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Papers by John Hess

Research paper thumbnail of Red blood cell metabolism, preservation, and oxygen delivery

Rossi's Principles of Transfusion Medicine, 2016

Research paper thumbnail of Advances in military, field, and austere transfusion medicine in the last decade

Transfusion and Apheresis Science, 2013

Research paper thumbnail of A self-assembling hydrophobically modified chitosan capable of reversible hemostatic action

Biomaterials, 2011

Blood loss at the site of a wound in mammals is curtailed by the rapid formation of a hemostatic ... more Blood loss at the site of a wound in mammals is curtailed by the rapid formation of a hemostatic plug, i.e., a self-assembled network of the protein, fibrin that locally transforms liquid blood into a gelled clot. Here, we report an amphiphilic biopolymer that exhibits a similar ability to rapidly gel blood; moreover, the self-assembly underlying the gelation readily allows for reversibility back into the liquid state via introduction of a sugar-based supramolecule. The biopolymer is a hydrophobically modified (hm) derivative of the polysaccharide, chitosan. When hm-chitosan is contacted with heparinized human blood, it rapidly transforms the liquid into an elastic gel. In contrast, the native chitosan (without hydrophobes) does not gel blood. Gelation occurs because the hydrophobes on hm-chitosan insert into the membranes of blood cells and thereby connect the cells into a sample-spanning network. Gelation is reversed by the addition of a-cyclodextrin, a supramolecule having an inner hydrophobic pocket: polymer hydrophobes unbind from blood cells and embed within the cyclodextrins, thereby disrupting the cell network. We believe that hm-chitosan has the potential to serve as an effective, yet low-cost hemostatic dressing for use by trauma centers and the military. Preliminary tests with small and large animal injury models show its increased efficacy at achieving hemostasis e e.g., a 90% reduction in bleeding time over controls for femoral vein transections in a rat model.

Research paper thumbnail of Hemostatic Efficacy of Modified Amylopectin Powder in a Lethal Porcine Model of Extremity Arterial Injury

Annals of Emergency Medicine, 2009

Study objective: Rapid hemostasis is crucial in controlling severe extremity hemorrhage. Our obje... more Study objective: Rapid hemostasis is crucial in controlling severe extremity hemorrhage. Our objective is to evaluate the hemostatic efficacy of a newly modified amylopectin powder in a model of severe extremity arterial hemorrhage. Methods: Anesthetized pigs underwent severe, reproducible femoral artery injuries. Animals were randomized (nonblinded) to either modified amylopectin powder (nϭ10) or standard gauze application (nϭ6). Each hemostatic agent was applied through a pool of blood with manual compression for 3-minute intervals until hemostasis was achieved. Fluid resuscitation was infused as necessary to reestablish a mean arterial pressure within at least 80% of the preinjury mean arterial pressure if possible. The primary measured outcome was total blood loss. Secondary endpoints were survival, time to hemostasis, resuscitation mean arterial pressure, and resuscitation volume. Results: Pretreatment blood losses were similar in both groups. Median (absolute average deviation of the median) posttreatment blood loss was significantly less in the modified amylopectin powder group than in the gauze group, 275 (108) mL versus 1,312 (171) mL. Resuscitation mean arterial pressure at 180 minutes after injury was 68% of preinjury mean arterial pressure in the modified amylopectin powder group and undetectable in all control animals. Fluid volume required for resuscitation was 1,962 (258) mL in the modified amylopectin powder group and 2,875 (150) mL in the gauze group. Time to hemostasis was 9.0 (2.1) minutes in the modified amylopectin powder group. Hemostasis was not achieved in any animal in the gauze group. Survival was 100% in the modified amylopectin powder group, whereas no animals survived in the gauze group. Conclusion: Modified amylopectin powder demonstrates the ability to control major vascular bleeding in a lethal arterial injury model during a 3-hour period.

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

The journal of trauma and acute care surgery, 2012

BACKGROUND: Chitosan is a functional biopolymer that has been widely used as a hemostat. Recently... more BACKGROUND: 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. METHODS: Twenty-four Yorkshire swine were randomized to receive hm-chitosan (n ϭ 8), unmodified chitosan (n ϭ 8), or standard Accu-Sorb gauze dressing (n ϭ 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. RESULTS: Blood loss before treatment was similar between groups (p Ͻ 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 Ϯ 28 minutes after application. Standard gauze provided no initial hemostasis after the 3-minute compression interval. CONCLUSIONS: Hm-chitosan is superior to unmodified chitosan sponges (p Ͻ 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.

Research paper thumbnail of Gender-Based Differences in Mortality in Response to High Product Ratio Massive Transfusion

