How long ffp lasts

Current massive transfusion guidelines recommend a 1 to 1 ratio of RBCs and plasma. Plasma can be given as a continuous infusion or during plasma exchange. Continuous infusion is not recommended because of its increased risk of fluid overload. Plasma can be used for prophylaxis in patients with hereditary angioedema who are undergoing oral surgery.

Prophylaxis will prevent attacks of angioedema which are commonly precipitated by dental procedures and head and neck surgery. Infusion of 2 units of FFP the day before and again just prior to the procedure is recommended. Although FFP is recommended for prophylaxis, its use for treatment of an angioedema attack has not been established. Plasma transfusions have been reported to arrest attacks of angioedema. However, FFP could be hazardous because it contains complement factors C2 and C4 that may exacerbate the attack.

FFP should be reserved for life threatening attacks. Future treatment options include C1 Inhibitor concentrates that have been used for years in Europe and are currently under clinical investigation in the United States. FFP should not be used as a volume expander, as a nutritional supplement, for the treatment of bleeding in the absence of documented coagulopathy, or as a standing order following surgery or massive transfusion. It is important to remember that transfusion of FFP is not free of risk.

As with any other blood component, the decision to transfuse FFP should be based on predictable benefit and clinically necessity.

Home Transfusion Plasma Transfusion Guidelines. Plasma Transfusion Guidelines. Pre-transfusion INR. Coagulation Defect. Liver disease — mild. Abnormal PT. Liver disease —moderate to severe. Acute DIC. Postoperative bleeding. Fresh frozen plasma FFP is a blood product that has been available since [ 1 ].

Initially used as a volume expander, it is currently indicated for the management and prevention of bleeding in coagulopathic patients [ 1 — 3 ]. The evidence on FFP transfusion is scant and of limited quality [ 4 ].

An audit on transfusion practices suggested that one-half of all FFP transfused to critical care patients is inappropriate [ 5 ].

Massive haemorrhage is among the most challenging issues in critical care, affecting trauma patients, surgical patients, obstetric patients and gastrointestinal patients [ 3 , 8 , 9 ]. In trauma, a recent series of retrospective clinical studies suggests that early and aggressive use of FFP at a ratio with red blood cells RBC improves survival in cases of massive haemorrhage [ 10 — 19 ].

This early formula-driven haemostatic resuscitation proposes transfusion of FFP at a near ratio with RBC, thus addressing coagulopathy from the beginning of the resuscitation and potentially reducing mortality.

Nevertheless, this strategy requires immediate access to large volumes of thawed universal donor FFP, which is challenging to implement. Despite conflict with existing guidelines, early formula-driven haemostatic resuscitation use is expanding and is gradually being used in nontraumatic bleedings in critical care [ 20 ].

Both the existing guidelines and early formula-driven haemostatic resuscitation are supported by limited evidence, generating controversies and challeng ing clinical decisions in critical care Table 1. The objective of the present article is to review the evidence on FFP in the management of massive traumatic haemorrhage and to critically appraise early formula-driven haemostatic resuscitation, providing the reader with resources to develop an informed opinion on the current controversy.

Fresh refers to timing from collection to freezing, and frozen refers to the long-term storage condition. FFP is prepared from either single units of whole blood a whole blood-derived unit is approximately ml or plasma collected by apheresis usually ml [ 1 , 2 , 22 ]. PF24 is common in countries using the buffy-coat method, in which RBC and plasma are extracted after hard spin from whole blood and platelets recovered after a second soft spin within 24 hours of collection.

PF24 has similar clinical indications as FFP [ 2 , 23 , 24 ]. FFP is commonly thawed in a water bath over 20 to 30 minutes, but US Food and Drug Administration-approved microwaves can thaw 2 units of plasma in 2 to 3 minutes [ 1 ].

After thawing, the activity of labile clotting factors such as factor V and factor VIII decline gradually, and most countries recommend FFP use within 24 hours [ 25 , 26 ]. In some countries, FFP is used up to 5 days after thawing. Photochemically treated FFP and solvent detergent FFP are approved methods of inactivating pathogens in some jurisdictions. Both methods cause loss of clotting factors, particularly factor VIII.

