| 1. |
|
|
| 2. |
- Dimakakos, Evangelos, et al.
(författare)
-
Thromboembolic Disease in Patients With Cancer and COVID-19 : Risk Factors, Prevention and Practical Thromboprophylaxis Recommendations-State-of-the-Art
- 2022
-
Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 1791-7530 .- 0250-7005. ; 42:7, s. 3261-3274
-
Forskningsöversikt (refereegranskat)abstract
- Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment. Universal thromboprophylaxis with a high prophylactic dose of low molecular weight heparins (LMWH) or therapeutic dose in select patients, is currentlyindicated for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is recommended for outpatients with COVID-19 at high risk for thrombosis or disease worsening. However, whether there is an additive risk of thrombosis when a patient with cancer is infected with SARS-CoV2 remains unclear In the current review, we summarize and critically discuss the literature regarding the epidemiology of thrombotic events in patients with cancer and concomitant COVID-19, the thrombotic risk assessment, and the recommendations on thromboprophylaxis for this subgroup of patients. Current data do not support an additive thrombotic risk for patients with cancer and COVID-19. Of note, patients with cancer have less access to intensive care unit care, a setting associated with high thrombotic risk. Based on current evidence, patients with cancer and COVID-19 should be assessed with well-established risk assessment models for medically ill patients and receive thromboprophylaxis, preferentially with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist.
|
|
| 3. |
- Gigante, Bruna, et al.
(författare)
-
Management of patients on antithrombotic therapy with severe infections : a joint clinical consensus statement of the ESC Working Group on Thrombosis, the ESC Working Group on Atherosclerosis and Vascular Biology, and the International Society on Thrombosis and Haemostasis
- 2023
-
Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:32, s. 3040-3058
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with severe infections and a pre-existing indication for antithrombotic therapy, i.e. antiplatelet agents, anticoagulant drugs, or their combinations, require integrated clinical counselling among coagulation, infectious disease, and cardiology specialists, due to sepsis-induced coagulopathy that frequently occurs. Bacterial and viral pathogens constitute an increasing threat to global public health, especially for patients with ongoing antithrombotic treatment who have a high risk of thrombotic recurrences and high susceptibility to severe infections with increased morbidity and mortality. Similarly, sepsis survivors are at increased risk for major vascular events. Coagulopathy, which often complicates severe infections, is associated with a high mortality and obligates clinicians to adjust antithrombotic drug type and dosing to avoid bleeding while preventing thrombotic complications. This clinical consensus statement reviews the best available evidence to provide expert opinion and statements on the management of patients hospitalized for severe bacterial or viral infections with a pre-existing indication for antithrombotic therapy (single or combined), in whom sepsis-induced coagulopathy is often observed. Balancing the risk of thrombosis and bleeding in these patients and preventing infections with vaccines, if available, are crucial to prevent events or improve outcomes and prognosis.
|
|
| 4. |
- Glise Sandblad, Katarina, 1982, et al.
(författare)
-
Association of type of oral anticoagulation with risk of bleeding in 45,114 patients with venous thromboembolism during initial and extended treatment-A nationwide register-based study.
