Fresh frozen plasma transfusion in critically ill medical patients with coagulopathy

OBJECTIVE: Although restrictive red cell transfusion practice has become a standard of care in the critically ill, data on the use of fresh frozen plasma (FFP) are limited. We hypothesized that the practice of FFP transfusion in the medical intensive care unit is variable and that liberal use may not be associated with improved outcome. DESIGN: Retrospective cohort study. SETTING: A 24-bed medical intensive care unit in a tertiary referral center. PATIENTS: All patients admitted to a medical intensive care unit during a 5-month period who had abnormal coagulation defined as international normalized ratio (INR) of > or = 1.5-times normal. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We collected data on demographics, severity of illness as measured by Acute Physiology and Chronic Health Evaluation (APACHE) III scores, INR, bleeding episodes, and transfusion complications. We identified 115 patients with coagulopathy (INR of > or = 1.5) but without active bleeding. A total of 44 patients (38.3%) received FFP transfusion. INR was corrected in 16 of 44 patients (36%) who received transfusion. Median dose of FFP was 17 mL/kg in patients who had INR corrected vs. 10 mL/kg in those who did not (p = .018). There was no difference in age, sex, APACHE III scores, liver disease, Coumadin treatment, or INR level between those who did and did not receive FFP. Invasive procedures (68.2% vs. 40.8%, p = .004) and history of recent gastrointestinal bleeding (41% vs. 7%, p < .001) were more frequent in the group with transfusion. Although there was no difference in new bleeding episodes (6.8% in transfused vs. 2.8% in nontransfused group, p = .369), new onset acute lung injury was more frequent in the transfused group (18% vs. 4%, p = .021). Adjusted for severity of illness, hospital mortality and intensive care unit length of stay among survivors were not different between the two groups. CONCLUSION: The risk-benefit ratio of FFP transfusion in critically ill medical patients with coagulopathy may not be favorable. Randomized controlled trials evaluating restrictive vs. liberal FFP transfusion strategies are warranted.     

Protocolized use of Factor Eight Inhibitor Bypassing Activity (FEIBA) for the reversal of warfarin induced coagulopathy

IntroductionCoagulopathy due to warfarin in patients with major bleeding was traditionally reversed with fresh frozen plasma and intravenous (IV) vitamin K, but prothrombin complex concentrates (PCC) are increasingly used in the treatment of these patients. Factor Eight Inhibitor Bypassing Activity (FEIBA) is an activated four-factor PCC most commonly used in patients with hemophilia. We aimed to evaluate the efficacy and safety of FEIBA and IV vitamin K for the reversal of warfarin-associated coagulopathy in patients with major bleeding, by measuring the percentage of patients who achieved target INR ≤ 1.5 and the incidence of thrombotic adverse events (TAE).MethodsIn this prospective observational study, we enrolled patients presenting to the Emergency Department (ED) with warfarin associated coagulopathy (INR > 1.5) and major bleeding. Patients received FEIBA using an INR based dosing strategy and IV vitamin K.ResultsIn 43 patients, median initial INR was 4.0 (2.7, 7.3 interquartile range (IQR)). Median time to result the second INR was 45 min (38, 55 IQR) and the median INR was 1.4 (1.3, 1.6 IQR). Out of the 43 patients, 93% achieved the target INR of ≤1.5. In-hospital mortality was 40% (17 patients). There were 11 TAEs in 6 patients (14%); 4 events in 2 patients (5%) were attributed to FEIBA.ConclusionA protocolized use of FEIBA and IV vitamin K resulted in the efficacious reversal of warfarin-induced coagulopathy in patients with major bleeding. TAEs occurred in 14% of patients and were attributed to FEIBA in 5% of patients.     

The blood bank: from provider to partner in treatment of massively bleeding patients

