Viscoelastic measurements of platelet function, not fibrinogen function, predicts sensitivity to tissue-type plasminogen activator in trauma patients.

BACKGROUND: Systemic hyperfibrinolysis is a lethal phenotype of trauma-induced coagulopathy. Its pathogenesis is poorly understood. Recent studies have support a central role of platelets in hemostasis and in fibrinolysis regulation, implying that platelet impairment is integral to the development of postinjury systemic hyperfibrinolysis. OBJECTIVE: The objective of this study was to identify if platelet function is associated with blood clot sensitivity to fibrinolysis. We hypothesize that platelet impairment of the ADP pathway correlates with fibrinolysis sensitivity in trauma patients. METHODS: A prospective observational study of patients meeting the criteria for the highest level of activation at an urban trauma center was performed. Viscoelastic parameters associated with platelet function (maximum amplitude [MA]) were measured with native thrombelastography (TEG), and TEG platelet mapping of the ADP pathway (ADP-MA). The contribution of fibrinogen to clotting was measured with TEG (angle) and the TEG functional fibrinogen (FF) assay (FF-MA). Another TEG assay containing tissue-type plasminogen activator (t-PA) (75 ng mL(-1) ) was used to assess clot sensitivity to an exogenous fibrinolytic stimulus by use of the TEG lysis at 30 min (LY30) variable. Multivariate linear regression was used to identify which TEG variable correlated with t-PA-LY30 (quantification of fibrinolysis sensitivity). RESULTS: Fifty-eight trauma patients were included in the analysis, with a median injury severity score of 17 and a base deficit of 6 mEq L(-1) . TEG parameters that significantly predicted t-PA-LY30 were related to platelet function (ADP-MA, P = 0.001; MA, P < 0.001) but not to fibrinogen (FF-MA, P = 0.773; angle, P = 0.083). Clinical predictors of platelet ADP impairment included calcium level (P = 0.001), base deficit (P = 0.001), and injury severity (P = 0.001). RESULTS AND CONCLUSIONS: Platelet impairment of the ADP pathway is associated with increased sensitivity to t-PA. ADP pathway inhibition in platelets may be an early step in the pathogenesis of systemic hyperfibrinolysis.

Viscoelastic hemostatic fibrinogen assays detect fibrinolysis early.

PURPOSE: Viscoelastic hemostatic assays are emerging as the standard-of-care in the early detection of post-injury coagulopathy. TEG and ROTEM are most commonly used. Although similar in technique, each uses different reagents, which may affect their sensitivity to detect fibrinolysis. Therefore, the purpose of this study is to determine the ability of each device to detect fibrinolysis. METHODS: TEG (Rapid, Kaolin, Functional Fibrinogen) and ROTEM (EXTEM, INTEM, FIBTEM) were run simultaneously on normal blood as well as blood containing tPA from healthy volunteers (n = 10). A two-tailed, paired t-test and ANOVA were used to determine the significance between parameters obtained from normal blood and blood with tPA, and individual TEG and ROTEM assays, respectively. RESULTS: TEG detected significant changes in clot strength and 30-min lysis after the addition of tPA (p < 0.0001). All ROTEM assays detected changes in the 30-min lysis (p < 0.0001), but only INTEM detected changes in clot strength (p < 0.05). Kaolin and Rapid TEG assays detected greater changes in clot strength and lysis, but INTEM and EXTEM had decreased lysis onset times compared to TEG (p < 0.001). Functional Fibrinogen and FIBTEM assays detected lysis sooner than other TEG/ROTEM assays, and were comparable. CONCLUSIONS: TEG assays detect greater changes in clot strength compared to ROTEM. Despite this, Functional Fibrinogen and FIBTEM assays detect fibrinolysis sooner than their corresponding intrinsic and extrinsic assays. Therefore, fibrinogen assays should be employed in actively bleeding trauma patients in order to provide timely antifibrinolytic therapy.

Trauma-Induced Coagulopathy: An Institution's 35 Year Perspective on Practice and Research.

INTRODUCTION: Injury is the second leading cause of death worldwide, and as much as 40% of injury-related mortality is attributed to uncontrollable hemorrhage. This persists despite establishment of regionalized trauma systems and advances in the management of severely injured patients. Trauma-induced coagulopathy has been identified as the most common preventable cause of postinjury mortality. METHODS: A review of the current literature was performed by collecting PUBMED references related to trauma-induced coagulopathy. Data were then critically analyzed and summarized based on the authors' clinical and research perspective, as well as that reported by other institutions and researchers interested in trauma-induced coagulopathy. A particular focus was placed on those aspects of coagulopathy in which agreement among clinical and basic scientists is currently lacking; these include, pathophysiology, the role of blood components and factor therapy, and goal-directed assessment and management. RESULTS: Trauma-induced coagulopathy has been recognized in approximately one-third of trauma patients. There is a vast range of severity, and the emergence of viscoelastic assays, such as thrombelastography and rotational thromboelastogram, has refined its diagnosis and management, particularly through the establishment of goal-directed massive transfusion protocols. Despite advancements in the diagnosis and management of trauma-induced coagulopathy, much remains to be understood regarding its pathophysiology. The cell-based model of hemostasis has allowed for characterization of endothelial dysfunction, impaired thrombin generation, platelet dysfunction, fibrinolysis, endogenous anticoagulants such as protein-C, and antifibrinolytic proteins. These concepts collectively compose the contemporary, but still partial, understanding of trauma-induced coagulopathy. CONCLUSION: Trauma-induced coagulopathy is a complex pathophysiological condition, of which some mechanisms have been characterized, but much remains to be understood in order to translate this knowledge into improved outcomes for the injured patient.

Neurogenic motor evoked potentials: a prospective comparison of stimulation methods in spinal deformity surgery.

