Manchester and Lancaster Regional

FFP

Elizabeth LoveNorth West England and North Wales RTC

Education symposium16 April 2006

Guidelines for the use of fresh-

cryosupernatant

-28http://www.bcshguidelines.com/pdf/freshfrozen_28

Indication codes derived from BCSHguidelines

F1 Single coagulation factor deficiencies/factorconcentrate unavailable (Factor V)

F2 Immediate reversal of warfarin in presence of severebleeding (not defined) PCC preferred.

F3 Acute DIC, bleeding, abnormal coagulation tests

F4 Thrombotic thrombocytopenic purpura (Solventdetergent-treated FFP preferred)

F5 Massive transfusion, guided by timely clotting testsincluding POCTLiver disease: prolonged PT: prevention of bleeding,bleeding, prophylaxis for invasive procedure(ambiguous)

• Hypovolaemia

• Plasma exchange (except for TTP)

• Reversal of prolonged INR in absence ofbleeding

Background• Disappointing

results NBSnational audit2001

• Failure toimplement BCSHguidelines 2004

•regional FFPissues 2005

Background

MonthUnits Issued (2005)

February 1647March 1698April 1939May 2177June 1914July 1412

Frozen Component issues 2004/2005 -2006/2007

Frozen Components Average Weekday Issues By Month - April 2004 onwards

1200

1250

1300

1350

1400

1450

1500

Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar

Month

Ave

rage

Wee

kday

Issu

es

2004/05 2005/06 2006/07 Plan

Data to 18th Mar 2007

•of results to hospitals via RTC and HTCChairs.

• Determine appropriateness of FFPtransfusions.

•• Identify potential wastage.• Ensure coagulation screening is performed

pre and post Transfusion.

Method• All hospitals served by NBS Manchester and Lancaster

were invited to participate• -31

May 2006).• Prospective and retrospective data collection.• Use of FFP Indication Codes (F1-F6) derived from

BCSH guidelines plus– bleeding, clotting abnormal, other indication– other

•

Results

• 19/25 hospitals participated•

10-20/hospital)•

annual adult FFP issues in the region– Caveat: FFP shelf life is 24 months so

issues may not accurately reflect usagebut assume re-stocking

Does your Trust have an FFP Policy?

Fig.1 Hospitals with FFP Policy (n=19)

13

15 YesNoNR

79%

16% 5%16%

Mean 61 yrs, range 2 days -93 years

5 children (age 2 days - 1 year

Fig. 3 Patient Age (n=302)

5 1027 29

44

7862

44

30

20

40

60

80

100

<16 16-29 30-39 40-49 50-59 60-69 70-79 Over80

NRAge (Years)

Num

ber

ofpa

tient

s

Weight of patients:

Mean: 75kgs Range 2-134 kgs NR=44%mean 75 kg; range 2-4 kg; 14% > 100 kg

Fig. 4 Weight (n=302)

020406080

100120140160

1-40 kgs 41-60 kgs 61-80 kgs 81-100kgs

Over 100kgs

NR

Weight (kg)

Num

ber

ofpa

tient

s

Location in hospital

Fig. 5 Location of patient

5 7

27

2 1

9

47

205

101520253035404550

A &E HDU ITU Other Out-patients

Theatre Ward Notrecorded

Locations

Per

cent

age

ofpa

tient

s

Fig. 6 Broad Speciality (n=302)

05

1015202530354045

%Pa

tient

s

Haematology/Medical Oncology

Medicine

Obstetrics

Paediatrics

Surgery

Other/NR9%

41%

2% 2%

42%

4%

Medication within 24 hours prior to

Alone/incombination

•61* (21%)

• Heparin32 (11%)

• Vitamin K81 (28%)

MedicationPatients

%

VitaminK 52 18Warfarin 36 12Heparin 21 7Anti-platelet 14 5Anti-fibrinolyticsVitaminK&WarfarinVitaminK&HeparinVitaminK&Anti-plateletVitaminK&Warfarin&Anti-plateletVitaminK&Warfarin&Heparin&Anti-plateletWarfarin&HeparinWarfarinandAnti-plateletHeparin&Anti-plateletNone

0204311125

131

0711

0.30.30.31245

* This no. differs from no. treated for indication F2

•No data in10% pre- and15% post-transfusion

•Furtheranalysis oftiming anddegree ofcorrectionrequired

Fig. 8aPre -Transfusion Clotting Results (n=291)

