Use of plasma: Clinical indications and types of plasma components in Sweden

The use of plasma in Sweden is relatively high compared to other countries in the European Union. An analysis of all transfusion recipients in Orebro county during the whole year 2000 was performed. There were 3159 transfusion recipients of whom 96% had a registered diagnosis and 50% had undergone a "true" operation. Seven hundred and eleven patients (23%) had received plasma. Significantly more operated than nonoperated and more men than women received plasma. The typical plasma recipient was a man undergoing cardiovascular surgery. In Sweden there are two main types of plasma components: fresh frozen (FFP) and nonfrozen liquid plasma stored for up to 14 days, both considered to be clinically equal for most indications. The quality of these components as well as stored thawed FFP has been studied. The major storage effect was cold-induced contact activation and thereby consumption of C1 esterase inhibitor (C1INH) by day 14 in 22%. The citrate content in plasma sustained the overall coagulation function over 14 days. Other studies have shown that the levels of FV and ADAMTS 13 after 14 days remain at 70% or more compared to those for FFP. Since it is immediately available, liquid, nonfrozen or thawed, plasma is of great value in emergencies. Quality criteria for plasma components need to be assessed against evidence based indications and published in guidelines.     

RBC alloimmunization is an important complication of FFP transfusion: A case report of immune anti-D induced by apheresis fresh frozen plasma

UK, Germany as well as the Council of Europe recommendation guide have set limits of RBC in clinical fresh frozen plasma (FFP), but current transfusion guidelines do not get the consensus opinion at recommending the D status of FFP to be considered before transfusion. We report a female group A, D- patient with cerebrovascular disease who was induced to develop IgG immune anti-D which can be detected on the 15th day of hospitalization after the relatively regular time interval of transfusion of 1800 ml apheresis FFP. Therefore, in making clinical decisions to transfuse FFP or apheresis FFP, the best choice is considered as the same or compatibility with RhD group, in case Rh immunization can be induced and trigger some potential serious problems in future emergent transfusion or pregnancy, especially in high incidence of D antigen countries.     

The use of Fresh Frozen Plasma (FFP) in 2007 in France

After a more than four-fold decrease in Fresh Frozen Plasma (FFP) consumption in the nineties in France, probably due to the consequences of HIV epidemics, the use of FFP is again increasing in recent years but at a slower rate. In the surgical and trauma area, recent data suggest that guidelines for the use of FFP may need to be modified. Indeed, contrary to traditional beliefs and guidelines, several studies evaluating conditions with severe hemorrhage (very often associated with coagulation abnormalities) have shown that early use of FFP may be associated with better patient outcome. This has indeed been shown in emergency major vascular surgery and in trauma patients. Although there is a trend to favor a larger use of FFP in specific circumstances (i.e., major hemorrhage), reasons to better control administration of FFP remain. Several audits have indeed shown that the rate of inappropriate FFP transfusion remains high, from 20 to almost 100% of cases. Moreover, FFP continues to be used in patients who may be better treated with other strategies. The best example is the frequently inappropriate use of FFP in bleeding patients with excess anticoagulation from vitamin K antagonists. Even recent studies have shown that prothrombin complex administration is efficient, safe and provides very rapid reversal. Many physicians continue however to administer FFP as a first line treatment with notably increasing the risk of fluid overload, delayed efficacy and increased risk of transfusion-related acute lung injury (TRALI).     

A survey of fresh frozen plasma use in a teaching hospital in Hong Kong

In response to an acute shortage of fresh frozen plasma (FFP), a survey of its use was conducted in our hospital. The survey was designed to separate the use of FFP into "appropriate use" and "inappropriate use" categories. Whether the use of FFP in a case could be assigned to "appropriate use" category or not was decided by pre-set criteria based on the consensus statement published by the United States National Institute of Health (NIH). We found that during a 30-day period, out of 746 units of FFP used, only 65 (8.7%) could be considered inappropriate use. Most of the FFP (67.6%) was used for liver disease with bleeding and/or abnormal coagulation tests, and for disseminated intravascular coagulopathy. In the "inappropriate use" category (8.7%), the leading causes were plasmapheresis, and hepatobiliary disease with normal coagulation tests and no abnormal bleeding.     

