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Background: The decision to admit into the hospital from the emergency department (ED) is considered to be important and challenging. The aim was to assess whether previously published results suggesting an association between hospital bed occupancy and likelihood of hospital admission from the ED can be reproduced in a different study population. Methods: A retrospective cohort study of attendances at two Swedish EDs in 2015 was performed. Admission to hospital was assessed in relation to hospital bed occupancy together with other clinically relevant variables. Hospital bed occupancy was categorized and univariate and multivariate logistic regression were performed. Results: In total 89,503 patient attendances were included in the final analysis. Of those, 29.1% resulted in admission within 24 h. The mean hospital bed occupancy by the hour of the two hospitals was 87.1% (SD 7.6). In both the univariate and multivariate analysis, odds ratio for admission within 24 h from the ED did not decrease significantly with an increasing hospital bed occupancy. Conclusions: A negative association between admission to hospital and occupancy level, as reported elsewhere, was not replicated. This suggests that the previously shown association might not be universal but may vary across sites due to setting specific circumstances. (Less)

Altered hemostasis with a subsequent hemorrhagic diathesis is common following traumatic brain injury (TBI), and progressive intracranial bleeding is among the leading causes of preventable death following TBI. Moreover, as patients suffering from TBI are getting older, the number of TBI patients on anticoagulant and antiplatelet medication is increasing with a further increased risk for hemorrhagic progression. Thromboembolic complications are also common following TBI, with extensive thromboembolic complications occurring in 6–13% of patients after TBI. Hemorrhagic progression and thromboembolic complications occur even when conventional coagulation measurements are normal, which had led to the introduction of complementary functional tests. Still, new biomarkers and laboratory tests are needed to enable us to follow the temporal course and support future preventive measures and targeted therapies.

Background: Rotational thrombelastometry/thrombelastography with ROTEM (R) and TEG (R) is becoming available bedside in an increasing number of intensive care units, where many patients with heparin-induced thrombocytopenia (HIT) are treated. The study has been performed in an effort to find out whether ROTEM (R) could be an alternative to activated partial thromboplastin time (aPTT) when argatroban is used for anticoagulation. Methods: Argatroban was added in vitro to a series of citrated whole-blood samples from 10 healthy volunteers to obtain whole-blood concentrations of 0, 0.125, 0.25, 0.5, 1.0, 2.0, 4.0 and 8.0 mg/l. ROTEM (R) and whole-blood aPTT analyses were performed at each argatroban concentration. Correlation analyses were performed using the Spearman correlation analysis. Results: There was a significant and strong correlation between argatroban concentrations and clotting time (CT in ROTEM (R) analysis with INTEM) (P < 0.0001 and r=0.98). Also, the ROTEM (R) time to maximum clot formation velocity (MAXV-t) appeared to have a very strong and highly significant correlation to argatroban concentrations (P < 0.0001 and r=0.95). When we studied the correlation between aPTT and CT, we found a highly significant and strong correlation between these two analyses (P < 0.0001 and r=0.97), especially so in the clinically relevant therapeutic range up to 100 s aPTT prolongation for HIT patients. Conclusion: A significant and strong correlation was found between argatroban concentrations and several ROTEM (R) parameters. Rotational thrombelastometry/thrombelastography has a potential role in increasing the safety of argatroban anticoagulation in critically ill patients. (Less)

BACKGROUND: Recombinant human activated protein C (rhAPC) is an anticoagulant that can be used for treatment of patients with severe sepsis. The use of rhAPC is accompanied by an increased risk of severe bleeding. Rotational thromboelastometry is a method for measuring the status of the coagulation. The aim of the study was to investigate whether rotational thromboelastometry could be used for monitoring the effects of rhAPC on the coagulation. METHODS: Whole blood was mixed in vitro with concentrations of rhAPC ranging from 0 to 75 ng/ml and analysed with rotational thromboelastometry. RESULTS: The parameter Coagulation Time was significantly prolonged by increasing the concentrations of rhAPC (P=0.002). Other parameters were not significantly affected. CONCLUSION: rhAPC dose dependently affects the early humoral parts of the coagulation, while platelet function and fibrinogen to fibrin conversion seem virtually unaffected. (Less)