Journal of Trauma-injury Infection and Critical Care, Aug 1, 2011

and the Trauma Outcomes Group Background: Recent data suggest that patients undergoing massive tr... more and the Trauma Outcomes Group Background: Recent data suggest that patients undergoing massive transfusion have lower mortality rates when ratios of plasma and platelets to red blood cells (RBCs) of Ն1:2 are used. This has not been examined independently in women and men. A gender dichotomy in outcome after severe injury is known to exist. This study examined gender-related differences in mortality after high product ratio massive transfusion. Methods: A retrospective study was conducted using a database containing massively transfused trauma patients from 23 Level I trauma centers. Baseline demographic, physiologic, and biochemical data were obtained. Univariate and logistic regression analyses were performed. Adjusted mortality in patients receiving high (Ն1:2) or low (Ͻ1:2) ratios of plasma or platelets to RBCs was compared in women and men independently. Results: Seven hundred four patients were analyzed. In males, mortality was lower for patients receiving a high plasma:RBC ratio at 24 hours (20.6% vs. 33.0% for low ratio, p ϭ 0.005) and at 30 days (34.9% vs. 42.8%, p ϭ 0.032). Males receiving a high platelet:RBC ratio also had lower 24-hour mortality (17.6% vs. 31.5%, p ϭ 0.004) and 30-day mortality (32.1% vs. 42.2%, p ϭ 0.045). Females receiving high ratios of plasma or platelets to RBCs had no improvement in 24-hour mortality (p ϭ 0.119 and 0.329, respectively) or 30-day mortality (p ϭ 0.199 and 0.911, respectively). Use of high product ratio transfusions did not affect 24-hour RBC requirements in males or females. Conclusion: Use of high plasma:RBC or platelet:RBC ratios in massive transfusion may benefit men more than women. This may be due to gender-related differences in coagulability. Further study is needed to determine whether separate protocols for women and men should be established.

Research paper thumbnail of Transfusion of Uncrossmatched Group O Erythrocyte-containing Products Does Not Interfere with Most ABO Typings

Anesthesiology, 2019

Background Group O erythrocytes and/or whole blood are used for urgent transfusions in patients o... more Background Group O erythrocytes and/or whole blood are used for urgent transfusions in patients of unknown blood type. This study investigated the impact of transfusing increasing numbers of uncrossmatched type O products on the recipient’s first in-hospital ABO type. Methods This was a retrospective cohort study. Results of the first ABO type obtained in adult, non–type O recipients (i.e., types A, B, AB) after receiving at least one unit of uncrossmatched type O erythrocyte-containing product(s) for any bleeding etiology were analyzed along with the number of uncrossmatched type O erythrocyte-containing products administered in the prehospital and/or in hospital setting before the first type and screen sample was drawn. Results There were 10 institutions that contributed a total of 695 patient records. Among patients who received up to 10 uncrossmatched type O erythrocyte-containing products, the median A antigen agglutination strength in A and AB individuals on forward typing (i....

Research paper thumbnail of Effect of Fibrin Bandage Fibrinogen Concentration on Blood Loss after Grade V Liver Injury in Swine

Military Medicine, 2001

Objective: To determine the effect of fibrinogen concentration of dry fibrin bandages on blood lo... more Objective: To determine the effect of fibrinogen concentration of dry fibrin bandages on blood loss after grade V liver injury. Methods: Twenty-four pigs were used. Grade V liver injuries were induced and treated with dry fibrin bandages containing 0,4,8, or 15 mg fibrinogen/cm''. Animals were monitored for 60 minutes. Blood loss, fluid use, hematological data, and hemostasis were assessed. Results: Post-treatment blood losses (mean and 95% confidence interval [CI]) were 1,560 mL (356-6,844), 372 mL (65-2,134), 225 mL (51-992), and 127 mL (22-732) in the 0-, 4-, 8-, and 15-mg groups, respectively. Only the 15-mg group had results significantly lower than the O-mg group (p < 0.05). Blood loss was negatively related to fibrinogen concentration (p < 0.05). Conclusion: Fibrinogen concentration was inversely related to blood loss after grade V liver injury. The 15-mg formulation was the only one that significantly reduced blood loss.

Research paper thumbnail of Proceedings of the Food and Drug Administration's public workshop on new red blood cell product regulatory science 2016

Transfusion, 2018

The US Food and Drug Administration (FDA) held a workshop on red blood cell (RBC) product regulat... more The US Food and Drug Administration (FDA) held a workshop on red blood cell (RBC) product regulatory science on October 6 and 7, 2016, at the Natcher Conference Center on the National Institutes of Health (NIH) Campus in Bethesda, Maryland. The workshop was supported by the National Heart, Lung, and Blood Institute, NIH; the Department of Defense; the Office of the Assistant Secretary for Health, Department of Health and Human Services; and the Center for Biologics Evaluation and Research, FDA. The workshop reviewed the status and scientific basis of the current regulatory framework and the available scientific tools to expand it to evaluate innovative and future RBC transfusion products. A full record of the proceedings is available on the FDA website (http://www.fda.gov/BiologicsBloodVaccines/NewsEvents/WorkshopsMeetingsConferences/ucm507890.htm). The contents of the summary are the authors' opinions and do not represent agency policy.

Research paper thumbnail of Resuscitating resuscitation science in TRANSFUSION

Research paper thumbnail of Clinical Outcomes in a Cohort of Patients with Heparin-induced Thrombocytopenia

American journal of hematology, Jan 7, 2017

Heparin-induced thrombocytopenia (HIT) is a thrombotic disorder usually prompting treatment with ... more Heparin-induced thrombocytopenia (HIT) is a thrombotic disorder usually prompting treatment with non-heparin anticoagulants. The benefits and risks of such treatments have not been fully assessed. We analyzed data for 442 patients having a positive heparin-platelet factor 4 antibody test and recent heparin exposure. The primary outcome was a composite endpoint (death, limb amputation/gangrene, or new thrombosis). Secondary outcomes included bleeding and the effect of anticoagulation. Seventy-one patients (16%) had HIT with thrombosis (HIT-T); 284 (64%) had HIT without thrombosis (isolated HIT); 87 (20%) did not have HIT. An intermediate or high "4T" score was found in 85%, 58%, and 8% of the three respective groups. Non-heparin anticoagulation was begun in 80%, 56% and 45%. The composite endpoint occurred in 48%, 36% and 17% (P=0.01) of which 61%, 38% and 40% were receiving non-heparin anticoagulation. Compared with the no HIT group, the composite endpoint was significantl...

