Perioperative safety and haematostatic efficacy of a new bypassing agent pd-FVIIa/FX (Byclot) in haemophilia patients with high-responding type inhibitors.

: The novel agent pd-FVIIa/FX is a 1 : 10 protein weight mixture of activated factor VII (FVIIa) and factor X (FX) derived from donated blood plasma. A phase III clinical trial of pd-FVIIa/FX revealed high efficacy for bleeding episodes in haemophilia patients with inhibitors. However, up to now, only one case of this new agent being used for surgery had been reported. The objective of this study is to evaluate the perioperative haemostatic efficacy and safety of pd-FVIIa/FX in haemophilia patients with inhibitors. We retrospectively reviewed 25 operation charts from 14 haemophilia patients with high-responding inhibitors using pd-FVIIa/FX during the perioperative period. Efficacy was evaluated by attending physicians and results divided into four groups (excellent, good, fair, and poor). The operation chart was provided by nine Japanese medical institutes with expertise in haemophilia management. Out of the total of 25 surgical procedures, 44% (11/25) were classified as major surgery and the remainders were minor surgeries. In all of the surgeries but one, rFVIIa and/or APCC were administered in combination or sequential method. In all cases except one, the haemostatic efficiency rate was judged as excellent or good by treating physicians for an overall efficacy rate of 96%. No thrombotic adverse effects were reported. This study's results suggest that both combination and sequential therapy of pd-FVIIa/FX and other bypassing agents are well tolerated and effective for the control of perioperative bleeding in haemophilia patients with high-responding inhibitors.

Pilot Study of a Novel Swine Model for Controlling Junctional Hemorrhage Using the iTClamp in Conjunction With Hemostatic Agents.

Exsanguinating hemorrhage is a primary cause of battlefield death. The iTClamp is a relatively new device (FDA approval in 2013) that takes a different approach to hemorrhage control by applying mechanism wound closure. However, no previous studies have explored the feasibility of utilizing the iTClamp in conjunction with hemostatic packing. To fill this important gap in the literature, a novel swine model was developed, and a total of 12 trials were performed using QuikClot Combat Gauze or XSTAT sponges in conjunction with the iTClamp to treat arterial injuries through 5 cm or 10 cm skin incisions in the groin, axilla, or neck. First-attempt application success rate, application time, and blood loss were recorded. Hemostasis was achieved on all wounds, though reapplication was required in one Combat Gauze and three XSTAT applications. Application averaged ~50% slower for Combat Gauze (M = 41 seconds, 95%CI: 22-32 seconds) than for XSTAT (M = 27 seconds, 95%CI: 35-47 seconds). XSTAT application was faster than Combat Gauze for each wound location and size. The 10 cm wounds took ~10 seconds (36%) longer to close (M = 27 seconds, 95%CI: 35-47 seconds) than the 5 cm wounds (M = 27 seconds, 95%CI: 35-47 seconds). Blood loss was similar for Combat Gauze (M = 51 mL, 95%CI: 25-76 mL) and XSTAT (M = 60 mL, 95%CI: 30-90 mL). Blood loss was roughly twice as great for 10 cm wounds (M = 73 mL, 95%CI: 47-100 mL) than for 5 cm wounds (M = 38 mL, 95%CI: 18-57 mL). This pilot study supports the feasibility of a novel model for testing the iTClamp in conjunction with hemostatic packing towards controlling junctional hemorrhage.

New hemostatic device for grade IV-V liver injury in porcine model: a proof of concept.

Background: The liver is the most injured organ following abdominal trauma. Uncontrolled bleeding remains the main cause of early liver injury-related death, with a mortality rate of 50-54% in the first 24 h after admission and with 80% of operative deaths. Packing and reoperation account for the increased survival in severe liver trauma, and they are recommended for severe liver injuries (grades IV-V).Perihepatic packing can lead to several potential complications. An excessive packing can cause complications due to abdominal compartment syndrome, while a soft packing may be ineffective, and thus, bleeding can continue inadvertently with the consequent hypovolemic shock and potentially death. Methods: We designed a new vacuum-based device to perform perihepatic packing without the negative side-effects of the classic technique. We conducted a prospective pilot feasibility study in a porcine model. We compared the traditional perihepatic packing (PHP) (n = 2) with the new VacBagPack device (VBP) (n = 2). Results: Both pigs survived with the new device and showed an equivalent outcome to the one that survived in the traditional technique group. Blood tests were similar too. This suggests that VBP could be at least as effective as traditional PHP. Conclusions: We establish a first step towards the development of a new packing device. A new study with a bigger sample size still in pigs will be conducted. Also, an industrial model of the device is currently in production.