Fondaparinux is a new anticoagulant that interacts with antithrombin III and activated coagulation factor X resulting in an inhibition of the coagulation system. It has been successful in doses of 2.5 mg for thromboprophylaxis as well as in higher therapeutic doses of 5-7.5 mg. No optimal method for monitoring the effects of fondaparinux has been proposed. The aim of the present study was to investigate whether a viscoelastic coagulation analyzer, the Sonoclot (Sienco, Denver, Colorado, USA), could be used for in-vitro monitoring of fondaparinux. Different concentrations of fondaparinux were added in vitro to whole blood taken from eight volunteers. The blood samples mixed with the various amounts of fondaparinux were analyzed using the Sonoclot. The whole-blood activated partial thromboplastin time with the Hemochron Jr (ITC, Edison, New Jersey, USA) was used as the reference coagulation analysis. All analyses were started expeditiously, within 30s from sampling, and were performed at 37 degrees C. The values of the Sonoclot parameter clot rate, which measures the rate of fibrin formation, fibrin polymerization and platelet-fibrin interactions, were significantly correlated to increasing concentrations of fondaparinux (R= -0.90). The Sonoclot parameters of activated coagulation time, time to peak and clot retraction had weaker, butstill significant, correlations to fondaparinux concentrations. At prophylactic doses (0.38 mu g/ml blood) the clot rate decreased 15% compared with the initial unanticoagulated value, whereas at therapeutic doses (1.53 mu blood) there was a 27% decrease. In conclusion, the Sonoclot parameter clot rate could be of clinical value to individualize the fonclaparinux dosage, especially the higher, therapeutic, dosages. Blood Coagul Fibrinolysis 18:619-622 (c) 2007 Lippincott Williams & Wilkins. (Less)

Coagulopathy is a contributor to and predictor of death in bleeding patients. Acidosis is known to be a predictor of worse outcome in trauma patients and to be a coexisting factor in coagulopathic patients, but it has not been studied if it is a causal factor in the development of coagulopathy.We have adjusted the pH level in blood samples from healthy volunteers to different levels between 7.4 and 6.8 by the use of hydrochloric acid. Thereafter we have studied the coagulation at the different pH levels by the use of thromboelastography.We found a strong correlation between pH levels and impairment of the coagulation, where the clot strength is increased much slower at pH levels below 7.4 even though the initiation of the clotting seems to be normal. The clot formation time was increased by 168% at pH 6.8 as compared with pH 7.4 (p0.00001, r = 0.89) whereas the clotting time was left unaffected.Acidosis causes a strong impairment of the coagulation as measured with thromboelastography. The impairment found when lowering pH from 7.4 to 7.15 was almost identical to the impairment seen in another study by Kettner et al. when the temperature was lowered from 36 degrees C to 32 degrees C.

Progressive intracerebral contusions are a major problem in the management of patients with severe traumatic brain injury that is also linked to worse outcome. Microdialysis studies have revealed that lactate levels are very high inside contusions, corresponding to significant acidosis. The current study was performed in an effort to investigate whether the lactate accumulation inside cerebral contusions may be a contributing factor to the prolonged bleeding inside contusions. We have investigated the effects of lactic acidosis on the coagulation system with rotational thromboelastometry. It was a laboratory study involving 6 healthy volunteers. Blood was drawn and the pH was adjusted by addition of lactic acid in vitro. The pH levels studied were 7.4, 7.2, 7.0, and 6.8. The pH was also readjusted to 7.4 by addition the buffer THAM to blood initially adjusted to a pH of 6.8 to study the reversibility of potential adverse effects induced by the lactic acidosis. We found the coagulation to be significantly impaired by lactic acidosis (P = 0.000l). The impairment found was reversible after correction of the acidosis by a buffer. In conclusion, we found that lactic acidosis impaired the coagulation system. The impairment caused by lactic acidosis may be one factor causing the progressive hemorrhage in posttraumatic cerebral contusions, known to have high levels of lactate and correspondingly low pH. It may also be important to consider in bleeding trauma patients.

