Hemostatic Control Research Articles

Abstract 494: Platelet Aggregation in a Model of Simulated Arterial Flow: Red Blood Cells Are Integral Players in Hemostatic Control Resuscitation

Background: Approximately one in four trauma patients exhibits an early bleeding diathesis, termed the acute coagulopathy of trauma and defined by an initial INR >1.2, which is associated with a 3-fold increase in mortality. In recent years, the concept of damage control resuscitation has been developed to address this problem. This approach emphasizes hemorrhage control and early resuscitation with blood products in a 1:1:1 ratio of plasma:platelets:RBCs in an attempt to replace whole blood lost in hemorrhage. The optimal ratio of blood components has not been established and few pre-clinical studies have explored this problem under arterial shear conditions. Objective: Our objective is to establish stepped ranges of hematocrit values and platelet counts to identify the component and concentration of that component most responsible for the largest loss of platelet-collagen interaction. Methods: Donor citrated whole blood containing calcein tagged platelets was flowed at an arterial shear rate of 1000/second through a 70μm x 350μm x 5mm collagen-coated chamber at 37°C for 10 min, n=6. Images were captured every 15 seconds and analyzed for fluorescence intensity. Results: Linear regression analysis generated slopes (fluorescent intensity units/second) that were most different as hematocrit dropped below physiologic levels (HCT40control=100%, HCT25=39.5%, HCT20=21.4%, HCT18=17.4%, HCT16=11.6%). Non-linear fitting of slopes vs. HCT yielded the equation y=1.27e4 x 2 -3.51e4 x +4.43e5 describing an exponential decrease in platelet-collagen interaction with linear decreases in HCT. Conclusions: The largest drop in platelet adherence to collagen in a physiological model of arterial flow occurs as hematocrit falls from 40%. The commonly suggested 30HCT target for minimal RBC transfusion during resuscitation may not adequately support hemostasis and should be reconsidered.

Thrombolysis With Recombinant Tissue Plasminogen Activator in 7 Children

The information about the thromboembolic events, the optimal treatment choice, the dose, and duration of antithrombotic therapy in children are limited. More clinical data are required. Recombinant tissue plasminogen activator (r-tPA) is increasingly used in pediatric thrombosis. We retrospectively analyzed the clinical course of 7 children (9.3 ± 2.1 years; 34 days to 16 years) with arterial thrombosis (n = 1) and intracardiac thrombosis (n = 6). The children were treated with r-tPA. The dose ranged between 0.2 and 0.4 mg/kg per h infused for 3 to 4 hours. This dose was repeated between 2 to 7 times till the thrombolysis was achieved. Treatment side effects were closely monitored. Complete clot lysis was achieved in all cases. None of them had severe bleeding except mild recurrent epistaxis occurring in 2 cases. In conclusion, r-tPA is an effective and safe therapy under close hemostatic control in children.

Determination of efficacy of novel modified chitosan sponge dressing in a lethal arterial injury model in swine

Chitosan is a functional biopolymer that has been widely used as a hemostat. Recently, its efficacy has been questioned due to clinical failures as a result of poor adhesiveness. The purpose of this study was to compare, in a severe groin injury model in swine, the hemostatic properties of an unmodified standard chitosan sponge with standard gauze dressing and a novel hydrophobically modified (hm) chitosan sponge. Previous studies have demonstrated that hm-chitosan provides greatly enhanced cellular adhesion and hemostatic effect via noncovalent insertion of hydrophobic pendant groups into cell membranes. Twenty-four Yorkshire swine were randomized to receive hm-chitosan (n = 8), unmodified chitosan (n = 8), or standard Accu-Sorb gauze dressing (n = 8) for hemostatic control. A complex groin injury involving arterial puncture (4.4-mm punch) of the femoral artery was made after splenectomy. After 30 seconds of uncontrolled hemorrhage, the randomized dressing was applied and compression was held for 3 minutes. Fluid resuscitation was initiated to achieve and maintain the baseline mean arterial pressure and the wound was inspected for bleeding. Failure of hemostasis was defined as pooling of blood outside the wound. Animals were then monitored for 180 minutes and surviving animals were killed. Blood loss before treatment was similar between groups (p < 0.1). Compared with the hm-chitosan sponge group, which had no failures, the unmodified chitosan sponge group and the standard gauze group each had eight failures over the 180-minute observation period. For the unmodified chitosan sponge failures, six of which provided initial hemostasis, secondary rebleeding was observed 44 minutes ± 28 minutes after application. Standard gauze provided no initial hemostasis after the 3-minute compression interval. Hm-chitosan is superior to unmodified chitosan sponges (p < 0.001) or standard gauze for controlling bleeding from a lethal arterial injury. The hm-chitosan technology may provide an advantage over native chitosan-based dressings for control of active hemorrhage.