BACKGROUND: Continued hemorrhage remains a major cause of mortality in massively transfused patients of whom many develop coagulopathy. Reviewing transfusion practice for these patients, we found that at our hospital more than 10 percent received a suboptimal transfusion therapy and that survivors had a higher platelet count than nonsurvivors. We therefore investigated whether the blood bank could improve its service and hence improve the outcome.
METHODS: The blood bank introduced monitoring of the delivery of blood products and contacted the clinician provided there was an imbalance in the transfusion practice. For massively transfused patients, transfusion packages, including five red blood cells, five fresh-frozen plasma, and two platelet concentrates, were introduced to improve hemostatic competence. The Thrombelastograph (TEG) Haemostatic System (Haemoscope Corp., Niles, IL) was implemented, aiding in the diagnosis and treatment of coagulopathy.
RESULTS: The fraction of suboptimally transfused patients declined from more than 10 percent to less than 3 percent. The transfusion package administered intraoperatively to patients operated on for a ruptured abdominal aortic aneurysm resulted in decreased postoperative transfusion requirements and improved 30-day survival (66% vs. 44%) compared with controls. Performing TEG alone in patients with significant bleeding as judged by the anesthetist reduced the number of analyses by approximately 85 percent, while those patients with coagulopathy remained identified. The TEG showed a 97 percent predictability in identifying a surgical cause of bleeding in postoperative patients. Ten percent of the massively bleeding trauma patients had hyperfibrinolysis as the major cause of bleeding, whereas 45 percent were hypercoagulable.
CONCLUSION: The initiative from the blood bank has improved the transfusion practice and, hence, survival in massively transfused patients at our hospital.     

Massive transfusion: a review

The most generally accepted definition of massive transfusion is the replacement of the patient's blood volume in under 24 hours. This corresponds to 3000ml of red cells or approximately 10 units of packed cells in an average weight person. The most frequent reasons for massive transfusion include trauma, GIT bleeding, obstetric bleeding, bleeding abdominal aortic aneurysm, and major elective vascular surgery. Survival in massively transfused patients will vary depending on the underlying disease process. Overall survivals of 45–67% have been reported and of these 90% regain full independence and 75% return to work. Massive transfusion imposes a considerable strain on blood banking resources and in many centres a relatively small number of patients consume 10–15% of the total blood supply annually. Severe coagulopathy (INR and/or APTT double normal) will develop in 40% of patients and severe thrombocytopenia (platelets <50 × 10⁹/L) in 30% of patients between 10 and 20 units of units transfused. Coagulopathy, hypothermia and tissue injury all contribute to the phenomenon of microvascular oozing which develops in approximately 30% of massively transfused patients. There is only a weak correlation between the severity of coagulopathy/thrombocytopoenia and the total units transfused suggesting that factors such as duration of tissue hypoperfusion and consumption are likely to play a more important role than simple haemodilution of coagulation factors. Because of the lack of clear correlation between coagulopathy/thrombocytopenia and the number of units transfused, “formula” replacement with plasma and platelets is not recommended. The approach to blood product support in the massively transfused patient will be discussed.     

The use of fresh‐frozen plasma in England: high levels of inappropriate use in adults and children

BACKGROUND: Fresh‐frozen plasma (FFP) is given to patients across a range of clinical settings, frequently in association with abnormalities of standard coagulation tests. STUDY DESIGN AND METHODS: A UK‐wide study of FFP transfusion practice was undertaken to characterize the current patterns of administration and to evaluate the contribution of pretransfusion coagulation tests. RESULTS: A total of 4969 FFP transfusions given to patients in 190 hospitals were analyzed, of which 93.3% were in adults and 6.7% in children or infants. FFP transfusions to adults were given most frequently in intensive‐treatment or high‐dependency units (32%), in operating rooms or recovery (23%), or on medical wards (22%). In adult patients 43% of all FFP transfusions were given in the absence of documented bleeding, as prophylaxis for abnormal coagulation tests or before procedures or surgery. There was wide variation in international normalized ratio (INR) or prothrombin times before FFP administration; in 30.9% of patients where the main reason for transfusion was prophylactic in the absence of bleeding the INR was 1.5 or less. Changes in standard coagulation results after FFP administration were generally very small for adults and children. CONCLUSIONS: This study raises important questions about the clinical benefit of much of current FFP usage. It highlights the pressing need for better studies to inform and evaluate quantitative data for the effect of plasma on standard coagulation tests.     

