Ravi Sarode, MD

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(Mis)use of Plasma in Clinical Practice

• Ravi Sarode, MD
• Director, Transfusion Medicine and Hemostasis
  Reference Laboratory
• Professor, Department of Pathology
• UT Southwestern Medical Center
• Dallas, Texas

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Plasma Consumption in the USA

• More than 3 million units annually
• Mostly, before invasive procedure or to correct
  abnormal coagulation test result in ICU
• Pre-surgical hemostatic assessment mostly done by
  labs rather than by good clinical history

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Palo et al Transfusion, 2006
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Why do Physicians Order FFP?
Dzik and Rao, Transfusion, 2004
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FFP Fails to Correct PT/INR in Cirrhosis

• 80 patients with elevated INR
• Indications for FFP
• 41 for prophylaxis
• 59 for bleeding
• Dose 75 received 2-4 units 25 gt 4 units
• Result With FFP, 89 of patients failed to
  correct PT to within 3 secs above normal range.
• Conclusion FFP frequently fails to correct INR.

Youssef et al., Am J Gastro 2003 98 1391.
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No Correlation Between Pre-biopsy PT and
Duration of Bleeding After Liver Biopsy
Ewe. Digestive Dis Sciences 1981 26 388
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Observational (Retrospective) Studies of PT/INR
Prior to Liver Biopsy
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What happens when.

• Hemoglobin is 11 g/dl? (gt12.5)
• Dont transfuse red cells!
• Platelet count is 105 K? (gt150 K)
• Dont transfuse platelets
• Creatinine is 2.1 mg/dl? (lt1.2 mg/dl)
• Dont do dialysis
• Why, then, transfuse FFP for a PT that is a few
  seconds long ????

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Evaluation of Hemostasis
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Normal Hemostasis

• Complex interaction between
• Procoagulants
• Natural anticoagulants
• Fibrinolytic system
• Platelets
• Endothelium

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PT and PTT

• Tests were developed to diagnose patients with
  bleeding disorder
• High pretest probability
• Never shown to assess bleeding risk in
  non-bleeding patient!!

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Prothrombin Time
Pt Plasma
Tissue Thromboplastin and Ca
Sources Brains Human Rabbit Goat Placenta
Human Recombinant
Clotting time 9 - 12.5
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What is INR?
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INR is the prothrombin time ratio that, by
calculation, would have been obtained, if the
original WHO Reference Thromboplastin had been
used to perform the PT
These plasmas were from patients on oral
anticoagulation
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PT of Patient PT of Control
PTR

24 12
2.0

PTR ISI
2.0 2.0
4.0

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Therapeutic Safety Range
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INNOVIN - The New Reagent

• Recombinant thromboplastin
• ISI 0.98-1.02
• Gives shorter PTs in normal people
• Very sensitive to vit K-dependent factor
  deficiencies, especially FVII
• Greater prolongation of PT
• On warfarin and liver diseases

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Hemostatic Factor Levels
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Indications for Plasma Therapy

• TTP
• Coagulopathy with bleeding
• Coagulopathy during surgery
• Reversal of coumadin overdose
• Ideal prothrombin complex concentrate
• Rare congenital factor deficiencies
• Often misused
• To correct mild to moderate abnormal PT/INR
  without bleeding
• As volume expander

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Published data provide no evidence-based guidance
for use of pre-procedure FFP (or platelet
transfusion) among patients with mild-moderate
coagulation test abnormalities
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I need FFP NOW because the PT is slightly
long!!!!!
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Neurosurgery Study Parkland Memorial Hospital

• Aims To show patients with a mild abnormality of
  INR 1.3 - 1.7 (N 38)
• Have hemostatically normal FII, FVII FVIII
• Do not require plasma therapy
• Plasma requests for 2 - 6 units
• Citrated plasma frozen within 8 hrs

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Results 1 (N38)
FVII of 15-25 recommended for surgery In
Kitchens-Consultative Hemostasis Thrombosis
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Results 2
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Effects of Study

• Results presented at Neurosurgery Grand Rounds
• Drastic reduction (85) in FFP orders for
  prophylactic plasma transfusions
• One year follow-up orders for FFP remain 74
  fewer than in pre-study period

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Parkland Hospital, DallasTransfusion Medicine
Practice

• 960 bed county teaching hospital
• BURC established Evidence-Based transfusion
  criteria
• Since 2003, TMR involved in non-RBC transfusion
  therapies
• Goals
• To reduce unnecessary transfusions
• Advise appropriate product and dose
• Reduce TRALI

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Patient received 10 FFP within 24 hours?
Notify the resident
Yes
Yes
Patient in the OR?
No
No
Fill order
Yes
INR result not available or gt12 hours old?
No
Yes
Is the INR lt1.6?
Notify resident
No
Yes
Is the INR gt5.0?
No
Yes
Have gt6 FFP been dispensed within the previous 12
hours?
No
Thawed Plasma Triage
Fill order
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Platelet Triage
Patient in the OR?
All ER Platelet Orders require Triage to avoid
TX to a TTP pt
Yes
No
Patient received 2 doses within 24hrs?
PLT gt20,000
Yes
No
Notify resident
Fill Order
No
Yes
Patient received 2 doses within 24 hrs?
Yes
Issue 3rd dose notify resident
No
Fill Order
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Yearly RBCs, TP and PLT Usage
60 reduction in TP PLT
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Yearly Hospital Admissions, Trauma, and OR
Procedures
2000 2001 2002 2003
2004 2005 2006
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Massive Transfusion Protocol
Goals 1. Provide rapid blood component
therapy 2. Prevent or treat coagulopathy
early 3. Reduce blood wastage
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Blood Products Shipments
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Pre-MTP vs. MTP
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Appropriate Products

• Cryoprecipitate
• Antifibrinolytic agents
• Protamine for heparin-induced bleeding
• FFP may make bleeding worse
• Prothrombin complex concentrates for reversal of
  coumadin effect

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Take Home Message

• Significant misuse of plasma
• Blood banks should practice transfusion medicine
  rather than function simply as blood dispensing
  units
• Greater need for clinicians and medical
  students education in transfusion medicine and
  hemostasis
• They like it and respond to education

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