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Biomedical subjects

D Fries

Publications and source records attributed to D Fries.

At least 19 recordsLinked to original sources
PubMed2006

Efficacy of fibrinogen and prothrombin complex concentrate used to reverse dilutional coagulopathy--a porcine model.

BACKGROUND: This study was conducted to assess whether the combined administration of fibrinogen and prothrombin complex concentrate (PCC) enables the reversal of dilutional coagulopathy resulting from intended blood loss and fluid replacement, and whether this treatment reduces further blood loss and mortality. METHODS: In 20 anaesthetized pigs, approximately 65% of the estimated blood volume was withdrawn and replaced with the same amount of hydroxyethyl starch (6% HES 130/0.4) to mimic blood loss and to develop a dilutional coagulopathy. Pigs (randomized) received either fibrinogen (200 mg kg(-1)) and PCC (35 IU kg(-1)) (n=10), or placebo (n=10). Thereafter, a standard liver laceration was performed to induce uncontrolled haemorrhage. The subsequent blood loss and survival time were determined as primary outcome variables. Throughout the experiment serial blood samples were obtained to assess the competence of the haemostatic system using standard coagulation tests, modified Thrombelastograph measurements (ROTEM) and electron microscopy clot imaging. RESULTS: As compared with baseline, after haemodilution both groups showed statistically significant impairment of haemostasis as measured with standard coagulation tests and thrombelastography. These parameters significantly improved after administration of the study drugs while aPPT measurements remained unchanged. Blood loss after liver injury was significantly less in the treatment group as compared with placebo: 240 ml (50-830) vs 1800 ml (1500-2500) (P<0.0001). All treated animals survived, whereas 80% of the placebo group died (P<0.0001). CONCLUSION: During haemodilution, substitution of fibrinogen and PCC causes an enhancement of coagulation and final clot strength. This reversal of dilutional coagulopathy may reduce blood loss and mortality when large amounts of colloids are needed to maintain normovolaemia during huge blood losses.

Animals↗
PubMed2006

Improvement of metabolic syndrome markers through altitude specific hiking vacations.

To study the influence of a 3-week hiking vacation at moderate (1700 m) and low altitude (LA) (200 m) on key-markers of the metabolic syndrome, 71 male volunteers (age 36-66 yr old) with the metabolic syndrome [according to the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) - or World Health Organization (WHO) - definition] participated in the study and were randomly assigned into a moderate altitude (MA) group (1700 m, no. 36) and a low altitude (LA) group (200 m, no. 35). The 3-week vacation program included 12 moderate- intensity guided hiking tours [4 times/week, 55-65% heart rate maximum (HRmax)] with a total exercise time of 29 h plus moderate recreational activities. Both study groups had a comparable and balanced nutrition with no specific dietary restrictions. Anthropometric, metabolic and cardiovascular parameters were measured 10-14 days before vacation, several times during the 3-week vacation, 7-10 days and 6-8 weeks after return. All participants tolerated the vacation without any adverse effects. Body weight, body fat, waist-circumference, fasting glucose, total cholesterol, LDL-cholesterol (LDL-C), plasma fibrinogen, resting systolic and diastolic blood pressure were significantly decreased over time in both study groups. In the LA group, fasting insulin and homeostasis model assessment (HOMA)-index were significantly decreased one week after return. Relative cycle ergometry performance was significantly increased after return compared to baseline. In both study groups, waist-to-hip ratio (WHR), 2-h oral glucose tolerance test (OGTT), HDL-cholesterol (HDL-C), and triglycerides remained unchanged. The 3-week vacation intervention at moderate and LA had a positive influence on all key-markers of the metabolic syndrome. No clinically relevant differences could be detected between the study groups. A hiking vacation at moderate and LA can be recommended for people with stable, controlled metabolic and cardiovascular risk factors.

Adult↗
PubMed2006

A nucleic acid sequence-based amplification assay for real-time detection of norovirus genogroup II.