Research paper thumbnail of Multi-omics Evidence for Inheritance of Energy Pathways in Red Blood Cells

Molecular & cellular proteomics : MCP, 2016

Each year over 90 million units of blood are transfused worldwide. Our dependence on this blood s... more Each year over 90 million units of blood are transfused worldwide. Our dependence on this blood supply mandates optimized blood management and storage. During storage, red blood cells undergo degenerative processes resulting in altered metabolic characteristics which may make blood less viable for transfusion. However, not all stored blood spoils at the same rate, a difference that has been attributed to variable rates of energy usage and metabolism in red blood cells. Specific metabolite abundances are heritable traits; however, the link between heritability of energy metabolism and red blood cell storage profiles is unclear. Herein we performed a comprehensive metabolomics and proteomics study of red blood cells from 18 mono- and di-zygotic twin pairs to measure heritability and identify correlations with ATP and other molecular indices of energy metabolism. Without using affinity-based hemoglobin depletion, our work afforded the deepest multi-omic characterization of red blood ce...

Research paper thumbnail of Different Hypotensive Responses to Intravenous Bovine and Human Thrombin Preparations in Swine

The Journal of Trauma: Injury, Infection, and Critical Care, 2001

Background: Accidental intravenous introduction of commercial bovine thrombin (BT) during use of ... more Background: Accidental intravenous introduction of commercial bovine thrombin (BT) during use of fibrin glue may result in profound hypotension. Commercial human thrombin (HT) is now available. This study compared the effects of intravenous BT versus HT in swine. Methods: Swine received 30 U/kg BT, 60 U/kg BT, 30 U/kg HT, or 60 U/kg HT intravenously. Mean arterial pressure (MAP) and survival were monitored for 30 minutes. Thrombin purities and in vitro activities were examined. Results: MAP nadir was lower (p < 0.05) after BT, 27.7 ؎ 3.3% (mean ؎ SEM) of pretreatment MAP, compared with 41.1 ؎ 3.7% after HT. Five of six animals died after 60 U/kg BT, whereas all others survived (p < 0.05). Histology suggested more severe disseminated intravas-cular coagulation after BT. HT was purer than BT. In vitro activities were similar. Conclusion: Both BT and HT produced hypotension. HT appeared safer, because of higher purity. Regardless of source and purity, thrombin must be used with caution.

Research paper thumbnail of Heritability of glutathione and related metabolites in stored red blood cells

Free Radical Biology and Medicine, 2014

Red blood cells (RBCs) collected for transfusion deteriorate during storage. This deterioration i... more Red blood cells (RBCs) collected for transfusion deteriorate during storage. This deterioration is termed the "RBC storage lesion". There is increasing concern over the safety, therapeutic efficacy, and toxicity of transfusing longer-stored units of blood. The severity of the RBC storage lesion is dependent on storage-time and varies markedly between individuals. Oxidative damage is considered a significant factor in development of the RBC storage lesion. In this study, the variability during storage and heritability of antioxidants and metabolites central to RBC integrity and function were investigated. In a classic twin study, we determined the heritability of glutathione (GSH), glutathione disulfide (GSSG), the status of the GSSG, 2H + /2GSH couple (E hc) and total glutathione (tGSH) in donated RBCs over 56 days of storage. Intracellular GSH and GSSG concentrations both decrease during storage (median net loss of 0.52 ± 0.63 mM (median ± SD) and 0.032 ± 0.107mM, respectively over 42 days). Taking into account the decline in pH, E hc became more positive (oxidized) during storage (median net increase of 35 ± 16 mV). In our study

Research paper thumbnail of Fibrin Sealant Foam Sprayed Directly on Liver Injuries Decreases Blood Loss in Resuscitated Rats

The Journal of Trauma: Injury, Infection, and Critical Care, 2000

The majority of early trauma deaths are attributable to uncontrolled hemorrhage from truncal site... more The majority of early trauma deaths are attributable to uncontrolled hemorrhage from truncal sites. A hemorrhage-control technique that reduced bleeding in the prehospital phase of treatment without requiring manual compression may improve the outcome of these patients. We conducted this preliminary study to determine whether an expanding fibrin sealant foam (FSF) would reduce bleeding from a severe liver injury even during resuscitation. Methods: Rats (n ‫؍‬ 31; 291 ؎ 5 g; 37.4 ؎ 0.3°C; mean ؎ SEM), underwent a 60 ؎ 5% excision of the median hepatic lobe. The animals received one of three treatments: (1) FSF, (2) immunoglobulin G placebo foam (IgGF), or (3) no treatment. All animals were resuscitated with 40°C lactated Ringer's solution at 3.3 mL/ min/kg to a mean arterial pressure of 100 mm Hg. Total blood loss, mean arterial pressure, and resuscitation volume were recorded for 30 minutes. A qualitative measure of foam coverage and adherence to the cut liver edge was recorded. Results: The total blood loss was less (p < 0.01) in the FSF group (21.2 ؎ 5.0 mL/kg) than in either IgGF (41.4 ؎ 4.3 mL/kg) or the no treatment group (44.6 ؎ 4.7 mL/kg), which did not differ. The resuscitation volume was not different. The amount of foam used in the treated groups, 9.1 ؎ 1.0 g in the FSF group and 10.0 ؎ 1.0 g in the IgGF group, did not differ. Survival for 30 minutes was not different among groups. There was no difference in the amount of cut liver covered by either foam, but the clots were more adherent (p < 0.05) in the FSF group than in the IgGF group. Conclusion: In rats with a severe liver injury, spraying fibrin foam directly on the cut liver surface decreased blood loss when compared with placebo foam and no treatment. This pilot study suggests a future possible treatment for noncompressible truncal hemorrhage.