Evaluation of a Novel Fibrin Sealant Patch in Hemorrhage Control After Vascular or Hepatic Injury.

INTRODUCTION: Acute hemorrhage remains the leading cause of death in potentially survivable injuries. The use of topical hemostatic agents has increased over the last two decades with the evolution of damage control surgery. By 2008, the military widely adopted Combat Gauze as the hemostatic dressing of choice for compressible hemorrhage. The goal of this study was to compare the performance of a novel fibrin sealant patch to Combat Gauze in two clinically relevant models of hemorrhage. MATERIALS AND METHODS: Yorkshire swine underwent unilateral femoral artery puncture or a grade V liver laceration with timed free bleeding then received either the fibrin patch or Combat Gauze packing with 3 minutes of standardized pressure. Animals were then resuscitated to maintain a mean arterial pressure of 60 mmHg for 4 hours. Hemostasis, blood loss, resuscitation volume, survival, vessel patency, and hematologic parameters were evaluated. RESULTS: Hemostasis was equivalent in both groups after hepatic and vascular injury. Survival was 80% in the fibrin patch vascular injury group and 100% in all other groups. Hematologic parameters were not significantly different between treatment groups. Femoral artery patency was 80% in both groups after vascular injury. With simulated ambulation after vessel injury, 60% of the Combat Gauze group and 80% of the fibrin patch group remained hemostatic (p > 0.05). In simulated re-exploration with packing removal, all animals rebled after hemostatic product removal. CONCLUSION: There was no significant difference in hemostasis between a novel fibrin patch and Combat Gauze after extremity arterial or hepatic injury. This novel fibrin patch may have a clinical advantage over the Combat Gauze, as it can be left in the body, thereby limiting the potential need for reoperation.

Prehospital haemostatic dressings for trauma: a systematic review.

BACKGROUND: Haemorrhage is a major cause of mortality and morbidity following both military and civilian trauma. Haemostatic dressings may offer effective haemorrhage control as part of prehospital treatment. AIM: To conduct a systematic review of the clinical literature to assess the prehospital use of haemostatic dressings in controlling traumatic haemorrhage, and determine whether any haemostatic dressings are clinically superior. METHODS: MEDLINE and EMBASE databases were searched using predetermined criteria. The reference lists of all returned review articles were screened for eligible studies. Two authors independently undertook the search, performed data extraction, and risk of bias and Grading of Recommendations, Assessment, Development and Evaluation quality assessments. Meta-analysis could not be undertaken due to study and clinical heterogeneity. RESULTS: Our search yielded 470 studies, of which 17 met eligibility criteria, and included 809 patients (469 military and 340 civilian). There were 15 observational studies, 1 case report and 1 randomised controlled trial. Indications for prehospital haemostatic dressing use, wound location, mechanism of injury, and source of bleeding were variable. Seven different haemostatic dressings were reported with QuikClot Combat Gauze being the most frequently applied (420 applications). Cessation of bleeding ranged from 67% to 100%, with a median of 90.5%. Adverse events were only reported with QuikClot granules, resulting in burns. No adverse events were reported with QuikClot Combat Gauze use in three studies. Seven of the 17 studies did not report safety data. All studies were at risk of bias and assessed of 'very low' to 'moderate' quality. CONCLUSIONS: Haemostatic dressings offer effective prehospital treatment for traumatic haemorrhage. QuikClot Combat Gauze may be justified as the optimal agent due to the volume of clinical data and its safety profile, but there is a lack of high-quality clinical evidence, and randomised controlled trials are warranted. LEVEL OF EVIDENCE: Systematic review, level IV.

Comparison of 3-Factor Versus 4-Factor Prothrombin Complex Concentrate With Regard to Warfarin Reversal, Blood Product Use, and Costs.