Percutaneous Biopsy Device Design with Haemostatic Bleeding Control

Percutaneous Biopsy Device Design with Haemostatic Bleeding Control

Massive haemorrhage: a current perspective

Trauma and massive haemorrhage are associated with coagulopathy secondary to tissue injury, hypoperfusion, dilution, and consumption of clotting factors and platelets occurring already at the scene of the accident. Concepts of damage control surgery have evolved prioritizing early control of the cause of bleeding by non-definitive means, while haemostatic control resuscitation seeks early control of coagulopathy. Haemostatic resuscitation provides transfusions with plasma and platelets in addition to red blood cells in an immediate and sustained manner as part of the transfusion protocol for massively bleeding patients and consequently limiting the amount of crystalloids and colloids are crucial for avoiding further impairment of haemostatic competence. Transfusion of red blood cells, plasma and platelets in a similar proportion as in whole blood prevents both hypovolaemia and coagulopathy. Results from recent before-and-after studies in massively bleeding patients indicate that trauma exsanguination protocols involving early administration of plasma and platelets are associated with improved survival. Furthermore, viscoelastic whole blood assays, such as thrombelastography (TEG) appear advantageous for identifying coagulopathy in trauma patients with severe haemorrhage as opposed the conventional coagulation assays. In our view, patients with uncontrolled bleeding, including trauma patients, should be treated with goal-directed haemostatic control resuscitation involving early administration of plasma and platelets and based on the results of TEG analysis. The aim of the goal-directed therapy should be to maintain a normal haemostatic competence until surgical haemostasis is achieved, as this appears to be associated with reduced mortality.

Postadenoidectomy hemorrhage: A two-year prospective study

Although postoperative complications are rare, postadenoidectomy hemorrhage is one of the most frequent. The aim of this prospective study was to evaluate the incidence and timing of postadenoidectomy hemorrhage requiring hemostatic control under endotracheal anesthesia. A two-year prospective study of patients undergoing inpatient adenoidectomy, with (n = 462) or without tonsillectomy (n = 589), was undertaken. Surgery was performed in endotracheal anesthesia using an adenoid curette. Every bleeding event which needed procedure in general anesthesia for its treatment was recorded. The timing of postadenoidectomy hemorrhage was classified as primary or secondary. Severe bleeding following adenoidectomy with tonsillectomy which needed hemostatic control under endotracheal anesthesia occurred in only 0.19% (2/1051) patients (average age = 7.5 years). Postadenoidectomy hemorrhage was primary in both of the patients. Severe postoperative hemorrhage requiring hemostasis under endotracheal anesthesia can be expected in a small number of children undergoing adenoidectomy with tonsillectomy.

Current management of massive hemorrhage in trauma.

Hemorrhage remains a major cause of potentially preventable deaths. Trauma and massive transfusion are associated with coagulopathy secondary to tissue injury, hypoperfusion, dilution, and consumption of clotting factors and platelets. Concepts of damage control surgery have evolved prioritizing early control of the cause of bleeding by non-definitive means, while hemostatic control resuscitation seeks early control of coagulopathy.Hemostatic resuscitation provides transfusions with plasma and platelets in addition to red blood cells in an immediate and sustained manner as part of the transfusion protocol for massively bleeding patients. Although early and effective reversal of coagulopathy is documented, the most effective means of preventing coagulopathy of massive transfusion remains debated and randomized controlled studies are lacking.Viscoelastical whole blood assays, like TEG and ROTEM however appear advantageous for identifying coagulopathy in patients with severe hemorrhage as opposed the conventional coagulation assays.In our view, patients with uncontrolled bleeding, regardless of it´s cause, should be treated with hemostatic control resuscitation involving early administration of plasma and platelets and earliest possible goal-directed, based on the results of TEG/ROTEM analysis. The aim of the goal-directed therapy should be to maintain a normal hemostatic competence until surgical hemostasis is achieved, as this appears to be associated with reduced mortality.