AIMS: To use molecular beacon based nucleic acid sequence-based amplification (NASBA) to develop a rapid, sensitive, specific detection method for norovirus (NV) genogroupII (GII). METHODS AND RESULTS: A method to detect NV GII from environmental samples using real-time NASBA was developed. This method was routinely sensitive to 100 copies of target RNA and intermittent amplification occurred with as few as 10 copies. Quantitative estimates of viral load were possible over at least four orders of magnitude. CONCLUSIONS: The NASBA method described here is a reliable and sensitive assay for the detection of NV. This method has the potential to be linked to a handheld NASBA device that would make this real-time assay a portable and inexpensive alternative to bench-top, lab-based assays. SIGNIFICANCE AND IMPACT OF THE STUDY: The development of the real-time NASBA assay described here has resulted in a simple, rapid (<1 h), convenient testing format for NV. To our knowledge, this is the first example of a molecular beacon based NASBA assay for NV.

Base Sequence↗
PubMed2006

[Dilutional coagulopathy: development, diagnostic options and management].

When no fresh frozen plasma is available, acute major blood loss is compensated above all with crystalloids, colloids and red blood cell concentrates, meaning that all plasma clotting factors are diluted. Consumption coagulopathy is almost always accompanied by dilutional coagulopathy. Formulas for calculating critical blood loss and standard coagulation tests are often not helpful in the case of massive transfusion. On the other hand, systems suitable for point of care, such as thrombelastography, have important advantages. In the case of consumption and dilutional coagulopathy plasma coagulation is disturbed and critical values are first seen for fibrinogen. Not only is fibrin polymerization impaired by the bleeding-induced loss and dilution of fibrinogen, but also by interaction with artificial colloids, particularly hydroxyethyl starch preparations. Therapy of consumption and dilutional coagulopathy calls for fresh frozen plasma. If this is not available in sufficient quantity or within a reasonable time, coagulation factor concentrates must be used. Neither fresh frozen plasma therapy nor treatment with coagulation factor concentrates has been the subject of detailed clinical study. Further studies are needed to work out guidelines for coagulation management in the case of massive blood loss.

Blood Coagulation↗
PubMed2005

Effects of protamine and heparin can be detected and easily differentiated by modified thrombelastography (Rotem): an in vitro study.

BACKGROUND: Precise coagulation monitoring might help prevent heparin-protamine mismatch and thus decrease postoperative blood loss. We therefore measured coagulation time (CT) by modified thrombelastography (Rotem) as a possible differential monitor of the effects of heparin and protamine. METHODS: Undiluted and diluted blood samples from 26 healthy volunteers were spiked with increasing concentrations of heparin (0.1, 0.2, 0.4, 0.8 and 1 U ml(-1)). In addition, undiluted blood was spiked with protamine hydrochloride (0.1, 0.2, 0.4, 0.8 and 1.6 U ml(-1)), and we tested the effect of protamine on the reversal of heparin 0.4 U ml(-1). Heparin-containing samples were analysed using the heparin-sensitive INTEM test and the heparinase-containing HEPTEM test; protamine series were also analysed with the EXTEM test (tissue factor activation). RESULTS: CT by the INTEM test [CT-INTEM; median (min/max)] increased significantly and dose-dependently with increasing concentrations of heparin [control, 175 s (146/226); heparin, 1.0 U ml(-1) 1320 s (559/2100); P<0.001] and protamine [control, 172 s (150/255); protamine, 1.6 U ml(-1) 527 s (300/1345); P<0.0001]. Up to heparin concentrations of 0.4 U ml(-1), results were similar in undiluted and diluted blood samples. As expected, CT-HEPTEM remained within the normal range for all tested heparin concentrations (median 180-183 s), but increased similarly to CT-INTEM for increasing protamine concentrations. CONCLUSION: CT measurement using the Rotem technique appears to be a valuable tool for heparin-protamine management. For detection of heparin alone, protamine alone and the two combined, the ratio of CT-INTEM:CT-HEPTEM can be used to distinguish the effects of heparin excess (CT-INTEM:CT-HEPTEM>1) from those of protamine excess (CT-INTEM:CT-HEPTEM=1).

Adult↗
PubMed2005

Effect of fibrinogen on reversal of dilutional coagulopathy: a porcine model.