BACKGROUND: Prothrombin complex concentrates (PCCs) are drug products containing varying amounts of vitamin K-dependent coagulation factors II, VII, IX, and X. The evidence comparing 3-factor PCC (3-PCC) versus 4-factor PCC (4-PCC) for warfarin reversal is conflicting. It has been hypothesized that 3-PCC may be less effective than 4-PCC because of relatively lower factor VII content. STUDY QUESTION: The primary objective of this study was to compare international normalized ratio (INR) reversal between 3-PCC and 4-factor PCC (4-PCC) in warfarin-treated patients. The secondary objectives include comparing blood product use, total reversal costs, and cost-effectiveness between the groups. STUDY DESIGN: This was a retrospective cohort study conducted in 2 affiliated, academic institutions in the United States. Consecutive adult patients who received 3-PCC or 4-PCC for warfarin reversal were included. MEASURES AND OUTCOMES: The primary outcome was adequate INR reversal defined as a final INR ≤1.5. Secondary outcomes were the utilization of plasma, red blood cells and platelets, reversal costs, and the cost-effectiveness ratio. RESULTS: There were 89 patients who were included in the overall cohort (3-PCC = 57, 4-PCC = 32). Adequate INR reversal occurred less commonly with 3-PCC (45.6%) compared with 4-PCC (87.5%) (P < 0.001). There was no significant difference in the proportion of patients who received plasma (32% vs. 28%, P = 0.813), red blood cells (37% vs. 47%, P = 0.377), or platelets (16% vs. 28%, P = 0.180) between the 3-PCC and 4-PCC groups, respectively. The median reversal cost of 3-PCC ($3663) was lower than 4-PCC ($5105) (P = 0.001). The cost-effective ratio favored 4-PCC ($5105/87.5% = $5834) compared with 3-PCC ($3663/45.6% = $8033). CONCLUSIONS: Four-PCC was more effective than 3-PCC with regard to INR reversal in patients taking warfarin, but blood product use was similar. Although 4-PCC is associated with increased reversal costs, it may be cost-effective in terms of INR reversal.

Experimental Evaluation of Tranexamic Acid-Loaded Porous Starch as a Hemostatic Powder.

We evaluated the effectiveness of a novel hemostatic powder called Tranexamic Acid-loaded Porous Starch (TAPS) developed recently on blood clotting activity and hemostasis. The effectiveness of TAPS was evaluated by comparing hemostatic properties with those of Quick-acting Styptic Powder (QSP) and Compound Microporous Polysaccharide Haemostatic powder (CMPHP). The blood clotting activities of human blood were analyzed by thromboela-stogram (TEG) assays in vitro. The hemostatic effectiveness in vivo was evaluated using a rat model with hepatic traumatic hemorrhage. The blood loss and standardized bleeding score, which reflects the degree of bleeding after treatment with styptic powder, were used to evaluate hemostatic efficacy. In vitro, the values of TEG parameters in TAPS group were significantly different, compared with untreated controls or CMPHP group (p < 0.05). In vivo, the application of QSP, CMPHP and TAPS led to significantly decreased post-treatment blood loss than in the control group (p < 0.01). The scores of the groups treated with QSP, CMPHP and TAPS (0, 0.2±0.422, 0.3±0.483, respectively) were significant lower than with gauze control (1.6±0.516) which success hemostatic was achieved at 5 minutes (p < 0.01). Hemostasis was achieved successfully within approximately 4 minutes after the application of TAPS. TAPS could help blood to form an artificial scab on a wound and to seal injuries for hemostasis to reduce blood loss in rats with hepatic trauma and hemorrhage. It was safe to use with no impact on blood clotting function or other apparent side effects.

Prospective randomized study evaluating the effects of PerClot® (Polysaccharide Hemostatic System) application in patients with high bleeding risk undergoing cardiac rhythm device implantation.