National comparative audit of the use of platelet transfusions in the UK

The objective of this national audit was to examine the use of platelet transfusions against audit standards developed from national guidelines. Hospitals were asked to provide data on 40 consecutive patients receiving platelet transfusions (15 haematology patients, 10 cardiac, 10 critical care and five in other clinical specialties). One hundred and eighty-seven UK hospitals participated, including 168/263 (64%) hospitals in England. A total of 4421 patients receiving platelet transfusions were audited. The reason for transfusion was documented in the medical records for 93% of transfusions and 57% were used for prophylaxis (in the absence of bleeding). Overall 3726/4421 (84%) of the transfusions were evaluable and 43% (1601/3726) were found to be non-compliant with the audit standards. A major non-compliance was failure to measure the platelet count before transfusion (29% of transfusions). Other non-compliances included the use of platelet transfusion in the absence of bleeding in 11% of cardiac surgery patients receiving platelet transfusions, the use of a threshold platelet count more than 10 x 10(9)/L for 60% of prophylactic platelet transfusions in haematology patients without risk factors indicating the need for a higher threshold, and a threshold platelet count more than 30 x 10(9)/L for 59% of prophylactic platelet transfusions in critical care. The reasons for the high rate of non-compliance were not explored in this audit, but this is a topic worthy of further study. The main recommendations were that hospitals should ensure there are written local guidelines for platelet transfusions, clinicians must be provided with training about their appropriate use, and hospitals should carry out regular audits of practice. More research should be carried out to develop the evidence base for the use of platelet transfusions, more detailed guidelines should be developed for platelet transfusions in critical care and cardiac surgery, and the audit should be repeated in about three years.     

Uses of plasma in Spain

In Spain, fresh frozen plasma (FFP) currently recovered either by whole blood centrifugation or by apheresis is mainly considered as a source of plasma derivates rather than a product to be transfused. Upon this consideration, the amount of plasma transfused in the last two decades has remained stable, while the production of FFP has grown steadily during all these years. Thus, much more plasma has been derived to industry for manufacturing. Although, since 1993 a consensus conference established the clinical situation where plasma has demonstrated its efficacy, the true situation is that many indications seem not to be supported on a scientific evidence basis. Only a few studies have been performed in the last years to assess the appropriateness of these indications. We present the initial result of an ongoing survey addressed by the Madrid Blood Transfusion Centre. Based on the criteria of total amount of RBC transfused per year, large hospitals (more than 10,000 units of RBC) transfused an average of 23.87% of FFP, while medium hospitals (5000-10,000 units of RBC) used 19.5% and small ones (less than 5000) about 12.5%. It is important to point out that inside each group there were some important differences in ratio values for similar hospitals. This could indicate that much more is necessary to cope with indications. Although national figures of uses of FFP, whether in ratio or absolute terms, show a moderate consumption in comparison with published figures of other European countries, there can be no doubt that plasma overuses still seem to be present.     

An audit of fresh frozen plasma usage in a tertiary referral centre in a developing country

This paper evaluates the practice of fresh frozen plasma (FFP) transfusion at the University Hospital, Kuala Lumpur, and analyses its usage by the various clinical departments. The aim of this study is to identify where it is inappropriately used and the clinical indications in which such misuse is common. A retrospective analysis of the blood bank request forms and work sheets during a 6-month period between January 1998 and June 1998 formed the basis of this study. Overall, 40% of 2665 units transfused were considered appropriate. However, out of the 931 episodes of FFP transfusions only 31% were for appropriate indications. The average FFP requirement when used for appropriate indication was about 4 units per episode, whereas for inappropriate indication it was 2.5 units per episode. Inappropriate use in terms of the number of units was highest by the surgical services (68%) and Orthopaedics (64%), while the Department of Paediatrics had the lowest incidence of inappropriate use (40%). When Paediatrics was used as the benchmark, the incidence of inappropriate use by other departments was significantly higher (p < 0.01). As for FFP usage in common clinical indications, there was a high incidence of inappropriate use in burns (82%), perioperative period (73%), cardiac surgery (68%), massive bleeding (62%) and trauma (60%). The findings in this study, specifically the use of FFP for volume support in trauma, massive bleeding and burns, routine requests without identified indication in cardiac bypass surgery, and prophylactic use in the perioperative period can be the basis for recommendations to minimize the inappropriate use of FFP in the future.     

