Use of FFP & Cryoprecipitate (2018)

 

Intro

 

Fresh Frozen Plasma

-       Since 2012 there has been a reduction in the use of FFP in UK, but a rise in SD-FFP use

-       2009 audit – 43% of FFP transfusion given as prophylaxis before procedures (not good)

Cryoprecipitate

-       Use is increasing, doubled since 2003. Reason is unclear.

 

Indications

 

FFP Indications

-       Correction of multi-factor deficiencies in major haemorrhage / DIC with bleeding

-       Plasma exchange only when for TTP

-       Limited role as prophylaxis prior to liver biopsy

-       Single factor deficiencies if no fractionated product available – i.e. Factor V

 

FFP NOT Indicated

-       DIC without bleeding

-       Warfarin reversal without bleeding

-       Correcting vit K deficiency in neonates or ITU adults.

-       Correction of hypovolaemia

 

Complications

 

Complications of particular concern with FFP

-       TRALI (reduced by use of male donors)

-       Donor anti-A and anti-B

-       Allergic reactions

-       vCJD (non-UK donors + Pathogen reduction for anyone born after 1.1.1996)

 

Choice of FFP

 

-       No difference between FFP recovered from whole blood versus plasmapheresis

-       If likely to receive multiple repeat transfusions

o   Consider pathogen-reduced plasma (MB or SD)

o   Consider Hep A and Hep B vaccination

-       Group O FFP must only be given to Group O patients

-       A,B,AB patients should receive there own group as first choice, but different group FFP may be used if high-titre negative.

-       Products of any Rh D group may be transfused, no anti-D prophylaxis is required.

FFP.jpeg

 

Preparation, Contents & Storage

 

FFP

-       180-400ml per pack

-       From male whole blood or apheresis donors

-       Not from first time donors

-       Na 48 mmol/unit, K 1.0 mmol/unit, glucose, calcium (low), citrate, lactate, phosphate

-       Collection rapidly frozen to -25oC

-       Plastic packs brittle whilst frozen, handle with care

-       Can be stored for 36 months at below -25 oC

-       Factor content requirement

o   Minimum of 70 IU/ml of FVIII in at least 75% of tested packs

 

Cryoprecipitate

-       1 unit = 20-60ml.

-       1 pool / 1 adult dose = 5 units = 200-280ml

-       The cryoglobulin fraction obtained from plasma by slow thawing of a single FFP donation at 4 degrees overnight (one unit). This is then re-suspended in small volume of plasma.

-       FVIII, VWF, FXIII, fibronectin and fibrinogen

-       Can be stored for 36 months at below -25 oC

-       Factor content requirement

o   Minimum of 70 IU/ml of FVIII & 140mg of FGN in at least 75% of tested packs

 

Pathogen Reduction

-       All patients born after 1st Jan 1996

-       Good at reducing levels of enveloped viruses

-       But not good at reducing non-enveloped viruses (Hep A/E, Parvo). Units tested for these.

-       MB-FFP (NHSBT) has 30-40% lower FVIII, FXI and fibrinogen activity

-       SD-FFP (Octaplas) also has lower Protein S and antiplasmin

 

Thawing FFP

 

Thawers

-       Dry heat agitators – limited capacity

-       Microwave – limited capacity, ?risk of hot spots

-       Water bath – most common, pack does not come into direct contact with water

 

Temperature of thawing

-       33-37oC recommended.

-       Ranges from 4 – 45oC have been used

 

Storage after thawing

 

Fresh Frozen Plasma

-       Store at 2-4oC

-       Transfuse within 24 hours of thawing

o   Transfuse within 4 hours of removal from temp-controlled storage

-       Pre-thawed plasma can be used up to 120 hours in major trauma.

o   It can be accepted back into temp-controlled storage on one occasion of <30 min

o   30 min is based on expert opinion. Further work ongoing. Advice may change.

o   Purpose of pre-thawing is to reduce delays in major trauma

o   With exception of protein C, all factors decrease between 24 and 120 hours, FVIII most rapidly and to the greatest extent.

 

MB-FFP

-       The shelf-life is not extended beyond 24 hours, due to already lower factor levels.

SD-FFP

-       Licensed medicinal product and so directed by manufacturer.

 

Cryoprecipitate

-       Use immediately once thawed

-       Store at ambient temperature for maximum of 4 hours

 

FFP in non-bleeding patients

 

Muller 2015

-       Non-bleeding, critically ill patients with INR 1.5-3.0 about to undergo invasive procedure

-       Randomised to 12ml/kg FFP or no FFP

-       FFP only marginal improvement in factor levels

-       Thrombin generation was unaffected, and anticoagulant levels rose

 

Unfortunately, no quality evidence yet to recommend abandoning use of FFP prior to procedures, although it seems that is probably safe. Someone needs to do the study!

 

Drolz 2016 (Liver disease)

-       PT bore no relevance to bleeding risk in acutely ill cirrhotic patients on ITU

-       FGN <0.6 and plt <30 were the most important predictors of bleeding

 

Garcia-Tsao 2017 (Variceal bleeds)

-       American association for the study of liver disease

-       Recommend against FFP in variceal bleed

-       May aggravate bleeding through an increase in portal hypertension