BACKGROUND: Thus far, the topic hemostatic agent PerClot® is used for surgical procedures. Data about the use of PerClot® for cardiac-rhythm-devices (CRD) implantation are missing. The aim of this study was to evaluate the safety and efficacy of PerClot® in patients with high bleeding risk. METHODS AND RESULTS: In this prospective randomized study we planned to include 150 patients admitted for CRD-Implantation receiving anticoagulation and/or dual-antiplatelet-therapy. Participants were randomized to receive PerClot® versus standard-of-care. The primary endpoint was the incidence of pocket hematoma. Safety endpoint was pocket infection. After a planned safety-interim-analysis the study was terminated early because of safety concerns. 51 patients were included. The two groups were comparable with regard to age (73±11years vs. 74±10years; p=0.71), CHA2DS2VASc (3.6±1.5 vs. 4.0±1.5; p=0.27) and HASBLED-Score (2.4±1.1 vs. 2.5±1.0; p=0.98), CRD or procedure type, anticoagulant or anti-platelet therapy. The use of PerClot® resulted in a higher incidence of postoperative fever (7 (28%) vs. 0 (0%); p=0.004), higher C-Reactive Protein (66.1±50.5mg/l vs. 25.9±22.5mg/l; p=0.002); and higher postoperative white blood cell count (13.5±4.3/nl vs. 8.8±2.6/nl; p<0.001). Hematoma formation did not differ significantly (p=0.14). Reoperation was not necessary in any patient. CONCLUSION: This first randomized controlled study for the topical use of the hemostatic agent PerClot® in CRD implantation was terminated early by the safety monitoring board because of an augmented rate of fever and inflammatory markers in the PerClot® group. The addition of PerClot® does not suggest a benefit with regard to the frequency of pocket hematoma.

Manejo y tratamiento dental quirúrgico de pacientes en terapia con antiagregantes plaquetarios: revisión de la literatura / Management and dental surgical treatment of patients under antiplatelet therapy: a review of the literature

El temor a desarrollar un sangrado excesivo lleva a los especialistas a suspender el tratamiento con antiagregantes plaquetarios -de rutina en pacientes con patología cardíaca isquémica, fibrilación atrial y stents coronarios, entre otros- antes de un procedimiento quirúrgico. La interrupción pone en riesgo la vida del paciente, pues estas terapias se utilizan para la prevención de accidentes trombóticos. Este trabajo se propuso realizar una revisión bibliográfica de los pacientes en terapia con antiagregantes plaquetarios sometidos a procedimientos quirúrgicos odontológicos. Labúsqueda se efectuó por medio del portal PubMed a partir de palabras clave como exodontia, aspirin, antiplatelet therapy y clopidogrel. Se incluyeron aquellos artículos que hacen referencia a la indicación y el manejo de la terapia con antiagregantes plaquetarios –en monoterapia o terapia dual– antes deuna cirugía dentoalveolar. El riesgo de sangrado intraoperatorio es ciertamente mayoren los pacientes en terapia con antiagregantes plaquetarios. Sin embargo, el sangrado posoperatorio no lo es, puespuede ser controlado satisfactoriamente con medidas locales. Además, la prevención del peligro de sangrado no compensael riesgo de tromboembolismo que implica la suspensión dela terapia.Los procedimientos quirúrgicos en pacientes con antiagregantes plaquetarios pueden llevarse a cabo de forma segura,sin alteración o modificación de la terapia, siempre y cuando se tomen las medidas pertinentes de hemostasia, y mientras sean realizados por un profesional con la experiencia necesaria. De todas formas, se aconseja consultar al médico especialista antes de interrumpir cualquier terapia.

The fear of developing an excessive bleeding leads thespecialists to discontinue the treatment with antiplatelet drugsbefore a surgical procedure increasing the risk of thromboembolicevents in patients. These therapies are used routinely forthe prevention of thrombotic events in patients with ischemicheart disease, atrial fibrillation and coronary stents, amongothers.The aim was to review the literature about the case ofpatients under antiplatelet therapy in need of surgical dentalprocedures. The following search terms were used in PubMed:exodontia, aspirin, antiplatelet therapy, clopidogrel. Articlesthat made a reference to the indication and management ofboth mono and dual antiplatelet therapy in patients who areundergoing dentoalveolar surgery were included.The risk of intraoperative bleeding is certainly greater forpatients on therapy with antiplatelet agents. However this isnot due to postoperative bleeding that can be satisfactorilycontrolled with local measures and this increased risk is notworth the risk of thromboembolism which the interruption ofthe therapy involves.Surgical procedures in patients receiving antiplateletagents can be safely carried out without alteration or modification of the therapy. It is important to implementappropriate hemostasis measures and the procedures haveto be conducted by a dentist with adequate experience inthis type of cases. Similarly, it is advisable to consult aphysician to decide if therapy discontinuation is appropriate.

Efficacy of Hemostatic Agents in Humans With Rotational Thromboelastometry: An in-vitro Study.