ROTEM in the setting of liver transplant surgery reduces frozen plasma transfusion

BackgroundINR is traditionally used as a marker of clinical coagulopathy, but is suboptimal in liver disease patients due to rebalanced hemostasis and its ineffectiveness to predict bleeding. Rotational thromboelastometry (ROTEM) testing evaluates whole blood hemostasis, which may provide more accurate assessments with the EXTEM CT parameter than INR. Thus, in end-stage liver disease (ESLD) patients, we hypothesized that elevated INRs are associated with normal EXTEM CT values.MethodsA retrospective study assessing adult (>18) patients with ESLD and elevated INRs undergoing liver transplantation, was performed to assess correlations between INR and EXTEM CT. This included patients post-ROTEM implementation where all had pre-operative ROTEM testing; and patients up to one year pre-ROTEM implementation to compare transfusion utilization. Data abstracted also included patient demographics, coagulation testing results, liver disease etiology, and MELD score.ResultsThe study included 138 patients in the post-ROTEM group and 59 patients in the pre-ROTEM group. Normal EXTEM CT was observed in 95.3 % and 93 % of patients with INR of 1.3–1.8 and up to 3 respectively. There was no correlation between INR of 1.3–1.8 and EXTEM CT (? = 0.239), and only moderate correlation was observed with higher INRs (? = 0.617 with INRs >1.8). ROTEM-guided transfusion in liver transplant surgeries was associated with reduced plasma transfusion (OR 0.27, 95 % CI 0.12?0.58, p = 0.001) after adjusting for red cell utilization and coagulation testing.ConclusionOur study suggests ROTEM may be advantageous for evaluating coagulopathy in patients with liver disease and ROTEM-guided transfusion reduces plasma transfusion.     

Prospective comparison of point‐of‐care international normalised ratio measurement versus plasma international normalised ratio for acute traumatic coagulopathy

Objective: Early detection of acute traumatic coagulopathy (ATC) might be useful to guide trauma resuscitation. This study aimed to compare results from a point‐of‐care (POC) international normalised ratio (INR) measuring device with plasma INR in acute trauma patients. Methods: This was a single‐centre, prospective, blinded comparative study. All trauma patients meeting trauma call‐out criteria in a major trauma centre were screened. Patients predicted to have ATC were identified by the Coagulopathy of Severe Trauma score and a convenience sample of 72 patients included in this study. Whole blood was used to measure INR at the bedside, whereas blood from the same sample was sent to the hospital laboratory for plasma INR testing. Agreement between the laboratory and bedside INR was determined using a Bland–Altman plot. Results: There were 38 (52.8%) patients with ATC by laboratory measure, defined as INR >1.5 or activated partial thrombin time >60 s, whereas the POC system identified 28 (38.9%) patients with an INR >1.5. Assuming the laboratory measure as the gold standard, the POC system had a specificity of 88.2% (95% confidence interval 71.6–96.2) and a sensitivity of 63.1% (95% confidence interval 46.0–77.7). Bland–Altman plots demonstrated inadequate agreement between the two methods of INR measurement for the major trauma patient. Conclusions: POC INR measurements using this method during the trauma reception and resuscitative phases cannot be used to identify or exclude patients with ATC. Further studies are required to determine if there is any role for POC INR measures during trauma resuscitation.     

Proactive administration of platelets and plasma for patients with a ruptured abdominal aortic aneurysm: evaluating a change in transfusion practice

BACKGROUND: Continued hemorrhage remains a major contributor of mortality in massively transfused patients and those who survive have a higher platelet (PLT) count and a shorter prothrombin time and activated partial thromboplastin time (APTT) than nonsurvivors. It was considered that early substitution with PLTs and fresh-frozen plasma (FFP) would prevent development of coagulopathy and thus improve survival. STUDY DESIGN AND METHODS: Survival of patients undergoing surgery for a ruptured abdominal aortic aneurysm (rAAA) was compared after implementing a proactive transfusion therapy encompassing two pooled buffy-coat PLT concentrates (PBPCs) immediately when a rupture of the aorta was suspected and again 30 minutes before aortic unclamping together with FFP administered in a 1:1 ratio to the amount of red blood cells (RBCs) with that of a control group receiving transfusion therapy according to existing recommendations. RESULTS: The intervention group (n = 50) had a higher PLT count at arrival at the intensive care unit compared to the control group (n = 82; 155 x 10(9)/L vs. 69 x 10(9)/L; p < 0.0001), shorter APTT (39 sec vs. 44 sec; p < 0.001), fewer postoperative transfusions (RBCs, 2 vs. 6; FFP, 2 vs. 4; and PBPCs, 0 vs. 1; p < 0.01), and a higher 30-day survival rate (66% vs. 44%; p = 0.02). CONCLUSION: This study suggests that proactive administration of PLTs and FFP improves coagulation competence, reduces postoperative hemorrhage, and increases survival in massively bleeding rAAA patients.     