BACKGROUND: This study was conducted to determine whether replacement of fibrinogen is useful in reversing dilutional coagulopathy following severe haemorrhage and administration of colloids. METHODS: In 14 anaesthetized pigs, approximately 65% of the estimated blood volume was withdrawn and replaced with the same amount of gelatin solution to achieve dilutional coagulopathy. Animals were randomized to receive either 250 mg kg(-1) fibrinogen (n=7) or normal saline (n=7). A standardized liver injury was then inflicted to induce uncontrolled haemorrhage. Modified thrombelastography and standard coagulation tests were performed at baseline, after blood withdrawal, after dilution, after injection of the study drugs, and on conclusion of the protocol. Further, electron microscopy imaging of the blood clots was performed and blood loss after liver injury was determined. RESULTS: Severely impaired haemostasis was observed after haemodilution with gelatin substitution. With administration of fibrinogen, clot firmness and dynamics of clot formation reached baseline values. Median blood loss following liver injury was significantly less (P=0.018) in the fibrinogen-treated animals (1100 ml; 800-1400 ml) than in the placebo group (2010 ml; 1800-2200 ml). CONCLUSIONS: Replacing 65% of the estimated blood volume with gelatin in swine resulted in dilutional coagulopathy; subsequent fibrinogen administration improved clot formation and reduced blood loss significantly.

Animals↗
PubMed2005

[Management of coagulation after multiple trauma].

Hemorrhage after traumatic injury results in coagulopathy which only worsens the situation. This coagulopathy is caused by depletion and dilution of clotting factors and platelets, increased fibrinolytic activity, hypothermia, metabolic changes and anemia. The effect of synthetic colloids used for compensating the blood loss, further aggravates the situation through their specific action on the hemostatic system. Bedside coagulation monitoring permits relevant impairment of the coagulation system to be detected very early and the efficacy of the hemostatic therapy to be controlled directly. Administration of fresh frozen plasma (FFP), platelet concentrates and antifibrinolytic agents is essential for restoring the impaired coagulation system in trauma patients. Clotting factor concentrates should be administered if coagulopathy is based on diagnosed depletion of clotting factors, if FFP is not available and if transfusion of FFP is insufficient to treat the coagulopathy. Recombined FVIIa is frequently employed during severe bleeding which could not be treated by conventional methods but the results of on-going clinical trials are not yet available.

Anticoagulants↗
PubMed2005

[Locoregional anesthesia and coagulation inhibitors. Recommendations of the Task Force on Perioperative Coagulation of the Austrian Society for Anesthesiology and Intensive Care Medicine].

More efficacious anticoagulant and antiplatelet agents have been introduced in vascular medicine and in the prevention of perioperative venous thromboembolisms. Patient management should be guided by familiarity with the pharmacology of coagulation-altering drugs and by consensus statements. The present paper reviews recommendations from the Austrian Task Force for Perioperative Coagulation which are based on thorough evaluation of the available pharmacological information and case reports. The consensus statement focuses on neuraxial and peripheral techniques and is designed to encourage safe and quality patient care.

Anesthesia, Conduction↗
PubMed2004

[Treatment of hemorrhagic shock. New therapy options].

The future of shock treatment depends on the importance of scientific results, and the willingness of physicians to optimize, and to reconsider established treatment protocols. There are four major potentially promising approaches to advanced trauma life support. First, control of hemorrhage by administration of local hemostatic agents, and a better, target-controlled management of the coagulation system. Second, improving intravascular volume by recruiting blood from the venous vasculature by preventing mistakes during mechanical ventilation, and by employing alternative spontaneous (i.e. use of the inspiratory threshold valve) or artificial ventilation strategies. In addition, artificial oxygen carriers may improve intravascular volume and oxygen delivery. Third, pharmacologic support of physiologic, endogenous mechanisms involved in the compensation phase of shock, and blockade of pathomechanisms that are known to cause irreversible vasoplegia (arginine vasopressin and K(ATP) channel blockers for hemodynamic stabilization). Fourth, employing potentially protective strategies such as mild or moderate hypothermia. Finally, the ultimate vision of trauma resuscitation is the concept of "suspended animation" as a form of delayed resuscitation after protection of vital organ systems.