OBJECTIVES: Hemorrhage is the leading cause of preventable death in military conflicts. Different types of hemostatic dressings have been compared in animal studies for their ability to control bleeding. However, the effects of hemostatic agents in animals may be different from those in humans. The aim of this study was to assess the efficacy of hemostatic dressings in human blood. METHODS: Clotting time, clot formation time, α-angle, maximum clot firmness, and lysis index of human blood incubated with QuikClot Gauze, Celox Gauze, QuikClot ACS+, and standard gauze, were compared using rotational thromboelastometry (ROTEM). Nonactivated, intrinsically activated, extrinsically activated, and fibrin-based ROTEM were used to elucidate different mechanisms of action of those dressings. RESULTS: QuikClot Gauze was the most efficacious hemostatic dressing, followed by Celox Gauze and standard gauze. QuikClot ACS+ was clearly outperformed. CONCLUSIONS: Modern hemostatic dressings such as QuikClot Gauze and Celox Gauze should be preferred to previous generations of hemostatic dressings, such as QuikClot ACS+. In vitro studies like ROTEM can provide valuable information about the mechanisms of action of hemostatic dressings. A combination of different mechanisms of action may increase the efficacy of hemostatic dressings.

Improved bleeding scores using Gelfoam(®) Powder with incremental concentrations of bovine thrombin in a swine liver lesion model.

Topical hemostatic agents are used intra-operatively to prevent uncontrolled bleeding. Gelfoam(®) Powder contains a hemostatic agent prepared from purified pork skin gelatin, the efficacy of which is increased when combined with thrombin. However, the effect of increasing concentrations of thrombin on resultant hemostasis is not known. This study sought to evaluate the ability of various concentrations of thrombin in combination with Gelfoam Powder to control bleeding using a swine liver lesion model. Ten pigs underwent a midline laparotomy. Circular lesions were created in the left medial, right medial, and left lateral lobes; six lesions per lobe. Gelfoam Powder was hydrated with Thrombin-JMI(®) diluted to 250, 375, and 770 IU/mL. Each concentration was applied to two lesion sites per lobe. Bleeding scores were measured at 3, 6, 9, and 12 min using a 6-point system; comparison of bleeding scores was performed using ANOVA with the post hoc Tukey test. The bleeding scores with thrombin concentrations at 770 IU/mL were significantly lower than at 250 and 375 IU/mL at all four time points. The percentage of biopsies with a clinically acceptable bleeding score rose from 37.9, 46.6, and 71.2 % at 3 min to 55.2, 69.0, and 88.1 % at 12 min in the 250, 375, and 770 IU/mL thrombin groups, respectively. The study showed that the hemostatic response to thrombin was dose-related: using higher concentrations of thrombin with Gelfoam Powder yielded improved hemostasis, as determined by lower bleeding scores.

A critical appraisal of one-stage and chromogenic assays of factor VIII activity.

Accurate and precise potency determination by manufacturers of different types of factor VIII product (plasma-derived and recombinant FVIII [rFVIII]) is vital to clinicians and patients using FVIII concentrates. A separate, but related, requirement is ascertaining the FVIII activity levels in clinical samples for diagnosing and treating hemophilia A. The one-stage clotting assay (OSA) and the chromogenic substrate assay (CSA) are the main assays used for these measurements, with both assays being used for potency assignments, and the OSA also being widely used for clinical monitoring. Although the assays can produce concordant results, discrepancies often occur, e.g. when measuring FVIII levels in patients with mild or moderate hemophilia A, or when assaying high-purity FVIII products. Modifications to rFVIII proteins, such as B-domain deletion (BDD), and technologies for improving the pharmacokinetic profile of rFVIII may exacerbate assay discrepancies. The CSA appears to be essentially unaffected by these modifications. However, the OSA underestimates the FVIII activity levels and therapeutic potential of some further modified BDD rFVIII products, especially those conjugated to poly(ethylene glycol); the extent of the effects is dependent on the specific OSA reagents used. Although the OSA remains the preferred choice for clinical monitoring in Europe and the USA, an awareness of the limitations of that assay has prompted more laboratories to adopt the CSA.

An evidence-based prehospital guideline for external hemorrhage control: American College of Surgeons Committee on Trauma.