Consensus and controversies in platelet transfusion: Trigger for indication, and platelet dose

Platelet transfusion is about to commemorate its 50th year since its introduction in therapeutics. It is then surprising to see, that in spite of reaching this respectful age, we have not been able to definitely establish all the aspects related to its clinical use. Some of these facets are platelet transfusion threshold and the platelet dose to administer. Historically, two different transfusion triggers have been used for prophylactic and therapeutic platelet transfusions. For prophylactic platelet transfusion an increasing body of evidences suggests that a transfusion trigger of 10 x 10(9) per liter is appropriate for most clinical settings. In contrast, evidence for supporting a certain therapeutic transfusion trigger is lacking. Nevertheless, there is consensus that the platelet count should not be allowed to fall below 50 x 10(9) per liter in patients with acute bleeding. Another important aspect still pending of clear definition is the issue of the platelet dose to be transfused. It has been addressed by some small studies but a definite answer to this important clinical issue is, at least so far, still pending. The results of two ongoing trials, one sponsored by NIH through the Clinical Trials Network in Transfusion Medicine and Hemostasis and the other promoted by the BEST Collaborative Group are expected to help us to clearly defining the more effective and efficient way to transfuse platelet concentrates.     

The effects of a computerized transfusion decision support system on physician compliance and its appropriateness for fresh frozen plasma use in a medical center

Fresh frozen plasma (FFP) transfusion remains a significant issue for blood banks because of a lack of consensus regarding its appropriate use. To study the factors influencing physician compliance, we evaluated FFP transfusion episodes in the year 2008, using a computerized transfusion decision support system. A total of 10,926 episodes were reviewed. The demographic data, physician compliance, and therapeutic efficacy were investigated. The physician noncompliance rate was 46.5%. The highest number was ordered by the hepatobiliary division, which might be due to the high incidence of liver cirrhosis and hepatoma in Taiwan. Excluding the cases for plasma exchange and emergency surgery, 31.2% of episodes had abnormal coagulation results before transfusions. The therapeutic efficacy is statistically significant in patients with abnormal pretransfusion coagulation tests (P < .001). Computerization may be a favorable trend in medical management systems, but it should be more functional to improve medical quality.     

Coagulopathy of massive transfusion: pathophysiology and monitoring

Coagulopathy associated with massive transfusion (MT) remains an important clinical problem. The author attempted to identify the causes of coagulopathy in massively transfused, adult and previously haemostatically competent patients and to differentiate between the elective surgical and the emergency settings. A MEDLINE search was conducted for articles published on ‘massive transfusion’, ‘transfusion’, ‘trauma’, ‘surgery’, ‘coagulopathy’ and ‘haemostatic defects’. A narrative format was adopted. Coagulopathy associated with MT is an intricate, multifactorial and multicellular event. In patients undergoing elective surgery, a decrease in fibrinogen concentration is observed initially while thrombocytopenia is a late occurrence. Critically low levels of coagulation factors were seldom reported when whole blood was in common use. With the use of packed red blood cells (PRBC), dilution or consumption of coagulation factors has become a significant issue requiring specific treatment with, primarily, fresh frozen plasma (FFP). In the emergency setting (e.g., trauma, ruptured abdominal aortic aneurysm), tissue trauma, shock, tissue anoxia and hypothermia contribute to the development of disseminated intravascular coagulation and microvascular bleeding. It has been shown that the proactive administration of platelets and FFP improves coagulation, decreases haemorrhage and improves survival in these massively bleeding patients. We can only speculate that in this specific context, the benefits of early and aggressive platelet and coagulation factor replacement are related to the ongoing consumption coagulopathy at the time of surgery.     