Neurogenic motor evoked potentials (NMEPs) elicited by spinal cord stimulation via the spinous processes (SP-NMEP) have been widely accepted as a sensitive method of monitoring motor tract function. SP-NMEP requires additional surgical dissection as well as electrodes within the wound, making the method somewhat inconvenient. A less invasive percutaneous method of spinal cord stimulation (PERC-NMEP) has more recently been described. We prospectively compared the SP-NMEP and PERC-NMEP methods in 184 patients undergoing 225 surgical procedures. Although SP-NMEP responses were more readily obtainable than PERC-NMEP, the reliability of the two methods was not significantly different. Both methods were found to be sensitive to neurologic deficit. The present study suggests that when responses are obtained, the percutaneous method is reliable enough to obviate the spinous process method of monitoring the motor function of the spinal cord.

Posterior arthrodesis in the skeletally immature patient. Assessing the risk for crankshaft: is an open triradiate cartilage the answer?

STUDY DESIGN: Thirty-three skeletally immature patients younger than 12 years of age and having posterior arthrodesis and evidence of solid posterior fusion without "adding on" were retrospectively reviewed. All patients had a minimum of 5 years of follow-up. OBJECTIVES: To ascertain factors associated with crankshaft and to determine how accurate a marker the triradiate cartilage was. SUMMARY OF DATA: All patients had Risser Stage 0 curves and all of the girls were premenarchal preoperatively. The average age was 9 years 3 months (range, 2 years-11 years 11 months). Preoperative diagnoses consisted of 14 idiopathic, 11 congenital, five dysplastic, and three neuromuscular etiologies. METHODS: Preoperatively, within 3 months after surgery, and at 2-year, 5-year, and final postoperative follow-up, the following radiographic parameters were reviewed: coronal Cobb, apical vertebral rotation, apical vertebral translation, rib vertebral angle difference, and trunkshift. RESULTS: The triradiate cartilage was open in 24 patients at the time of operation. Of those 24, only nine (37.5%) had documented proof of crankshaft. Patients with closed triradiate cartilage had no significant postoperative increase in radiographic parameters (0 of 9). The subgroup of patients with idiopathic scoliosis had an average age of 11 years 3 months (range, 9 years 2 months-11 years 11 months). Five of 14 patients had an open triradiate cartilage. All were followed up to skeletal maturity. None had significant progression in postoperative radiographic parameters. CONCLUSION: This study did not find an open triradiate cartilage to be an absolute prognostic indicator for the occurrence of crankshaft. Additional refinement of markers of maturity are needed to determine who requires anterior arthrodesis.

The use of pedicle screw fixation to improve correction in the lumbar spine of patients with idiopathic scoliosis. Is it warranted?

STUDY DESIGN: A retrospective assessment of coronal, sagittal, and axial correction using convex lumbar pedicle screw constructs compared with hook constructs in patients with idiopathic scoliosis. OBJECTIVE: To determine if pedicle screw constructs can improve coronal, sagittal, and axial correction without increased complications and therefore warrant their use in the lumbar spine. SUMMARY OF BACKGROUND DATA: Although hooks have been the traditional fixation choice for posterior scoliosis correction of the lumbar spine, pedicle screws may offer advantages for improved correction of lumbar spinal deformity. METHODS: Twenty-two patients constituted Group A (hooks), in which 17 were double major and five were King Type IV curves. These patients had a minimum follow-up period of 2 years and an average of one hook per lumbar fusion segment. Twenty-two patients constituted Group B (screws), in which 20 were double major and two were King Type IV curves. These patients had a minimum follow-up period of 2 years, and screw configuration consisted of pedicle fixation on the convex side for correction and at times on the concave side for fixation. RESULTS: Pedicle screw fixation constructs had improved lumbar Cobb correction (P < 0.05), lowest instrumented vertebra tilt (P < 0.05), lowest instrumented vertebra translation (P < 0.01), and segmental sagittal alignment from T12 to lowest instrumented vertebra (P < 0.01). There was no significant change in axial rotation using either surgical method. CONCLUSIONS: The use of pedicle screw fixation on the convex portion of the lumbar spine in patients with double major idiopathic scoliosis allows for improved correction of the lumbar Cobb measurement, horizontalization and translation of the lowest instrumented vertebra, and improved segmental lordization over the instrumented levels without increased complications.

Studies of functional site of origin of native coronary collaterals.

Studies were performed to determine the pressure at the origin of the native coronary collaterals (Pstem) and thus assess the contribution of collaterals arising from proximal conduit coronary vessels vs. those arising from distal microvessels. Nine isolated blood-perfused dog hearts were studied. Aortic pressure was maintained at 80 mmHg. Collateral flow to the circumflex perfusion field was measured (radioactive microspheres) repeatedly before and after successive 25-micron nonradioactive microsphere embolization of the circumflex vasculature. After each microembolization, collateral flow decreased and peripheral coronary pressure (PCP) increased. After all embolizations collateral flow decreased from an initial value of 17 +/- 4 to 2 +/- 0.4 ml X min-1 X 100 g-1 and PCP increased from an initial value of 15 +/- 3 to 65 +/- 3 mmHg. The relationship between decreasing collateral flow and increasing PCP was linear with a pressure intercept of 74 +/- 3 mmHg. This pressure intercept predicts the PCP that would be observed if microembolization produced complete cessation of collateral flow. Accordingly, this pressure intercept allowed an accurate estimate of Pstem. This estimate of Pstem was similar to left anterior descending pressure (75 +/- 2 mmHg). These studies show that Pstem may be accurately estimated by measuring pressure in a nonoccluded large epicardial vessel. The contribution of microvascular anastomoses to total collateral flow is likely small.