Research paper thumbnail of Trauma and Military Applications of Blood Substitutes

Artificial Cells, Blood Substitutes, and Biotechnology, 1994

This docume.;t has been approved for public 2bDE-CLASSFINC-ATION I DO , W release, distribution i... more This docume.;t has been approved for public 2bDE-CLASSFINC-ATION I DO , W release, distribution is unlimited. 4. PERFORMNO ORGANIZATIONRE(-S. MONITORING ORGANIZATION REPORT NUMBER(S) 6a. NAME OF PERFORMING ORGANIZATION 6b OFFICE SYMBOL.-7a-NAME OF MONITORING ORGANIZATION Division of filitary Trauma. (itappliable)

Research paper thumbnail of Advanced Hemostatic Dressing Development Program: Animal Model Selection Criteria and Results of a Study of Nine Hemostatic Dressings in a Model of Severe Large Venous Hemorrhage and Hepatic Injury in Swine

The Journal of Trauma: Injury, Infection, and Critical Care, 2003

Background: An advanced hemostatic dressing is needed to augment current methods for the control ... more Background: An advanced hemostatic dressing is needed to augment current methods for the control of life-threatening hemorrhage. A systematic approach to the study of dressings is described. We studied the effects of nine hemostatic dressings on blood loss using a model of severe venous hemorrhage and hepatic injury in swine. Methods: Swine were treated using one of nine hemostatic dressings. Dressings used the following primary active ingredients: microfibrillar collagen, oxidized cellulose, thrombin, fibrinogen, propyl gallate, aluminum sulfate, and fully acetylated poly-N-acetyl glucosamine. Standardized liver injuries were induced, dressings were applied, and resuscitation was initiated. Blood loss, hemostasis, and 60-minute survival were quantified. Results: The American Red Cross hemostatic dressing (fibrinogen and thrombin) reduced (p < 0.01) posttreatment blood loss (366 mL; 95% confidence interval, 175-762 mL) and increased (p < 0.05) the percentage of animals in which hemostasis was attained (73%), compared with gauze controls (2,973 mL; 95% confidence interval, 1,414-6,102 mL and 0%, respectively). No other dressing was effective. The number of vessels lacerated was positively related to pretreatment blood loss and negatively related to hemostasis. Conclusion: The hemorrhage model allowed differentiation among topical hemostatic agents for severe hemorrhage. The American Red Cross hemostatic dressing was effective and warrants further development.

Research paper thumbnail of Advanced Hemostatic Dressing Development Program: Animal Model Selection Criteria and Results of a Study of Nine Hemostatic Dressings in a Model of Severe Large Venous Hemorrhage and Hepatic Injury in Swine

The Journal of Trauma: Injury, Infection, and Critical Care, 2003

Background: An advanced hemostatic dressing is needed to augment current methods for the control ... more Background: An advanced hemostatic dressing is needed to augment current methods for the control of life-threatening hemorrhage. A systematic approach to the study of dressings is described. We studied the effects of nine hemostatic dressings on blood loss using a model of severe venous hemorrhage and hepatic injury in swine. Methods: Swine were treated using one of nine hemostatic dressings. Dressings used the following primary active ingredients: microfibrillar collagen, oxidized cellulose, thrombin, fibrinogen, propyl gallate, aluminum sulfate, and fully acetylated poly-N-acetyl glucosamine. Standardized liver injuries were induced, dressings were applied, and resuscitation was initiated. Blood loss, hemostasis, and 60-minute survival were quantified. Results: The American Red Cross hemostatic dressing (fibrinogen and thrombin) reduced (p < 0.01) posttreatment blood loss (366 mL; 95% confidence interval, 175-762 mL) and increased (p < 0.05) the percentage of animals in which hemostasis was attained (73%), compared with gauze controls (2,973 mL; 95% confidence interval, 1,414-6,102 mL and 0%, respectively). No other dressing was effective. The number of vessels lacerated was positively related to pretreatment blood loss and negatively related to hemostasis. Conclusion: The hemorrhage model allowed differentiation among topical hemostatic agents for severe hemorrhage. The American Red Cross hemostatic dressing was effective and warrants further development.

Research paper thumbnail of Hepatic abscess-associatedClostridialbacteraemia presenting with intravascular haemolysis and severe hypertension

Research paper thumbnail of Modelling the effects of blood component storage lesions on the quality of haemostatic resuscitation in massive transfusion for trauma

Blood transfusion = Trasfusione del sangue, 2017

BACKGROUND All blood components undergo loss of potency during storage. These loss-of-potency sto... more BACKGROUND All blood components undergo loss of potency during storage. These loss-of-potency storage lesions are important in trauma resuscitation because they reduce the haemostatic capacity of mixtures of components that attempt to reconstitute whole blood. Even red cell storage-related loss of potency, which averages 17% with modern additive solutions, is important because 6 units of red cells must be given to achieve the effect of 5 fully potent units. MATERIALS AND METHODS Loss of potency of stored units of red blood cells, plasma, platelets, and cryoprecipitate were summed for dilutional, storage-related, pathogen reduction-related, and splenic sequestration-related causes and expressed as fractional plasma coagulation factor concentrations and platelet counts. RESULTS Production of reconstituted whole blood from 1:1:1 unit ratios of red cells:plasma:platelets is associated with a 38% loss of plasma coagulation factor concentration and 56% loss of platelets. Storage losses of...