A primer on evidence-based plasma therapy

Background and Objectives  Although traditionally fresh-frozen plasma (FFP) has been the product of choice for reversing a significant coagulopathy, the modern blood bank will have several different plasma preparations for use in reversing a significant coagulopathy or arresting coagulopathic bleeding. These products include the aforementioned FFP which is frozen within 8 h of collection, plasma frozen within 24 h after phlebotomy (FP24), and thawed plasma (TP) prepared from either FFP or FP24. Based on their factor levels, these products should all be equally efficacious in reversing a significant coagulopathy although a head-to-head comparison between these products has not been performed. Evidence from two systematic literature reviews and numerous observational studies suggest that for a stable patient with a mild coagulopathy, transfusing plasma for an INR ≤ 1·5 does not confer a hemostatic benefit. This lack of benefit is due to the exponential relationship that exists between factor levels and a mildly elevated INR, that is, a large quantity of plasma would be required to produce a reduction in the INR when its pre-transfusion value is <1·6. By contrast, the relationship becomes more linear when the INR is more significantly prolonged. Thus, even if a reduction in a mildly elevated INR could be achieved with plasma transfusion, the clinical significance of the decrease is dubious and the transfusion itself exposes the recipient to a variety of adverse events such as allergic reactions and transfusion-related acute lung injury (TRALI). Furthermore, emerging evidence indicates that transfusion-associated circulatory overload (TACO) following plasma transfusion is an important and under reported adverse event. This review will discuss the various plasma products that are available, describe why the commonly used markers of hemostasis (such as the PT/INR) are not effective markers of perioperative hemostasis, and present some of the current literature on the clinical uses of plasma. Strategies to reduce non-evidence-based plasma transfusion, ranging from automated interventions at the time plasma is ordered to more labour-intensive manual attempts to dissuade providers from ordering plasma unnecessarily, will also be addressed.     

Prise en charge des troubles de l’hémostase chez l’insuffisant hépatique

Patients with end-stage liver disease have complex alterations that involve all components of hemostasis, with changes both in prohemostatic and in antihemostatic pathways. Routine haemostasis tests such as prothrombin time and platelet count are unable to reflect a bleeding tendency. Bleeding complications are much less related to abnormal hemostasis than previously thought, with portal hypertension playing a more critical role. Systematic prophylactic measures based upon the use of fresh frozen plasma and/or platelet concentrates to improve or correct the abnormalities of the routine coagulation tests are most often inappropriate and may occasionally be deleterious.     

Heparin-like anticoagulant associated with plasma cell myeloma

A 54-year-old man with plasma cell myeloma had sustained bleeding develop after prophylactic hip hemiarthroplasty. Routine coagulation studies revealed significant prolongation of the prothrombin time, activated partial thromboplastin time, and thrombin time. Further evaluation showed failure of the activated partial thromboplastin time to correct in a 1:1 mixture with pooled normal plasma, correction of the prolonged thrombin time by addition of protamine, and a normal reptilase time. A purified preparation of the immunoglobulin component of patient plasma produced the same pattern of coagulation abnormalities, suggesting the paraprotein possessed heparin-like anticoagulant activity. This appears to be a rare mechanism of bleeding diathesis in plasma cell myeloma.     

