plasma and pccs nearly there · 2017. 4. 19. · ffp indications • plasma should be administered...

Plasma and PCCsPlasma and PCCs

Dr Charles MusukaDr Charles MusukaMBChB FRCPC FRCPathMBChB FRCPC FRCPath

PlasmaPlasma

•• Constitutes 55% of blood volumeConstitutes 55% of blood volume•• Has many functionsHas many functions•• CoagulationCoagulation

PlasmaPlasma

•• Frozen PlasmaFrozen Plasma•• Fresh Frozen PlasmaFresh Frozen Plasma

Frozen PlasmaFrozen Plasma

•• DifferenceDifference

Fresh Frozen PlasmaFresh Frozen Plasma•• ComponentsComponents

FP/FFPFP/FFP

•• Plasma transfusion should be considered Plasma transfusion should be considered for patients with acquired multiple for patients with acquired multiple coagulation factor deficiencies under the coagulation factor deficiencies under the following circumstances:following circumstances:

FFP usesFFP uses

•• a. Plasma is recommended when serious a. Plasma is recommended when serious bleeding has occurred or when preparing bleeding has occurred or when preparing for an emergency surgical or in patients for an emergency surgical or in patients with vitamin K deficiency or on warfarin with vitamin K deficiency or on warfarin therapy with significantly increased PT, therapy with significantly increased PT, INR or PTT. INR or PTT.

FFP usesFFP uses

•• bb. Plasma is recommended when there is . Plasma is recommended when there is actual bleeding in patients with liver actual bleeding in patients with liver disease and increased PT, INR or PTT. disease and increased PT, INR or PTT. Plasma may be administered to prepare Plasma may be administered to prepare for surgery or liver biopsy when the results for surgery or liver biopsy when the results of PT, INR or PTT or other appropriate of PT, INR or PTT or other appropriate coagulation assays are deemed coagulation assays are deemed sufficiently abnormal.sufficiently abnormal.

FFP indicationsFFP indications

•• Plasma is recommended in patients with Plasma is recommended in patients with acute disseminated intravascular acute disseminated intravascular coagulation with active bleeding coagulation with active bleeding associated with increased PT, INR or PTT, associated with increased PT, INR or PTT, provided that the triggering condition can provided that the triggering condition can also be treated effectively. also be treated effectively.

FFP indicationsFFP indications

•• Plasma should be administered in the Plasma should be administered in the context of massive transfusion (more than context of massive transfusion (more than 1 blood volume) if there is microvascular 1 blood volume) if there is microvascular bleeding associated with a significantly bleeding associated with a significantly increased PT, INR or a PTT. If the PT, INR increased PT, INR or a PTT. If the PT, INR or PTT cannot be measured quickly, or PTT cannot be measured quickly, plasma may be transfused in an attempt to plasma may be transfused in an attempt to stop diffuse nonsurgical bleeding. stop diffuse nonsurgical bleeding.

•• Plasma should be used in patients with Plasma should be used in patients with congenital or acquired deficiencies of a single congenital or acquired deficiencies of a single coagulation factor only when DDAVP or coagulation factor only when DDAVP or appropriate factor concentrates are ineffective or appropriate factor concentrates are ineffective or unavailable. Plasma should be used in these unavailable. Plasma should be used in these patients only when bleeding has occurred or is patients only when bleeding has occurred or is reasonably expected to occur from surgery or reasonably expected to occur from surgery or other invasive procedures. Plasma may be used other invasive procedures. Plasma may be used depending on the specific factor involved. depending on the specific factor involved.

MisuseMisuse

•• Nutritional SupportNutritional Support

Complications of FP/FFP UseComplications of FP/FFP Use

•• DonorDonor•• ABOABO•• Patient IssuesPatient Issues•• Special issues: TRALI, TACO, Special issues: TRALI, TACO,

RisksRisks

•• Disease transmission, Disease transmission, •• Allergic reactions, Allergic reactions, •• TraliTrali•• Allergic reactionsAllergic reactions•• Transfusion Associated Cardiac OverloadTransfusion Associated Cardiac Overload•• Alloimmunisation Alloimmunisation

Table 1

Table 1. Recommendations for Treating Oral Anticoagulation Patients Who Need Their INR Decreased Because of Actual or Potential Bleeding

Copyright © 2010 Anesthesiology. Published by Lippincott Williams & Wilkins. 15

Perioperative Hemostatic Management of Patients Treated with Vitamin K Antagonists�

Levy, Jerrold H.; Tanaka, Kenichi A.; Dietrich, Wulf

Anesthesiology. 109(5):918‐926, November 2008.doi: 10.1097/ALN.0b013e3181895bd8

DoseDose

•• No good randomised trialsNo good randomised trials•• Most published consensus documents Most published consensus documents

recommended 10recommended 10--15ml/kg15ml/kg•• Essential to monitor efficacyEssential to monitor efficacy•• Repeat Repeat

Table IV. Haemostatic factor content of thawed fresh-frozen plasma (FFP), and after storage at 4°C. A typical unit of 300 ml includes (IU/ml), except fibrinogen (g/l).

Levels when freshly thawedLevels when freshly thawed Levels at 24Levels at 24 hh Levels at 5Levels at 5 dd

FibrinogenFibrinogen 22··6767 22··2525 22··2525

FIIFII 8080 8080 8080

FVFV 8080 7575 6666

FVIIFVII 9090 8080 7272

FVIIIFVIII 9292 5151 4141

FIXFIX 100100

FXFX 8585 8585 8080

FXIFXI 100100

FXIIFXII 8383

FXIIIFXIII 100100

Antithrombin IIIAntithrombin III 100100

Is FFP clinically effective? A Is FFP clinically effective? A systematic review of randomised systematic review of randomised controlled trials.controlled trials.

•• Dr S J Stanworth, John Radcliffe Hospital, Dr S J Stanworth, John Radcliffe Hospital, Oxford, UK.Oxford, UK.

•• BloodmedBloodmed

Epidemiology Epidemiology

• FDA(2004):the leading cause of transfusion-related death in the United States

►► Mortality rate:5Mortality rate:5--8%8%►► Incidence: not well establishedIncidence: not well established Underrecognition and underreportingUnderrecognition and underreporting

►► All plasmaAll plasma--containing blood and blood containing blood and blood compartmentscompartments•• 1/5,000 blood & blood component1/5,000 blood & blood component•• 1/2,000 plasma1/2,000 plasma--containing componentcontaining component•• 1/7,900 units of FFP1/7,900 units of FFP•• 1/432 units of whole blood derived platelets1/432 units of whole blood derived platelets

Clinical Presentation

• Sudden onset, within 6 hours, but usually begin within 1~2 hours, of respiratory distress after transfusion

Risk FactorsRisk Factors

•• No definite risk factors for TRALINo definite risk factors for TRALIImplicated in some, not all:Implicated in some, not all:–– prolonged storage of transfused productsprolonged storage of transfused products–– administration of fresh FFPadministration of fresh FFP–– an underlying condition such as recent surgeryan underlying condition such as recent surgery–– cytokine treatmentcytokine treatment–– ThrombocytopeniaThrombocytopenia–– massive blood transfusionmassive blood transfusion

–– active infectionactive infection

•• Dose Dose not not correlate with the correlate with the volume volume of plasma of plasma infused or the titer of the antiinfused or the titer of the anti--leukocyte antibodyleukocyte antibody

Prevention Prevention

•• Producing FFP only from male donorsProducing FFP only from male donors•• Screening previouslyScreening previously--pregnant and pregnant and

previouslypreviously--transfused apheresis donors for transfused apheresis donors for HLA antibodiesHLA antibodies

•• Improving tests for the detection of white Improving tests for the detection of white blood cell antibodies blood cell antibodies

Prothrombin Complex Prothrombin Complex ConcentratesConcentrates

•• Produced by fractionationProduced by fractionation•• Rich in Vitamin K dependant clotting Rich in Vitamin K dependant clotting

factors: II, VII, IX, X as well as the factors: II, VII, IX, X as well as the anticoagulants Protein C and S.anticoagulants Protein C and S.

•• For most of the last 40 years PCCs were For most of the last 40 years PCCs were the mainstay for the treatment of the mainstay for the treatment of Haemophilia BHaemophilia B

•• Activated PCCs are used in the treatment Activated PCCs are used in the treatment of Haemophilia A patients with inhibitors.of Haemophilia A patients with inhibitors.