- 2023
-
Ingår i: Journal of internal medicine. - 1365-2796. ; 294:6, s. 743-60
-
Tidskriftsartikel (refereegranskat)abstract
- Safety data for different anticoagulant medications in venous thromboembolism (VTE) are scarce, in particular for extended treatment.To compare major bleeding rates depending on the choice of anticoagulation during initial (first 6 months) and extended treatment (6 months up to 5 years).A nationwide register-based study including cancer-free patients with a first-time VTE between 2014 and 2020. Cox proportional hazards models were used to compare bleeding rates.We included 6558 patients on warfarin, 18,196 on rivaroxaban, and 19,498 on apixaban. At 6 months, 4750 (72.4%) remained on warfarin, 11,366 (62.5%) on rivaroxaban, and 11,940 (61.2%) on apixaban. During initial treatment, major bleeding rates were 3.86 (95% CI 3.14-4.58), 2.93 (2.55-3.31), and 1.95 (1.65-2.25) per 100 patient-years for warfarin, rivaroxaban, and apixaban, respectively, yielding adjusted hazard ratios (aHRs) of 0.89 (95% CI 0.71-1.12) for rivaroxaban versus warfarin, 0.55 (0.43-0.71) for apixaban versus warfarin, and 0.62 (0.50-0.76) for apixaban versus rivaroxaban. During extended treatment, major bleeding rates were 1.55 (1.19-1.91), 1.05 (0.85-1.26), and 0.96 (0.78-1.15) per 100 patient-years for warfarin, rivaroxaban, and apixaban, respectively, with aHRs of 0.72 (0.53-0.99) for rivaroxaban versus warfarin, 0.60 (0.44-0.82) for apixaban versus warfarin, and 0.85 (0.64-1.12) for apixaban versus rivaroxaban. Previous bleeding and increasing age were risk factors for bleeding both during initial and extended treatment.Apixaban had a lower bleeding risk than warfarin or rivaroxaban during initial treatment. During extended treatment, bleeding risk was similar for apixaban and rivaroxaban, and higher with warfarin.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Kristinsson, Sigurdur Y, et al.
(författare)
-
Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma : a population-based study
- 2010
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 115:24, s. 4991-4998
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with multiple myeloma (MM) have an increased risk of venous thrombosis. Interestingly, excess risk of venous thromboembolism has been observed among patients with monoclonal gammopathy of undetermined significance (MGUS). Using population-based data from Sweden, we assessed the risks of venous and arterial thrombosis in 18,627 MM and 5326 MGUS patients diagnosed from 1958 to 2006, compared with 70,991 and 20,161 matched controls, respectively. At 1, 5, and 10 years after MM diagnosis, there was an increased risk of venous thrombosis: hazard ratios (95% confidence intervals) were 7.5 (6.4-8.9), 4.6 (4.1-5.1), and 4.1 (3.8-4.5), respectively. The corresponding results for arterial thrombosis were 1.9 (1.8-2.1), 1.5 (1.4-1.6), and 1.5 (1.4-1.5). At 1, 5, and 10 years after MGUS diagnosis, hazard ratios were 3.4 (2.5-4.6), 2.1 (1.7-2.5), and 2.1 (1.8-2.4) for venous thrombosis. The corresponding risks for arterial thrombosis were 1.7 (1.5-1.9), 1.3 (1.2-1.4), and 1.3 (1.3-1.4). IgG/IgA (but not IgM) MGUS patients had increased risks for venous and arterial thrombosis. Risks for thrombosis did not vary by M-protein concentration (> 10.0 g/L or < 10.0 g/L) at diagnosis. MGUS patients with (vs without) thrombosis had no excess risk of MM or Waldenström macroglobulinemia. Our findings are of relevance for future studies and for improvement of thrombosis prophylaxis strategies.
|
|
| 9. |
|
|
| 10. |
- Kyriakoulis, Konstantinos G, et al.
