Informed Consent for Blood Transfusions

1
Informed Consent for Blood Transfusions

• Should you Leave on the Prion?
• Dr. Jason Hart
• Dr. Susan Nahirniak
• Medical Grand Rounds
• University of Alberta Hospitals
• March 28, 2003

2
Introduction

• Significant media attention since the emergence
  of Bovine Spongiform Encephalopathy (Mad Cow
  Disease) in UK
• Documented spread from cattle to humans
• Difficult epidemic to trace due to long
  incubation times
• Raises concern of transmission between humans
• Is prion disease transmitted by blood?

3
Introduction

• Complicating the issue is the questions of
  whether this unproven risk or theoretical risk
  should be mentioned to patients
• Would the mention of CJD in the blood supply
  cause unfounded fear and skepticism of our blood
  supply?

4
Case Presentation

• 56 y.o. male, admitted to General Medicine Unit,
  metastatic lung CA, PE1
• Presents with shortness of breath
• Dx Recurrent PE despite adequate
  anticoagulation (INR 2.4 on admission)
• Also anemicHb 80, no obvious source of blood
  loss
• Requiring 7L O2 to maintain saturation above 90
• _________________
• 1. Pulmonary embolism

5
Case Presentation

• Over 1 week, Hb dropped to 71
• Blood transfusion ordered by Jr. Resident but
  patient declines
• Next day Hb 68
• Explained risks of transfusion
• Emphasized the benefits of receiving blood

6
Case Presentation

• The last thing I need now is to get AIDS.
• Adamantly refused blood
• Wife in agreement
• Discontinued monitoring hemoglobin
• Placed in Hospice bed

7
Case Presentation

• What went wrong?
• What are my obligations for disclosure?
• Did I have to tell him of HIV risks?
• What about CJD?

8
Objectives

• Science
• What is the current evidence for the transmission
  of CJD by blood transfusion?
• Ethics
• What are the ethical principles involved in
  informed consent?
• Risks
• What are the risks associated with blood
  transfusions?
• Approach
• How should you approach informed consent for
  transfusions?
• Logistics
• What are the logistics of implementing informed
  consent?

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Informed Consent for Blood Transfusions

• True or False. It is okay to withhold disclosure
  of the risks of a procedure if you think it may
  potentially cause harm.
• A. True
• B. False

10
Informed Consent for Blood Transfusions

• What is the most common infectious risk of a
  blood transfusion?
• A. Hepatitis B
• B. Hepatitis C
• C. Bacterial contamination
• D. HIV

11
Informed Consent for Blood Transfusions

• CJD should be part of informed consent for blood
  transfusion?
• A. Agree
• B. Disagree

12
What is Creutzfeldt-Jakob Disease?

• CJD is a rapidly progressive neurodegenerative
  disease caused by an infectious proteina prion
• Affected patients develop ataxia, myoclonus and
  dementia, resulting in death within weeks to
  months
• Long incubation timevarying from 18 months to 30
  years from time of exposure to onset of symptoms
• No serologic testing and no treatment
• Uniformly fatal

13
What does it have to do with blood transfusions?

• 1994 - American Red Cross and US blood
  manufacturers recommended voluntary withdrawal of
  donated blood
• 3 donors developed CJD
• Same year, similar incident in Canada
• Canadian Red Cross and Bayer
• Blood and blood product recall the largest in
  Canadian history
• Cost 11 million
• Implemented donor screening for people at risk of
  CJD

14
What is a Prion?

• Stanley Prusiner
• Born in 1942
• Nobel Prize in Medicine in 1997 for the discovery
  of prions
• The first year of his residency (1972) in
  Neurology, he had a patient with CJD
• 10 years later, described the prion

15
What is a Prion?

• Prions are infectious proteins
• The only infectious agent devoid of nucleic acid
• Reproduce by recruiting normal cellular prion
  protein (PrPc) and stimulating its conversion
  into the disease causing isoform (PrPSc)

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What is a Prion?

• Conformational change from predominantly
  alpha-helix structure to beta-pleated sheets
• Proteolysis of PrPSc produces a
  protease-resistant molecule (PrP 27-30) which
  polymerizes into amyloid

PrPc
PrPSc
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What is a Prion?