Research paper thumbnail of Red blood cell metabolism, preservation, and oxygen delivery

Rossi's Principles of Transfusion Medicine, 2016

Research paper thumbnail of Advances in military, field, and austere transfusion medicine in the last decade

Transfusion and Apheresis Science, 2013

Research paper thumbnail of A self-assembling hydrophobically modified chitosan capable of reversible hemostatic action

Biomaterials, 2011

Blood loss at the site of a wound in mammals is curtailed by the rapid formation of a hemostatic ... more Blood loss at the site of a wound in mammals is curtailed by the rapid formation of a hemostatic plug, i.e., a self-assembled network of the protein, fibrin that locally transforms liquid blood into a gelled clot. Here, we report an amphiphilic biopolymer that exhibits a similar ability to rapidly gel blood; moreover, the self-assembly underlying the gelation readily allows for reversibility back into the liquid state via introduction of a sugar-based supramolecule. The biopolymer is a hydrophobically modified (hm) derivative of the polysaccharide, chitosan. When hm-chitosan is contacted with heparinized human blood, it rapidly transforms the liquid into an elastic gel. In contrast, the native chitosan (without hydrophobes) does not gel blood. Gelation occurs because the hydrophobes on hm-chitosan insert into the membranes of blood cells and thereby connect the cells into a sample-spanning network. Gelation is reversed by the addition of a-cyclodextrin, a supramolecule having an inner hydrophobic pocket: polymer hydrophobes unbind from blood cells and embed within the cyclodextrins, thereby disrupting the cell network. We believe that hm-chitosan has the potential to serve as an effective, yet low-cost hemostatic dressing for use by trauma centers and the military. Preliminary tests with small and large animal injury models show its increased efficacy at achieving hemostasis e e.g., a 90% reduction in bleeding time over controls for femoral vein transections in a rat model.

Research paper thumbnail of Hemostatic Efficacy of Modified Amylopectin Powder in a Lethal Porcine Model of Extremity Arterial Injury

Annals of Emergency Medicine, 2009

Study objective: Rapid hemostasis is crucial in controlling severe extremity hemorrhage. Our obje... more Study objective: Rapid hemostasis is crucial in controlling severe extremity hemorrhage. Our objective is to evaluate the hemostatic efficacy of a newly modified amylopectin powder in a model of severe extremity arterial hemorrhage. Methods: Anesthetized pigs underwent severe, reproducible femoral artery injuries. Animals were randomized (nonblinded) to either modified amylopectin powder (nϭ10) or standard gauze application (nϭ6). Each hemostatic agent was applied through a pool of blood with manual compression for 3-minute intervals until hemostasis was achieved. Fluid resuscitation was infused as necessary to reestablish a mean arterial pressure within at least 80% of the preinjury mean arterial pressure if possible. The primary measured outcome was total blood loss. Secondary endpoints were survival, time to hemostasis, resuscitation mean arterial pressure, and resuscitation volume. Results: Pretreatment blood losses were similar in both groups. Median (absolute average deviation of the median) posttreatment blood loss was significantly less in the modified amylopectin powder group than in the gauze group, 275 (108) mL versus 1,312 (171) mL. Resuscitation mean arterial pressure at 180 minutes after injury was 68% of preinjury mean arterial pressure in the modified amylopectin powder group and undetectable in all control animals. Fluid volume required for resuscitation was 1,962 (258) mL in the modified amylopectin powder group and 2,875 (150) mL in the gauze group. Time to hemostasis was 9.0 (2.1) minutes in the modified amylopectin powder group. Hemostasis was not achieved in any animal in the gauze group. Survival was 100% in the modified amylopectin powder group, whereas no animals survived in the gauze group. Conclusion: Modified amylopectin powder demonstrates the ability to control major vascular bleeding in a lethal arterial injury model during a 3-hour period.

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

The journal of trauma and acute care surgery, 2012

BACKGROUND: Chitosan is a functional biopolymer that has been widely used as a hemostat. Recently... more BACKGROUND: 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. METHODS: Twenty-four Yorkshire swine were randomized to receive hm-chitosan (n ϭ 8), unmodified chitosan (n ϭ 8), or standard Accu-Sorb gauze dressing (n ϭ 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. RESULTS: Blood loss before treatment was similar between groups (p Ͻ 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 Ϯ 28 minutes after application. Standard gauze provided no initial hemostasis after the 3-minute compression interval. CONCLUSIONS: Hm-chitosan is superior to unmodified chitosan sponges (p Ͻ 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.

Research paper thumbnail of Gender-Based Differences in Mortality in Response to High Product Ratio Massive Transfusion