These solvent detergent preparations are extensively used in some European countries, while solvent detergent FFP was withdrawn in North America due to concerns of Parvovirus transmission [ 1 ]. FFP can transmit infectious diseases, albeit rarely. Screen ing and pathogen inactivation reduced transmission rates of HIV to In the UK, concerns over Creutzfeldt-Jakob disease - a rare but rapidly progressive spongiform encephalopathy - led to leukocyte depletion in all blood products and recommendations to use FFP from areas of low epidemicity [ 31 , 32 ].

Other important complications relate to blood immunogenicity, increasingly recognized over the past two decades, particularly transfusion-related acute lung injury TRALI and transfusion-associated circulatory overload [ 33 , 34 ]. TRALI is the commonest cause of transfusion-related death [ 33 , 34 ]. Donor plasma antibodies react with human leukocyte antigens, causing complement activation, endothelial damage, neutrophil activation and lung capillary leak. Anti-human leukocyte antigens and anti-neutrophil antibodies are commonly found in plasma from multiparous female donors, and the TRALI frequency is higher in recipients from female donors [ 35 — 37 ].

Another potential mechanism involves interactions of biologically active mediators in stored plasma and lung endothelial cells. Other important transfusion-related complications include acute haemolytic reaction from anti-A and anti-B antibodies, and anaphylaxis [ 22 ].

The physiological derangements and complications are proportional to the blood loss and to the time to correct shock. Lower levels significantly prolong the prothrombin time and the activated partial thromboplastin time above 1.

FFP transfusion to replace clotting factors is often recommended for these patients but no studies exist supporting this practice [ 4 ]. Replacing one blood volume or more without FFP results in dilutional coagulopathy, diffuse microvascular bleeding and increased mortality [ 40 , 41 ].

The principles of managing massive haemorrhage include rapid control of bleeding; replenishing the intravascular volume with crystalloid followed by RBC and, once coagulopathy is present or suspected, then adding FFP, platelets and cryoprecipitate; along with correction of acidosis and hypothermia.

Most current guidelines [ 1 , 39 , 42 — 44 ], including the European and US guidelines, recommend transfusing FFP, platelets and cryoprecipitate only when laboratory assays detect a deficit.

Where a laboratory is not available, these products are recommended after large infusions of crystalloid and RBC. Current crystalloid-based resuscitation guidelines initiate FFP transfusion late, often after more than one blood volume is lost and the patients have clinically overt coagulopathy [ 40 , 41 ].

Most recommendations are based on observations and expert opinion, often lacking high-level evidence. Many recommendations originated in studies conducted in nontrauma settings and when RBC units had to ml plasma [ 1 ]. Despite worldwide acceptance of similar resuscitation principles, bleeding remains the second overall cause of death in trauma - becoming the first cause of death following hospital admission [ 45 — 47 ].

Current resuscitation strategies invariably fail to prevent coagulopathy in massive bleedings. Multiple causes have traditionally been implicated in trauma coagulopathy, including clotting factor consumption and dilution, hypothermia and acidosis - all linked to large-volume crystalloid infusion and late replacement of clotting elements [ 40 , 41 ]. Further studies suggest that early coagulopathy is initiated by shock and the amount of tissue destruction, independent of clotting factor consumption or dilution Figure 1 , and is associated with a threefold mortality increase [ 48 , 49 ].

Recently proposed mechanism for coagulopathy in trauma. Early coagulopathy develops when there is an imbalance in this process, with excessive anticoagulation, hyperfibrinolysis and consumption of clotting factors. PAI-1, plasminogen activator inhibitor 1. A unique coagulopathy in traumatic brain injury has long been suspected, where the release of brain tissue factor causes systemic activation of coagulation dissemi-nated intravascular coagulation , exhaustion of clotting elements and hyperfibrinolysis [ 50 , 51 ].

While coagulo-pathy is common and critically important in traumatic brain injury, the controversial existing evidence suggests it may not differ from trauma coagulopathy in general [ 51 ]. The early trauma coagulopathy concept has challenged the current crystalloid-based resuscitation that ignores coagulopathy until it becomes overt.

