Ola E Dahl
Thrombosis Research Institute,...

Clinical Trials, Clinical Chemistry, Epidemiology

DocMedSci (Dr.Med)
37.78

Publications

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    ABSTRACT: A variety of harmful effects can be triggered by trauma and major orthopedic surgery. One of the key players involved in this process is thrombin. The clinical consequence of this process has, for several decades, been considered to be formation of deep vein thrombosis and pulmonary embolism. Controlling thrombin generation and activation has therefore been the goal of thromboprophylaxis regimens administered to patients suffering from trauma or undergoing major surgery. Protecting patients from venous thromboembolism has, for many years, been the main goal of preventive strategies. However, our knowledge of cell destruction and release of substances that may cause organ damage has expanded in recent years. Release of molecules such as RNA and histones from destroyed tissues may cause cell destruction and organ damage at distal sites if released in huge amounts and disseminated systemically. This new knowledge points toward an unmet need for therapies that prevent both vascular events and organ deterioration. This article briefly reviews molecular mechanisms associated with the occurrence of vascular events and cellular destruction in patients with major bone damage caused by trauma. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 02/2015; 41(2). DOI:10.1055/s-0035-1544230 · 3.69 Impact Factor
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    ABSTRACT: Introduction We have recently reported that increased levels of urine prothrombin fragment 1 + 2 reflected radiologically verified deep vein thrombosis. In this study we evaluated whether urine prothrombin fragment 1 + 2 was associated with pulmonary embolism in non-selected patients. Materials and methods Patients with clinical suspected pulmonary embolism were interviewed on comorbidities and medications. Urine was collected from each patient before radiological examination and snap frozen until analysed on urine prothrombin fragment 1 + 2 with an ELISA kit. Imaging of the pulmonary arteries were conducted with contrast enhanced computer tomography. Results Pulmonary embolism was diagnosed in 44/197 patients. Non-significantly higher urine prothrombin fragment 1 + 2 levels were found in non-selected patients with pulmonary embolism vs. those without (p = 0.324). Significantly higher urine prothrombin fragment 1 + 2 levels were found in the pulmonary embolism positive patients without comorbidities (n = 13) compared to the control group (n = 28) (p = 0.009). The calculated sensitivity, specificity and negative predictive value using the lowest detectable urine prothrombin fragment 1 + 2 level was 82%, 34% and 87%, respectively. Conclusions There was no significant urine prothrombin fragment 1 + 2 level difference in patients with and without pulmonary embolism. In non-comorbide pulmonary embolism positive patients the urine prothrombin fragment 1 + 2 levels were significantly higher compared to the control group. The negative predictive value found in this study indicates that uF1 + 2 has the potential to identify patients with a low risk of PE.
    Thrombosis Research 07/2014; 134(1):68–71. DOI:10.1016/j.thromres.2014.04.011 · 2.43 Impact Factor
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    ABSTRACT: Introduction: Bone cement for fixation of prostheses, comorbidity and age have been previously shown to be associated with increased relative risk of mortality within the first day of surgery. However, the proportion of mortalities associated to each of these exposures is not adequately expressed by relative risk estimates. Materials and methods: The attributable fraction (AF), i.e. the fraction of diseased individuals attributed to a given risk factor, was estimated for cemented fixation of hip prostheses in the elderly (>65 years) with a hip fracture. Dementia, symptomatic comorbidity (American Society of Anesthesiologists (ASA)≥ 3), old age (≥85 years), male gender, and a delay of 24 hours or more from fracture to operation were considered as additional risk factors for a fatal outcome in close proximity to surgery. Results: In the entire study population (n = 11210), the unadjusted and adjusted population AFs of cemented fixation on mortalities within the first day after surgery were 0.58 (95% CI 0.28-0.76) and 0.59 (95% CI 0.29-0.76), respectively. Symptomatic comorbidity and old age as risk factors had population AFs of 0.71 (95% CI 0.51-0.83) and 0.55 (95% CI 0.39-0.67), respectively. Male gender, dementia and time from fracture to operation all had considerably lower population AFs. Conclusions: The estimated AFs on perioperative mortality in hip fracture patients treated by hemiarthroplasty showed that about half of the mortalities within the first day of surgery could be associated with the use of bone cement.