Journal of Trauma-injury Infection and Critical Care, Aug 1, 2011

and the Trauma Outcomes Group Background: Recent data suggest that patients undergoing massive tr... more and the Trauma Outcomes Group Background: Recent data suggest that patients undergoing massive transfusion have lower mortality rates when ratios of plasma and platelets to red blood cells (RBCs) of Ն1:2 are used. This has not been examined independently in women and men. A gender dichotomy in outcome after severe injury is known to exist. This study examined gender-related differences in mortality after high product ratio massive transfusion. Methods: A retrospective study was conducted using a database containing massively transfused trauma patients from 23 Level I trauma centers. Baseline demographic, physiologic, and biochemical data were obtained. Univariate and logistic regression analyses were performed. Adjusted mortality in patients receiving high (Ն1:2) or low (Ͻ1:2) ratios of plasma or platelets to RBCs was compared in women and men independently. Results: Seven hundred four patients were analyzed. In males, mortality was lower for patients receiving a high plasma:RBC ratio at 24 hours (20.6% vs. 33.0% for low ratio, p ϭ 0.005) and at 30 days (34.9% vs. 42.8%, p ϭ 0.032). Males receiving a high platelet:RBC ratio also had lower 24-hour mortality (17.6% vs. 31.5%, p ϭ 0.004) and 30-day mortality (32.1% vs. 42.2%, p ϭ 0.045). Females receiving high ratios of plasma or platelets to RBCs had no improvement in 24-hour mortality (p ϭ 0.119 and 0.329, respectively) or 30-day mortality (p ϭ 0.199 and 0.911, respectively). Use of high product ratio transfusions did not affect 24-hour RBC requirements in males or females. Conclusion: Use of high plasma:RBC or platelet:RBC ratios in massive transfusion may benefit men more than women. This may be due to gender-related differences in coagulability. Further study is needed to determine whether separate protocols for women and men should be established.

Research paper thumbnail of Transfusion of Uncrossmatched Group O Erythrocyte-containing Products Does Not Interfere with Most ABO Typings

Anesthesiology, 2019

Background Group O erythrocytes and/or whole blood are used for urgent transfusions in patients o... more Background Group O erythrocytes and/or whole blood are used for urgent transfusions in patients of unknown blood type. This study investigated the impact of transfusing increasing numbers of uncrossmatched type O products on the recipient’s first in-hospital ABO type. Methods This was a retrospective cohort study. Results of the first ABO type obtained in adult, non–type O recipients (i.e., types A, B, AB) after receiving at least one unit of uncrossmatched type O erythrocyte-containing product(s) for any bleeding etiology were analyzed along with the number of uncrossmatched type O erythrocyte-containing products administered in the prehospital and/or in hospital setting before the first type and screen sample was drawn. Results There were 10 institutions that contributed a total of 695 patient records. Among patients who received up to 10 uncrossmatched type O erythrocyte-containing products, the median A antigen agglutination strength in A and AB individuals on forward typing (i....

Research paper thumbnail of Effect of Fibrin Bandage Fibrinogen Concentration on Blood Loss after Grade V Liver Injury in Swine

Military Medicine, 2001

Objective: To determine the effect of fibrinogen concentration of dry fibrin bandages on blood lo... more Objective: To determine the effect of fibrinogen concentration of dry fibrin bandages on blood loss after grade V liver injury. Methods: Twenty-four pigs were used. Grade V liver injuries were induced and treated with dry fibrin bandages containing 0,4,8, or 15 mg fibrinogen/cm''. Animals were monitored for 60 minutes. Blood loss, fluid use, hematological data, and hemostasis were assessed. Results: Post-treatment blood losses (mean and 95% confidence interval [CI]) were 1,560 mL (356-6,844), 372 mL (65-2,134), 225 mL (51-992), and 127 mL (22-732) in the 0-, 4-, 8-, and 15-mg groups, respectively. Only the 15-mg group had results significantly lower than the O-mg group (p < 0.05). Blood loss was negatively related to fibrinogen concentration (p < 0.05). Conclusion: Fibrinogen concentration was inversely related to blood loss after grade V liver injury. The 15-mg formulation was the only one that significantly reduced blood loss.

Research paper thumbnail of Proceedings of the Food and Drug Administration's public workshop on new red blood cell product regulatory science 2016

Transfusion, 2018

The US Food and Drug Administration (FDA) held a workshop on red blood cell (RBC) product regulat... more The US Food and Drug Administration (FDA) held a workshop on red blood cell (RBC) product regulatory science on October 6 and 7, 2016, at the Natcher Conference Center on the National Institutes of Health (NIH) Campus in Bethesda, Maryland. The workshop was supported by the National Heart, Lung, and Blood Institute, NIH; the Department of Defense; the Office of the Assistant Secretary for Health, Department of Health and Human Services; and the Center for Biologics Evaluation and Research, FDA. The workshop reviewed the status and scientific basis of the current regulatory framework and the available scientific tools to expand it to evaluate innovative and future RBC transfusion products. A full record of the proceedings is available on the FDA website (http://www.fda.gov/BiologicsBloodVaccines/NewsEvents/WorkshopsMeetingsConferences/ucm507890.htm). The contents of the summary are the authors' opinions and do not represent agency policy.

Research paper thumbnail of Resuscitating resuscitation science in TRANSFUSION

Research paper thumbnail of Clinical Outcomes in a Cohort of Patients with Heparin-induced Thrombocytopenia

American journal of hematology, Jan 7, 2017

Heparin-induced thrombocytopenia (HIT) is a thrombotic disorder usually prompting treatment with ... more Heparin-induced thrombocytopenia (HIT) is a thrombotic disorder usually prompting treatment with non-heparin anticoagulants. The benefits and risks of such treatments have not been fully assessed. We analyzed data for 442 patients having a positive heparin-platelet factor 4 antibody test and recent heparin exposure. The primary outcome was a composite endpoint (death, limb amputation/gangrene, or new thrombosis). Secondary outcomes included bleeding and the effect of anticoagulation. Seventy-one patients (16%) had HIT with thrombosis (HIT-T); 284 (64%) had HIT without thrombosis (isolated HIT); 87 (20%) did not have HIT. An intermediate or high "4T" score was found in 85%, 58%, and 8% of the three respective groups. Non-heparin anticoagulation was begun in 80%, 56% and 45%. The composite endpoint occurred in 48%, 36% and 17% (P=0.01) of which 61%, 38% and 40% were receiving non-heparin anticoagulation. Compared with the no HIT group, the composite endpoint was significantl...

