Thomas J. Reid

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.

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.

Massive transfusion and nonsurgical hemostatic agents.

Background:Hemorrhage in trauma is a significant challenge, accounting for 30% to 40% of all fatalities, second only to central nervous system injury as a cause of death. However, hemorrhagic death is the leading preventable cause of mortality in combat casualties and typically occurs within 6 to 24 hrs of injury. In cases of severe hemorrhage, massive transfusion may be required to replace more than the entire blood volume. Early prediction of massive transfusion requirements, using clinical and laboratory parameters, combined with aggressive management of hemorrhage by surgical and nonsurgical means, has significant potential to reduce early mortality. Discussion:Although the classification of massive transfusion varies, the most frequently used definition is ten or more units of blood in 24 hrs. Transfusion of red blood cells is intended to restore blood volume, tissue perfusion, and oxygen-carrying capacity; platelets, plasma, and cryoprecipitate are intended to facilitate hemostasis through prevention or treatment of coagulopathy. Massive transfusion is uncommon in civilian trauma, occurring in only 1% to 3% of trauma admissions. As a result of a higher proportion of penetrating injury in combat casualties, it has occurred in approximately 8% of Operation Iraqi Freedom admissions and in as many as 16% during the Vietnam conflict. Despite its potential to reduce early mortality, massive transfusion is not without risk. It requires extensive blood-banking resources and is associated with high mortality. Summary:This review describes the clinical problems associated with massive transfusion and surveys the nonsurgical management of hemorrhage, including transfusion of blood products, use of hemostatic bandages/agents, and treatment with hemostatic medications.

A modified thromboelastographic method for monitoring c7E3 Fab in heparinized patients.

The monoclonal antibody, c7E3 Fab, binds to the platelet surface fibrinogen receptor (GPIIb/IIIa), inhibiting platelet aggregation and clot retraction.We performed an in vitro study to assess the ability of a modification of the thromboelastograph (MTEG) to detect inhibition of clot strength by c7E3 Fab and its reversal with platelet-rich plasma (PRP). In the modified assay (MTEG), thrombin was added to whole blood (WB) and platelet-poor plasma (PPP) and the resultant maximum amplitude (MA) was measured, MAWB and MAPPP, respectively. Anticoagulated blood samples from 17 patients scheduled for cardiac surgery were collected for a dose response (Part I; n = 5) and c7E3 Fab reversal (Part II; n = 12) study. Clot strength was reduced in a dose-dependent manner by c7E3 Fab. Ecteola cellulose effectively reversed the effect of heparin on the thrombin time and the addition of PRP significantly increased the MAWB (P < 0.0001) and MAWB-ppp (P < 0.0001). Subtracting the MAPPP from MAWB significantly magnified the response of MA to the addition of c7E3 Fab (P = 0.002) and its reversal with PRP (P = 0.005). This in vitro study indicates that the MTEG is a responsive assay demonstrating that inhibition by the antiplatelet c7E3 Fab is reversible with PRP. (Anesth Analg 1997;84:31-8)

Frozen platelets and platelet substitutes in transfusion medicine

uring the past few years, efforts to improve platelet storage by cryopreservation and to develop platelet substitutes have been undertaken in multiple academic and commercial settings. A major goal for the researchers and regulators who work with these products is to establish methods for the assessment of hemostatic function in vitro, in animal models, and in clinical trials. To understand how platelet products can be developed for field medicine and to facilitate research in this area, the Combat Casualty Care Programs of the Naval Research and Development Command and the Medical Research and Materiel Command of the United States Army sponsored a conference called “Frozen Platelets and Platelet Products in Transfusion Medicine” on March 7 and 8, 1996, at the Uniformed Services University of the Health Sciences in Bethesda, MD. Co-organizers and participants were the Center for Biologics Evaluation and Research, the Food and Drug Administration (FDA), and the Blood Resources Program of the National Heart, Lung, and Blood Institute, National Institutes of Health.

Hb-based oxygen carriers: are we there yet?