0 10 20 30 40 50 60 70 80 90

%Patients

None

All

Fib

APTT

PT/INR

Fig. 8b Post Transfusion Clotting Results (n=291)

0 10 20 30 40 50 60 70 80

%Pat ient s

None

All

Fib

APTT

PT/INR

How many units of FFP were transfused?Fig. 7 Units Transfused (n=1018)

Transfused

Not Transfused

95%

•initial intention to treat

•49 (5%) units not transfused, presumed wasted

FFP units requested/transfused per hospitalHospID Units Requested Units Transfused % Transfused

1 64 52 812 77 77 1003 63 60 954 61 60 985 54 53 986 26 26 1007 65 61 948 67 63 949 57 57 100

10 37 37 10011 82 78 9512 66 65 9913 28 28 10014 30 26 8715 84 80 9516 33 33 10017 25 25 10018 63 60 9519 36 28 67

Total 1018 969 95

Clinical indications recorded

In some cases > 1 indication was selected. We havemade a judgement, from the data provided, about the

predominant code

Indication Code Number %F1 Replacement of Specific Coagulation Factor Deficiencies 11 4F2 Reversal of Warfarin Effect 64 22F3 Disseminated Intravascular Coagulation (DIC) 23 8F4 ThromboticThrombocytopenic Purpura (TTP) 0 -F5 Massive Transfusion (1.5 x blood volume) 45 15F6a Liver Disease 31 11F6b Liver Disease – tocover invasive procedure (biopsy/surgery) 27 9BCO Bleeding, clotting abnormal, other reason 54 19Other Any Other Indication 32 11No Indication Recorded 4 1Total 291 100

Final panel consensusFigure 11. Panel Review including 4th Consultant (291)

020406080

100120140

Appropriatetransfusion

Inappropriatetransfusion

Split clinicalpanel decision

Not enoughinformation toform clinical

decision

Clinical Decisions

Num

bero

fpat

ient

s

40% 37%

4%

19%

Panel consensus according to indication code

Indication Total App. (no) App. (%)F1 11 6 54F2 64 2 3F3 23 21 91F4 0F5 45 No decisionF6 58 45 76Other 86 42 49Not recorded 4 1

Was the dose of FFP appropriate?Assumptions

• -15 mg/kg (or more ifclinical circumstances dictate)

• Average vol/bag (adult) = 250 ml–

268 ml (range 186-339 ml)• An initial dose of 4 bags (~1000ml) is

kg in the audit)– 67 - 100 kg @ 15 - 10 ml/kg respectively

Adequacy of FFP dosage for appropriateindications (n=113 adults)

Number %Patients with current weight recorded 7310 ml/kg dose achieved 49 6715 ml/kg dose achieved 14 19Patients without current weight recorded 404 units FFP achieved 28 70

•No weight recorded in 40/113 (35%)••31/113 (27%) given 2 units (adequate in only 2)•4/113 (3%) given 3 units (adequate in 2)

Efficacy of transfusion for appropriateindications (n=117)

Number of patientsAppropriate indications 117Pre-&post- treatment test results available 103Post-test = 12 hours after pre-test 40

C 2P 11N 26X 1

•Only 34% (40/117) could be assessed

•Correction/partial correction in 13 (32%)

•No attempt to correlate with dose

•Judged on all/any tests

•Too many unknowns therefore of limited value

Adverse reactions

• One adverse reaction was reported in–– 1/969 units of FFP (0.1%)

•

Replacement of single coagulation factordeficiencies where a specific concentrate

is not available e.g. factor V– 11 patients: ? mis-interpreted. No

further information available.

Comments about clinical indications: F2Immediate reversal of warfarin in presence of

life-threatening haemorrhage.•• 201 (21%) of FFP units transfused• 2 (3%) indicated; 5 possibly indicated (panel

split)•

bleeding - could not ascertain severityProthrombin Complex Concentrate is the

in addition to II, IX, X*1 patient = insufficient information to decide

Comments about clinical indications: F5

Massive transfusion: the use of FFP shouldbe guided by timely tests of coagulation

including near patient testingThe panel could not decide on this group of patients:

– Insufficient information– Unwilling to “give the benefit of the doubt”– There is a need to review how guidelines on the

management of massive transfusion work inpractice.