Acute traumatic coagulopathy: Incidence,risk stratification and therapeutic options

BACKGROUND:

Uncontrolled hemorrhage is responsible for over 50% of all trauma-related deaths within the first 48 hours after admission. Clinical observations together with recent research resulted in an appreciation of the central role of coagulopathy in acute trauma care. A synopsis is presented of different retrospective analyses based upon datasets from severe multiply injured patients derived from the TR-DGU database (Trauma Registry of the Deutsche Gesellschaft fur Unfallchirurgie (DGU)/ German Society of Trauma Surgery) with respect to frequency, risk stratification and therapeutic options of acute traumatic coagulopathy (ATC).

METHODS:

The synopsis of different analyses based upon the datasets from severe multiply injured patients derived from the TR-DGU database and development/validation of a scoring system (TASH-score = Trauma Associated Severe Hemorrhage) that allows an early and reliable estimation for the probability of massive transfusion as a surrogate for life-threatening hemorrhage after severe multiple injuries.

RESULTS:

The high frequency of ATC upon emergency room admission is associated with significant morbidity and mortality in multiply injured patients. The TASH-score is recognized as an easy-to-calculate and valid scoring system to predict the individual''s probability for massive transfusion and thus ongoing life-threatening hemorrhage at a very early stage after severe multiple injuries.

CONCLUSION:

An early aggressive management of ATC including a more balanced administration of blood products to improve outcome is advocated.KEY WORDS: Coagulopathy, Epidemiology, Management, Risk stratification, Trauma     

Reduction in plasma transfusion after enforcement of transfusion guidelines

BACKGROUND: The majority of fresh‐frozen plasma (FFP) is transfused in the United States in the management of acquired bleeding disorders. The prothrombin time (PT), and its derivative the international normalized ratio (INR), is the most common test used to detect the presence and gauge the severity of these disorders. Observation studies have shown that the PT correlates poorly with clinical bleeding and that transfusion of plasma often achieves no measurable change in the INR nor is of any known clinical benefit. STUDY DESIGN AND METHODS: Data on FFP and red blood cell transfusions and measures of hospital activity and mortality were collected over a 12‐year period. The first 3 years were baseline years, the next 3 years were physician education years, and in the last 6 years all requests for FFP were screened. Orders were discouraged if the INR was less than 2.0 in the absence of active bleeding and the use of vitamin K was encouraged if the patient was taking warfarin. RESULTS: This program ultimately resulted in an approximate 80% reduction in transfused FFP using the average of the baseline years compared to the average of the last 3 years (157 ± 19 units FFP/1000 discharges vs. 30 ± 15, p < 0.01, respectively). Overall, hospital activity remained largely unchanged or increased. No unexpected bleeding was reported, which was attributed to a failure to transfuse FFP, and inpatient mortality rate decreased during these 12 years. CONCLUSIONS: A program of engagement and interdiction using evidence‐based guidelines can successfully decrease the use of FFP without any observable increase in unexpected bleeding.     

A national clinical scenario-based survey of clinicians' attitudes towards fresh frozen plasma transfusion for critically ill patients

Background: It is known that 20–30% of fresh frozen plasma (FFP) is used in intensive care units (ICUs), but little is known about variations in decision making between clinicians in relation to coagulopathy management. Our aim was to describe ICU clinicians' beliefs and practice in relation to FFP treatment of non‐bleeding coagulopathic critically ill patients. Methods: Two patient‐based scenarios were developed and sent to 2700 members of two UK intensive care professional societies. Scenario 1 was a non‐bleeding septic patient with coagulopathy; scenario 2 was a non‐bleeding critically ill patient with hepatic cirrhosis and coagulopathy. Responses were sought in relation to FFP prophylaxis, and prior to central venous cannulation. A supplementary question asked clinicians' view of prophylaxis in relation to other ICU procedures. Results: Two‐thousand‐and‐seven‐hundred clinicians were surveyed from whom 601 responses were received (22·3% response rate). For scenario 1 52% of respondents stated that they would never routinely administer prophylactic FFP, but this decreased to 9% when central venous cannulation was planned (P < 0·01). There was wide variation in the ‘trigger’ INR (international normalised ratio) value used prior to central vein cannulation, the most common range being 2·0–2·4. For scenario 2, responses were very similar. More than 80% of clinicians stated that they would routinely treat coagulopathy prior to lumbar puncture, epidural catheterisation, intracranial pressure monitoring and tracheostomy; and 54% prior to chest drain insertion. Conclusion: Our survey demonstrated a wide range of responses consistent with important variations in clinical practice and substantial clinical uncertainty in relation to FFP treatment for non‐bleeding ICU patients.     

