How does ffp lower inr

Effect of fresh-frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities.

Fresh frozen plasma transfusion fails to influence the hemostatic balance in critically ill patients with a coagulopathy. J Thromb Haemost. The International Normalized Ratio overestimates coagulopathy in stable trauma and surgical patients. J Trauma Acute Care Surg. Harrison MF. The misunderstood coagulopathy of liver disease: a review for the acute setting. West J Emerg Med.

Bio Twitter Latest Posts. Bio Twitter Facebook Latest Posts. Bryan D. 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. Whereas, as many as 4 bags of plasma may be necessary to correct an INR of 1. When the INR is 1. Physicians performing invasive procedures want to avoid hemorrhagic complications and often regard a mild elevation of a coagulation test result as an indication to order plasma.

The decision to prophylactically transfuse plasma is based on two unproven assumptions:. An analysis of the Vitamin K dependent coagulation factors at different INR values clearly contradicts the first assumption. These results explain why a mildly elevated INR is not usually associated with spontaneous hemorrhage and does not increase the risk of bleeding during routine invasive procedures. Studies during the last 20 years in patients undergoing liver biopsies, bronchoscopic biopsies, renal biopsies, central line vein cannulation, thoracentesis and angiography have repeatedly demonstrated that INR and PTT are not predictive of hemorrhage.

While a patient with an INR of 1. However, it must be remembered that the risk of bleeding is greater if the platelet count is decreased, platelet function is abnormal, the patient has received antiplatelet medication, has experienced massive trauma or is undergoing extensive surgery. In view of this information, the common practice of prescribing plasma to correct a mildly elevated INR prior to an invasive procedure needs to be reevaluated.

It is usually not necessary or efficacious to correct an INR below 1. In summary, plasma transfusion has minimal effect on normalizing the INR in patients with mildly prolonged INRs for the following reasons:.

For elective surgery, the best strategy for warfarin reversal is to discontinue warfarin 3 to 5 days prior to the procedure. Patients presenting with minor bleeding may be treated by withholding the next dose of warfarin and giving oral Vitamin K. When vitamin K replacement therapy is used, its effect does not begin until hours after administration and is not complete until 36 hours.

Acquired abnormalities of hemostasis may occur with a variety of other clinical disorders. These usually involve multiple plasma coagulation factor deficits and are more common than inherited plasma deficiencies that usually involve single coagulation factor deficiencies.

Consequently, there is a concurrent derangement of several coagulation tests as shown in following table. The lower dose corresponds to 3 to 6 bags of plasma in an average 70 kg adult, while the higher dose corresponds to 8 to 14 bags. FFP is the treatment of choice for congenital factor deficiencies when more specific concentrates are not available.

Examples include factors V and XI. Dosing of plasma for congenital factor deficiencies is dependent upon the degree of factor deficiency and the half-life of the deficient factor s.

All of the factors noted above, except V and VII, have a half-life greater than 12 hours and do not need to be replaced more often than every 12 hours.