    Hip international: the journal of clinical and experimental research on hip pathology and therapy 02/2014; 24(4). DOI:10.5301/hipint.5000123 · 0.76 Impact Factor
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    ABSTRACT: Venous thrombosis is common in elective hip surgery, and prophylaxis is recommended. Clinical trials suggest that the drug dose and timing of initiating prophylaxis significantly influence antithrombotic effectiveness and safety. We studied the time course and gradient of plasma coagulation and fibrinolysis during total hip arthroplasty (THA) in twenty patients that were randomly assigned to have the first dose of 5000 IU dalteparin subcutaneously (sc) injected 12 hours before or 6 hours after surgery. Baseline characteristics were similar in both groups. Specific biomarkers on coagulation (prothrombin fragment 1+2 (F1+2)) and fibrinolytic activity (plasmin/ α 2-antiplasmin complex (PAP) and D-dimer) were collected at six events during hospitalization and analysed. There were no significant group differences in the biomarkers at any time point. The highest concentrations were measured 6 hours after surgery and before the first postoperative injection. A marked decrease followed at the first postoperative day, and then a second increase in plasma concentrations was observed 6 days after surgery. This study showed that activation of coagulation and fibrinolysis by the operative trauma was the same when the first dose of dalteparin was injected 12 hours before or 6 hours after surgery.
    12/2013; 2013:563217. DOI:10.1155/2013/563217
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    ABSTRACT: We describe annual incidences and 6-month postoperative patterns of clinical venous thromboembolism (VTE) in 9078 patients undergoing major joint surgery in a Scandinavian hospital. In cohort I (1989-1999), low-molecular-weight heparin thromboprophylaxis for 7 to 10 days was uniformly introduced, 5-week thromboprophylaxis becoming routine after total hip replacement (THR), partially applied after hip fracture surgery (HFS), but not used after total knee replacement (TKR) thereafter (2003-2011; cohort II). Mean annual VTE incidence was lower in cohort II than in cohort I after THR and HFS but not after TKR. In cohort I, the cumulative VTE incidence increased sharply during the first 5 postoperative weeks in all groups, subsequently plateauing up to 6 months postsurgery. In cohort II, this incidence remained low and stable during 5 weeks post-THR, rising gradually up to 6 months, with a comparable but less pronounced pattern following HFS but not TKR. In conclusion, the VTE risk after major joint surgery seems to persist after 5- and 1-week prophylaxis in patients undergoing hip surgery and TKR, respectively.
    Clinical and Applied Thrombosis/Hemostasis 10/2013; 20(2). DOI:10.1177/1076029613499820 · 1.58 Impact Factor
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    Journal of Thrombosis and Haemostasis 07/2013; 11(7). DOI:10.1111/jth.12269 · 5.55 Impact Factor
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    ABSTRACT: INTRODUCTION: The appearance of prothrombin fragment 1+2 (F1+2) in urine has been associated with postoperative hypercoagulability and thromboembolism. We wanted to assess if F1+2 was released in urine (uF1+2) in patients with procoagulant disorders, and if higher levels were found in patients with radiological verified deep vein thrombosis (DVT). MATERIALS AND METHODS: Consecutive patients were interviewed on comorbidities and medications. An unselected total cohort (n=534) and a control cohort (n=177) were analysed. A urine sample (10ml) was collected and snap frozen before levels of uF1+2 were measured with an ELISA kit. Visualisation of DVT was done with compression ultrasound, supplied with venography when feasible. All patients were followed up for 3-6months. RESULTS: DVT was diagnosed in 108/534 patients. Statistical significant higher uF1+2 levels were found in patients with DVT (p<0.001), in DVT positive patients with ongoing malignancy (p=0.034) and in pregnant women compared to the control cohort (p<0.001). Non-significant increased urine concentrations were found in DVT positive vs. DVT negative patients with infections and traumas. CONCLUSIONS: Levels of uF1+2 was associated with DVT both in the total cohort and in the control cohort as well as in most patients with coexisting conditions.
