Plasma FFP Evidence based usage

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Plasma (FFP) Evidence based usage

• Jed B. Gorlin MD, MBA
• Memorial Blood Centers
• AABB-Jeddah Saudi Arabia 4/09

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Goals and Objectives

• Review AABB TRALI guideline and update
• Review evidence based medicine ordering
  guidelines
• Discuss studies of plasma usage
• Discuss use and abuse of plasma

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Transfusion Recipient Fatalities 03-08-FDA

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TRALI

• Popovsky and Moore, 1985, 36 cases
• Respiratory distress
• Hypoxemia
• Hypotension
• Within 16 hrs (usually within 12 hrs after
  transfusion of plasma containing blood components
• Mechanical ventilation 72
• Rapid resolution within 96 hrs 81
• Mortality 6

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Consensus Statement
TRALI is a clinical diagnosis
From Kleinman S et al. Toward an understanding
of transfusion-related acute lung injury
statement of a consensus panel.  Transfusion.
2004441774-89.
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Pathogenesis

• Priming and activation Neutrophils
• Passive transfusion of donor Antibodies of HLA
  Class I II/Granulocyte Antibodies 90 of the
  cases
• Anti-granulocyte antibodies in the recipient
  (10)
• Lipid breakdown products in the blood product
• Complement activation, release neutrophil enzymes
• Damage endothelial lining
• Pulmonary edema (exudate)

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Gajic O, Moore SB. Mayo Clin Proc. 200580766
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Transfusion Related Acute Lung Injury (TRALI)
Who Is at Risk?

• Male Female 11
• No age predilection
• No disease or diagnosis predilection
• No medication pattern

CP1155325-49
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Laboratory Testing

• Donor testing
• HLA class I II and HNA antibodies
• Broad screening test and then antibody ID
• Recipient testing
• HLA class I II typing
• neutrophil typing, if possible
• If antibody is found, perform cross--match
  (recipient cells and donor serum)
• Recipient antigen testing or crossmatch is
  necessary to implicate a donor

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UK-SHOT TRALI

• UK hemovigilance reporting-Serious hazards of
  transfusion (SHOT) on-line reporting 1999-2005
• Risk-high plasma (FFP, Platelets) 175,000
• Low cryo, RBC 1500,000-gt1,000,000
• All cases investigated including both male and
  female donors. Only female donors with antibodies
  against patient antigens were implicated.
• UK SHOT conclusion Femme Fatale!

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UK-NBS National Blood Service

• Avoid additional questions label M, F
• Implemented male only plasma 2004 but no
  inventory replacement-note some US imported
• Marked reduction in incidence of plasma
  associated TRALI noted from 2005-7.
• Recent reports up, but deaths still down
• (Platelets in UK are most derived from whole
  blood using the buffy coat method. They are
  pooled but then resuspended in male plasma)

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AABB TRALI guidance-Nov 06

• Blood Centers must provide reduced risk (for
  TRALI) products
• 11/07-Must have implemented strategy to reduce
  TRALI from plasma
• 11/08-Platelet strategy
• Not specific about what strategy
• Hospitals Use evidenced-based medicine
  transfusion guidelines Reduce the Use
• Improve reporting of severe adverse events (SAE)

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Relative risk of components

• HIGH
• FFP from whole blood or apheresis
• FP-24
• Plasma, Cryoprecipitate reduced
• Apheresis platelets
• Whole blood

• LOWER
• Red Blood Cells from whole blood or apheresis
• Platelets prepared from whole blood
• Cryoprecipitate

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Testing for WBC antibodies
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Approach to whole blood plasma

• Plasma-Whole blood-
• Divert female plasma from A, B, O donors to
  recovered plasma, selectively use male plasma for
  FFP (or 24hour FP)-done June 2007
• Ability to do this is predicated upon RBCPlasma
  usage gt 31 (Note some RBC are collected as 2
  unit collections and need to have reserves for
  inventory management)

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AABB TRALI guidance

• 11/07-Must have implemented strategy to reduce
  TRALI from plasma
• Most centers using male whole blood plasma
• 11/08-Platelet strategy may screen for HLA
  antibodies in apheresis platelets (or AB plasma)
• Ordering practitioners should be using evidenced
  based guidelines Reduce the Use
• Improve reporting of Severe Adverse Events
• Revised guideline requires some intervention, not
  full implementation by target date

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Transfusion Guidelines

• The purpose of quality assurance is to maximize
  patient care and minimize risk.
• The most risk-free transfusion is the one never
  given. Hence, eliminating unnecessary
  transfusions yields many benefits
• Minimize risks from transfusion
• Economic savings
• Saves blood products for those recipients who
  most need them.