Bioabsorbable Staple-Line Reinforcement for Pancreatectomy in a Porcine Model: A Preliminary Study

Background: We conducted an exploratory study to assess the use of FOREseal® bioabsorbable reinforcement sleeves in stapling of the pancreatic parenchyma. Methods: A left pancreatectomy was carried out with linear stapler on 12 pigs: in the FOREseal group (n = 6), the stapling was reinforced with FOREseal, while in the control group (n = 6), simple stapling was applied. Results: The mean operating time was not different between the two groups. No additional haemostasis of the stapling transection was necessary with FOREseal, while in the control group, four pigs required additional haemostasis (p = 0.03). The mean postoperative drainage volume and the mean duration of drainage were, respectively, in the FOREseal group versus the control group: 82 versus 204 ml (p = 0.2) and 3.2 versus 4.7 days (p = 0.3). No adverse event occurred in the FOREseal group. There was no anatomopathological difference between the two groups. Conclusion: A good tolerance of FOREseal was observed when used on the pancreatic stump. In this study, it was demonstrated a better haemostatic control of the pancreatic stump with FOREseal which also tends to reduce the volume of postoperative drainage liquid.

Possible Anaphylaxis Due to Recombinant Factor VIIa Administration During Thoracic Aortic Surgery

Possible Anaphylaxis Due to Recombinant Factor VIIa Administration During Thoracic Aortic Surgery

Liver Hemorrhage Due to Idiopathic Peliosis Hepatis Successfully Treated With Hepatic Artery Embolization

Peliosis hepatis is an extremely rare condition that may cause fatal hepatic hemorrhage and liver failure. We report a case of liver hemorrhage due to idiopathic peliosis hepatis. A 60-year-old woman was admitted to our hospital with slight right hypochondriac pain. She went into hemorrhagic shock, and computed tomography (CT) showed multiple low-density areas in the right liver with massive subcapsular blood collection. Selective transfemoral arteriography of the celiac artery revealed no signs of vascular malformation or tumor stain, but showed signs of pooling in the right posterior segmental artery. The artery was embolized with particles of gelatin sponge, and hemostatic control was successful. Although peliosis hepatis is extremely rare, the diagnosis is significant because of its urgent clinical status, and transarterial embolization is a useful and minimally invasive procedure for liver hemorrhage due to peliosis hepatis.

Advances in bypassing agent therapy for hemophilia patients with inhibitors to close care gaps and improve outcomes.

In the past, patients with hemophilia and inhibitors have had less-than-optimal treatment and have experienced more orthopedic complications than patients without inhibitors. Bypassing agents offer the potential to close treatment gaps between inhibitor and noninhibitor patients by helping the former better attain key treatment goals, including: facilitating early initiation of treatment and hemostatic control in hemarthroses; providing effective treatment in serious hemorrhagic episodes; and performance of major surgery. Effective treatment with a bypassing agent minimizes joint and/or muscle damage and potentially can serve as an effective prophylactic agent to minimize the number of hemarthroses experienced per year, thereby mitigating the development of arthropathy. The reported efficacy of the currently available bypassing agents ranges from approximately 50-80% (50-64% in controlled studies) for plasma-derived activated prothrombin complex concentrate (pd-aPCC) and 81-91% (in controlled studies) for recombinant activated factor VII (rFVIIa), including use in major orthopedic surgery. Both bypassing agents have undergone key improvements in their formulation and/or properties in recent years. The nanofiltered, vapor-heated formulation of pd-aPCC has diminished the risk of acquiring blood-borne viral infections and the room temperature stable formulation of rFVIIa allows more convenient storage, increased ease to dissolve and inject, and smaller volumes, thereby increasing overall ease of administration. Use of recommended dosing has been demonstrated to provide effective hemostasis with a minimal number of injections for both agents. In this paper, we review the individual characteristics of pd-aPCC and rFVIIa and discuss clinical data from studies conducted in inhibitor patients that demonstrate the potential benefits of these bypassing agents in this difficult-to-treat population, and underscore the potential opportunities to close the gap in care between inhibitor and noninhibitor hemophilic patients.