Research paper thumbnail of Multi-omics Evidence for Inheritance of Energy Pathways in Red Blood Cells

Molecular & cellular proteomics : MCP, 2016

Each year over 90 million units of blood are transfused worldwide. Our dependence on this blood s... more Each year over 90 million units of blood are transfused worldwide. Our dependence on this blood supply mandates optimized blood management and storage. During storage, red blood cells undergo degenerative processes resulting in altered metabolic characteristics which may make blood less viable for transfusion. However, not all stored blood spoils at the same rate, a difference that has been attributed to variable rates of energy usage and metabolism in red blood cells. Specific metabolite abundances are heritable traits; however, the link between heritability of energy metabolism and red blood cell storage profiles is unclear. Herein we performed a comprehensive metabolomics and proteomics study of red blood cells from 18 mono- and di-zygotic twin pairs to measure heritability and identify correlations with ATP and other molecular indices of energy metabolism. Without using affinity-based hemoglobin depletion, our work afforded the deepest multi-omic characterization of red blood ce...

Research paper thumbnail of Different Hypotensive Responses to Intravenous Bovine and Human Thrombin Preparations in Swine

The Journal of Trauma: Injury, Infection, and Critical Care, 2001

Background: Accidental intravenous introduction of commercial bovine thrombin (BT) during use of ... more Background: Accidental intravenous introduction of commercial bovine thrombin (BT) during use of fibrin glue may result in profound hypotension. Commercial human thrombin (HT) is now available. This study compared the effects of intravenous BT versus HT in swine. Methods: Swine received 30 U/kg BT, 60 U/kg BT, 30 U/kg HT, or 60 U/kg HT intravenously. Mean arterial pressure (MAP) and survival were monitored for 30 minutes. Thrombin purities and in vitro activities were examined. Results: MAP nadir was lower (p < 0.05) after BT, 27.7 ؎ 3.3% (mean ؎ SEM) of pretreatment MAP, compared with 41.1 ؎ 3.7% after HT. Five of six animals died after 60 U/kg BT, whereas all others survived (p < 0.05). Histology suggested more severe disseminated intravas-cular coagulation after BT. HT was purer than BT. In vitro activities were similar. Conclusion: Both BT and HT produced hypotension. HT appeared safer, because of higher purity. Regardless of source and purity, thrombin must be used with caution.

Research paper thumbnail of Heritability of glutathione and related metabolites in stored red blood cells

Free Radical Biology and Medicine, 2014

Red blood cells (RBCs) collected for transfusion deteriorate during storage. This deterioration i... more Red blood cells (RBCs) collected for transfusion deteriorate during storage. This deterioration is termed the "RBC storage lesion". There is increasing concern over the safety, therapeutic efficacy, and toxicity of transfusing longer-stored units of blood. The severity of the RBC storage lesion is dependent on storage-time and varies markedly between individuals. Oxidative damage is considered a significant factor in development of the RBC storage lesion. In this study, the variability during storage and heritability of antioxidants and metabolites central to RBC integrity and function were investigated. In a classic twin study, we determined the heritability of glutathione (GSH), glutathione disulfide (GSSG), the status of the GSSG, 2H + /2GSH couple (E hc) and total glutathione (tGSH) in donated RBCs over 56 days of storage. Intracellular GSH and GSSG concentrations both decrease during storage (median net loss of 0.52 ± 0.63 mM (median ± SD) and 0.032 ± 0.107mM, respectively over 42 days). Taking into account the decline in pH, E hc became more positive (oxidized) during storage (median net increase of 35 ± 16 mV). In our study

Research paper thumbnail of Fibrin Sealant Foam Sprayed Directly on Liver Injuries Decreases Blood Loss in Resuscitated Rats

The Journal of Trauma: Injury, Infection, and Critical Care, 2000

The majority of early trauma deaths are attributable to uncontrolled hemorrhage from truncal site... more The majority of early trauma deaths are attributable to uncontrolled hemorrhage from truncal sites. A hemorrhage-control technique that reduced bleeding in the prehospital phase of treatment without requiring manual compression may improve the outcome of these patients. We conducted this preliminary study to determine whether an expanding fibrin sealant foam (FSF) would reduce bleeding from a severe liver injury even during resuscitation. Methods: Rats (n ‫؍‬ 31; 291 ؎ 5 g; 37.4 ؎ 0.3°C; mean ؎ SEM), underwent a 60 ؎ 5% excision of the median hepatic lobe. The animals received one of three treatments: (1) FSF, (2) immunoglobulin G placebo foam (IgGF), or (3) no treatment. All animals were resuscitated with 40°C lactated Ringer's solution at 3.3 mL/ min/kg to a mean arterial pressure of 100 mm Hg. Total blood loss, mean arterial pressure, and resuscitation volume were recorded for 30 minutes. A qualitative measure of foam coverage and adherence to the cut liver edge was recorded. Results: The total blood loss was less (p < 0.01) in the FSF group (21.2 ؎ 5.0 mL/kg) than in either IgGF (41.4 ؎ 4.3 mL/kg) or the no treatment group (44.6 ؎ 4.7 mL/kg), which did not differ. The resuscitation volume was not different. The amount of foam used in the treated groups, 9.1 ؎ 1.0 g in the FSF group and 10.0 ؎ 1.0 g in the IgGF group, did not differ. Survival for 30 minutes was not different among groups. There was no difference in the amount of cut liver covered by either foam, but the clots were more adherent (p < 0.05) in the FSF group than in the IgGF group. Conclusion: In rats with a severe liver injury, spraying fibrin foam directly on the cut liver surface decreased blood loss when compared with placebo foam and no treatment. This pilot study suggests a future possible treatment for noncompressible truncal hemorrhage.