This report describes the development of an evidence-based guideline for external hemorrhage control in the prehospital setting. This project included a systematic review of the literature regarding the use of tourniquets and hemostatic agents for management of life-threatening extremity and junctional hemorrhage. Using the GRADE methodology to define the key clinical questions, an expert panel then reviewed the results of the literature review, established the quality of the evidence and made recommendations for EMS care. A clinical care guideline is proposed for adoption by EMS systems. Key words: tourniquet; hemostatic agents; external hemorrhage.

[Quality evaluation of bletillae rhizoma based on hemostatic biopotency].

This dissertation is to determine the biopotency of hemostat which processed in different places by establishing a bioassay method of Bletillae Rhizoma based on the thrombin time. Contrast test is the main methodology. Specifically, the reference substance of Bletillae Rhizoma is determined by comparing with the control substance of vitamin K1 using thrombin time, which is calibrated the Bletillae Rhizoma. The hemostatic biopotency is calculated by using the method of "parallel line assay method based on quantitative responses" (3.3) from different processed products. It indicates that there is a strong linear correlation between Bletillae Rhizoma and control drugs (Y = 66.332-23.913X, R2 = 0.995 3). The hemostatic biopotency of Bletillae Rhizoma from different processed products ranged between 821.93-1 187.53 U x g(-1) shown in the paper, and all of them can meet the requirements of the test. The methodology has an appropriate instrument precision (RSD 3.8%), intermediate precision (RSD 4.6%), repeatability (RSD 3.2%) and stability (RSD 3.7%). Therefore, it can be turned out that the methodology which established in the dissertation is good at determinating the hemostatic biopotency of Bletillae Rhizoma and it is reliable, simple and repeatable.

Hemostats, sealants, and adhesives III: a new update as well as cost and regulatory considerations for components of the surgical toolbox.

The hemostat, sealant, and adhesive components of the surgical toolbox continue to evolve and enter clinical practice at a rapid rate. The goal of this comprehensive, sequential review is to update these components to include those now available (February 2012) as well as to explore cost and regulatory factors that impact the development and use of these materials. A unique system of definitions for organizing these components based on group, category, and class is used as a means of improving the understanding and appropriate use of these materials. The system will be used here to present the most recent additions to the toolbox, which are evaluated based on safety, efficacy, usability, and cost. These new additions include pooled human plasma fibrinogen and thrombin embedded in an equine collagen patch for cardiac surgical hemostasis, polyethylene glycol (PEG) and human serum albumin for lung surgical pneumostasis, modified PEG and trilysine amine for spinal sealing, octyl and butyl lactoyl cyanoacrylate for vascular sealing, and a variety of octyl and butyl cyanoacrylates with or without dyes and/or polyester mesh for skin closure with the creation of a bacterial barrier. The system of definitions will also be used to clarify key strategies in the current health care environment for reducing costs and for increasing understanding of Food and Drug Administration regulatory decisions for these materials.

Nonhormonal treatments for heavy menstrual bleeding.

BACKGROUND: The purpose of this review is to identify and compare nonhormonal medications for the treatment of idiopathic heavy menstrual bleeding (HMB) or menorrhagia. METHODS: Clinical trials were identified through a PubMed literature search. Titles and abstracts of identified studies were reviewed. Controlled clinical trials that evaluated nonhormonal medications in women with HMB in the absence of anatomic abnormalities other than small fibroids were selected for retrieval. Additional studies were identified from the reference lists of selected articles. Selected articles were comprehensively reviewed. RESULTS: All medications evaluated reduced menstrual blood loss (MBL); however, mean reductions in MBL were greatest with the hemostatic agents, tranexamic acid (TA) and ε-aminocaproic acid. Several TA studies also included evidence of improvement in health-related quality of life (HRQOL). Reductions in MBL were generally smaller and less consistent with nonsteroidal anti-inflammatory drug (NSAID) treatment. All medications reviewed were well tolerated. CONCLUSIONS: Nonhormonal medications used for HMB treatment differ in the extent of MBL reduction. TA was notable for consistent MBL reductions and improvement in HRQOL; other agents reviewed indicated less reduction in MBL or sufficient data were lacking for comparison.

Clinical trials of direct thrombin and factor Xa inhibitors in atrial fibrillation.