Blood Coagulation↗
PubMed2004

[Monitoring of Perioperative Dilutional Coagulopathy Using the ROTEM Analyzer: Basic Principles and Clinical Examples].

Recent changes in quality of transfusion supply, transfusion triggers as well as fluid therapy promote the development of dilutional coagulopathy. Nevertheless, up to now guidelines generally assume presence of hypocoagulability when more than one individual circulating blood volume is lost. This might be true for some patients under some conditions but is not necessarily true for every patient. Routine coagulation tests are insufficient in predicting increased bleeding and, moreover, available after an unacceptable time delay. Therefore the occurrence of diffuse microvascular bleeding is often used as clinical sign to start hemostatic therapy. However, such severe derangement of hemostasis might lead to the development of secondary tissue damage and frequently is unresponsive to conventional treatment. Coagulopathy occurring during extensive surgery or after polytrauma can be detected and treated early when using the ROTEM monitoring. Recent data showing a direct beneficial effect of hemostatic therapy on blood loss and final outcome are scarce. However, evidence exists that the amount of blood loss, presence of coagulopathy and number of transfusions needed are associated with poor outcome in bleeding patients. Although manifold articles have been published already using thrombelastography for various indications (medline research "thrombelastography", 2022 articles), further data are needed to confirm the clinical experience that this technique is an excellent tool for safe patient management.

Autoanalysis↗
PubMed2004

[Dilutional coagulopathy, an underestimated problem?].

When no fresh frozen plasma is available, acute major blood loss is compensated above all with crystalloids, colloids and erythrocyte concentrates, meaning that all plasma clotting factors are diluted. Consumption coagulopathy is almost always accompanied by dilutional coagulopathy. Formulas for calculating critical blood loss and standard coagulation tests are often not helpful in the case of massive transfusion. On the other hand, systems suitable for point of care, such as thrombelastography, have important advantages. In the case of consumption and dilutional coagulopathy plasma coagulation is disturbed and critical values are first seen for fibrinogen. Not only is fibrin polymerization impaired by the bleeding-induced loss and dilution of fibrinogen, but also by interaction with artificial colloids, particularly hydroxyethyl starch preparations. Therapy of consumption and dilutional coagulopathy calls for fresh frozen plasma. If this is not available in sufficient quantity or within a reasonable time, coagulation factor concentrates must be used. Neither fresh frozen plasma therapy nor treatment with coagulation factor concentrates has been the subject of detailed clinical study. Further studies are needed to work out guidelines for coagulation management in the case of massive blood loss.

Blood Coagulation↗
PubMed2002

Antifactor Xa activity in intensive care patients receiving thromboembolic prophylaxis with standard doses of enoxaparin.

BACKGROUND: Low-molecular-weight heparins (LMWHs) have become increasingly used to prevent thromboembolic complications in intensive care patients. Unlike in medical and surgical patients, no data on the anticoagulant effectiveness of standard LMWH dosages exist in intensive care patients. Therefore, we prospectively investigated antifactor Xa (aFXa) levels after subcutaneous administration of 40 mg of enoxaparin in 89 intensive care patients over a 24-h period. METHODS: AFXa levels were measured before, 4, 12 and 24 h after subcutaneous administration of enoxaparin. Laboratory parameters including prothrombin time, activated partial thromboplastin time, antithrombin III, fibrinogen as well as platelet count were collected at same intervals. Demographics included age, sex, height, weight, body mass index, admission diagnosis, a thromboembolic risk score and a modified Goris multiple organ dysfunction score. RESULTS: At 4, 12 and 24 h, 56.5%, 39.3% and 12.6% of the study patients were within recommended antithrombotic aFXa levels (0.1-0.3 U ml(-1)). Presence of multiple organ dysfunction as well as high body weight were significantly correlated with low aFXa levels. CONCLUSION: European standard dosages of 40 mg of enoxaparin once daily proved to be ineffective in achieving recommended antithrombotic aFXa levels in intensive care patients. This was most pronounced in patients with high body weight and presence of multiple organ dysfunction.