Effective management of intracranial haemorrhage with continuous infusion of highly purified von Willebrand factor/factor VIII complex concentrate in an adult with severe haemophilia A.

Effective management of intracranial haemorrhage with continuous infusion of highly purified von Willebrand factor/factor VIII complex concentrate in an adult with severe haemophilia A.

Single Instrument for Hemostatic Control in Laparoscopic Partial Nephrectomy in a Porcine Model Without Renal Vascular Clamping

To test the viability of a new device to obtain hemostasis during laparoscopic partial nephrectomy (LPN) without vascular clamping. We performed a comparative experimental study between a new radiofrequency (RF)-assisted device consisting of a handheld instrument that simultaneously conducts coagulation and cutting tasks without hilar clamping vs a standard technique with hilar clamping. A porcine model was used (10 animals per group) with survival of 17 days. The estimated blood loss with the new device was significantly lower than with the standard technique (15.5±23.7 vs 79.4±76.3 mL). Although transection time was longer with the new device (10.7±13.7 vs 2.1±1.2 min), the total operative time was significantly shorter (35.3±13.7 vs 60.2±10.5 min). Evidence of localized urinary extravasation (urinoma) was identical in both groups (five cases). The group subjected to the new device, however, showed a significantly higher number of cases of leakage after conducting the methylene-blue test: eight (80%) cases vs only one (11%) with the standard technique. Necrosis depth was significantly greater with the new device (6.6±0.9 vs <1 mm). The experimental results suggest that the proposed RF-assisted device provides adequate hemostatic control during transection of the renal parenchyma without additional instruments or surgical maneuvers and could therefore be a valuable adjunct for LPN without vascular clamping. The device was unsuccessful in effectively sealing the collecting system.

Energy source instruments for laparoscopic colectomy

Colectomy is a common procedures for both benign and malignant conditions. Increasingly more colectomy has been performed laparoscopically and there are several available instruments being used for this procedure. Of which three common dissecting instruments are: monopolar electrocautery scissors (MES), ultrasonic coagulating shears (UCS) and electrothermal bipolar vessel sealers (EBVS). The aim is to assess the safety and effectiveness of these instruments. Studies were identified from PubMed, EMBASE, Cochrane Controlled Trials Register, Cochrane Colorectal Cancer Group Trials Register. Major journals were specifically hand searched. All randomised controlled trials were included. All patients underwent elective laparoscopic or laparoscopic-assisted right, left or total colectomy or anterior resection for either benign or malignant conditions were included in the study. Two reviewers independently selected studies from the literature searches, assessed the methodological quality of the trials and extracted data. The three primary outcomes were: overall blood loss, complications and operating time. Six randomised controlled trials including 446 participants. Two trials compared three types of instruments (MES vs UCS vs EBVS). One trial compared MES and UCS. One trial compared UCS and EBVS. One trial compared 5 mm versus 10 mm EBVS. One trial compared the technique of laparoscopic staplers and clips versus EBVS in pedicle ligation during laparoscopic colectomy. The limitation of this review is the heterogeneity of the trials included. The measured outcomes were covered by one to three studies with small number of participants. With this in mind, there was significant less blood loss in UCS compared to MES. The operating time was significantly shorter with the use of EBVS than MES. No difference between UCS and EBVS apart from EBVS appeared to be handling better than UCS in one study. Haemostatic control was better in UCS and EBVS over MES. No definite conclusion on the cost difference between these three instrument but this would lie in the balance between the instrument cost and the operating time. The handling of 5 mm EBVS was better than 10 mm and its main advantage was trocar flexibility. Laparoscopic staplers/clips used for pedicle ligation in colectomy associated with more failure in vessel ligation and cost more when compared to EBVS. The limitations of this review is the small number of trials and heterogeneity of the studies included. With the current evidence it is not possible to demonstrate which is the best instrument in laparoscopic colectomy. Hopefully more data would follow and subsequent updates of this review could become more informative.