(författare)
-
Practical Recommendations for Optimal Thromboprophylaxis in Patients with COVID-19 : A Consensus Statement Based on Available Clinical Trials
- 2022
-
Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 11:20, s. 1-18
-
Forskningsöversikt (refereegranskat)abstract
- Coronavirus disease 2019 (COVID-19) has been shown to be strongly associated with increased risk for venous thromboembolism events (VTE) mainly in the inpatient but also in the outpatient setting. Pharmacologic thromboprophylaxis has been shown to offer significant benefits in terms of reducing not only VTE events but also mortality, especially in acutely ill patients with COVID-19. Although the main source of evidence is derived from observational studies with several limitations, thromboprophylaxis is currently recommended for all hospitalized patients with acceptable bleeding risk by all national and international guidelines. Recently, high quality data from randomized controlled trials (RCTs) further support the role of thromboprophylaxis and provide insights into the optimal thromboprophylaxis strategy. The aim of this statement is to systematically review all the available evidence derived from RCTs regarding thromboprophylaxis strategies in patients with COVID-19 in different settings (either inpatient or outpatient) and provide evidence-based guidance to practical questions in everyday clinical practice. Clinical questions accompanied by practical recommendations are provided based on data derived from 20 RCTs that were identified and included in the present study. Overall, the main conclusions are: (i) thromboprophylaxis should be administered in all hospitalized patients with COVID-19, (ii) an optimal dose of inpatient thromboprophylaxis is dependent upon the severity of COVID-19, (iii) thromboprophylaxis should be administered on an individualized basis in post-discharge patients with COVID-19 with high thrombotic risk, and (iv) thromboprophylaxis should not be routinely administered in outpatients. Changes regarding the dominant SARS-CoV-2 variants, the wide immunization status (increasing rates of vaccination and reinfections), and the availability of antiviral therapies and monoclonal antibodies might affect the characteristics of patients with COVID-19; thus, future studies will inform us about the thrombotic risk and the optimal therapeutic strategies for these patients.
|
|
| 11. |
- Lind, Marcus, 1975-
(författare)
-
Determinants of adverse events during oral anticoagulant treatment
- 2012
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Treament with oral anticoagulation is highly effective in reducing the burden of thromboembolic complications in several clinical conditions. The number of patients receiving oral anticoagulation is growing steadily. InSwedenabout 1.5 percent of the population receives treatment. Although the treatment is highly effective in preventing thromboembolic complications, it is also associated with a substantial increase in the risk of bleeding. In clinical practice every physician has to balance the potential benefit of treatment against the risk of bleeding complications in the individual patient. To aid in this decision making, risk scores addressing the likelihood of thromboembolic events, as well as the risk of bleeding complications, have been developed. These scores are imperfect and, to some degree limited by the fact that the risk factors predictive of thromboembolic events are also often associated with bleeding complications. The addition of biomarkers has the potential to increase the predictive ability of risk scores and further enhance the net benefit of oral anticoagulant treatment in the individual patient. In this thesis several potential biomarkers for thromoboembolic and haemorrhagic complications of anticoagulant therapy have been investigated in a longitudinal cohort study of 719 patients with a median follow-up time of 4.2 years. Thrombomodulin is a key component in the generation of activated protein C and hence, a coagulation inhibitor. Conversely, it is also a key component in the inhibition of fibrinolysis by activation of trombin-activated fibrinolysis inhibitor. In warfarin-treated patients we demonstrate that thrombomodulin predicts an increased risk of bleeding complications, but not cardiovascular events. Thus, thrombomodulin has potential as a biomarker specifically for bleeding complications. Von Willebrand factor plays a central and intricate role in the aggregation of platelets and low levels of VWF have been associated with bleeding as a manifestation of von Willebrand’s disease. In our study we noted that high levels of von Willebrand factor predict an increased risk of cardiovascular as well as all-cause mortality, possibly as an expression of endothelial dysfunction. We also noted that high levels of WVF seem to be associated with serious bleeding complications. Decreased renal function is usually measured by an increase in the levels of creatinine and cystatin C, or a decrease in the calculated glomerular filtration rate. A decrease in kidney function is regarded as a marker of an increased risk of bleeding complications. We investigated all the mentioned markers of kidney function and no association with bleeding complications became apparent. However, a clear association between a decrease in kidney function and mortality was noted. Our findings indicate that the emphasis on impaired kidney function as a risk marker needs to be shifted from bleeding complications toward thromboembolic events. Fibrinolysis is important in containing coagulation and several constituents of the fibrinolytic pathway have been shown to predict cardiovascular events and mortality. We found that fibrinolytic factors seem to predict cardiovascular events in patients with oral anticoagulation and that D-dimer also predicts bleeding complications. In conclusion, we have found several biomarkers which exhibit different predictive abilities in patients with oral anticoagulation. It is likely that biomarkers, either alone, in combination, or as ancillary components of risk scores, can contribute to improved risk stratification in patients with oral anticoagulation.
|
|
| 12. |
- Majeed, Ammar, et al.