Object. Intracerebral microdialysis has attracted increasing interest as a monitoring technique during neurological/neurosurgical intensive care. The purpose of this study was to compare cerebral energy metabolism, an indicator of secondary excitotoxic injury and cell membrane degradation close to focal traumatic lesions (“penumbra zones”) and in remote and apparently intact brain regions of the ipsilateral and contralateral hemispheres. Methods. The study included 22 consecutive patients with a mean age 44 ± 17 years and an estimated postresuscitation Glasgow Coma Scale motor score less than 5. Altogether 40 microdialysis catheters with radiopaque tips were inserted. Two catheters could not be localized on postoperative computerized tomography (CT) scans and were excluded from the analysis. The perfusates were analyzed at the patient's bedside for levels of glucose, pyruvate, lactate, glutamate, and glycerol with the aid of a CMA 600 Analyzer. The positions of eight (22%) of the 36 catheters were reclassified after a review of findings on CT scans. Except for pyruvate the values of all biochemical variables and the lactate/pyruvate (L/P) ratio were significantly different in the penumbra zone when compared with mean values found in “normal” tissue ipsilateral to the parenchymal damage and in contralateral normal tissue (p < 0.001). In the penumbra zone a slow normalization of the L/P ratio and levels of glutamate and glycerol were observed. In normal tissue these parameters remained within normal limits. Conclusions. Data obtained from intracerebral microdialysis can be correctly interpreted only if the locations of the catheters as they relate to focal brain lesions are visualized. A “biochemical penumbra zone” surrounds focal traumatic brain lesions. It remains to be proven whether therapeutic interventions can protect the penumbra zone from permanent damage.

Patients with traumatic brain injury (TBI) often show progression of hemorrhagic injuries (PHI) after admission to the hospital. This progression is correlated with poor outcome. In this study, we have investigated if thrombocytopenia was a risk factor for PHI. The study was performed on patients admitted to the hospital with severe TBI during year 2000. In total, 50 patients were admitted with severe TBI. Twenty-seven out of these had complete platelet counts at admission and 24 hours thereafter and were included for further study. We found thrombocytopenia at admission to be a risk factor for PHI (p=0.008). We also found that the platelet count decreased more significantly during the first 24 h after injury in patients with PHI compared to patients without PHI (p=0.009). A trend towards longer periods of mechanical ventilation in patients with PHI compared to patients without PHI was identified. These findings support a causal relationship between thrombocytopenia and PHI. The findings provide a rationale for future studies of hemostatic agents in the treatment of TBI in order to minimise complications caused by PHI.

Background: Endotoxin (lipopolysaccharide, LPS) up-regulates inducible nitric oxide synthase (iNOS) in blood vessels during septic shock. This promotes the production of nitric oxide (NO), leading to dilation of the vessels. The aim of the study was to investigate the effects of the LPS-binding endogenous antibiotic bactericidal/permeability-increasing protein (BPI) on the action of LPS on the blood vessels wall and to identify possible influence on underlying NO-related mechanisms. Methods: Isolated segments of rat thoracic aorta and cultured primary smooth muscle cells were incubated for 5–48 h in the presence of the following combinations of compounds: (a) LPS; (b) interleukin-1b (IL-1b); (c) BPI; (d) BPI π LPS; (e) BPI π IL-1b or (f) neither BPI, LPS nor IL-1b (control). After incubation of intact segments, we measured smooth muscle contraction in response to phenylephrine and accumulation of the NO end products nitrate and nitrite in surrounding medium. Western blot was used to assess the levels of inducible nitric oxide synthase (iNOS) in cultured cells.

Dabigatran is a new oral direct thrombin inhibitor. No specific antidote exists in the event of hemorrhage, but prothrombin complex concentrate (PCC) and recombinant activated factor VII (rFVIIa) are suggested therapies. Sonoclot is a bedside viscoelastic instrument for monitoring the coagulation process in whole blood. The aim of this study was to investigate the effect of dabigatran and reversal with PCC and rFVIIa, as monitored by the Sonoclot.Citrated whole blood was drawn and mixed in vitro with dabigatran, dabigatran + PCC or dabigatran + rFVIIa and analyzed with three different Sonoclot cuvettes: Glassbead, kaolin and tissue factor (diluted) activated.The Sonoclot detected in vitro-induced anticoagulation due to dabigatran with the glassbead- and kaolin-activated cuvettes. There was no reversing effect of PCC, probably due to the presence of heparin in the PCC we used. There was no certain reversing effect of rFVIIa.The Sonoclot can detect the anticoagulant effect of dabigatran. Our results do not support efficient reversal of dabigatran with PCC and rFVIIa, or alternatively do not support the ability of Sonoclot to detect a reversing effect of the PCC and rFVIIa in our study. Clinical studies of dabigatran-treated patients with severe bleeding are called for, as well as the continued development of specific antidotes and monitoring techniques.