Epsilon aminocaproic acid reduces blood transfusion and improves the coagulation test after pediatric open-heart surgery: a meta-analysis of 5 clinical trials

Background: Excessive postoperative blood loss after cardiopulmonary bypass is a common problem, especially in patients suffering from congenital heart diseases. The efficacy of epsilon aminocaproic acid (EACA) as a prophylactic treatment for postoperative bleeding after pediatric open-heart surgery has not been determined. This meta-analysis investigates the efficacy of EACA in the minimization of bleeding and blood transfusion and the maintenance of coagulation tests after pediatric open-heart surgery. Methods: A comprehensive literature search was performed to identify all randomized clinical trials on the subject. PubMed, Embase, the Cochrane Library, and the Chinese Medical Journal Network were screened. The primary outcome used for the analysis was postoperative blood loss. Secondary outcomes included postoperative blood transfusion, re-exploration rate and postoperative coagulation tests. The mean difference (MD) and risk ratio (RR) with 95% confidence intervals (CI) were used as summary statistics. Results: Five trials were included in this meta-analysis of 515 patients. Prophylactic EACA was associated with a reduction in postoperative blood loss, but this difference did not reach statistical significance (MD: -7.08; 95% CI: -16.11 to 1.95; P = 0.12). Patients treated with EACA received fewer postoperative blood transfusions, including packed red blood cells (MD: -8.36; 95% CI: -12.63 to -4.09; P = 0.0001), fresh frozen plasma (MD: -3.85; 95% CI: -5.63 to -2.08; P < 0.0001), and platelet concentrate (MD: -10.66; 95% CI: -18.45 to -2.87; P = 0.007), and had a lower re-exploration rate (RR: 0.46; 95% CI: 0.23 to 0.92; P = 0.03). Prophylactic EACA also improved coagulation tests 6 hours after open-heart surgery. Conclusions: Prophylactic EACA minimizes postoperative blood transfusion and helps maintain coagulation in pediatric patients undergoing open-heart surgery. Therefore, the results of this study indicate that adjunctive EACA is a good choice for the prevention of postoperative blood transfusion following pediatric cardiac surgery.     

Use of random versus apheresis platelet concentrates

The respective use of random (RPC) and apheresis (APC) platelet concentrates is highly heterogeneous among countries, ranging from 10 to 98% RPC in countries supposed to provide a similar transfusion service to patients. Moreover, when considering each country in the past 10 years, one can observe that some have changed their policy, switching from a majority of APC to RPC or vice versa. This presentation intends to analyse which factors may impact such decisions. For many years, the only available platelet component was a RPC obtained from whole blood donation by a two centrifugation steps process, the "platelet rich plasma" or PRP method. Since the beginning of the 1970s, APCs became available, with in fact many different techniques leading to many APCs that may not be equivalent. Since the end of the 1980s, a new method of RPC preparation was developed, using the buffy-coat (BC-PC), providing a blood component with highly preserved platelet functions as compared to RPCs prepared by the PRP technique. Finally, the use of each of these components either native, or leuco-reduced, or suspended in a storage solution, or processed with a pathogen inactivation technique adds new layers of complexity to compare them. Innumerable references can be found in the literature describing in vitro functional parameters of platelet concentrates. Although it is clear that BC-RPC retain much more their in vitro functions than PRP-RPC, indicating that no one should use the latter any more, it is much more difficult to distinguish differences between other PCs. Conversely, only a very few studies have been published related to a comparison of clinical efficacy of RPC versus APC, the endpoints being mainly CCI. Similarly to the in vitro studies, although RPC prepared with the PRP method show the lowest CCIs, no clear difference exists between "modern" RPC and APC. Another factor that may impact policy decision is the occurrence of adverse reactions in recipients. When considering only comparable data, for example leuco-reduced RPC versus leuco-reduced APC, there is now evidence that the latter is more associated with adverse reactions in recipients: data from hemovigilance in France show that, although no difference is noted for febrile non haemolytic transfusion reactions, nor for bacteria contamination, the incidence of allergic adverse reactions is about four times higher with APC as compared with RPC. Other aspects may impact the decision: the fact that using APC in place of RPC reduces the total donor exposure of patients was considered critical in some countries to reduce the risk of transmission of blood transmissible disease. Finally, the cost of the components, much higher for APC may be considered.     