Adult↗
PubMed2002

[Travel-induced thrombosis: an update].

Travel-related disorders are a well known problem. In the last years many cases of deep venous thrombosis (DVT) and pulmonary thromboembolism (VTE) were published after several hours lasting journeys by airplane, but also by car, bus and railway. This condition was termed "travel-thrombosis" or "economy class syndrome" for long haul flights. At present the precise incidence for travel-thrombosis is not known. Accepted contributing factors for the development of travel-thrombosis are sitting in a cramped position for several hours, low humidity due to climatisation with the risk for dehydration and increased blood viscosity, reduced fluid intake as well as travellers related risk factors. Whether the special situation in the cabin of an airplane, e.g. mild hypoxia, is an essential contributing factor for DVT and VTE, is controversially discussed. This review will present very recent guidelines of an expert meeting concerning the risk groups for travel-thrombosis (low, moderate and high risk). In addition recommendations for prophylaxis of travel-thrombosis adapted to the different risk groups (leg exercise, adequate fluid intake, compression stockings, low molecular weight heparins) are given.

Aerospace Medicine↗
PubMed2001

Blunted erythropoietic response to anemia in multiply traumatized patients.

OBJECTIVES: To assess the relations between anemia, serum erythropoietin (EPO), iron status, and inflammatory mediators in multiply traumatized patients. DESIGN: Prospective observational study. SETTING: Intensive care unit. PATIENTS: Twenty-three patients suffering from severe trauma (injury severity score > or =30). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples were collected within 12 hrs after the accident (day 1) and in the morning on days 2, 4, 6, and 9 to determine blood cell status, serum EPO, tumor necrosis factor-alpha (TNF-alpha), soluble tumor necrosis factor-receptor I (sTNF-rI), interleukin-1 receptor antagonist (IL1-ra), interleukin-6 (IL-6), neopterin, and iron status, respectively. Hemoglobin concentration was low at admission (mean, 10.0 g/dL; range, 6.8-12.9 g/dL) and did not increase during the observation time. Serum EPO concentration was 49.8 U/L (mean value) on day 1 and did not show significant increases thereafter. No correlation was found between EPO and hemoglobin concentrations. TNF-alpha remained within the normal range. sTNF-rI was high at admission and increased further. IL1-ra was above the normal range. IL-6 was very high at admission and did not decrease thereafter. The initial neopterin concentration was normal, but increased until day 9. Serum iron was significantly decreased on day 2 posttrauma and remained low during the study. Serum ferritin increased steadily from day 2, reaching its maximum on day 9. In contrast, concentrations of transferrin were low from admission onward. CONCLUSIONS: Multiply traumatized patients exhibit an inadequate EPO response to low hemoglobin concentrations. Thus, anemia in severe trauma is the result of a complex network of bleeding, blunted EPO response to low hemoglobin concentrations, inflammatory mediators, and a hypoferremic state.

Adult↗
PubMed2000

Increase in immune activation, vascular endothelial growth factor and erythropoietin after an ultramarathon run at moderate altitude.

The present study was performed to investigate the effects of exhaustive long lasting exercise at moderate altitude on the time course of serum immunomodulatory peptides, vascular endothelial growth factor (VEGF) and serum erythropoietin (EPO). Thirteen well trained runners participated at the Swiss Alpine Marathon of Davos (distance 67 km, altitude difference 2300 m). Interleukin-6 was significantly elevated in the first 2h after the run. In contrast, tumor necrosis factor-alpha and both soluble tumor necrosis factor-a receptors I and II were increased after exercise termination and showed sustained serum concentrations the following days. Neopterin, a serum marker for the activation of the cellular immune system, was increased until day two after the run. Immediately after the run VEGF was significantly elevated and further increased 2.4-fold until day five post exercise (p = 0.005). EPO was also increased after exercise but reached its maximum 2 h after the run (2-fold increase; p = 0.004) and decreased thereafter. The main findings of our study are that prolonged strenuous exercise at moderate altitude induced a significant long lasting increase in serum VEGF and EPO which was accompanied by an activation of the immune system.

Adult↗