Definition and drivers of acute traumatic coagulopathy: clinical and experimental investigations

Summary. Background: Acute traumatic coagulopathy (ATC) is an impairment of hemostasis that occurs early after injury and is associated with a 4‐fold higher mortality, increased transfusion requirements and organ failure. Objectives: The purpose of the present study was to develop a clinically relevant definition of ATC and understand the etiology of this endogenous coagulopathy. Patients/methods: We conducted a retrospective cohort study of trauma patients admitted to five international trauma centers and corroborated our findings in a novel rat model of ATC. Coagulation status on emergency department arrival was correlated with trauma and shock severity, mortality and transfusion requirements. 3646 complete records were available for analysis. Results: Patients arriving with a prothrombin time ratio (PTr) > 1.2 had significantly higher mortality and transfusion requirements than patients with a normal PTr (mortality: 22.7% vs. 7.0%; P < 0.001. Packed red blood cells: 3.5 vs. 1.2 units; P < 0.001. Fresh frozen plasma: 2.1 vs. 0.8 units; P < 0.001). The severity of ATC correlated strongly with the combined degree of injury and shock. The rat model controlled for exogenously induced coagulopathy and mirrored the clinical findings. Significant coagulopathy developed only in animals subjected to both trauma and hemorrhagic shock (PTr: 1.30. APTTr: 1.36; both P < 0.001 compared with sham controls). Conclusions: ATC develops endogenously in response to a combination of tissue damage and shock. It is associated with increased mortality and transfusion requirements in a dose‐dependent manner. When defined by standard clotting times, a PTr > 1.2 should be adopted as a clinically relevant definition of ATC.     

Transfusion of Blood Products in Trauma: An Update

Background: Blood transfusion in the management of severely injured patients can be lifesaving. These patients are susceptible to developing early coagulopathy, thus perpetuating bleeding. Objectives: This article presents recent advances in both the civilian and military clinical arena to improve the treatment of trauma patients with severe hemorrhage, the use of agents to support coagulation, perspectives on restrictive transfusion strategies, and transfusion-related risks. Discussion: Massive blood transfusion is an adjunct to surgical care. The volume of blood products transfused and the ratio of blood components have been associated with increased morbidity and mortality rates. The adverse clinical effects of transfusion and the limited supply of blood products have resulted in modern resuscitation protocols to limit the volume of blood transfused. Conclusion: A restrictive blood transfusion strategy and the use of hemostatic agents may decrease morbidity and mortality in trauma patients, but insufficient data are available for their use in trauma patients. Massive transfusion should reflect an equal ratio of packed red cells and plasma to limit coagulopathy. Prospective randomized trials are needed to standardize an effective protocol.     

急诊科华法林相关致命性出血114例分析

目的调查综合医院急诊科华法林相关致命性出血患者抗凝病因、出血易感因素和临床特点。方法收集温州医科大学附属第一医院急诊科抢救室2017年1月至2020年2月期间收治的华法林相关致命性出血患者,用描述性研究方法分析其抗凝病因、出血易感因素和临床特点。根据出血时国际标准化比值(international normalized ratio,INR),分为INR超范围组和INR未超范围组,采用卡方检验、t检验和Wilcoxon秩和检验对比INR超范围组和非超范围组各项指标的差异。Wilcoxon秩和检验和t检验用于消化道出血和脑出血特点分析。结果共纳入114例华法林相关致命性出血患者。①华法林相关致命性出血分别占急救病例的0.36%(114/32040)、服用华法林病例的9.84%(114/1158)。②抗凝病因:与心房颤动(atrial fibrillation,AF)相关77例(67.5%),与心瓣膜置换术后相关32例(28.1%)。③出血易感因素:HAS-BLED评分4.0(3.0,5.0)分,既往使用药物史84例(73.7%),年龄>65岁77例(67.5%),不定期监测INR65例(57.0%),近期增加剂量29例(25.4%)。④出血部位:消化道出血40例(35.1%),血红蛋白(hemoglobin,Hb)最低,HAS-BLED评分最高;脑出血21例(18.4%),凝血酶原时间(prothrombin time,PT)最短,INR最低,Hb最高,HAS-BLED评分最低。⑤临床预后:死亡(或病危放弃治疗)12例(10.5%),其中脑出血6例、消化道出血5例、咯血1例。⑥INR超范围组(n=86)与INR未超范围组(n=28)比较,在既往抗血小板治疗、近期增加剂量、HAS-BLED评分和出血部位上差异有统计学意义(均P<0.05)。结论在华法林相关致命性出血患者中,AF和心瓣膜置换术后是华法林抗凝的主要原因,INR超范围与既往抗血小板治疗、近期增加剂量和HAS-BLED评分高相关。消化道出血最常见,该组患者Hb最低、HAS-BLED评分最高;脑出血次之,该组患者PT最短、INR最低、Hb最高。华法林服用致相关致命性出血的发生率和病死率均较高。     

