dxy

Recommendation
Whether and how much FFP should be used for treating a patient with major blood loss should be guided by timely tests of coagulation (including near-patient tests). ‘Formulae’ to guide replacement strategies should not be used (grade B recommendation, level IIb evidence).

11. Paediatric use of FFP (see BCSH, 2004)

Children born after 1 January 1996 should only receive PRP (see Section 3). MBFFP is available in small packs. SDFFP has been used in neonates and infants and no short-term toxicity has been reported, but clinical experience is limited. From early 2004, MBFFP, used for children, should be available from North America.

The most common causes of neonatal bleeding are vitamin K de?ciency and inherited de?ciencies of clotting factor activities. Prematurity may predispose to longer clotting times but on its own is not an indication for FFP. It should be noted that the clotting times of normal infant blood are longer than those of adults; those of premature infants (with reduced protein synthesis by the liver) may be even longer even in the absence of further pathology (Male et al, 1999).

11.1. Inherited de?ciencies of clotting factors See Section 10.1.

11.2. Haemorrhagic disease of the newborn (HDN)

Vitamin K prophylaxis for HDN has been routine in many countries since the 1960s. Without such prophylaxis, one in 200–400 live births will suffer from HDN (Zipursky, 1998). Those de?ned as at ‘high risk’ are babies born prematurely, born with liver disease or born to mothers on anticonvulsant drugs, or on isoniazid or warfarin (Department of Health, 1998). Early HDN (within 24 h) and classic HDN (2–5 d) are usually severe, while late HDN (2–12 weeks) is not often severe.

11.2.1. Management of acute haemorrhages. FFP

Recommendation
When haemorrhage due to HDN occurs, FFP (10–20 ml/kg) is indicated, as well as intravenous vitamin K (grade C recommendation, level IV evidence).

PCC (see Section 10.6). At present these agents are only conveniently available for use in centres with large paediatric ICUs and are not available to most paediatricians. As yet there is no data to guide dosage for their use, but they should be considered for severe HDN because of rapid reversibility of the abnormal coagulopathy. All acute service hospitals should have access to PCCs.

Recommendation
Although the coagulation defect in HDN may be reversed by PCC, there are no data to guide dosage in this situation (grade C recommendation, level IV evidence).

11.3. Neonates with coagulopathy and bleeding, or at risk of bleeding from an invasive procedure Fresh-frozen plasma is indicated for sick infants with hypoxia (respiratory distress), hypotension, sepsis or liver disorders associated with signi?cant coagulopathy and bleeding, or who are at risk of bleeding from an invasive procedure because of signi?cant coagulopathy.

Recommendation
Neonates with signi?cant coagulopathy, and risk of bleeding or who are about to undergo an invasive procedure, should receive approximately 15 ml/kg of FFP as well as a dose of vitamin K (grade C recommendation, level IV evidence). Shortening of the prolonged clotting times is unpredictable and should be checked following administration.

11.4. Prevention of intraventricular haemorrhage in preterm infants

A trial by the Northern Neonatal Nursing Initiative Trial Group (1996) showed that there was no evidence that the routine early use of FFP, or some other form of intravascular volume expansion, affects the risk of death or disability in babies born more than 8 weeks before term.

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

11.5. Polycythaemia in infancy

There is no indication for the use of FFP in this situation.

11.6. Red cell T antigen activation

T activation can occur through exposure of the crypt antigen ‘T’ on neonatal red cells when the patient is infected with clostridia, streptococcus or pneumococcus in conditions such as necrotizing enterocolitis (NEC). ‘Anti-T’ antibody occurs naturally in virtually all donor plasma, but the clinical signi?cance of T activation in relation to transfusion policies is not certain. Debate regarding appropriate transfusion management centres on whether transfusing plasma actually causes haemolysis (Eder & Manno, 2001). If clinically signi?cant haemolysis occurs in this situation, a logical approach would be to restrict plasma transfusions to preparations containing only ‘low-titre anti-T’, which are not common. This approach has its advocates, but requires donations with low titres of anti-T to be identi?ed.

T activation is associated with signi?cant morbidity and mortality, and has been reported in up to 27% of selected infants with NEC requiring surgery, in contrast to 11% not requiring surgery and up to only 1% of otherwise normal infants. There are subtypes (T, Th, Tk, Tx, etc.) which may or may not be exposed by different infections; but Eder and Manno (2001) stated that discriminating types of T activation may not be practical or useful in a clinical setting, while Osborn et al (1999) found that the clinical course of NEC in infants with T-activated cells did not differ from those with Tk-activated cells. Furthermore, haemolysis rarely follows transfusion even in critically ill children with NEC and T activation, and when haemolysis does occur, it may not be immune mediated. De?nitive data to support clinical decisions in these circumstances are lacking.
A randomized controlled trial of screening for T activation in high-risk infants, and provision of low titre anti-T plasma components, may provide de?nitive data on which to base recommendations (Eder & Manno, 2001), but such products may not be readily available and delay in treating with standard blood productes may be more hazardous for the patient.

Recommendations
In the absence of de?nitive data, each clinical unit should formulate its own policies and protocols for the investigation of any unexpected haemolysis associated with a transfusion of plasma to a baby with NEC or a similar septic condition. A selective testing strategy and transfusion management protocol may be required (grade C recommendation, level IV evidence). If there is a high suspicion of T-activated haemolysis, an exchange transfusion using low titre anti-T plasma and red cell products may be indicated. In this situation, administration of low anti-T titre (washed/resuspended) platelet concentrates may be indicated (grade C recommendation, level IV evidence). Note, avoiding transfusion of plasma-containing blood components in infants with T-activated red cells may risk suboptimal treatment for patients requiring haemostasis support (grade B recommendation, level II/III evidence).

12. Advance directive for patients who, for reasons of conviction, refuse transfusion These patients include ‘Jehovah’s Witnesses’, who usually refuse plasma (FFP) but sometimes accept blood fractions (such as clotting factor concentrates even if they are not recombinant and contain donor-derived albumin as a vehicle). Every hospital should have an advance directive consent form which all such patients are required to sign on admission to hospital and before products are issued.

13. No justification for the use of FFP

13.1. Hypovolaemia

Fresh-frozen plasma should never be used as a simple volume replacement in adults or in children. Crystalloids are safer, cheaper and more readily available.

13.2. Plasma exchange (except for TTP)

Although using plasma-free replacement ?uids results in the progressive reduction of coagulation factors, immunoglobulins, complement and ?bronectin; haemorrhage and/or infections are not encountered. In the rare event that haemorrhage occurs, a platelet count check before giving FFP is advisable. There may be a problem with pseudocholinesterase levels being low as a result of many plasma exchanges with saline/albumin if the patient then needs an anaesthetic. This can be corrected with FFP, although alternative drugs are available that can be used providing the anaesthetist is aware.

13.3. Reversal of prolonged INR in the absence of bleeding

There is no justi?cation for using FFP to reverse a prolonged INR in the absence of bleeding.

Disclaimer

While the advice and information in these guidelines is believed to be true and accurate at the time of going to press, neither the authors nor the publishers can accept any legal responsibility or liability for any omissions or errors that may be made.

References(Ellipsis)


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