• The result is a spongiform appearance swiss
  cheese with amyloid plaques, and reactive
  gliosis
• The amyloid plaques stain positive for antibodies
  against PrPSc with immunohistochemistry

Immunohistochemical stain for prion protein
18
What is a Prion?

• Different strains of prion affect different
  animals
• Bovine Spongiform Encephalopathy (BSE) affects
  cattle (Mad Cow Disease)discovered in 1986
• Scrapie in sheep
• Classical CJD (cCJD) makes up 85 of prion
  disease in humans
• Kurucannibalism in Papua New Guinea

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The Epidemic

• Before identification of BSE in 1986, 700,000
  infected cattle may have been consumed
• Extent of spread not known
• 5.8 million cattle have been destroyed on
  suspicion of carrying BSE

20
The Epidemic

• In 1996, a novel form of prion disease discovered
  in the UK
• Called Variant CJD (vCJD)
• Epidemiologic and experimental evidence quickly
  linked BSE with vCJDsame prion
• Spread felt to be by consumption

21

• Classic CJD (cCJD)
• vs
• Variant CJD (vCJD)

22
Classic CJD

• cCJD can be acquired, inherited, or sporadic
• Sporadic form has an incidence of 1/million/yr
  and is found throughout the world
• Inherited forms make up 15 of cases per year and
  can be diagnosed with genetic markers
• Follows familial inheritance
• Acquired is from exposure during medical or
  surgical procedures
• neurosurgical procedures
• Corneal transplant
• Parenteral injection of cadaveric derived growth
  hormones

23
Classic CJD

• Classic CJD (cCJD) is not associated with BSE
• Median age of onset 69 years old
• Never been found outside of CNS
• Never been associated with transmission by blood
  transfusion
• No transmission seen after lookback studies on
  patients who received blood products from a donor
  later diagnosed with CJD
• Hemophiliacsno identified cases
• Case-control studies showed no transmission

24
Variant CJD

• Associated with BSE
• Spread by ingestion of infected meat
• Median age of onset 29 years old
• Found only in Europe
• UK132 cases
• France5 cases
• Italy1 case

25
Variant CJD

• Several studies documenting the presence of vCJD
  outside of the CNS
• First documented in a patients appendix which was
  removed 8 months prior to developing symptoms of
  CJD
• Similar studies looking at tonsils, spleen, and
  lymph node biopsies
• positive for vCJD
• Negative for other prion diseases
• Lymphocytes express PrPC

26
vCJD Transmission by Blood

• No direct evidence for transmission in humans
• Animal model created using New Zealand sheep
• Infected with BSE by eating small amount of cow
  brains
• Whole blood was transfused from asymptomatic
  infected sheep to healthy sheep 319 days after
  the inoculation
• One of the recipients has contracted the prion
• First documentation of BSE transmission by blood
  transfusion

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Classic CJD vs. Variant CJD
28
Ethics
29
Informed Consent

• Consent stems from the ethical principle of
  respect for patient autonomy
• Patients make decisions for their own health care
• Treating patients without their consent is
  battery
• If inadequate information is supplied to
  patients, this constitutes negligence

30
Informed Consent

• Beyond protection from litigation, consent has
  been found to improve patient satisfaction and
  reduce negative feeling and distress
• Impossible to include every side effect, reaction
  or risk for every procedure
• What should be included?

31
Informed Consent

• Reibl and Hughes, Supreme Court of Canada
• 10 years of litigation
• Reibl stroked after endarterectomy
• Asymtomatic carotid artery stenosis
• better off not knowing
• The physician needs to disclose information that
  a reasonable person, under the same
  circumstances, would want to know to make an
  informed decisionMaterial Risk

32
Informed Consent

• Material risk
• High incidence of a minor side effect
• Bruising after having blood drawn
• What the patient can expect
• Remote risk of a very serious outcome
• Transmission of an infectious disease through
  blood transfusion
• Worst case scenario

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Informed Consent

• Arguments for including CJD as part of informed
  consent
• Given that CJD is irreversible, untreatable and
  universally fatal, it should be considered a
  material risk of a blood transfusion, even though
  it is unlikely
• People want to know what they are up against,
  even when the news is unfavorable

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Does disclosure cause harm?
35
Therapeutic Privilege

• This is the counter-argument against disclosure
  of CJD
• Concern of causing unnecessary harm or suffering
• Patient is better off not knowing
• Disclosure may cause the patient harm

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Does disclosure cause harm?