Hepatic Arterial Embolization in the Management of Blunt Hepatic Trauma: Indications and Complications

The objective was to clarify the role of hepatic arterial embolization (AE) in the management of blunt hepatic trauma. Retrospective observational study of 183 patients with blunt hepatic trauma admitted to a trauma referral center over a 9-year period. The charts of 29 patients (16%) who underwent hepatic angiography were reviewed for demographics, injury specific data, management strategy, angiographic indication, efficacy and complications of embolization, and outcome. AE was performed in 23 (79%) of the patients requiring angiography. Thirteen patients managed conservatively underwent emergency embolization after preliminary computed tomography scan. Six had postoperative embolization after damage control laparotomy and four had delayed embolization. Arterial bleeding was controlled in all the cases. Sixteen patients (70%) had one or more liver-related complications; temporary biliary leak (n=11), intra-abdominal hypertension (n=14), inflammatory peritonitis (n=3), hepatic necrosis (n=3), gallbladder infarction (n=2), and compressive subcapsular hematoma (n=1). Unrecognized hepatic necrosis could have contributed to the late posttraumatic death of one patient. AE is a key element in modern management of high-grade liver injuries. Two principal indications exist in the acute postinjury phase: primary hemostatic control in hemodynamically stable or stabilized patients with radiologic computed tomography evidence of active arterial bleeding and adjunctive hemostatic control in patients with uncontrolled suspected arterial bleeding despite emergency laparotomy. Successful management of injuries of grade III upward often entails a combined angiographic and surgical approach. Awareness of the ischemic complications due to angioembolization is important.

Use of an Ultrasonic Blade Facilitates Muscle Repair After Incision Injury

The ultrasonic Harmonic Blade cuts and coagulates soft tissue at temperatures lower than conventional electrosurgery. This study investigated whether improved hemostatic control and reduced collateral damage in skeletal muscle incisions translates into improved myofiber regeneration, reduced fibrosis and faster muscle recovery. Transections in the left gastrocnemius muscles of mice were made with the Harmonic Blade, and contralaterally, with either cold steel scissors or electrosurgery. Histology up to 8 wk after surgery was performed to evaluate myofiber regeneration and fibrosis. Tissue inflammation (Gr1+ neutrophils) and vascularization (CD31+ capillaries) were assessed immunohistochemically at 1 wk . Overall the Harmonic Blade showed significantly higher level of muscle regeneration than cold steel. Fibrosis for both the Harmonic Blade and cold steel decreased three-fold over the 8 wk period, whileelectrosurgery yielded significantly increasing fibrosis through wk 4 before declining. At 1 wk post-surgery the Harmonic Blade induced less inflammation than electrosurgery, and higher vascularization than electrosurgery and cold steel. Harmonic Blade-incised tissue showed accelerated vascularization, slight reduction of inflammation, enhanced muscle regeneration and decreased scarring, demonstrating a more effective healing process than electrosurgery.

The need for speed in the management of haemophilia patients with inhibitors

Rapid control of bleeding is the key to reducing bleeding complications and thereby preserving joint and musculoskeletal function in haemophilia patients with inhibitors. However, this requires early diagnosis following the onset of bleeding and strategies for rapid treatment in an outpatient setting. Overarching themes on the need for speed in managing bleeds in haemophilia patients were examined by a panel of clinicians experienced in managing inhibitor patients and joint disease during the Third Zürich Haemophilia Forum on 8 May 2009. This report summarizes the opinions of the panel on how to achieve rapid bleeding control in inhibitor patients and areas that were identified by the panel for future research or as needing new consensus guidelines. The consensus was that home treatment should be established for haemophilia patients with inhibitors, as it is associated with a faster time to treatment, as well as improvements in the quality of life of patients and their carers. In addition, as improved haemostatic control now allows inhibitor patients to participate in a wider range of physical activities, specific guidelines are required on which types of sport and work are appropriate. It was agreed that clear, systematic approaches are needed for early diagnosis of joint and muscle bleeds in inhibitor patients, which could facilitate rapid treatment. There may be opportunities for exploiting new diagnostic techniques from osteoarthritis to enable earlier diagnosis of haemophilic arthropathy. Overall, it was concluded that greater emphasis should be placed on education and patients' psychological needs, to enable inhibitor patients to cope up more effectively with their disease.

