The Evidence-Based Use of FFP and Cryoprecipitate for Abnormalities of Coagulation Tests and Clinical Coagulopathy

Abstract

There continues to be a general but unfounded enthusiasm for fresh frozen plasma (FFP) or frozen plasma (FP) usage across a range of clinical specialties in hospital practice. Plasma for transfusion is most often used where there are abnormal coagulation screening tests, either therapeutically in the face of bleeding, or prophylactically in nonbleeding patients prior to invasive procedures or surgery. Little evidence exists to inform best therapeutic transfusion practice, and most studies describe plasma use in a prophylactic setting. Laboratory abnormalities of coagulation are considered by many clinicians to be a predictive risk factor for bleeding prior to invasive procedures or in other clinical situations where bleeding risk exists, and plasma for transfusion is presumed to improve the laboratory results and reduce this risk. However, most guideline indications for the prophylactic use of plasma for transfusion are not supported by evidence from good-quality randomized trials. Arguably, the strongest randomized controlled trial (RCT) evidence indicates that prophylactic plasma for transfusion is not effective across a range of different clinical settings, and this is supported by data from nonrandomized studies in patients with mild to moderate abnormalities in coagulation tests. There is a need to undertake new trials evaluating the efficacy and adverse effects of plasma, both in bleeding and non-bleeding patients, to understand whether the presumed benefits outweigh the real risks. In addition, new hemostatic tests that better define the risk of bleeding and monitor the effectiveness of the use of FFP should be validated. Last, there is an opportunity to develop effective educational strategies aimed at addressing understanding and compliance with recommendations in guidelines. What Is Plasma for Transfusion?Frozen plasma (FP) is human donor plasma, either recovered from a single whole-blood donation or obtained by plasmapheresis, frozen within a specific time period after collection and then stored at a defined temperature, typically -30°C. Plasma frozen within 8 hours is called fresh frozen plasma (FFP); plasma frozen at slightly longer intervals (typically up to 24 hours) after collection is referred to as frozen plasma (known as F24 in the U.S.). Levels of the labile coagulation factors V and VIII may be slightly lower in FP in comparison with FFP. Although both components (FFP and F24) are largely considered clinically equivalent by physicians, and for the purposes of this review will be covered (interchangeably) by the common term FP, evidence for equivalence has not been documented. After thawing, FP contains near-normal levels of most plasma proteins, including procoagulant and inhibitory components of the coagulation system, acute phase proteins, immunoglobulins and albumin, although all levels are diluted by the citrate anticoagulant solution. Factor VIII (FVIII) is typically the only plasma protein whose level is quality controlled in the specification of the product, and as required by UK 1 an...

Adherence to NICU transfusion guidelines: data from a multihospital healthcare system

“…Stanworth and co-workers reviewed 12 studies of FP use in the NICU, and concluded that no benefit of FP could be identified in non-bleeding patients, for its use either as a volume expander, for immunological effects or for preventing hemorrhage. 21,22 In the present study, we identified 456 transfusions, during a one-year period, that were given in violation of our transfusion guidelines. We speculate that some of these transfusions conveyed little or no benefit to the recipient, but each unneeded transfusion conveyed known and unknown risks.…”

Bleeding and Clotting Disorders in Pediatric Liver Disease

“…57 Allergic reactions to FFP are common, with a frequency of 1%-3% of all transfusions, and can be a cause of frequent morbidity and a potential risk of mortality in multiply transfused patients. 58 Infectious risks with known agents such as HIV, hepatitis B, and hepatitis C are low, but the rate of prion transmission via transfusion of blood products, while probably low, remains unknown. 56,58,59 Significant concern has been raised about increased vascular volume and fluid overload after FFP infusions causing increased bleeding.…”

“…58 Infectious risks with known agents such as HIV, hepatitis B, and hepatitis C are low, but the rate of prion transmission via transfusion of blood products, while probably low, remains unknown. 56,58,59 Significant concern has been raised about increased vascular volume and fluid overload after FFP infusions causing increased bleeding. 24 In a randomized trial comparing a restrictive transfusion policy (that maintained a low central venous pressure) with liberal transfusion during liver transplantation, Feng et al showed that the restrictive policy led to a significant reduction in intraoperative blood loss and transfusion requirements.…”

Rationalizing the clinical use of frozen plasma

“…However, there is little evidence to support the efficacy of frozen plasma in these circumstances or to define criteria for the degree of coagulopathy required before any benefit can be expected. 2 Coagulation screening assays have little value in predicting bleeding associated with invasive procedures in patients with mild to moderate coagulopathy 5 (international normalized ratio 1.5-3.0), and transfusion of frozen plasma has a negligible effect on correcting trivial coagulation abnormalities (international normalized ratio < 1.5). 6 The dose of frozen plasma required to effect major reductions in substantially prolonged clotting times is considerable (15-20 mL/kg) 7 and poses a risk of circulatory overload.…”

“…We have compiled broad categories of appropriate and inappropriate indications for use of frozen plasma (Box 1) from critical reviews 2 and various published guidelines. 1,3,4 Frozen plasma is usually prescribed to correct coagulopathy from various causes, as identified from laboratory test results, with or without bleeding or expected invasive procedures.…”