• From strict evidence-based medicine, we have no
  reason to disclose CJD because transmission by
  blood has never been proven
• Incidence is very low
• Nothing we can do about it
• No screening
• No therapy
• Just causing unnecessary panic

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What do people want to know?

• 1995, Canadian Red Cross recommended recipient
  notification of possibly receiving contaminated
  blood products with CJD
• Responses of 528 transfusion recipients (or
  guardians) were documented after notification
• 2/3 felt fearful and anxious about receiving the
  news
• 80 wanted to be notified, and would want another
  notification if a similar situation occurred

38
What do people want to know?

• 80 wanted to know, but 20 did not!
• Potential harm
• Canadian CJD Society has members that received
  potential tainted blood who feel they have early
  CJD
• Withholding this information, constitutes
  therapeutic privilege

39
Therapeutic Privilege

• Therapeutic Privilege as a defense
• Mr. Pittman received a blood transfusion during
  cardiac surgery 1984
• 1989, physician notified that Pittman may have
  received HIV-contaminated blood
• Patient was not notified
• Dr. felt he was probably not sexually active
• Did not want to jeopardize cardiac status, and
  mental health of the patient

40
Therapeutic Privilege

• Pittman died of AIDS-related illness in 1990
• His wife was notified of the possible infection
  AFTER he died
• She later died of AIDS
• Judgefelt physician was below the standard of
  care, and therapeutic privilege was not
  justified, with inadequate surveillance for
  watchful waiting

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Therapeutic Privilege

• Meyer Estate v. Rogers
• 37 y.o. woman died after intravenous injection of
  a contrast medium for a routine radiologic
  procedure
• Radiologist claimed therapeutic privilege as a
  defense against allegations of failure to warn
• Losing argument
• Sup. Court of Canada has not adopted or even
  approved the therapeutic privilege exception in
  Canada.

42
Does disclosure cause harm?

• Conclusions on Therapeutic Privilege
• It has yet to be successful as a defense
• Exceptions to Informed Consent yet to be
  clarified
• Perception of harm came from warning patients
  after the fact
• Does not necessarily generalize to forewarning a
  patient of the risks
• Violation of the trust that is central to the
  physician/patient relationship

43
Does disclosure cause harm?
44
Does disclosure cause harm?

• Studies show that patient-doctor communication
  and trust are improved by disclosure
• The physician/patient relationship is founded on
  trust
• Patient willing to accept more risk, because a
  doctor recommends it
• Better patient satisfaction and physician/patient
  relationship
• Disclosure promotes patient autonomy
• Less of a victim, more of a participant in the
  care

45
Does disclosure cause harm?

• Physicians role in not to shield patients from
  bad news and risks but to explain the situation
  and break it to them in a compassionate way

46
What are the risks of blood transfusions? Common
Risks of Little Consequence

• Fever
• More frequent with platelet transfusion
• Urticaria
• 1 in 100-300
• Pain or bleeding from the IV site

47
Rare but Serious Hazards

• Acute Hemolysis
• 1 in 25,000 units with 1 in 600,000 fatal
• Anaphylaxis
• 1 in 20 -50,000
• Bacterial Contamination
• ? 1 in 10,000 platelet transfusions Fatal lt1 in
  million
• TRALI
• lt 1, but 50 mortality rate

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Risks of Viral Transmission

• HIV
• With NAT 11,930,000
• Hepatitis C
• With NAT 1 250,000 - 500,000
• Hepatitis B
• 163,000 to 1200,000

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Risks for Specific Patients

• Fluid Overload - elderly, cardiac renal
  patients
• Hemolytic Transfusion Reactions
• Patients with allo- or auto-antibodies to rbc
• CMV Transmission
• Neonates transplant patients
• Iron Overload
• Chronically transfused

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Obtaining Consent

• Krever recommends
• Explain risks, benefits, alternatives
• Suitable language, time to think and to question
• Sufficient time to implement alternatives (ie.,
  autologous donation)
• Documentation
• Post-treatment debriefing
• Charted on discharge summary

51
Obtaining Consent

• First emphasize need for transfusion and
  consequences of not being transfused
• Most important factor!
• Then discuss the risks
• Three broad categories
• Risks associated with the transfusion itself
• Infectious risks
• Theoretical or unknown risks