Evolution of Vertebrate Hemostatic and Inflammatory Control Mechanisms in Blood-Feeding Arthropods

Arthropods evolved blood-feeding lifestyles on more than 20 independent occasions. A comparison of sialomes (secretory salivary gland protein family repertoires) corroborates this and indicates that unique protein families are found for different blood-feeding lineages. Closely related lineages considered to have evolved blood-feeding behavior independently might share similar sets of protein families in their sialomes. No orthologous relationships or conserved functional mechanisms have, however, been found for these apparently related protein family members. This implies that sialomes were already defined before the divergence of these related lineages, but that the functions involved in blood feeding evolved at a later stage. Protein families prone to lineage-specific expansion (gene duplication) tend to be abundant with specialized functions associated with various gene duplicates. A central theme that seems to emerge from comparative sialomic analysis is that of the convergent evolution of modulatory strategies that targets host defenses even if the molecular mechanisms differ.

Goal-directed hemostatic resuscitation for massively bleeding patients: The Copenhagen concept

BackgroundContinued hemorrhage remains a major cause of mortality in massively transfused patients, many of whom develop coagulopathy. A review of transfusion practice for these patients at our hospital revealed that a significant proportion received suboptimal transfusion therapy. Survivors had higher platelets count than non-survivors. MethodsFor massively transfused patients with hemodynamic instability, we introduced the concept of transfusion packages comprising five units of red blood cells, five units of fresh frozen plasma and two units of platelet concentrates. Thrombelastogram analysis was validated for routine laboratory use and implemented in the blood bank for monitoring coagulopathy and guiding transfusion therapy. Anaesthetists at our hospital were trained in functional haemostasis management based on analysis of thrombelastograms. ResultsIntraoperative administration of transfusion packages for patients operated on for a ruptured abdominal aortic aneurysm was associated with a reduction in mortality from 56% to 34% (p=0.02). When comparing massively transfused patients treated with hemostatic control resuscitation, i.e., transfusion package therapy during hemodynamic instability and thromboelastogram – monitored and guided transfusion therapy, with controls treated in accordance with existing transfusion guidelines, mortality was reduced from 31% to 20% (p=0.002). ConclusionThe initiative from the blood bank, i.e., transfusion packages for patients with uncontrollable bleeding and based on the thromboelastogram when hemodynamic control is established, has improved the transfusion practice and survival in massively transfused patients at our hospital.

Management of major blood loss: An update

Haemorrhage remains a major cause of potentially preventable deaths. Trauma and massive transfusion are associated with coagulopathy secondary to tissue injury, hypoperfusion, dilution and consumption of clotting factors and platelets. Concepts of damage control surgery have evolved, prioritizing the early control of the cause of bleeding by non-definitive means, while haemostatic control resuscitation seeks early control of coagulopathy. Haemostatic resuscitation provides transfusions with plasma and platelets in addition to red blood cells (RBCs) in an immediate and sustained manner as part of the transfusion protocol for massively bleeding patients. Transfusion of RBCs, plasma and platelets in a similar proportion as in whole blood prevents both hypovolaemia and coagulopathy. Although an early and effective reversal of coagulopathy is documented, the most effective means of preventing coagulopathy of massive transfusion remains debated and randomized controlled studies are lacking. Results from recent before-and-after studies in massively bleeding patients indicate that trauma exsanguination protocols involving the early administration of plasma and platelets are associated with improved survival. Furthermore, viscoelastic whole blood assays, such as thrombelastography (TEG)/rotation thromboelastometry (ROTEM), appear advantageous for identifying coagulopathy in patients with severe haemorrhage, as opposed to conventional coagulation assays. In our view, patients with uncontrolled bleeding, regardless of its cause, should be treated with goal-directed haemostatic control resuscitation involving the early administration of plasma and platelets and based on the results of the TEG/ROTEM analysis. The aim of the goal-directed therapy should be to maintain a normal haemostatic competence until surgical haemostasis is achieved, as this appears to be associated with reduced mortality.