(författare)
-
Effectiveness and outcome of management strategies for dabigatran- or warfarin-related major bleeding events
- 2016
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 140, s. 81-88
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Strategies used for the management of dabigatran-related major bleeding events (MBEs), and their effectiveness have not been systematically evaluated.Methods: Reports on 1034 individuals experiencing 1121 MBEs (696 on dabigatran, and 425 on warfarin) in 5 phase III randomized controlled trials were assessed independently by two investigators.Results: MBEs were managed either by drug discontinuation only (37%), or drug discontinuation with either transfusion of only red cell concentrates (38%), or plasma (23%). Few MBEs (2%) were treated with coagulation factor concentrates. The effectiveness of the management was assessed as good in significantly larger proportion of MBEs on dabigatran (91%) than on warfarin (84%, odds ratio [OR] 1.68; 95% confidence interval [CI], 1.14-2.49), which was consistent with the lower 30-day mortality (OR (OR 0.66; 95% CI, 0.44-1.00)). The effectiveness of bleeding management in non-traumatic bleeding was better in patients with dabigatran than with warfarin (OR 1.82; 95% CI, 1.18-2.79) but was similar in traumatic bleeding (OR 0.75; 95% CI, 0.25-2.30). The relative effectiveness of management of bleeding and 30-day mortality rates across other key subgroups of patients or sites of bleeding, the use of platelet inhibitors, age-, sex-and renal function subgroups, were comparable in MBEs on dabigatran or warfarin.Conclusion: Despite the unavailability of a specific antidote at the time of these studies, bleeding in patients receiving dabigatran was managed in the overwhelming majority of patients without coagulation factor concentrates, with comparable or superior effectiveness and lower 30-day mortality rates versus those who bleed while receiving warfarin.
|
|
| 13. |
- Majeed, Ammar, et al.
(författare)
-
Management and Outcomes of Major Bleeding During Treatment With Dabigatran or Warfarin
- 2013
-
Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 128:21, s. 2325-2332
-
Tidskriftsartikel (refereegranskat)abstract
- Background The aim of this study was to compare the management and prognosis of major bleeding in patients treated with dabigatran or warfarin. Methods and Results Two independent investigators reviewed bleeding reports from 1034 individuals with 1121 major bleeds enrolled in 5 phase III trials comparing dabigatran with warfarin in 27 419 patients treated for 6 to 36 months. Patients with major bleeds on dabigatran (n=627 of 16 755) were older, had lower creatinine clearance, and more frequently used aspirin or non-steroid anti-inflammatory agents than those on warfarin (n=407 of 10 002). The 30-day mortality after the first major bleed tended to be lower in the dabigatran group (9.1%) than in the warfarin group (13.0%; pooled odds ratio, 0.68; 95% confidence interval, 0.46-1.01; P=0.057). After adjustment for sex, age, weight, renal function, and concomitant antithrombotic therapy, the pooled odds ratio for 30-day mortality with dabigatran versus warfarin was 0.66 (95% confidence interval, 0.44-1.00; P=0.051). Major bleeds in dabigatran patients were more frequently treated with blood transfusions (423/696, 61%) than bleeds in warfarin patients (175/425, 42%; P<0.001) but less frequently with plasma (dabigatran, 19.8%; warfarin, 30.2%; P<0.001). Patients who experienced a bleed had shorter stays in the intensive care unit if they had previously received dabigatran (mean 1.6 nights) compared with those who had received warfarin (mean 2.7 nights; P=0.01). Conclusions Patients who experienced major bleeding on dabigatran required more red cell transfusions but received less plasma, required a shorter stay in intensive care, and had a trend to lower mortality compared with those who had major bleeding on warfarin.
|
|
| 14. |
|
|
| 15. |
- Majeed, Ammar, et al.
