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Factor V Leiden is the commonest hereditary prothrombotic allele, affecting 1% to 5% of the world’s population. The objective of this study was to characterize the perioperative and postoperative outcomes of patients with Factor V Leiden compared to patients without a diagnosis of hereditary thrombophilia. This was a focused systematic review of studies including adult (>18 years) patients with Factor V Leiden (heterozygous or homozygous) undergoing noncardiac surgery. Included studies were either randomized controlled trials or observational. The primary clinical outcomes of interest were thromboembolic events occurring from the perioperative period up to 1 year postoperatively, defined as deep venous thrombosis, pulmonary embolism, or other clinically significant thrombosis occurring during or after a surgical procedure. Secondary outcomes included cerebrovascular events, cardiac events, death, transplant-related outcomes, and surgery-specific morbidity. Pediatric and obstetrical patients were excluded, as were case reports and case series. Databases searched included MEDLINE and EMBASE from inception until August 2021. Study bias was assessed through the CLARITY (Collaboration of McMaster University researchers) Risk of Bias tools, and heterogeneity through analysis of study design and end points, as well as the I2statistic with its confidence interval and the Q statistic. A total of 5275 potentially relevant studies were identified, with 115 having full text assessed for eligibility and 32 included in the systematic review. On the whole, the literature suggests that patients with Factor V Leiden have an increased risk of perioperative and postoperative thromboembolic events compared to patients without the diagnosis. Increased risk was also seen in relation to surgery-specific morbidity and transplant-related outcomes, particularly arterial thrombotic events. The literature did not support an increased risk for mortality, cerebrovascular, or cardiac complications. Limitations of the data include predisposition toward bias due in many study designs and small sample sizes across the majority of published studies. Variable outcome definitions and durations of patient follow-up across different surgical procedures resulted in high study heterogeneity precluding the effective use of meta-analysis. Factor V Leiden status may confer additional risk for surgery-related adverse outcomes. Large, adequately powered studies are required to accurately estimate the degree of this risk by zygosity.

Although unnecessary blood component transfusions are costly and pose substantial patient risks, the extent of unnecessary blood use in a community hospital setting has not been systematically measured.

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Direct oral anticoagulants (DOACs) have at least noninferior efficacy compared with other oral anticoagulants and have ancillary benefits, including overall better safety profiles, lack of the need for routine monitoring, rapid onset of action, and ease of administration. Reversal of these agents may be indicated in certain situations such as severe bleeding and for perioperative management. DOAC-associated bleeding should be risk stratified: patients with moderate or severe bleeding should have the DOAC discontinued and reversal strategies should be considered. Laboratory testing has limited utility in the acute management of bleeding; thrombin time and activated partial thromboplastin time may be useful for excluding clinically relevant levels of dabigatran. Prothrombin time is potentially useful for rivaroxaban and edoxaban, but calibrated anti-Xa assays are optimal for determining clinically relevant levels of factor Xa inhibitors. Because specific reversal agents are not widely available, supportive care and interventions for local hemostasis remain the cornerstones of therapy in the patient with DOAC-associated bleeding. Nonspecific reversal agents should be considered only in the event of severe bleeding because their efficacy is unknown, and they are associated with risk of thrombosis. Recent results from phase 3/4 studies demonstrate efficacy for an antidote to dabigatran (idarucizumab, a monoclonal antibody fragment with specificity for dabigatran) and an antidote to factor Xa inhibitors (andexanet alfa, a recombinant and inactive form of factor Xa that binds inhibitors). A universal reversal agent (ciraparantag) for many anticoagulants, including the DOACs, shows promise in results from phase 1 and 2 studies.

Arnold: Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy; UCB: Consultancy; Amgen: Consultancy, Research Funding.

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No relevant conflicts of interest to declare.

Introduction:

Although frozen plasma (FP) transfusion is ubiquitous in clinical practice there is growing evidence that calls into question its administration outside a few selected clinical disorders. Indications for FP have been further reduced by the introduction of prothrombin complex concentrates (PCCs), which are now recommended for reversal of coagulopathies due to vitamin K antagonists (VKA).Audits consistently demonstrate that FP is administered to patients who do not have a specific indication for its use; in some cases “inappropriate” FP use exceeds “appropriate” FP use. This audit sought to determine if the introduction of PCCs has changed patterns of practice and the appropriateness of FP use.After ethics review we performed a quality assurance retrospective chart audit at a single tertiary care hospital of consecutive patients receiving FP over a 3 month period. Baseline characteristics were obtained for each of these patients via chart review. Each episode of FP use over a 24 hour period was adjudicated independently by two Hematology fellows and determined to be appropriate, inconsistent (with guidelines) yet appropriate, or inappropriate in accordance to Canadian and AABB guidelines. Episodes where a consensus could not be reached were adjudicated independently by a consultant hematologist. Specific criteria for “appropriateness” were developed based on the chart review; for example, transfusion of more than 5 units of packed red blood cells in a 2:1 ratio or greater with FP was considered inconsistent yet appropriate. Bleeding was defined as a decrease in hemoglobin of 2 g/dL over 24 hours, a transfusion of 2 units of red blood cells without a rise in hemoglobin, or bleeding in an enclosed space. Reversal of oral VKAs with FP was always deemed inappropriate. FP usage during the study period was also compared to 3-month periods from previous years.Over the study period, 111 episodes and 466 units of frozen plasma use were recorded. Comparisons to the three month period between January to March of previous years are shown in Figure 1. Interobserver agreement was good between the two Hematology fellows (weighted kappa=0.736) and very good with the fellows to the consensus adjudication (weighted kappa=0.824 and 0.810). After exclusion of FP use for plasmapheresis (always considered appropriate), 33/89 (37.1%), 16/89 (18.0%), and 40/89 (44.9%) episodes were deemed to be appropriate, inconsistent yet appropriate, or inappropriate, respectively. The most common reasons for inappropriate use were the absence of bleeding with an increased INR or VKA reversal. Results are presented in further detail in Table 1. FP transfusion occurred in the ICU 74.8% of the time.Our study is the first to audit FP transfusions in the post-PCC era. FP usage remains inappropriately high. FP transfusion to patients who are not bleeding or having procedures despite INR prolongation and the use of FP to reverse VKA are the main reasons for inappropriate FP usage. The majority of FP usage occurred in the ICU. Targeted interventions to reduce FP usage in the future should include both educational and administrative programs, with a focus on the ICU. Clearer evidence on the role of FP in massive transfusions may also reduce FP usage.Crowther: Pfizer: Consultancy, Honoraria, Research Funding; Octapharma: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Merck: Consultancy; Leo Pharma: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; CSL Behring: Speakers Bureau; Boehringer Ingelheim: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Baxter: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Asahi Kasai: Membership on an entity’s Board of Directors or advisory committees; Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Viropharma: Membership on an entity’s Board of Directors or advisory committees.

Although frozen plasma (FP) transfusion is ubiquitous in clinical practice there is growing evidence that calls into question its administration outside a few selected clinical disorders. Indications for FP have been further reduced by the introduction of prothrombin complex concentrates (PCCs), which are now recommended for reversal of coagulopathies due to vitamin K antagonists (VKA).