PURPOSE OF REVIEW: To review the large phase 3 clinical trials that compare direct thrombin or factor Xa inhibitors with dose-adjusted warfarin in patients with atrial fibrillation who have an increased risk of stroke. RECENT FINDINGS: In large clinical trials, the oral direct thrombin inhibitor ximelagatran and the long-acting factor Xa inhibitor idraparinux were effective for reducing the risk of thromboembolic stroke, but were not marketed because of liver toxicity and excessive bleeding, respectively. In separate clinical trials, the oral direct thrombin inhibitor dabigatran etexilate and the short-acting oral factor Xa inhibitor rivaroxaban were noninferior or superior to dose-adjusted warfarin for prevention of thromboembolic stroke and systemic embolism, without increasing the risk of bleeding, and were well tolerated. Apixaban, another oral factor Xa inhibitor, is effective in reducing thromboembolic stroke compared with aspirin alone. Results of a trial comparing apixaban with dose-adjusted warfarin are awaited. SUMMARY: Dabigatran and rivaroxaban are effective, safe alternatives to dose-adjusted warfarin for reducing thromboembolic risk in patients with atrial fibrillation at high risk of stroke.

An approach to prevent the severe adverse events associated with transfusion of FDA-approved blood products.

There have been several retrospective studies reporting severe adverse events of mortality and morbidity associated with blood transfusions. Mortality and morbidity associated with posttransfusion infection, transfusion related acute lung injury (TRALI), and systemic inflammatory response syndrome (SIRS) have been reported in patients undergoing cardiac surgery, after massive transfusions for severe traumatic injuries, and after transfusions for elective and emergency indications. After 35 days of storage at 4 degrees C in additive solutions, RBC have 24-h posttransfusion survival values of 75% but do not function satisfactorily. For RBC to function satisfactorily shortly after transfusion, they should be stored at 4 degrees C for no more than 2 weeks. Yet while the FDA requires a 24-h posttransfusion survival value of 75%, there is no requirement for the function of the transfused RBC. It has been shown that red blood cells that circulate and function immediately or shortly after transfusion exert a very important hemostatic effect to reduce the bleeding time and nonsurgical blood loss in anemic and thrombocytopenic patients. Greater restoration of hemostasis is seen with viable and functional RBC transfusions than with platelets or plasma even though the platelets and plasma proteins may have satisfactory viability and function. The length of storage of the blood products affects their survival and function and the transfusion of nonviable compatible RBC, antibodies to granulocytes and WBC HLA antigens and biologically active substances affects the patient's clinical outcome. One of the easiest ways to prevent the severe adverse events that have been observed is to ensure that the transfused blood products survive and function at an optimum level and that the levels of antibodies to granulocytes and WBC HLA antigens and biologically active substances are eliminated or reduced. The best way to ensure this is to store liquid-preserved leukoreduced human red blood cells at 4 degrees C in additive solutions for no more than 2 weeks and leukoreduced platelets at room temperature for no more than 2 days. These liquid-preserved blood products can be used in conjunction with frozen RBC, platelets, and plasma stored in -80 degrees C mechanical freezers and will avoid the need for fresh whole blood and prevent the severe adverse events associated with the transfusion of blood products.

Rapid Rhino nasal packs: demonstration of depressurisation but not deflation.

OBJECTIVES: Following a suggestion by ward patients that Rapid Rhino nasal packs may deflate over time, allowing recurrence of epistaxis, we aimed to demonstrate deflation of 7.5 cm Rapid Rhino packs when used in vivo for post-operative nasal packing. MATERIALS AND METHODS: The volume of air insufflated and retrieved from Rapid Rhino nasal packs used for post-operative nasal packing was recorded, as was the pressure following inflation and prior to removal. The time taken for the initial inflation pressure to stabilise was monitored in a number of packs. Similar pressure and volume measurements were repeated in a series of in vitro packs for comparison. RESULTS: Fourteen consecutive patients undergoing septoplasty were recruited. High but unsteady pressure values were obtained in the first patient's packs. In the subsequent five patients, continuous pressure monitoring demonstrated that gradual depressurisation occurred over the first 16 to 22 minutes following inflation. A typical pressure was 35 cmH2O after inflating with 8 ml of air. Only one Rapid Rhino pack was demonstrated to leak air in vivo. CONCLUSION: When used in vivo, Rapid Rhino nasal packs initially depressurise over a period of about 20 minutes. Actual leakage (deflation) was not demonstrated to be an expected feature of Rapid Rhino packs in this study.