(författare)
-
Management of rivaroxaban- or apixaban-associated major bleeding with prothrombin complex concentrates : a cohort study
- 2017
-
Ingår i: Blood. - : AMER SOC HEMATOLOGY. - 0006-4971 .- 1528-0020. ; 130:15, s. 1706-1712
-
Tidskriftsartikel (refereegranskat)abstract
- There is uncertainty regarding the effectiveness and occurrence of thromboembolic events in patients treated with prothrombin complex concentrates (PCCs) for the management of major bleeding events (MBEs) onrivaroxabanor apixaban. We investigated the effectiveness of PCCs given for the management of MBEs in patients on rivaroxaban or apixaban. Between 1 January 2014 and 1 October 2016, we prospectively included patients on rivaroxaban or apixaban treated with PCCs for the management of MBEs. The effectiveness of PCCs was assessed by using the International Society of Thrombosis and Hemostasis Scientific and Standardization Subcommittee criteria for the assessment of the effectiveness of major bleeding management. The safety outcomes were thromboembolic events and all-cause mortality with in 30 days after treatmentwith PCCs. Atotal of 84 patients received PCCs for the reversal of rivaroxaban or apixaban due to a MBE. PCCs were given at amedian (interquartile range) dose of 2000 IU (1500-2000 IU). Intracranial hemorrhage (ICH) was themost common site of bleeding requiring reversal (n = 5 59; 70.2%), followed by gastrointestinal bleeding in 13 (15.5%) patients. Management with PCCs was assessed as effective in 58 (69.1%) patients and ineffective in 26 (30.9%) patients. Most patients with ineffective hemostasis with PCCs had ICH (n 5 16; 61.5%). Two patients developed an ischemic stroke, occurring 5 and 10 days after treatment with PCC. Twenty seven (32%) patients died within 30 days after a MBE. The administration of PCCs for the management of MBEs associated with rivaroxaban or apixaban is effective inmost cases and is associated with a low risk of thromboembolism. Our findings are limited by the absence of a control group in the study.
|
|
| 16. |
- Majeed, Ammar, et al.
(författare)
-
Optimal timing of resumption of warfarin after intracranial hemorrhage
- 2010
-
Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 41:12, s. 2860-2866
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE:The optimum timing of resumption of anticoagulation after warfarin-related intracranial hemorrhage in patients with indication for continued anticoagulation is uncertain. We performed a large retrospective cohort study to obtain more precise risk estimates.METHODS:We reviewed charts of 2869 consecutive patients with objectively verified intracranial hemorrhage over 6 years at 3 tertiary centers. We calculated the daily risk of intracranial hemorrhage or ischemic stroke with and without resumption of warfarin; we focused on patients who survived the first week and had cardiac indication for anticoagulation or previous stroke. Using a Cox model, we estimated rates for these 2 adverse events in relation to different time points of resumed anticoagulation. The combined risk of either a new intracranial hemorrhage or an ischemic stroke was calculated for a range of warfarin resumption times.RESULTS:We identified warfarin-associated intracranial hemorrhage in 234 patients (8.2%), of whom 177 patients (76%) survived the first week and had follow-up information available; the median follow-up time was 69 weeks (interquartile range [IQR] 19-144). Fifty-nine patients resumed warfarin after a median of 5.6 weeks (IQR 2.6-17). The hazard ratio for recurrent intracranial hemorrhage with resumption of warfarin was 5.6 (95% CI, 1.8-17.2), and for ischemic stroke it was 0.11 (95% CI, 0.014-0.89). The combined risk of recurrent intracranial hemorrhage or ischemic stroke reached a nadir if warfarin was resumed after approximately 10 to 30 weeks.CONCLUSIONS:The optimal timing for resumption of warfarin therapy appears to be between 10 and 30 weeks after warfarin-related intracranial hemorrhage.
|
|
| 17. |
- Majeed, Ammar, et al.