52
Obtaining Consent

• Risks associated with the transfusion
• Allergic responses
• Febrile reactions
• Shortness of breathoverload, TRALI
• Hemolytic reactions
• On very rare occasions may be life threatening

53
Obtaining Consent

• These reactions are the material risks of a blood
  transfusion
• Common reactions that may happen to anyone
  (allergic, febrile, dyspnea)
• Acute hemolytic reaction is also a material risk,
  because although rare, it is potentially life
  threatening
• Worst case scenario

54
Obtaining Consent

• Infectious Risks
• Patient should be informed of the possibility of
  bacterial contamination
• most common infection transmitted by blood
• HIV, Hep B and C are also material risks because
  most people are aware that these can be
  contracted by blood
• A reasonable person would want to know
• A material risk
• Other infectious agents

55
Obtaining Consent

• Unknown Risks
• Despite rigorous testing and research, there
  still remains unknown risks associated with blood
  transfusion
• Infectious agents yet to be identified
• Known diseases that cannot be screened (CJD)
• Does not jeopardize the physician-patient
  relationship

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Obtaining Consent

• CJD - a representative of unknown risk
• High level of public awareness
• Life threatening condition
• Theoretical risk of transmission

57
Lessons from History

• HIV
• Known to exist, but risk of transmission in blood
  was not known
• Estimated 25,000 cases of transfusion associated
  AIDS from untested blood prior to 1985

• Hepatitis C
• Non-A non-B hepatitis first described in 1975
• Known to exist, but risk of transmission in blood
  was not known
• Identified in 1989
• Likely tens of thousands infected

58
Lessons from History

• Hepatitis C
• Non-A non-B hepatitis first described in 1975
• Known to exist, but risk of transmission in blood
  was not known
• Identified in 1989
• Likely tens of thousands infected

59
Obtaining Consent

• Unknown if CJD will follow a similar pattern as
  HIV and Hep C
• Including CJD in informed consent is a
  recognition that although our blood is as safe as
  we can make it, there are still some
  uncertainties that remain

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Obtaining Consent

• If CJD is included in consent, and studies
  document transmissibility, patient will not feel
  victimized or tricked into the transfusion
• Preservation of the trust relationship
• Patient will be part of the decision process
• At the time of the transfusion, the benefits of
  blood outweighed the risk
• Conversely, if CJD is not transmitted then
  physicians appear only overprotective

61
Implementation of Informed Consent What can
drive implementation?

• Provincial Directives
• Directive by Ministry of Health in BCconsent by
  1999
• College of Physicians and Surgeons Policy
• Ontario and Manitoba Colleges have Policy
  Statements
• Regional Policy
• The Alberta College feels Regions are overseeing
• Medical Staff Bylaws
• Health Canada Standards

62
Barriers to Implementation

• Where does the responsibility for monitoring and
  regulating the process lie?
• Lack of educational resources to ensure health
  care professionals are informed
• Lack of access to alternatives
• Confusion as to the extent of the consent

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Who should be obtaining informed consent?

• Someone who
• knows the options, and the risks / benefits of
  the options
• knows the patient and their concerns
• knows the patients medical history and current
  condition to best assess risks/benefits
• has sufficient time to devote to the discussion

64
Conclusion

• CJD is a severe, universally fatal neurologic
  disease that cannot be detected by screening the
  blood supply
• vCJD is different from cCJD
• Linked with BSE
• Found outside CNS
• Sheep model suggests transmittable by blood

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Conclusion

• Informed consent should include
• Reasons for why the transfusion is needed
• Material Riskswhat a reasonable person in the
  same circumstances would want to know
• Transfusion itself
• Infectious risks
• Unknown risks

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Conclusion

• CJD should be included in informed consent
• It is a material risk
• A representative for unknown risks of blood
• Patients prefer disclosure
• Therapeutic privilege is indefensible
• The result will be an improved patient-physician
  relationship
• Better sense of autonomy
• Better trust in physicians
• Overall better patient satisfaction

67
Conclusion

• There still remains complex regarding informed
  consent
• Who should be the driving force to implementing
  consent?
• Who should regulate the process?
• Who should be responsible for getting informed
  consent?