Plasma transfusion in critically Ill patients with abnormal coagulation tests before invasive procedures: A propensity-adjusted cohort study

ObjectiveTo evaluate the association between plasma transfusion and bleeding complications in critically ill patients with an elevated international normalized ratios undergoing invasive procedures.MethodsA retrospective study was conducted to evaluate a consecutive sample of critically ill adult patients undergoing invasive procedures (N = 487) with an international normalized ratio ≥ 1.5 between January 1, 2019 and December 31, 2019. Among the followed patients, 125 were excluded due to incomplete case records and 362 were finally included in this investigation. The exposure was whether plasma had been transfused within 24 h before the invasive procedure. The primary outcome was the occurrence of postprocedural bleeding complications. Secondary outcomes included transfusion of red blood cells within 24 h of the invasive procedure, and additional patient-important outcomes such as mortality and length of stay. Tests were performed with univariate and propensity-matched analyses.ResultsOf the 362 study participants, 99 (27.3 %) received a preprocedural plasma transfusion. In the propensity score-matched analysis, the rate of the occurrence of postprocedural bleeding complications between two groups was not statistically different (OR, 0.605[95 % CI, 0.341–1.071]; P = .085). The rate of postoperative red blood cell transfusion in the plasma transfusion group was higher than that in the non-plasma transfusion group (35.5 % vs 21.5 %; P < .05). No statistically significant difference in mortality was observed between the two groups (29.0 % vs 31.6 %; P = .101).ConclusionsProphylactic plasma transfusion failed to reduce postprocedural bleeding complications in ill critically patients with a coagulopathy. Meanwhile, it was associated with increased red blood cell transfusion after invasive procedures. Findings suggest that abnormal preprocedural international normalized ratios should be managed more conservatively.     

The effect of plasma transfusion on morbidity and mortality: a systematic review and meta‐analysis

BACKGROUND: Plasma transfusion is increasingly performed without clear consensus on indications. We systematically reviewed the literature to summarize the available evidence regarding the benefits and harms of plasma transfusion in common clinical settings. STUDY DESIGN AND METHODS: We searched electronic databases from inception through August 2009. Eligible studies enrolled adult patients transfused with plasma and compared to a control group. Paired reviewers independently assessed studies for eligibility and extracted quality and outcome data. RESULTS: Thirty‐seven studies met eligibility criteria, most of which were observational. In patients undergoing massive transfusion, plasma infusion at high plasma : red blood cell ratios was associated with a significant reduction in the risk of death (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.24‐0.60) and multiorgan failure (OR, 0.40; 95% CI, 0.26‐0.60). However, the quality of this evidence was very low due to significant unexplained heterogeneity and several other biases. In a single retrospective study, plasma transfusion was associated with reduced mortality in anticoagulated patients with intracranial hemorrhage (OR, 0.29; 95% CI, 0.09‐0.98). In patients undergoing surgery without massive transfusion, plasma infusion was associated with a trend toward increased mortality (OR, 1.22; 95% CI, 0.73‐2.03). Plasma transfusion was associated with increased risk of developing acute lung injury (OR, 2.92; 95% CI, 1.99‐4.29). CONCLUSIONS: Very‐low‐quality evidence suggests that plasma infusion in the setting of massive transfusion for trauma patients may be associated with a reduction in the risk of death and multiorgan failure. A survival benefit was not demonstrated in most other transfusion populations.     