More later!

Indication Number ofpatients

No.appropriate

InappropriateSplit

No.units

F6ableeding 21 19 2 0 69F6anot bleeding 7 3 2 2 25F6ableedingstatusnot known 3 2 0 1 10F6bpre-invasiveprocedure 27 21 5 1 84Total 58 45 9 4 188

•20% of all treated patients

•19% of all FFP units

•78% appropriate - lenient assessment!

•Efficacy of treatment unclear

Comments about clinical indications: F6Liver disease: what the BCSH guidelines say

• FFP advocated by some for prevention of bleedingwhen PT is prolonged

• Response may be unpredictable• Complete normalisation of haemostatic defect may

not occur• Coagulation tests should be repeated post-infusion

to guide decision-making• No evidence to substantiate practice of only doing

liver biopsy if PT is within 4 secs of control (grade C,level IV evidence)

The guidelines are vague and evidence lacking

FFP administered outside indication codesLocation Other Indication

Bleeding, clottingabnormal other indication

Total (%)

Ward 16 20 36 (42)Theatre 2 5 7 (8)ITU 10 24 34 (40)HDU 2 5 7 (8)A&E 2 0 2 (2)Total patients 32 54 86Total FFP used 108 172 280

•

•29% of FFP transfused

•49% appropriate as judged by diagnosis and clottingtests

Indication code Number of patients Number of FFP unitsF1 Replacement of Specific Coagulation

Factor Deficiencies8 22

F2 Reversal of Warfarin Effect 9 23F3 Disseminated Intravascular

Coagulation (DIC)4 16

F4 Thrombotic ThrombocytopenicPurpura (TTP)

0 0

F5 Massive Transfusion (1.5 x bloodvolume)

15 53

F6 Liver Disease 7 28Bleeding Clotting Abnormal Other (BCO) 24 78Any Other Indication (Other) 10 36Not Recorded 2 8Total 79 264

27% of patients; 27% of FFP

43% of episodes outside recognised indication codes

Key observations (1)

Audit criterion %expected %compliance

Transfusionappropriate according toguidelines 100 40Transfusionappropriate but dosage inappropriate 0 30 *FFPrequested andusednot wasted 100 95Coagulation screenperformed pre-transfusion 100 89Coagulation screenperformed post-transfusion 100 87

* dependent on which dosage criteria used

Key observations (2)• High level of participation and

representative of ~ 94% FFP issues• Decisions not always easy - a panel of

haematologists could not agree on somecases, notably massive transfusion

• Factors which affected assessment:– lack of data: is this a reflection of lack

of documentation/failure to followguidelines/design of audit?

– mis-understanding of F codes (F1)

Key observations (3)• Management of warfarin reversal poorly

understood and must be improved• Suspicion that FFP is being used to treat

haemostatic defects associated with theuse of heparin

• Massive transfusion management - notwrong but not enough information to makean assessment against the guidelines– audit not sufficiently well-designed for this

purpose

• Liver disease and FFP - are we achievinganything?

• - ditto• “Other indications”: large group, ITU

patients prominent - ditto• Dosage - does this need to be reviewed?• What tests should be used to measure

efficacy?

Key observations (5)

Overall inappropriate use 37%• potential for savings @ £31.89/unit

adult FFP• potential for reduction of risk• but cost of under-dosing/alternative

treatment must be taken into account

• General: the RTC should develop a programme ofaction based on– education about appropriate use of FFP– measures to reduce inappropriate use– promoting further audit of specific areas

• Warfarin:– the RTC should develop a specific

– BCSH guidelines should be updated to reflectthe role of PCC

Recommendations (2)• Massive transfusion

– the RTC could act as a focus for developing anagreed regional protocol

– detailed audit of massive transfusionmanagement is needed

• Liver disease– detailed audit is needed (SHIP study may help)– BCSH guidelines should be reviewed with the

aim of providing more specific recommendations• ITU patients

– the RTC should note the findings (when

with ITU networks to disseminate best practice

Gordon HodgsonAnna BarclayBarbara StearnRebecca GerrardVikki Sandland

Paula Bolton-MaggsDavid AldersonMark Grey

Expert panel

Hospital TransfusionTeams