Processing of FP/FFP

24

Cryoprecipitate-poor plasma

Heparin and pH adjustment

Ion Exchange Chromatography

S/D Virus inactivation

Ion exchange chromatography

Virus removal: Nanofiltration

Diafiltration

Ultrafiltration

Heparin and pH adjustment

Sterile filtration, filling

Lyophilisation

PCC

Table 3

Table 3. Studies Comparing PCCs with FFP for Anticoagulation Reversal





Complications

Author, year (reference) Study design Inclusion criteria N. of patients Thromboembolic events (%)

Evans, 2001 (37) Prospective non‐randomised Major bleeding and INR > 14 10 0/10

Preston, 2002 (38) Prospective non‐randomised Major bleeding or need for urgent

reversal of anticoagulation42 1/42 (2.4)

Lorenz, 2007 (39) Prospective cohort Need for urgent reversal of

anticoagulation8 0/8

Pabinger, 2008 (40) Prospective multicentre Emergency anticoagulation reversal 43 1/43 (2.3)

Bruce, 2008 (41) Retrospective analysis Severe bleeding 24 0/24

Schick, 2008 (42) Retrospective Major bleeding or urgent

anticoagulation reversal50 0/50

Staudinger, 1999 (43) Prospective Overt bleeding or planned invasive

procedures in critically ill patients16 0/16

Lorenz, 2003 (44) Prospective multicentre Acute bleeding or surgical/invasive

procedures in patients with liver disease

22 0/22

Total 165 2/215 (0.9)

Word of CautionWord of Caution

•• Many case reports in literature in which Many case reports in literature in which patients with severe Haemophilia B have patients with severe Haemophilia B have developed thrombotic events.developed thrombotic events.

•• Blamed on the Blamed on the ““cocktailcocktail”” nature of PCCs.nature of PCCs.•• New indications are to treat patients who New indications are to treat patients who

already have one or more prothrombotic already have one or more prothrombotic risk factors.risk factors.

PCCs todayPCCs today

•• New recombinant FIX concentrates are New recombinant FIX concentrates are availableavailable

•• The use in Haemophilia B is waningThe use in Haemophilia B is waning•• Vitamin K antagonistsVitamin K antagonists

Table 2

Table 2. Constituents of Commercially Available PCCs (Based on Product Labeling)





Brand Brand (Company)(Company)

PurificationPurification Viral inactivationViral inactivation Clotting factors Clotting factors (U/mL)(U/mL)

Anticoagulant proteins Anticoagulant proteins (U/mL)(U/mL)

IIII VIIVII IXIX XX PCPC PSPS ATAT HeparinHeparinUman Complex Uman Complex D.I. (Kedrion)D.I. (Kedrion)

IonIon--exchange exchange chromatographychromatography

Solvent/detergent + Solvent/detergent + 100100°°C for 30 minC for 30 min

2525 -- 2525 2020 -- -- NQNQ NQNQ

Prothromplex Prothromplex TIM 3 (Baxter)TIM 3 (Baxter)


Vapour heat 60Vapour heat 60°°C C for 10 h, 80for 10 h, 80°°C for 1 C for 1 hh

3030 -- 3030 3030 -- -- -- 0.50.5

Confidex (CSL Confidex (CSL Behring)Behring)


Pasteurization 60Pasteurization 60°°C C for 10 h + for 10 h + nanofiltration (75 nanofiltration (75 nmnm--35 nm)35 nm)

2020––4848

1010––2525

2020––3131

2222––6060

1515––4545

1313––3838

0.60.6 0.50.5

Table I

PCCs vs FFPPCCs vs FFP

•• Rapid reversal of INRRapid reversal of INR•• Small volumeSmall volume•• Contains HeparinContains Heparin•• Pooled product and Pooled product and

therefore exposure to therefore exposure to hundreds of donorshundreds of donors

•• Dual viral inactivation Dual viral inactivation steps (do not cover steps (do not cover unencapsulated viruses)unencapsulated viruses)

•• Small costSmall cost•• Paid donors (some Paid donors (some

PCCs)PCCs)

•• Delay in thawingDelay in thawing•• Once thawed, limited Once thawed, limited

shelf lifeshelf life•• Large volumes requiredLarge volumes required•• ABO blood group ABO blood group

required.required.•• No viral inactivation stepsNo viral inactivation steps•• Reduced donor exposureReduced donor exposure•• TRALITRALI•• Lower thrombotic Lower thrombotic

potentialpotential•• Traceability of donorsTraceability of donors•• Most centres have Most centres have

experience using FFP.experience using FFP.

plasma and pccs nearly there · 2017. 4. 19. · ffp indications • plasma should be administered...

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