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. It is not surprising that patients with lower INRs 1. The latter finding can be explained by considering that 1 unit of FFP approximately mL , when administered to a 70 kg recipient, translates into a dose of 3.
Receipt of 2 units of FFP by a 70 kg recipient would amount to a dose of 6. Furthermore, each recipient in this study received on average 2. Thus the low rate of correction could be attributable to the small volume of FFP transfused. Additionally, consider that the plasma volume of a 70 kg recipient with a Hct of 0. This might also explain the popular perception of the success of prophylactically administering plasma to recipients with modestly elevated INRs; when these patients tolerate the surgical procedure without excessive bleeding, this positive outcome is attributed to the administration of the plasma.
In reality, these recipients were unlikely to have had a coagulopthic bleed owing to their significant reserve of clotting factors even with their slightly elevated INR. Figure 1: Adapted from Dzik [7]. Since the INR only provides limited information regarding a single aspect of anticoagulation status, complete normalization for the INR to control bleeding is usually not necessary [6]. An INR elevation alone does not indicate a patient is coagulopathic or at an increased risk of bleeding [7].
Additionally, an INR elevation in patients with liver dysfunction likely reflects an overall state of decreased factor production, both procoagulant and anticoagulant factors [8]. Complete normalization of the INR is not required to achieve hemostasis or prevent bleeding from a procedure. Want to learn more about EM Pharmacology? Fresh frozen plasma is ineffective for correcting minimally elevated international normalized ratios.
PMID: Clin Appl Thromb Hemost. Toward rational fresh frozen plasma transfusion: The effect of plasma transfusion on coagulation test results.
Am J Clin Pathol. On average, INR decreased by only 0. Further, a retrospective study by Holland and Brooks introduced the use of a control group to examine the effect of medical treatment alone on mildly prolonged coagulation factors. In this study, patients receiving FFP transfusions and a control group of 71 patients were included in the analysis.
Findings showed that mildly elevated INRs 1. While there may be a consumptive process occurring that depletes factors at a quicker rate than they are replaced by FFP transfusions, another likely explanation is the that the dose of FFP may be inadequate.
The above studies support the modification in recent guidelines indicating FFP transfusion as prophylaxis in non-bleeding patients with hereditary coagulation defects prior to invasive procedures. Coagulation activity is determined by ordering coagulation factor levels, such as factor V and factor VII, which are assayed from the PT [6].
These newer guidelines do not clearly define the recommendations for critically ill patients or patients with acquired coagulation deficits prior to invasive procedure. Regardless of the guidelines, mild elevations in INR may be normal. Additionally, INR levels may be influenced by multiple factors. Most commonly, elevated hematocrit has a proportionally reduced volume of plasma, and therefore the ratio of anticoagulant to plasma is increased, resulting in a prolonged bleeding time and spurious elevation in the INR [8].
It is important to recognize the limitations of the INR. INR is validated for patients who are stably Coumadin anticoagulated, but not for patients with coagulopathy of liver disease or isolated factor VII deficiency.
In the latter settings the interlaboratory agreement may be poor and the bleeding risks poorly correlated with INR. The purpose of FFP transfusion is to lower the risk of bleeding in patients with coagulopathy. However, studies have found no difference in bleeding events in patients receiving FFP compared to those not.
In a retrospective study of patients, 44 critically-ill, non-bleeding patients received FFP. Results showed no statistically significant decrease in INR or bleeding episodes, hospital deaths or length of stay in ICU [9].
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