Over the past 2 years, a haemostatic blood-based resuscitation - commonly termed damage control resuscitation - proposes a series of early and aggressive strategies to treat or prevent early trauma-associated coagulopathy [ 52 , 53 ].

This resuscitation entails the use of thawed plasma as the primary resuscitation fluid, limited use of crystalloid, targeted systolic blood pressure at approximately 90 mmHg to prevent renewed bleeding, early activation of a massive transfusion protocol with fixed ratios of FFP:platelets:cryoprecipitate:RBC approximately , liberal use of recombinant activated factor VII rFVIIa and the use of fresh whole blood for the most severely injured combat casualties [ 52 , 53 ].

The first reports suggesting aggressive FFP transfusions were computer simulation models. In , Hirshberg and colleagues published a haemodilution model of exsanguination, calculated the changes in coagulation and predicted an optimal FFP:RBC ratio of to adequately replenish clotting factors [ 54 ].

Ho and colleagues predicted 1 to 1. Since , growing numbers of retrospective military and civilian papers have studied early formula-driven haemostatic resuscitation with different FFP:RBC ratios mostly near and mortality [ 11 — 20 , 56 , 57 ]. These figures surpass any predictions of potentially preventable deaths in trauma [ 47 ].

While the survival advantage of early and aggressive FFP transfusion in early formula-driven resuscitation cannot be ignored, the evidence behind it has limitations that are discussed next. These data suggest that lower ratio patients may not have lived long enough to receive FFP. Another study by the same group on civilian trauma patients reported a similarly impressive survival advantage for higher ratios than lower ratios, but also a markedly dissimilar time to death 35 hours versus 4 hours [ 58 ].

Both studies disclose survivorship bias, where arguably patients had to survive long enough to receive FFP, thus questioning their conclusions. Scalea and colleagues used stepwise logistic regression analysis on patients, demonstrating no survival benefit for higher ratios when early deaths were excluded [ 56 ].

These two studies dispute the survival advantage suggested by the previous studies with such bias. Early formula-driven resusci-tation proposes that FFP should be initiated early, ideally with the first RBC unit at the start of resuscitation [ 52 , 53 ]. Considering that even laboratory-guided resuscitation eventually results in a high FFP:RBC ratio, a critical difference in formula-driven resuscitation is the early implementation of a high ratio. No studies to date have reported on transfusing pre-thawed FFP along with the first RBC units or on the time to reach the ratio.

Snyder and colleagues stated that the median time to the first RBC was 18 minutes from arrival, while the first FFP was transfused more than 1 hour later [ 57 ]. This could have ramifications if plasma units with relatively higher INRs are used to try to reverse a recipient's mildly elevated INR see below. If the FFP is not used within 24 hours, it must either be discarded or relabeled as thawed plasma TP. The decreases in factor V levels were smaller [ 6 , 8 ] even after 28 days of storage [ 5 ].

TP has the advantage of already being in a liquid state thus eliminating the time delay caused by thawing the frozen FFP, and it effectively extends the shelf-life of a unit of plasma that would otherwise have been discarded, thereby reducing wastage of a limited resource.

In an effort to reduce the risk of transfusion related acute lung injury TRALI from plasma components, many blood centers have limited the collection of plasma from female donors due to their propensity for developing anti-HLA alloimmunization after pregnancy [ 11 ].

To avoid a shortfall in the plasma supply, there is increasing reliance on the production of plasma from male whole blood donations that have been stored between hours prior to freezing. The levels of most clotting factors are not significantly diminished compared to regular FFP at the time of thawing [ 7 , 12 - 15 ], and recently 2 studies have demonstrated that the levels of clotting factors remain hemostatic during 5 days of refrigerated storage of TP prepared from FP24 [ 16 , 17 ].

These minor changes are unlikely to be clinically significant. Recently Alhumaidan et al. Furthermore, neither FP24 nor the TP products have been directly compared to FFP in terms of their efficacy in reversing coagulopathies or arresting coagulopathic bleeding, however based on the well preserved coagulation factors there is no a priori reason why these products would be inferior to FFP.

