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.

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.

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.

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.

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.

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.

Commercial fibrin sealants are not equivalent in a rabbit liver-resection model which quantitatively evaluates hemostasis and formation of adhesions.

A rabbit partial liver resection model was used to determine the hemostatic effectiveness of a new fibrin sealant. Persistent bleeding, with a mean bleeding time of 372 s and blood loss of 18 ml, from a resected lobe of the liver was achieved after rabbits in the untreated control group had been infused continuously with unfractionated heparin over 20 min with 0.2 IU/ml at a rate of 1 ml/min. Spraying the resected surface with the new fibrin sealant, Quixil, reduced bleeding to < 1 ml and the post-resection bleeding times was 25 s. Bleeding time, blood loss and the volume of sealant used in the rabbit model were inversely correlated with the thrombin concentration in the sealant. In direct comparisons with Tissucol and Beriplast, Quixil was associated with the shortest bleeding times, the lowest volume of sealant used and the lowest score of abdominal adhesions.

The use of human fibrin glue in the surgical operations.

Human Fibrin Glue (HFG) is made of two components contained in separate vials: a freeze dried concentrate of clotting proteins, mainly fibrinogen, Factor XIII and fibronectin (the sealant) and freeze dried thrombin (the catalyst). The first component is reconstituted with an aprotinin solution that inhibits tissue fibrinolysis. The second component (thrombin), available in 500 I.U. concentration, is dissolved with calcium chloride. It is so a set of substances involved in the hemostatic process and in the wound healing, conferring to the product the following important properties: hemostatic and sealing action, through the strengthening of the last step of the physiological coagulation; biostimulation, which favors the formation of new tissue matrix. The indications for the use of human fibrin sealant are numerous and present in all the surgical branches. A randomized controlled trial of 50 patients undergoing hernia repair according to Lichtenstein's technique under local anesthesia was performed. Patients had concurrent coagulopathies as a consequence of liver disease or long-term treatment with anticoagulants for ischemic heart disease or cardiac rhythm disturbances. Coagulopathies were defined according to the following criteria: prothrombin time < 10.5 seconds, activated partial thromboplastin time < 21 seconds, and fibrinogen < 230 mg/dL. Patients were randomized in a 1:1 ratio with (group A) or without (control group B) use of human fibrin glue: Postoperative hemorrhagic complications were significantly reduced in group A (4%) compared with group B (24%). This study showed that human fibrin glue is effective in preventing local hemorrhagic complications after inguinal hernia repair in patients with concurrent coagulation disorders.

Management of anticoagulation and its reversal during paediatric cardiopulmonary bypass: a review of current UK practice.

Protocols for management of heparin and protamine administration in patients undergoing open-heart surgery have been developed from experience gained mainly in adult practice. However, it has been demonstrated that there are marked differences between paediatric and adult patients in their response to systemic anticoagulation and its reversal. The aim of this study was to obtain an overview of current practice of management of anticoagulation and its reversal from paediatric cardiac surgical units of Great Britain and Ireland. All centres performing paediatric cardiac surgery agreed to participate in the survey (n = 16). Telephone interviews were carried out with the chief or a senior perfusionist from all participating institutions, which were based on a structured questionnaire compiled specifically for the purpose. The answers were anonymised. At present, in the UK and Ireland, unfractionated heparin is the anticoagulant of choice in all units, with a slight prevalence of porcine mucosal (9/16, 56.5%) versus bovine lung preparation (7/16, 44.0%). The policy for administration of heparin to the patient is uniform, with a dose of 300 IU/kg. However, there is great variability in the amount of heparin added to the prime and to the volume infused during cardiopulmonary bypass (CPB). Monitoring of anticoagulation is achieved by activated coagulation time alone in all but one centre, with lower limits varying between 400 and 750 s. Use of aprotinin is widely accepted, but clinical indications are highly variable. No centre adopts heparin-bonded or heparin-coated circuitry for CPB. Calculation of initial and additional protamine doses followed a variety of criteria, resulting in a very wide distribution of doses. The data obtained highlighted the lack of uniformity among paediatric cardiac surgical units of Great Britain and Ireland with regard to most of the issues related to the management of anticoagulation and its reversal. The striking heterogeneity of our cross-sectional observations clearly underlines the need for prospective, multicentre studies on a national basis to relate different clinical practices to outcome measures.

Evaluation of the hemostatic function of stored platelet concentrates using the platelet function analyzer (PFA-100 ).

BACKGROUND AND OBJECTIVE: Progressive functional impairment is known to occur in platelet concentrates through the storage period. Standardized methods providing direct measurement of residual platelet function in stored platelets are lacking. The purpose of this study was to determine whether a new platelet function analyzer (PFA-100 ) could provide standardized methods for assessing the hemostatic capacity of stored platelets. DESIGN AND METHODS: The PFA-100 was used to evaluate platelet function in stored platelets. The instrument can process citrated whole blood but it is unable to process platelet suspensions. Accordingly, the function of platelet concentrates should be measured following reconstitution of pseudo-whole blood. The analysis of the results included the closure time (sec) and a predictive index, an arithmetical index computed on the basis of the instrument's output data: the flow rate, the flow volume, the closure time. RESULTS: A final hematocrit of 58+/-2 and a final platelet concentration of 230+/-20x10(9)/L were used as standardized operative conditions to measure the function of stored platelet concentrates. The closure time (PFA-CT) and the predictive index (PFA-PI) both resulted to be capable of discriminating platelet concentrates with maintained or impaired function. PFA-PI was more informative than PFA-CT in terms of description of the residual platelet function. Of the two agonists used, epinephrine (EPI) resulted to be particularly sensitive for the detection of initial platelet hyporeactivity, whereas adenosine 5'-diphosphate (ADP) was particularly useful for measuring the residual platelet reactivity. INTERPRETATION AND CONCLUSIONS: PFA-CT and PFA-PI can be standardized; they provide new information about the hemostatic function of stored platelet concentrates and can be used to assess the quality of platelet concentrates.

[Follow-up study on coagulation stabilizing filling of bone defects using the new Gelastypt M after cystectomy of large mandibular cysts and after extraction of ectopic teeth]. / Untersuchungen zur koagulumstabilisierenden Knochendefektfüllung mit dem neuen Gelastypt M nach Zystektomie grossvolumiger Kieferzysten und nach Entfernung verlagerter Zähne.

The good results were confirmed in a follow-up examination of 23 patients two to six months after surgery. No signs of disturbed wound healing and/or inadequate organization of the clot could be observed catamnestically, clinically, and roentgenologically. The late infections often observed after implantation of Gelastypt S (with Surfen) did not develop after use of Gelastypt M 1/2. This preparation therefore may be recommended without restriction.