(författare)
-
Optimal timing of vitamin K antagonist resumption after upper gastrointestinal bleeding
- 2017
-
Ingår i: Thrombosis and Haemostasis. - : MEDIZIN NATURWISSENSCHAFTEN. - 0340-6245 .- 2567-689X. ; 117:3, s. 491-499
-
Tidskriftsartikel (refereegranskat)abstract
- The optimal timing of vitamin K antagonists (VKAs) resumption after an upper gastrointestinal (GI) bleeding, in patients with continued indication for oral anticoagulation, is uncertain. We included consecutive cases of VKA-associated upper GI bleeding from three hospitals retrospectively. Data on the bleeding location, timing of VKA resumption, recurrent GI bleeding and thromboembolic events were collected. A model was constructed to evaluate the 'total risk', based on the sum of the cumulative rates of recurrent GI bleeding and thromboembolic events, depending on the timing of VKA resumption. A total of 121 (58%) of 207 patients with VKA-associated upper GI bleeding were restarted on anticoagulation after a median (interquartile range) of one (0.2-3.4) week after the index bleeding. Restarting VKAs was associated with a reduced risk of thromboembolism (HR 0.19; 95 % CI, 0.07-0.55) and death (HR 0.61; 95% CI, 0.39-0.94), but with an increased risk of recurrent GI bleeding (HR 2.5; 95% CI, 1.4-4.5). The composite risk obtained from the combined statistical model of recurrent GI bleeding, and thromboembolism decreased if VKAs were resumed after three weeks and reached a nadir at six weeks after the index GI bleeding. On this background we will discuss how the disutility of the outcomes may influence the decision regarding timing of resumption. In conclusion, the optimal timing of VKA resumption after VKA-associated upper GI bleeding appears to be between 3-6 weeks after the index bleeding event but has to take into account the degree of thromboembolic risk, patient values and preferences.
|
|
| 18. |
|
|
| 19. |
- Majeed, Ammar, et al.
(författare)
-
Thromboembolic safety and efficacy of prothrombin complex concentrates in the emergency reversal of warfarin coagulopathy
- 2012
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 129:2, s. 146-151
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:There is uncertainty regarding the efficacy and incidence of thromboembolic events in patients treated with prothrombin complex concentrates (PCC) for the emergency reversal of warfarin effect.METHODS:During 2002 to 2010 we prospectively included 160 patients treated with PCC for emergency reversal of warfarin either for bleeding or because of the need of emergency surgery. A possible relationship to PCC was considered if objectively verified thromboembolism occurred within 7days of PCC administration. Efficacy was adjudicated as good if the bleeding was controlled promptly or if the surgeon did not report excessive perioperative bleeding.RESULTS:We included 160 patients; 72% received PCC for bleeding. The median international normalized ratio (INR) before and after treatment with PCC was 3.5 (interquartile range [IQR] 2.6-5.4) and 1.4 (IQR 1.2-1.6). The mean dose of PCC was 1800IU (IQR 1200-2000). In addition to PCC, 74% of the patients received vitamin K and 34% received plasma. Six patients (3.8%; 95% confidence interval [CI], 1.4-8.0%) developed thromboembolic events (3 strokes, 1 myocardial infarction, 1 deep vein thrombosis, 1 splenic infarction), possibly related to PCC. The clinical efficacy was good in 146 (91%), moderate in 6 (4%), poor in 4 (2.5%) and non-evaluable in 4 patients.CONCLUSION:The administration of PCC for the emergency reversal of warfarin may be associated with a low risk of thromboembolism. The contribution of an unmasked thrombotic process by cessation of anticoagulation or of activation of coagulation by the hemorrhagic event should also be considered.
|
|
| 20. |
- Nilsson, Dag, et al.
