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The indications for transfusing fresh-frozen plasma (FFP), cryoprecipitate and cryosupernatant plasma are very limited. When transfused they can have unpredictable adverse effects. The risks of transmitting infection are similar to those of other blood components unless a pathogen-reduced plasma (PRP) is used. Of particular concern are allergic reactions and anaphylaxis, transfusion-related acute lung injury, and haemolysis from transfused antibodies to blood group antigens, especially A and B. FFP is not indicated in disseminated intravascular coagulation without bleeding, is only recommended as a plasma exchange medium for thrombotic thrombocytopenic purpura (for which cryosupernatant is a possible alternative), should never be used to reverse warfarin anticoagulation in the absence of severe bleeding, and has only a very limited place in prophylaxis prior to liver biopsy. When used for surgical or traumatic bleeding, FFP and cryoprecipitate doses should be guided by coagulation studies, which may include near-patient testing. FFP is not indicated to reverse vitamin K deficiency for neonates or patients in intensive care units. PRP may be used as an alternative to FFP. In the UK, PRP from countries with a low bovine spongiform encephalopathy incidence is recommended by the Departments of Health for children born after 1 January 1996. Arrangements for limited supplies of single donor PRP of non-UK origin are expected to be completed in 2004. Batched pooled commercially prepared PRP from donors in the USA (Octaplas) is licensed and available in the UK. FFP must be thawed using a technique that avoids risk of bacterial contamination. Plastic packs containing any of these plasma products are brittle in the frozen state and must be handled with care.

Keywords: fresh-frozen plasma, clinical use, guideline.

Clinical indications for the use of fresh-frozen plasma (FFP), cryoprecipitate and cryosupernatant (see Section 10)

Single coagulation factor deficiencies (Section 10.1)

Fresh-frozen plasma should only be used to replace single inherited clotting factor deficiencies for which no virus-safe fractionated product is available. Currently applies mainly to factor (F) V.

Multiple coagulation factor deficiencies (Section 10.2); disseminated intravascular coagulation (DIC) (Sections 10.3 and 10.4)

Fresh-frozen plasma and platelets are indicated when there are demonstrable multi-factor deficiencies associated with severe bleeding and/or DIC.

Cryoprecipitate may be indicated if the plasma fibrinogen is less than 1 g/l, although there is no clear threshold for clinically significant hypofibrinogenaemia.

Fresh-frozen plasma is not indicated in DIC with no evidence of bleeding. There is no evidence that prophylactic replacement regimens prevent DIC or reduce transfusion requirements.

Thrombotic thrombocytopenic purpura (TTP) (Section 10.5)

Single volume daily plasma exchange should be commenced at presentation (grade A recommendation, level Ib evidence) and ideally within 24 h (grade C recommendation, level IV evidence). Daily plasma exchange should continue for a minimum of 2 d after remission is obtained (grade C recommendation, level IV evidence).

Reversal of warfarin effect (Section 10.6)

Over-anticoagulation from excessive effects of warfarin should be managed according to the British Committee for Standards in Haematology Guidelines (BCSH, 1998). FFP has only a partial effect, is not the optimal treatment, and should never be used for the reversal of warfarin anticoagulation in the absence of severe bleeding (grade B recommendation, level IIa evidence).

Vitamin K deficiency in the intensive care unit (ICU) (Section 10.7)

Fresh-frozen plasma should not be used to correct prolonged clotting times in ICU patients; this should be managed with vitamin K (grade B recommendation, level IIa evidence).

Liver disease (Section 10.8)

Fresh-frozen plasma is advocated by some for the prevention of bleeding in patients with liver disease and a prolonged prothrombin time (PT), although the response may be unpredictable and complete normalization of the haemostatic defect does not always occur.

If FFP is given, coagulation tests should be repeated postinfusion to guide decision-making.
There is no evidence to substantiate the practice in many liver units of undertaking liver biopsy only if the PT is within 4 s of the control (grade C recommendation, level IV evidence).

Surgical bleeding and massive transfusion (Section 10.9)

Whether and how much FFP should be used for treating a patient with massive blood loss should be guided by timely tests of coagulation, including near-patient tests. FFP should never be used as a simple volume replacement in adults or children (grade B recommendation, level IIb evidence).

Paediatric use of FFP (Section 11.0) (see BCSH, 2004)

Children born after 1 January 1996 should only receive pathogen-reduced FFP (PRFFP) (see Section 3).

When bleeding due to haemorrhagic disease of the newborn (HDN) occurs, FFP 10–20 ml/kg is indicated, as well as intravenous vitamin K. Prothrombin complex concentrate (PCC) would reverse the defect, but there are no data to guide dosage in this situation (grade C recommendation, level IV evidence).

Neonates with coagulopathy who are bleeding, or who are about to undergo an invasive procedure, should receive FFP and vitamin K (grade C recommendation, level IV evidence). Shortening of prolonged clotting times is unpredictable and should be checked following administration.

Routine administration of FFP to prevent periventricular haemorrhage (PVH) in preterm infants is not indicated (grade A recommendation, level IIb evidence).

Fresh-frozen plasma is not indicated in polycythaemia in infancy.

There are no definitive data to support clinical decisions regarding the use of FFP with low anti-T activity in neonates with T activation.

Choice of FFP

Fresh-frozen plasma prepared from units of whole blood (recovered FFP) and from plasmaphaeresis are therapeutically equivalent in terms of haemostasis and side-effect profile (grade A recommendation, level I evidence).

The risks of pathogen transmission are very small (see Section 9.5); the clinical benefits anticipated from using FFP should be weighed against the sequelae of possible pathogen transmission (grade B recommendation, level II/III evidence).

Patients likely to receive multiple units of FFP should be considered for vaccination against hepatitis A and B (grade C recommendation, level IV evidence).

In addition, patients likely to receive large or repeated doses of FFP may benefit from products with a reduced risk of transmitting infection, such as pathogen-reduced plasma (PRP). Such patients include those with congenital factor deficiencies for whom no pathogen-reduced concentrate is available and patients undergoing intensive plasma exchange, e.g. for TTP (grade C recommendation, level IV evidence).