual or hearing impairment, and infant development) • The primary outcome of the study was a composite score of death or any single measure of neuro-cognitive deficit • Those who assessed the children where blinded to the original allocation • The study was powered to detect a 13% absolute difference in outcomes with 95% confidence

27. Baseline data

28. Primary outcome

29. Their take on their results • “Our study provides some weak evidence of benefit from a higher hemoglobin threshold for transfusion primarily through a secondary analysis of cognitive delay. Because this finding combines a protocol-defined analysis of borderline statistical significance with a posthoc analysis of both clinical and statistical significance, it is not conclusive in its own right but is hard to dismiss as simply the play of chance.”

30. Second paper suggestsliberal may better • Pediatrics 2005; 115: 1685-91. • N=100 (much smaller) • Birth weights of 500 to 1300 g into a randomized clinical trial comparing 2 levels of hematocrit threshold • Infants in the restrictive-transfusion group were more likely to have: • intraparenchymal brain hemorrhage • periventricular leukomalacia • more frequent episodes of apnea ( mild and severe episodes)

31. What do you do at your hospital while you await the next trial 10 years from now? Hi Jeannie I think our group is holding steady for now but I am happy to explore that with the group in the coming months. I will tell you there are some preliminary discussions taking place to try for another RCT that is powered for 2 year outcome and be done internationally (n=1200). I will have more details in the coming weeks. Liz

34. Error rates by locationUnit Transfusion Denominator 123,766 of 187,297 (66%) products issued

35. Dr. Transfusalot in the operating room with the blood

36. ABO-Fatalities from SHOT • 6 of 8 transfusion fatalities reported to SHOT occurred in the operating room • Janatpour, Kim A., et al. Clinical Outcomes of ABO-Incompatible RBC Transfusions. American Journal of Clinical Pathology 2008;129:276-281.

37. Interruptions and blood transfusion checks: Lessons from the simulated operating room. Liu D, Grundgeiger T, Sanderson PM, et al. Anesth Analg 2009; 108: 219-222. • 12 anesthesiologists from the Royal Adelaide Hospital and The University of Queensland • Intentionally distracted at the time of arrival of blood for a simulated ‘bleeding patient’ • They were given 180 seconds to detect a transfusion error - blood hung by the nurse without a pre-transfusion check

38. 3 groups • Head mounted device – none • Head mounted device – near • Head mounted device – far • Plus the regular operating room displays

39. Interruptions and blood transfusion checks: Lessons from the simulated operating room. Liu D, Grundgeiger T, Sanderson PM, et al. Anesth Analg 2009; 108: 219-222. • The authors classified the response of the anesthesiologist into four behavioral options: • Engaging – they engaged with the distraction and organized transfer; • Multitasking – discussed transfer while helping start the transfusion; • Deferring – acknowledged the surgeon and then focused on the transfusion; • Blocking – told the surgeon that the patient did not need a high dependency unit and returned to the transfusion task • Two researchers coded the responses of the anesthesiologists based on the video tapes.

40. Interruptions and blood transfusion checks: Lessons from the simulated operating room. Liu D, Grundgeiger T, Sanderson PM, et al. Anesth Analg 2009; 108: 219-222. • 2 of 12 missed the omitted check in the 180 second grace period • Both ‘engaged’ with the distraction • One ‘multitasker’ just detected the error at 117 seconds • The remaining 9 anesthesiologists detected the omission within 30 seconds, 4 were ‘deferrers’ and 5 were ‘blockers’.

43. Blood transfusion, thrombosis and mortality in hospitalized patients with cancer. • AA Khorana, CW Francis, N Blumberg, et al. Arch Intern Med 168:2377-2381, 2008

44. Methods • The authors queried the University Health System Consortium database which consists of 60 academic medical centers • Using ICD-9 codes, they identified adult patients admitted with cancer from 1995-2003 • WE ALL HAVE PROBLEMS WITH CODING! • They further used coding to determine comorbidities, diagnosis of arterial or venous thromboembolism (ATE, VTE) and whether blood transfusions were administered

45. Blood transfusion happens tosick patients VTE happens to sick patients

46. Patients • Of the 504,208 patient studied, approximately 15% of patients received a blood transfusion • 80% received only red cell transfusions and 5% received only platelet transfusions (rest both red cells and platelets) • Average person in the database – white, hypertensive, aged 65

47. Rates • The rate of VTE 6.4 to 7.2% • The rate of ATE 3.1 to 5.2% • These rates were overall higher than those for VTE and ATE in the non-transfused patients (3.7 and 3%).

48. Note: ESAs Missing!

49. Limitations • Reliance on administrative coding • The diagnostic criteria to identify VTE included superficial thrombophlebitis • Underreporting of transfusion • ESAs data missing • Data regarding compliance with appropriate thromboprophylaxis unavailable • Inability to determine the time of administration of transfusion in relation to the development of VTE/ATE • It is possible that anemia/transfusion is a surrogate for aggressive tumor biology, more intense chemotherapy, or “sicker” patients – can’t completely ‘control’ in multivariate analysis

50. Rich’s bottom line • This study is very limited in its ability to determine whether transfusions directly lead to unwanted clots in hospitalized cancer patients • Hypothesis generating only