Transfusion support in acquired coagulation disorders

Transfusion support for acquired coagulation defects can be life-saving when used correctly. There should be laboratory evidence of such defects combined with clinical evidence of excessive bleeding. The laboratory values alone should not be treated except in preparation for an invasive procedure. Then plasma defects are best treated with fresh frozen plasma immediately before surgery since many of the factors have short half-lives. Platelet infusions are better withheld until the platelet-destroying features of some surgical procedures are completed, as in splenectomy or extracorporeal circulation.     

La vérification ultime au lit du malade: résultats d''une enquête nationale sur les réactifs et dispositifs utilisés en France

The national reference Center for blood groups checked samples of reagents and devices used in France for a definitive verification of pretransfusion ABO tests performed at the patient's bedside, as defined by French health authority regulations. The results of an initial inquiry was published in 1991. The new study shows no significant improvement of the quality of reagents and devices. This is a major concern considering the importance of ABO incompatibility in severe hemolytic transfusion reactions.     

Unappreciated risk factors for transplant patients: HLA antibodies in blood components

One of the more aggressive approaches in renal transplantation is the use of plasmapheresis (PP) and intravenous immunoglobulin to eliminate donor-directed human leukocyte antigen (HLA) alloantibodies. A potential complication of a PP protocol is iatrogenic hypocoagulability resulting from the removal of coagulation factors. To prevent bleeding, hypocoagulable patients may require transfusions with fresh frozen plasma (FFP) and/or cryoprecipitate (Cryo). Although HLA alloantibodies in these components have been linked to complications, such as transfusion-related acute lung injury (TRALI), whether they cause complications following transfusion into allograft recipients is unknown. The incidence of complications would be dependent, in part, upon the frequency of HLA alloantibodies in the various blood components. In this study, segments from 77 units of FFP, 66 units of Cryo, 106 units of packed red blood cells (RBCs), and 59 units of apheresis platelets (Plts) were tested for antibodies to HLA class I and class II antigens using FlowPRA, an HLA antigen-specific flow cytometric assay. On average, 22% of blood components tested contained HLA alloantibodies, tenfold greater than previously reported. This unappreciated frequency of HLA alloantibodies in blood components may pose a risk to transplant patients requiring transfusions by promoting allograft dysfunction or loss.     

Congenital factor XIII deficiency in the south of Tunisia

Factor XIII deficiency is a rare autosomal recessive congenital disorder of haemostasis characterised by a plasmatic factor XIII level less than 1% in homozygote and bleeding as of the youth. We report a study about ten patients with congenital factor XIII deficiency from seven south-Tunisian families, there are seven females. Umbilical bleeding was common and only two patients had intracranial bleeding. The standard screening tests are normal. Factor XIII activity was less than 1% in all patients. A sub-unit A deficit was detected for the ten patients. Out hemorrhagic context, five patients receive regular prophylactic transfusion with fresh frozen plasma.     

Fibrinogen concentrates in bleeding trauma patients

Background A balanced transfusion of red blood cells, fresh frozen plasma (FFP) and platelets are recommended for massively bleeding trauma patients. Fibrinogen concentrates could potentially lessen or replace the need for FFP and/or platelet transfusions. Aim To provide a review of the literature covering the application of fibrinogen concentrates in trauma care. Methods PubMed and Cochrane database search: fibrinogen and (concentrate or trauma), not congenital, published between 2000 and 2012. Results Six papers were identified. None were randomized controlled trials. The main conclusion of these papers was that administration of fibrinogen sometimes together with prothrombin complex concentrate might improve haemostasis in trauma patients resuscitated with synthetic colloids. Data regarding the effect of fibrinogen concentrate together with a more physiological resuscitation fluid, i.e. FFP, or as the only intervention in bleeding trauma patients is lacking. Conclusions Evidence for the use of fibrinogen concentrate to trauma patients with massive bleeding is sparse, of poor quality and confined to patients resuscitated with synthetic colloids. Well-designed prospective, randomized, double-blinded studies evaluating the effect of fibrinogen concentrate, as the only intervention, are urgently needed.