Research paper thumbnail of Trauma and Military Applications of Blood Substitutes

Artificial Cells, Blood Substitutes, and Biotechnology, 1994

This docume.;t has been approved for public 2bDE-CLASSFINC-ATION I DO , W release, distribution i... more This docume.;t has been approved for public 2bDE-CLASSFINC-ATION I DO , W release, distribution is unlimited. 4. PERFORMNO ORGANIZATIONRE(-S. MONITORING ORGANIZATION REPORT NUMBER(S) 6a. NAME OF PERFORMING ORGANIZATION 6b OFFICE SYMBOL.-7a-NAME OF MONITORING ORGANIZATION Division of filitary Trauma. (itappliable)

Research paper thumbnail of Advanced Hemostatic Dressing Development Program: Animal Model Selection Criteria and Results of a Study of Nine Hemostatic Dressings in a Model of Severe Large Venous Hemorrhage and Hepatic Injury in Swine

The Journal of Trauma: Injury, Infection, and Critical Care, 2003

Background: An advanced hemostatic dressing is needed to augment current methods for the control ... more Background: An advanced hemostatic dressing is needed to augment current methods for the control of life-threatening hemorrhage. A systematic approach to the study of dressings is described. We studied the effects of nine hemostatic dressings on blood loss using a model of severe venous hemorrhage and hepatic injury in swine. Methods: Swine were treated using one of nine hemostatic dressings. Dressings used the following primary active ingredients: microfibrillar collagen, oxidized cellulose, thrombin, fibrinogen, propyl gallate, aluminum sulfate, and fully acetylated poly-N-acetyl glucosamine. Standardized liver injuries were induced, dressings were applied, and resuscitation was initiated. Blood loss, hemostasis, and 60-minute survival were quantified. Results: The American Red Cross hemostatic dressing (fibrinogen and thrombin) reduced (p < 0.01) posttreatment blood loss (366 mL; 95% confidence interval, 175-762 mL) and increased (p < 0.05) the percentage of animals in which hemostasis was attained (73%), compared with gauze controls (2,973 mL; 95% confidence interval, 1,414-6,102 mL and 0%, respectively). No other dressing was effective. The number of vessels lacerated was positively related to pretreatment blood loss and negatively related to hemostasis. Conclusion: The hemorrhage model allowed differentiation among topical hemostatic agents for severe hemorrhage. The American Red Cross hemostatic dressing was effective and warrants further development.

Research paper thumbnail of Advanced Hemostatic Dressing Development Program: Animal Model Selection Criteria and Results of a Study of Nine Hemostatic Dressings in a Model of Severe Large Venous Hemorrhage and Hepatic Injury in Swine

The Journal of Trauma: Injury, Infection, and Critical Care, 2003

Background: An advanced hemostatic dressing is needed to augment current methods for the control ... more Background: An advanced hemostatic dressing is needed to augment current methods for the control of life-threatening hemorrhage. A systematic approach to the study of dressings is described. We studied the effects of nine hemostatic dressings on blood loss using a model of severe venous hemorrhage and hepatic injury in swine. Methods: Swine were treated using one of nine hemostatic dressings. Dressings used the following primary active ingredients: microfibrillar collagen, oxidized cellulose, thrombin, fibrinogen, propyl gallate, aluminum sulfate, and fully acetylated poly-N-acetyl glucosamine. Standardized liver injuries were induced, dressings were applied, and resuscitation was initiated. Blood loss, hemostasis, and 60-minute survival were quantified. Results: The American Red Cross hemostatic dressing (fibrinogen and thrombin) reduced (p < 0.01) posttreatment blood loss (366 mL; 95% confidence interval, 175-762 mL) and increased (p < 0.05) the percentage of animals in which hemostasis was attained (73%), compared with gauze controls (2,973 mL; 95% confidence interval, 1,414-6,102 mL and 0%, respectively). No other dressing was effective. The number of vessels lacerated was positively related to pretreatment blood loss and negatively related to hemostasis. Conclusion: The hemorrhage model allowed differentiation among topical hemostatic agents for severe hemorrhage. The American Red Cross hemostatic dressing was effective and warrants further development.

Research paper thumbnail of Hepatic abscess-associatedClostridialbacteraemia presenting with intravascular haemolysis and severe hypertension

Research paper thumbnail of Modelling the effects of blood component storage lesions on the quality of haemostatic resuscitation in massive transfusion for trauma

Blood transfusion = Trasfusione del sangue, 2017

BACKGROUND All blood components undergo loss of potency during storage. These loss-of-potency sto... more BACKGROUND All blood components undergo loss of potency during storage. These loss-of-potency storage lesions are important in trauma resuscitation because they reduce the haemostatic capacity of mixtures of components that attempt to reconstitute whole blood. Even red cell storage-related loss of potency, which averages 17% with modern additive solutions, is important because 6 units of red cells must be given to achieve the effect of 5 fully potent units. MATERIALS AND METHODS Loss of potency of stored units of red blood cells, plasma, platelets, and cryoprecipitate were summed for dilutional, storage-related, pathogen reduction-related, and splenic sequestration-related causes and expressed as fractional plasma coagulation factor concentrations and platelet counts. RESULTS Production of reconstituted whole blood from 1:1:1 unit ratios of red cells:plasma:platelets is associated with a 38% loss of plasma coagulation factor concentration and 56% loss of platelets. Storage losses of...