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Review of FFP use

• Prevent bleeding in patients with abnormal
  coagulation results who need urgent surgery or
  procedure
• Treat bleeding in patients with abnormal
  coagulation test results
• Thrombotic thrombocytopenic purpura
• Not indicated fluid resuscitation, nutrition

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AABB FFP guidance

• An evidenced based plasma transfusion guidance is
  being prepared
• Studies including both retrospective and
  prospective are being reviewed for their level of
  evidence and outcomes
• Various indications, prophylactic, interventional
  are being evaluated

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FFP for intervention

• Segal Transfusion (2005) 451413
• No evidence that abnormal coagulation tests
  predicted bleeding with invasive procedures
• Dzik The James Blundell Award Lecture 2006
  transfusion and the treatment of haemorrhage
  past, present and future
• Transfus Med. 2007 Oct17(5)367-74.

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Lack of correlation between blood loss and coag
values
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Prospective Review

• Many transfusions occur in ER or OR where
  clinical information may not be readily available
  to transfusion service.
• Rapidly bleeding patient may not have a low hct,
  or a low hct is documented using point of care
  (POC) testing, not apparent to blood bank

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Adult Plasma Guidelines

• Given to correct multiple deficiencies of plasma
  coagulation factors
• PT or PTT gt 1.5 times mean normal
• (Not for INRs of 1.2 or 1.3!!!!!)
• Diffuse microvascular bleeding in patient
  transfused gt 1 blood volume (massive transfusion)
  (but check platelets first!)
• Therapeutic apheresis for TTP

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Plasma mistransfusion

• 2 units of plasma may be insufficient to correct
  significant coagulopathy. Patients with INR gt2
  typically need 10-15cc/kg
• If fibrinogen is very low (lt50) you probably
  cant transfuse enough FFP to correct
  coagulopathy-you need a concentrated fibrinogen
  source instead cryoprecipitate
• INRs lt 1.5 rarely need correction and correction
  is rarely achievable by FFP transfusion!

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MBC-HCMC- Plasma usage reduction project
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FFP transfusions volume Tx

• Transfusion (2006) 461921 Population-based audit
  of fresh-frozen plasma transfusion practices
  Riikka Palo et al.
• Clearly, physicians order FFP in multiples of 2
  instead of a more physiologic order of 10-15
  ml/kg!

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TABLE 1. FFP and RBC use per 1000 population and
FFP use per 100 RBC units
Transfusion (2006) 461921 Population-based audit
of fresh-frozen plasma transfusion practices
Riikka Palo et al.
 
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Mean INR of Fresh Frozen Plasma (n  20 units)
Fresh frozen plasma is ineffective for correcting
minimally elevated international normalized
ratios L L. Holland, T M. Foster, R A. Marlar, J
P Brooks, Transfusion 2005 45 1234 
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Change in INR after plasma transfusion
N10 within transfusions guidelines
(INRgt1.6)(open circles) N68 units outside of
guidelines, 22 Pts, 10 mL/kg (mean INR pre1.37,
post1.32)
Fresh frozen plasma is ineffective for correcting
minimally elevated international normalized
ratio. L L. Holland et al Transfusion 2005
45 1234 
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Dzik . Chap 1. 2005 Mintz. Transf Ther AABB.2005
p 5
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Effect of FFP on PT in pts with mild coagulation
abnormalities

• Abdel Wahab O, Healy B, Dzik WH (Transfusion
  (2006) 461279-1285
• Reviewed all cases of FFP transfusion in patients
  with PT 13-17 (INR 1.1-1.85)
• ONLY 0.8 of patients (N121) normalized!
• ONLY 15 achieved ½ way correction
• Median decrease was 0.2 seconds (INR0.07)

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The effect of fresh frozen plasma in severe
closed head injury

• Etemadrezaie H, Clin Neurol Neurosurg.
  (2007)109166
• METHODS Double-blind randomized clinical trial.
  90 patients in two parallel groups FFP or normal
  saline (N/S). Severe closed head injury (GCS lt
  8), no mass lesion required evacuation and no
  history of coagulopathy.
• RESULTS 44 FFP 46 N/S. New intracerebral
  hematoma more common in the FFP (p0.012). Both
  groups showed similar frequency of poor outcome
  (p0.343). The mortality was significantly more
  common in the FFP group than in the N/S group
  (63 versus 35) CONCLUSION early empirical FFP
  lead to adverse effects, including an increase in
  the frequency of delayed traumatic intracerebral
  hematoma and increased mortality.

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FFP in trauma

• Multiple studies both in military and civilian
  trauma document correlation of better outcomes
  with prevention of dilutional coagulopathy in
  massive, and especially blunt trauma
• Meta-analyses of trauma trials do observe trends
  toward superior outcome

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Ratio of Blood Products Transfused Affects
Mortality in Patients Receiving Massive
Transfusions in Civilian Hospitals