BACKGROUND: In this study, we assessed the immediate effects of platelet transfusion on whole blood coagulation. METHODS: Ten thrombocytopenic patients given a single unit platelet transfusion of 200-300 x 10(9) platelets had their coagulation status assessed before and immediately after transfusion using rotational thromboelastometry. RESULTS: Transfusion increased the median platelet count from 31.5 to 43.5 x 10(9)/L. Clot formation time decreased by 32% (P = 0.005), whereas maximum clot strength increased by 47% (P = 0.005). CONCLUSION: Statistically significant improvements in rotational thromboelastometry-measured parameters were observed in association with a mean increase of 12 x 109/L in platelet count after platelet transfusion in these patients. (Less)

Increased fibrinolysis with the risk of bleeding is a consequence of thrombolytic therapy and can also be seen in clinical situations such as acute trauma. Thrombelastography and thrombelastometry are viscoelastic coagulation instruments that can detect higher degrees of fibrinolysis; hyperfibrinolysis. A newer viscoelastic instrument is the ReoRox, which uses free oscillation rheometry to detect clot formation, strength and fibrinolysis. The ReoRox has a new test for detection of fibrinolysis, called ReoLyse. The aim of this study was to compare ReoRox with its new ReoLyse test with rotational thrombelastometry (ROTEM) in the monitoring of in vitro-induced fibrinolysis.Whole blood from 10 healthy volunteers was mixed with tissue plasminogen activator (t-PA) to obtain seven different plasma concentrations (0, 0.25, 0.5, 0.75, 1, 3 and 5 μg/mL). Whole blood samples with the different t-PA plasma concentrations were analyzed with ROTEM EXTEM and FIBTEM tests, ReoRox standard test Fib1 (clot formation/strength) and ReoLyse (fibrinolysis) tests.The fibrinolysis variables with the best dose-response effect were the ReoRox ReoLyse lysis variables and ROTEM EXTEM Time to complete lysis. However, these variables only detected high t-PA levels (1 μg/mL).The new ReoRox ReoLyse test provides more information on fibrinolysis compared to the ReoRox Fib1 program. Neither ReoRox nor ROTEM could detect lower degrees of fibrinolysis. ReoRox is a valuable alternative to ROTEM to study high degrees of fibrinolysis and should be evaluated in clinical situations with increased fibrinolysis and during therapeutic thrombolysis.

Calponin (4.1–5.9 μM, pig stomach) inhibited maximal shortening velocity (Vmax) by 20–25% with only minor influence on force in skinned smooth muscle from guinea-pig taenia coli activated at different Ca2+ levels and with thiophosphorylation. Similar results were obtained with a fragment of the N-terminal 1–228 amino acids engineered using a mouse cDNA construct (5.4 μM). Both the native calponin and the fragment inhibited actin filament sliding in a graded manner in an in vitro motility assay. We conclude that calponin influences the kinetics of the actin-myosin interaction in the organised smooth muscle contractile system and that engineered fragments of calponin can be used to probe its action in muscle fibres. The effects can be due to an introduction of an internal load during filament sliding, possibly by decreasing the detachment rates and increasing the cross-bridge time spent in the attached state.

Objectives: Sonoclot was used in this study to monitor low molecular weight heparin (LMWH) during haemodialysis. Material and Methods: Two different intravenous doses (standard / half-dose) of dalteparin were studied in eight patients. Blood was sampled for coagulation analyses with Sonoclot, thrombin-antithrombin (TAT) and anti-Xa. A visual fibrin deposition score (VFS) in the venous drip chamber was also evaluated. Results: All patients completed their dialysis. There was a progressive increase in TAT levels, which correlated to the dalteparin dose. Significant differences (p Conclusion: Both Sonoclot and TAT failed to predict the VFS. No patient had any clinical clotting events and all dialyses were completed successfully.

BACKGROUND: Hypothermia may be accidental or therapeutic. Therapeutic hypothermia is increasingly used as treatment for various conditions, e.g., neuroprotection after cardiac arrest. Hypothermia leads to an impairment of the coagulation system, but the degree of impairment has been difficult to determine. Most studies have been performed on plasma instead of whole blood. We therefore evaluated whole blood investigating the effects of hypothermia on the coagulation system over a wide range of temperatures (25-40 degrees C). METHODS: Blood was drawn from six healthy volunteers into citrated test tubes. Samples were then placed in water baths with temperatures ranging from 25 to 40 degrees C for 30 min before the coagulation system was studied using rotational thromboelastometry. A contact activator (Ellagic acid) was used for initiation of coagulation. Clotting time, clot formation time, a angle, and maximum clot strength were measured. All tests were run for 60 min and they were performed at the same temperature as the temperature in the water bath. RESULTS: Coagulation was increasingly impaired with decreasing temperatures in the temperature range studied. All variables measured were significantly impaired in a stepwise pattern (P < 0.0001). CONCLUSIONS: Evaluation using a whole blood analysis shows that hypothermia progressively impairs the coagulation system. (Less)