    Thrombosis Research 05/2013; DOI:10.1016/j.thromres.2013.04.019 · 2.43 Impact Factor
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    ABSTRACT: INTRODUCTION: Laboratory and human mechanical studies indicated that chemical substances in bone cement had toxic and prothrombotic effects. Impaction of cement added a mechanical trauma to the reaming and broaching procedure and contributed to a substantial local and systemic thrombin generation. Case reports and materials have indicated bone cement as the immediate trigger of cardiorespiratory and vascular dysfunction, occasionally fatal, and described as the bone cement implantation syndrome. In spite of this knowledge, bone cement has gained popularity and is widely used for prosthesis fixation, possibly due to a lack of clinical evidence supporting the basic science indicating bone cement as a mortality risk factor. METHOD: This is a prospective, randomized study comparing cemented and non cemented hemiprosthesis on patients suffering a dislocated cervical hip fracture. Perioperative characteristics and 1 year mortality differences between the groups were estimated. PATIENTS: Hundred and thirty-four patients over 75 years were enrolled from two hospitals in Norway. Average age was 84 years, 75 % were female and 60 % had symptomatic comorbidities. RESULTS: We find no difference in mortality between cemented and uncemented hemiprosthesis up to 1 year (HR 0.77, 95 % CI 0.51-1.18, p = 0.233). However, statistically significant reduced operation time and blood loss were found in the non-cemented group. (mean difference of 13 min, 95 % CI 4-22, p = 0.004 and 92 ml 95 % CI 3-181, p = 0.043, respectively). CONCLUSION: Installation of non-cemented hemiprostheses in elderly with hip fracture may have benefits perioperatively regarding operation time and bleeding, and do not seem to influence 1 year mortality relative to cemented implants.
    Archives of Orthopaedic and Trauma Surgery 03/2013; 133(6). DOI:10.1007/s00402-013-1726-5 · 1.36 Impact Factor
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    ABSTRACT: PURPOSE: Adverse events associated with the use of bone cement for fixation of prostheses is a known complication. Due to inconclusive results in studies of hip fracture patients treated with cemented and uncemented hemiprostheses, this study was initiated. METHODS: Our study is based on data reported to the Norwegian Hip Fracture Register on 11,210 cervical hip fractures treated with hemiprostheses (8,674 cemented and 2,536 uncemented). RESULTS: Significantly increased mortality within the first day of surgery was found in the cemented group (relative risk 2.9, 95 % confidence interval 1.6-5.1, p=0.001). The finding was robust giving the same results after adjusting for independent risk factors such as age, sex, cognitive impairment and comorbidity [American Society of Anesthesiologists (ASA) score]. For the first post-operative day the number needed to harm was 116 (one death for every 116 cemented prosthesis). However, in the most comorbid group (ASA worse than 3), the number needed to harm was only 33. CONCLUSIONS: We found increased mortality for the cemented hemiprosthesis the first post-operative day compared to uncemented procedures. This increased risk is closely related to patient comorbidity estimated by the patient's ASA score.
    International Orthopaedics 03/2013; 37(6). DOI:10.1007/s00264-013-1851-3 · 2.02 Impact Factor
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    ABSTRACT: No difference in mortality between cemented and uncemented hemiprosthesis for elderly patients with cervical hip fracture.A prospective randomized study on 334 patients over 75years
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    Ola E Dahl
    Thrombosis Research 10/2012; 130 Suppl 1:S32. DOI:10.1016/j.thromres.2012.08.268 · 2.43 Impact Factor
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    ABSTRACT: New oral anticoagulant (NOAC) regimens [dabigatran 150 mg (D150) and 220 mg (D220), rivaroxaban 10 mg (R20), and apixaban 2.5 mg bid (A5)] were effective and safe compared to enoxaparin for the prevention of venous thromboembolism (VTE) following elective total knee (TKR) or hip replacement (THR) surgery. First a cluster analysis was used to identify homogeneous studies for the trial programs of each NOAC. Second, only studies reporting VTE and VTE-related death, major bleeding, and mortality were included. The odds ratio (OR) and 95% confidence interval (CI) were calculated for each NOAC regimen versus the comparator. Third, these data were used for the indirect comparison between NOACs. Cluster analysis identified duration of treatment (10 ± 5 and 34 ± 5 days) as the only homogeneous parameter across all NOAC programs (p>0.05) except for A5 and VTE over 10 ± 5 days (analysis not performed). The results of the calculated OR and 95% CI of the four NOAC regimens over 10 ± 5 and 34 ± 5 days showed inferiority of D150 and D220 compared to R10 for VTE (p<0.01, p<0.001). Comparisons of major bleeding and mortality were not different for all indirect comparisons. Despite the lack of standard definitions for VTE and bleeding outcomes, cluster analysis seems to be an appropriate tool to identify homogeneity across trial programs and to perform an indirect comparison for NOACs for prevention of VTE following TKR and THR surgery.