When the INR starts to exceed 1. Factor VII has a short half life hours thus if plasma is administered more than hours before the planned procedure, it will have gone through at least 2 half-lives thus reducing its hemostatic efficacy at the time of surgery. Approximately 8 hours after the plasma infusion point C the PT began to rise steeply reflecting the end of the plasma's efficacy. Thus transfusing plasma as close to the time of an invasive procedure as possible will produce its maximum hemostatic efficacy.

On the other hand once plasma is transfused it, like all blood products, it remains almost entirely in the intravascular space; unlike crystalloids that distribute themselves between the intra- and extra-vascular spaces, plasma remains nearly entirely in the circulation. This needs to be borne in mind because rapid infusion rates, intended to facilitate the administration of the entire dose of plasma before the start of the surgery, could lead to circulatory volume overload.

Thus there is a significant reserve of clotting factors the physiologic reserve. Refer to text for explanation of the labels. Modified and reprinted from reference [ 23 ], with permission from the AABB. PT values in healthy individuals who first received oral anticoagulation, then 1 L of autologous plasma, then oral vitamin K at the end of the study. The therapeutic effect of FFP lasted for approximately hours C.

Modified and reprinted with permission from the AABB from reference [ 19 ]. The use of plasma in the USA is growing. In approximately 4 million units were transfused [ 2 ], which is several orders of magnitude higher than in several other developed countries [ 20 ].

Neither its use as a replacement fluid for therapeutic aphersis in thrombotic thrombocytopenic purpura TTP patients, nor the pharmacological procoagulant agents such as rfVIIa that might also be used to reverse a significant coagulopathy will be discussed in this report. The use of plasma as part of fixed ratio RBC: plasma protocols for the resuscitation of trauma patients is controversial and is extensively reviewed in reference [ 21 ].

Often times the question facing the clinician when trying to decide whether to transfuse plasma is: When is a coagulopathy significant enough for the benefits of plasma transfusion to outweigh its potential adverse events such as TRALI and volume overload? To answer this question, 2 important meta-analyses have been performed.

The vast majority of the reports included in this meta-analysis were observational studies, and only 1 was a clinical trial. The authors concluded that the strongest evidence suggesting that the pre-procedure INR does not likely predict the bleeding risk lies with central vein cannulation, although just how coagulopathic patients can be and still tolerate the procedure safely has not been elucidated.

As for the literature on the other procedures, the variability in study size and quality makes drawing firm conclusions about the bleeding risk difficult. In these studies, the risk of bleeding between the 2 groups of patients undergoing the same procedure could be estimated [ 22 ].

Although the confidence intervals of some of these comparisons were relatively large due to the small number of patients in these studies, there was no significant difference in the risk of major bleeding between the patients who underwent these varied procedures with and without coagulopathies. While further study is required, especially for coagulopathic patients undergoing kidney biopsy, overall it would appear that patients with mild coagulopathies undergoing various surgical procedures might not require normalization of their laboratory coagulation parameters with plasma to reduce their risk of bleeding.

The second meta-analysis can shed some light on the question, if plasma is administered to peri-surgical patients, does it have a beneficial effect in reducing transfusion requirements or surgical blood loss? Stanworth and colleagues searched various medical publication databases looking exclusively for randomized controlled trials RCT where FFP was the therapeutic intervention [ 24 ].

While 57 such trials were identified, 19 were focused on surgical or potentially surgical patients; there were 11 studies based on cardiovascular surgery in children and adults, 3 studies on liver disease with or without GI bleeding, and 1 study each on warfarin reversal with intracerebral hemorrhage, massive transfusion, hip surgery, hysterectomy, and renal transplantation. Most of these studies concluded that FFP administration did not reduce blood loss or transfusion requirements [ 24 ].

To explain why prophylactic plasma administration does not reduce peri-operative bleeding, consider a study of 22 non-trauma patients who received a total of 68 units of FFP mL units [ 4 ]. The average pre-transfusion INR was 1.

Furthermore, given that some FFP units can have INRs approaching that of these recipient's [ 4 ], it is not surprising that the decreases in the post-transfusion INRs were quite modest. Abdel-Wahab and colleagues studied FFP recipients from a wide variety of hospital wards, and with and an assortment of clinical diagnoses [ 25 ].

In this retrospective study, FFP units were transfused to recipients who had relatively low pre-transfusion INRs, 1.