The objective was to study the effects of ethanol on coagulation and fibrinolysis in whole blood. Blood samples from healthy volunteers were analyzed before and after in-vitro addition of ethanol in order to achieve ethanol concentrations of 0, 1, 2 and 4[per mille sign], respectively (0, 22, 44 and 88 mmol/l). Coagulation and fibrinolysis were then assessed using rotational thromboelastometry. We found that increasing ethanol levels increasingly impaired coagulation as evaluated with rotational thromboelastometry, with a maximum prolongation of the clot formation time of 118% at an ethanol level of 4[per mille sign] (P < 0.000001). We also found a very strong impairment of fibrinolysis already at an ethanol level of 1[per mille sign]. This is the first study assessing the effects of ethanol on coagulation and fibrinolysis in a whole blood model. The impairment of coagulation is similar in nature to the impairment found in patients suffering from hypothermia. The impairment is at a level that may be of clinical importance (e.g. in patients suffering from trauma). The inhibition of fibrinolysis is obvious already at an ethanol level of 1[per mille sign] and it may be a contributing factor to the increased amount of coronary and cerebrovascular ischemic events after binge drinking.

Background Rotational thromboelastography (ROTEG) has been proposed as a monitoring tool that can be used to monitor treatment of hemophilia with recombinant factor VIIa (rFVIIa). In these studies special non-standard reagents were used as activators of the coagulation. The aim of this study was to evaluate if standard ROTEG analysis could be used for monitoring of effects of recombinant factor VIIa (rFVIIa) on Hydroxy Ethyl Starch-induced dilutional coagulopathy. Methods The study was performed in vitro on healthy volunteers. Prothrombin time (PT) and ROTEG analysis were performed after dilution with 33% hydroxy ethyl starch and also after addition of rFVIIa to the diluted blood. Results PT was impaired with INR changing from 0.9 before dilution to 1.2 after dilution while addition of rFVIIa to diluted blood lead to an overcorrection of the PT to an International Normalized Ratio (INR) value of 0.6 (p = 0.01). ROTEG activated with the contact activator ellagic acid was impaired by hemodilution (p = 0.01) while addition of rFVIIa had no further effects. ROTEG activated with tissue factor (TF) was also impaired by hemodilution (p = 0.01) while addition of rFVIIa lead to further impairment of the coagulation (p = 0.01). Conclusions The parameters affected in the ROTEG analysis were Clot Formation Time and Amplitude after 15 minutes while the Clotting Time was unaffected. We believe these effects to be due to methodological problems when using standard activators of the coagulation in the ROTEG analysis in combination with rFVIIa.

Background Several studies have described hypercoagulability in neurosurgery with craniotomy for brain tumor resection. In this study, hydroxyethyl starch (HES) 130/0.42 was used for hemodynamic stabilization and initial blood loss replacement. HES can induce coagulopathy with thromboelastographic signs of decreased clot strength. The aim of this study was to prospectively describe perioperative changes in coagulation during elective craniotomy for brain tumor resection with the present fluid regimen. Methods Forty patients were included. Perioperative whole-blood samples were collected for EXTEM and FIBTEM assays on rotational thromboelastometry (ROTEM) and plasma fibrinogen analysis immediately before surgery, after 1 L of HES infusion, at the end of surgery and in the morning after surgery. Factor (F)XIII activity, thrombin-antithrombin complex (TAT) and plasmin-α2-antiplasmin complex (PAP) were analysed in the 25 patients receiving ≥1 L of HES. Results Most patients (37 of 40) received HES infusion (0.5–2 L) during surgery. Preoperative ROTEM clot formation/structure, plasma fibrinogen and FXIII levels were generally within normal range but approached a hypocoagulant state during and at end of surgery. ROTEM variables and fibrinogen levels, but not FXIII, returned to baseline levels in the morning after surgery. Low perioperative fibrinogen levels were common. TAT levels were increased during and after surgery. PAP levels mostly remained within the reference ranges, not indicating excessive fibrinolysis. There were no differences in ROTEM results and fibrinogen levels in patients receiving