Fresh Frozen Plasma

Fresh frozen plasma is plasma separated from whole blood or collected by apheresis and frozen soon after collection to preserve coagulation factors. It replaces multiple clotting factors at once in bleeding patients or those at high risk of bleeding with a documented deficiency. It is not a volume expander, a nutritional product or a general reversal agent.

Composition. All coagulation factors, natural anticoagulants and fibrinogen, with levels of about 1 unit/mL for most factors. Factor V and factor VIII fall with processing and storage. A unit from whole blood is usually 200 to 300 mL, and an apheresis unit is larger.

Source and preparation. Frozen within about 6 to 8 hours of collection at minus 25 degrees Celsius or colder (minus 18 degrees Celsius or colder for a shorter shelf life), with a shelf life of up to 12 months at the colder temperature. Plasma frozen within 24 hours and thawed plasma are variants, with lower labile factors.

Variants. Solvent detergent treated pooled plasma and other pathogen reduced plasma have lower infection and transfusion related acute lung injury risk, and are not available everywhere.

Thawing. In a validated water bath or dry thawing device at about 30 to 37 degrees Celsius, taking about 20 to 30 minutes. Use as soon as possible after thawing. Thawed plasma may be stored at 2 to 6 degrees Celsius for up to 24 hours, and longer where policy allows with loss of labile factors.

ABO. Plasma must be ABO compatible with the recipient red cells. Group AB is the universal plasma donor, and group O plasma suits only group O recipients. RhD does not matter for plasma.

Special groups. Neonates and children need volume adjusted doses. In East Africa, freezing and thawing capacity is limited, so plasma may only be available in larger centres and delays are common.

Indications.

• Bleeding with multiple coagulation factor deficiency (dilutional, liver disease, vitamin K deficiency not yet corrected, disseminated intravascular coagulation).

• Massive haemorrhage as part of balanced resuscitation.

• Thrombotic thrombocytopenic purpura, as plasma exchange replacement, or by infusion when exchange is unavailable.

• Single factor deficiency (for example factor V, factor XI) when no concentrate exists.

• Reversal of warfarin with major bleeding only when prothrombin complex concentrate is unavailable.

Non-indications. Volume expansion, nutritional support, hypoalbuminaemia, burns resuscitation, a minor isolated prolongation of prothrombin time or activated partial thromboplastin time without bleeding, and reversal of direct oral anticoagulants.

Contraindications and cautions. Heart failure and volume sensitive states, IgA deficiency with anti-IgA, and prior severe reactions.

Dose.

• Adults and children: 10 to 15 mL/kg, about 3 to 4 units in a 70 kg adult.

• Expected response: a rise in factor levels of about 10 to 20%, with correction of prothrombin time only when the baseline is clearly prolonged. Plasma has little effect on a mildly prolonged international normalised ratio under about 1.7.

• Larger doses may be needed in massive haemorrhage, where plasma is given with red cells in balanced proportions directed by response and laboratory or viscoelastic results.

• Neonates: 10 to 20 mL/kg depending on the indication.

Compatibility and testing. ABO compatible plasma (plasma rules, which differ from red cell rules), with no crossmatch.

Timing, rate and time limit. Give promptly before the procedure or bleeding, because factor VII has a half-life of about 4 to 6 hours. Adult units over 30 to 60 minutes each, and 10 to 20 mL/kg over 1 to 2 hours in stable patients (slower with overload risk, about 5 mL/kg/hour), and rapid infusion in haemorrhage. Complete within the time the hospital sets after thawing (often 4 hours at room temperature).

Equipment and fluids. Blood giving set with a 170 to 200 micrometre filter, and a warmer in rapid infusion. Only 0.9% sodium chloride in the same line, and no drugs added.

Laboratory monitoring. Prothrombin time, activated partial thromboplastin time and fibrinogen before and 15 to 60 minutes after the dose, with clinical bleeding as the main endpoint.

Special groups.

• Liver disease: international normalised ratio does not predict bleeding well, and large volumes cause overload. Use viscoelastic results where available.

• Pregnancy: fibrinogen is often the first deficiency in obstetric haemorrhage and plasma is a poor source.

• Heart failure and renal failure: small volume, slow rate.

Expected effects. Correction of clotting factor deficiency and reduced bleeding.

Serious reactions. Allergic reactions (urticaria is the most frequent), anaphylaxis, transfusion related acute lung injury, transfusion associated circulatory overload (volume related), citrate toxicity with hypocalcaemia in massive transfusion, and haemolysis from ABO incompatible plasma. Infection risk is very low.

Immediate interruption criteria. Dyspnoea, hypoxia, hypotension, urticaria with systemic signs, fever with rigors or unexpected deterioration. Stop the transfusion, assess the patient, keep intravenous access, recheck identity of patient and unit, and inform the blood bank. Do not restart without authorised clinical evaluation.

Follow up. Repeat coagulation tests and fibrinogen after the dose, and repeat if bleeding continues. Record the response.

Referral and escalation. Haematology for refractory coagulopathy, thrombotic thrombocytopenic purpura, and unusual factor deficiencies. Report reactions.