The patterns of anticoagulation control and the risk of stroke,bleeding and mortality in patients with non‐valvular atrial fibrillation

Summary. Background: Anticoagulation control is often summarized using the percentage of time spent in a therapeutic range (TTR). This method does not describe the timing and severity of fluctuations in the International Normalised Ratio (INR).Objective: To evaluate whether the TTR method can be improved by considering the patterns of INR over time.Methods: The cohort included adults aged 40+ years with atrial fibrillation (AF) and laboratory records of INR as recorded in the UK Clinical Practice Research Datalink. Statistical clustering techniques based on simple INR measures were used to describe the patterns of INR. Nested case–control studies calculated the odds ratios (ORs) for the risk of stroke, bleeding and mortality with TTR and different INR patterns. It was also evaluated whether cluster analyses improved the prediction of outcomes over TTR.Results: A number of 27 381 patients were studied with a mean age of 73 years. The OR for mortality was 3.76 (95% confidence interval [CI] 3.03–4.68) in patients with < 30% TTR compared with patients with 100% TTR. INR patterns were found to be best described by six different clusters. The cluster with the most unstable pattern was associated with the largest risk of mortality (OR 10.7, 95% CI 8.27–13.85) and stroke (OR 3.42, 95% CI 2.08–5.63). INR measures that predicted death independent of the TTR‐included absolute difference between two subsequent INR measurements and change relative to the mean over time.Conclusion: Cluster analysis of INR patterns improved the prediction of clinical outcomes over TTR and may help to identify warfarin users who need additional anticoagulation monitoring.     

Use and effectiveness of prothrombin complex concentrates vs fresh frozen plasma in gastrointestinal hemorrhage due to warfarin usage in the ED

Objectives

High International Normalized Ratio (INR) level resulting from warfarin use increases the risk of gastrointestinal hemorrhages. We aimed to compare the efficacy of prothrombin complex concentrates (PCC) and fresh frozen plasma (FFP) at lowering the INR level, decreasing active hemorrhages visible by endoscopy, and shortening the length of stay at the emergency department (ED).

Method

This study is a prospective cohort study of consecutive patents with gastrointestinal hemorrhages that received either PCC or FFP. With strict exclusion criteria, only patients over 18 years of age with a high INR level (> 2.1) due to warfarin usage were included.

Results

A total of 40 patients (18 female) were included in the study, 20 each in the PCC and FFP groups. For the PCC group, the mean INR levels at the second and sixth hours were lower than those for the FFP group (second hour INR: 1.53 vs 4.50, P < .01, sixth hour INR: 1.52 vs 2.41, P < .01). Seven patients experienced active bleeding (Forrest 1) in the FFP group, whereas no patient experienced active bleeding in the PCC group based on the Forrest classification (35% vs 0%, P < .01), and only 3 patients in the FFP group underwent invasive/surgical treatment (15% vs 0%, P < .01). The ED length of stay was lower for the PCC group (1.62 days vs 3.46 days, P < .01).

Conclusion

For patients experiencing a gastrointestinal hemorrhage, INR levels were reversed more quickly, there was less active bleeding on endoscopy, and the ED length of stay was lower in the PCC group than in the FFP group.     

Nonvariceal upper gastrointestinal bleeding

Nonvariceal upper gastrointestinal bleeding (NVUGIB) remains an important cause of morbidity and mortality. The etiological role and the relative risk of nonsteroidal anti-inflammatory drugs (NSAIDs) in association with other clinical factors are the focus of several papers published in the last year. Data from studies that evaluate the interaction of NSAIDs with Helicobacter pylori suggest that there is a clear role for eradication in aspirin-related bleeding. Although the benefit of H. pylori eradication in nonaspirin NSAID-related bleeding is being debated, they should both be eliminated given their relative contribution to the causation of peptic ulcer hemorrhage. The search for reliable and accurate tools to predict outcomes after NVUGIB continues. Recent important contributions in this area of research are the use of a clinical prediction guide to identify patients who are likely to require endoscopic intervention, and the use of Doppler ultrasound examination of the ulcer base to predict rebleeding. The role of antisecretory therapy in the setting of acute NVUGIB has been revisited in two meta-analyses and one randomized, placebo-controlled trial of omeprazole as an adjunct to endoscopic intervention. Until more definitive data are available, it appears that the effect of acid-decreasing medications is more important when endoscopic therapy is not provided than when effective endoscopic intervention is instituted. With regard to therapeutic endoscopy for upper gastrointestinal bleeding, the few randomized trials that have been published in full form in the last year focus on the use of mechanical methods of hemostasis for peptic ulcer bleeding and other etiologies such as Mallory-Weiss tears and Dieulafoy lesions.