I n a recent issue of TRANSFUSION, Lanzkron and coworkers1 describe a patient with sickle cell disease, glucose-6-phosphate dehydrogenase deficiency, and acute chest syndrome who, on religious conviction, refused RBC transfusion. Improved oxygenation is the major goal of the treatment for acute chest syndrome,2,3 and this is accomplished with supplemental oxygen (O2), bronchodilator therapy, and/or RBC transfusions.2,3 Multiple factors contributed to tissue hypoxia in this patient: diminished O2 exchange (pulmonary embolism, pulmonary vasoocclusion from irreversibly sickled cells with sickling further exacerbated by hypoxia, and hypoxia-induced pulmonary vasoconstriction), O2 transport (anemia), and O2 delivery (methemoglobin subunits generated during oxidative stress in glucose-6-phosphate dehydrogenase deficiency led to a left-shifted, i.e., higher-affinity, O2 dissociation curve). In such a patient, transfusion therapy would be expected to improve oxygenation by reducing the relative content of sickled cells through hemodilution (minimizing the procoagulant properties of irreversibly sickled cells4 and vasoocclusion) as well as enhancing O2 delivery and exchange. As RBC transfusions were unacceptable to this patient, our clinical experience would suggest that the prospect of failing to improve oxygen delivery would have placed her at very high risk certainly for continued and worsening morbidity and possibly for mortality. This patient’s reduced heart rate after transfusion of a solution of chemically modified Hb derived from human blood (PolyHeme, Northfield Laboratories Inc., Evanston, IL) is interpreted to reflect improved tissue oxygenation as a consequence of this intervention and her subsequent clinical course suggests a benefit from PolyHeme. Her recovery may have further been influenced through Hb-based oxygen carrier (HBOC) stimulation of erythropoiesis, an effect concluded from studies with other HBOCs.5 PolyHeme was well tolerated in this patient, a result supported in a report of asymptomatic sickle cell patients.6 The HBOCs are a class within the larger family of oxygen therapeutics that includes perfluorocarbon emulsions and liposome-encapsulated Hb. The primary function of all these agents is to provide oxygen-carrying capacity, whether serving as RBC substitutes or primary resuscitation solutions. The purpose of this review is to provide a brief history of the field, examine the current status of HBOCs under development, propose a clinical framework to study and use these products, and offer suggestions for the future.

Digital vasculitis associated with interferon therapy

Abstract : Several drugs have been shown to cause necrotizing vasculitis. When occlusion of the digital arteries of the hands occurs, the cause is usually small vessel disease rather than thromboembolic events. We report a patient who developed digital vasculitis after treatment with interferons. We add this form of toxicity to those known to be caused by interferons and emphasize such toxicity may be seen in patients who are receiving long-term interferon therapy. This complication is considered clinically important because long-term interferon therapy is used in the treatment of chronic hepatitis B infection, inflammatory and viral dermatoses, rheumatoid arthritis and with increasing frequency in hematologic malignancies such as CML, myeloma and non-Hodgkins lymphoma. Interferon, vasculitis, chronic myelogenous leukemia.

Hemostatic efficacy of a fibrin sealant dressing in an animal model of kidney injury.

OBJECTIVE The purpose of this study is to determine the hemostatic efficacy of a fibrin sealant dressing compared with a standard collagen control dressing in an animal model of kidney injury. METHODS Twenty adult male Sprague-Dawley rats were administered general anesthesia and underwent partial nephrectomy with heparin anticoagulation (300 U/kg intravenous). Treatment of the cut surface of the kidney was randomized to three groups: group I, no hemostatic agent; group II, collagen dressing; and group III, fibrin sealant dressing. RESULTS Blood loss was significantly less in group III (3.39+/-0.63 mL) than in group I (8.64+/-2.26 mL) and group II (8.63+/-1.72 mL; p < 0.001). The percentage decrease in the mean arterial pressure was significantly less in group III (34.09+/-15.58%) than in group I (59.66+/-16.19%) and group II (60.35+/-15.66%; p=0.015). CONCLUSION Fibrin sealant dressings provide effective hemostasis and are superior to collagen dressings in an animal model of kidney injury. Additional development of fibrin sealant dressings for potential clinical use is warranted.

Generation of annexin V‐positive platelets and shedding of microparticles with stimulus‐dependent procoagulant activity during storage of platelets at 4°C

BACKGROUND: The ability of propyl gallate to activate platelet factor 3 has been determined through the activated partial thromboplastin time, but its effect on phosphatidylserine has not been established.

Platelet membrane integrity during storage and activation

BACKGROUND: The platelet cell membrane appears to undergo a lipid‐phase transition on cooling from 23°C to 4°C. Consequences of this phase transition are leakage of cellular material and irreversible cellular damage. Whether agents, of known benefit in protecting membranes and proteins from cooling and drying injury, could also protect platelets was investigated. Leakage of cytosolic components was assessed by measuring the release of fluorescein into the surrounding medium.

The viability of autologous human red cells stored in additive solution 5 and exposed to 25°C for 24 hours

BACKGROUND: No data exist on the viability of red cells (RBCs) storsed in modern additive solution systems and allowed to warm above 10°C.