    Thrombosis and Haemostasis 09/2012; 108(5). DOI:10.1160/TH12-07-0482 · 5.76 Impact Factor
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    ABSTRACT: INTRODUCTION: In the elderly, hip fracture is a common injury associated with high early mortality dominated by cardiorespiratory and thromboembolic events. Identification of risk factors that can be modified by treatment has caught attention over the last years. This study was conducted to assess biological markers on perioperative organ dysfunction and its association with early mortality within 3 months after surgery. METHOD: Blood samples were collected before, during and until 4 days after surgery. Analyses on PaO(2), alanine aminotransaminase (ALAT), gamma-glutamyl transpeptidase (g-GT) and creatinine were performed and used as markers on lung, liver and kidney functions. PATIENTS: Three hundred and two patients over 75 years of age with acute dislocated hip fracture were consecutively enrolled from two hospitals in Norway. RESULTS: We found a positive correlation between the plasma levels of ALAT, creatinine and death, and an inverse relationship between PaO(2) and death. After controlling for confounding factors such as sex, age and comorbidity, ALAT and creatinine levels were shown to be significantly and independently related to risk for fatal outcome. CONCLUSION: Our results provide data on clinically important biomarkers in patients undergoing hip fracture surgery. We suggest a stronger emphasis on monitoring and correcting these biomarkers when possible.
    Archives of Orthopaedic and Trauma Surgery 09/2012; 132(12). DOI:10.1007/s00402-012-1611-7 · 1.36 Impact Factor
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    ABSTRACT: INTRODUCTION: Oral thromboprophylaxis with dabigatran etexilate should be initiated as a half dose 1 to 4h after major orthopaedic surgery. However, a delay in dosing could occur for clinical or logistical reasons. A post hoc analysis was carried out to determine if patients with delayed dosing received adequate anticoagulation. PATIENTS AND METHODS: The RE-MODEL™ and RE-NOVATE® trials compared 220mg and 150mg dabigatran etexilate with 40mg enoxaparin. Pooled data for major venous thromboembolism (VTE) and VTE-related mortality (efficacy outcome) and major bleeding events (MBE), MBE/clinically relevant bleeding events, and all bleeding events (safety outcomes) were analysed. Results in patients with dosing delayed more than 4h postsurgery were compared with those of patients without a delay. RESULTS: Onset of treatment was delayed in 724 (13.3%) of 5425 patients. Efficacy of 220mg dabigatran etexilate was similar in patients without delayed dosing, patients with a delay and patients with a delay until the day after surgery. Rates of efficacy outcome were higher in patients on 150mg dabigatran etexilate, but more than 80% of these patients were undertreated based on age or renal clearance status. Some differences in bleeding events were seen among patient groups by treatment arm. CONCLUSION: Dabigatran etexilate thromboprophylaxis should be initiated 1 to 4h postsurgery. Results from our post-hoc analysis indicate that no loss of efficacy appears to occur if initiation of dabigatran etexilate 220mg needs to be delayed.
    Thrombosis Research 09/2012; 130(6). DOI:10.1016/j.thromres.2012.08.315 · 2.43 Impact Factor

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