(författare)
-
NXY-059 does not affect bleeding time in healthy volunteers : A randomized, double-blind, placebo-controlled, 3-period crossover phase I study
- 2007
-
Ingår i: Journal of clinical pharmacology. - : Wiley. - 0091-2700 .- 1552-4604. ; 47:2, s. 264-272
-
Tidskriftsartikel (refereegranskat)abstract
- NXY-059 is a novel free radical-trapping neuroprotectant that reduces infarct size and preserves brain function in animal models of acute ischemic stroke. It is the first neuroprotectant to demonstrate a reduction in global disability in a phase III clinical trial, as measured by the modified Rankin Scale. Any effect of NXY-059 on hemostasis may be important when treating stroke patients. This phase I randomized, double-blind, placebo-controlled, 3-period crossover study compared the effect of NXY-059, desmopressin, and placebo on bleeding time, platelet aggregation, and adhesion in 30 healthy volunteers. NXY-059 did not prolong bleeding time compared with placebo: mean (SD) time for NXY-059, 369.5 seconds (125.0 seconds) versus placebo, 369.1 seconds (136.0 seconds). There were no significant effects on platelet aggregation or adhesion. At a mean unbound plasma concentration (Cu-ss) of 335 mu mol/L, NXY-059 was well tolerated, with no major safety concerns identified. In conclusion, NXY-059 does not appear to affect primary hemostasis.
|
|
| 21. |
- Schulman, Sam, et al.
(författare)
-
A benefit-risk assessment of dabigatran in the prevention of venous thromboembolism in orthopaedic surgery
- 2011
-
Ingår i: Drug Safety. - : Springer Science and Business Media LLC. - 0114-5916 .- 1179-1942. ; 34:6, s. 449-463
-
Tidskriftsartikel (refereegranskat)abstract
- Dabigatran etexilate is a novel orally administered anticoagulant that exerts its action through reversible direct thrombin inhibition. This anticoagulant has been approved for prophylaxis against venous thromboembolism (VTE) after hip or knee arthroplasty, and in a few countries also for atrial fibrillation. This article reviews the efficacy and safety of dabigatran for the prophylaxis of VTE-indication compared with data on the most common current regimen with low-molecular-weight heparin (LMWH), specifically enoxaparin. Alternative prophylactic agents are also discussed. The results regarding efficacy and safety are very similar for dabigatran and LMWH. Bleeding and gastrointestinal reactions are the most frequently reported adverse events with a comparable incidence on LMWH and are probably the result of surgery and anaesthaesia. No adverse event that is specific for dabigatran has been observed in these studies, although dyspepsia has been reported as significantly more frequent than warfarin in long-term studies on other indications. The fact that dabigatran has no antidote has so far not been a problem in patients undergoing orthopaedic surgery. The use of the lower dose of dabigatran (150 mg) appears beneficial to reduce the risk of bleeding in patients over 75 years of age and in those with moderate renal impairment to avoid drug accumulation. The convenience of oral administration is an advantage for dabigatran over LMWH, particularly for extended prophylaxis up to 1 month after surgery. In conclusion, the benefit-risk profile of dabigatran is favourable for use as prophylaxis against VTE after major orthopaedic surgery with its convenient oral administration without need for laboratory monitoring and a low risk of bleeding or other adverse events.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Schulman, Sam, et al.
(författare)
-
New concepts in optimal management of anticoagulant therapy for extended treatment of venous thromboembolism
- 2006
-
Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 96:3, s. 258-266
-
Tidskriftsartikel (refereegranskat)abstract
- Recent trials on secondary prophylaxis after venous thromboembolism (VTE) have provided a wealth of data on the risk factors for recurrence and, to some extent, also for bleeding. Some of the results are consistent across the studies, but there are also conflicting data. Certain risk factors, such as pulmonary embolism versus deep vein thrombosis or presence of cardiolipin antibodies, have a more pronounced influence on the risk early in the course of disease. Others, such as hereditary thrombophilic defects, seem to gain importance over many years of follow-up. Therefore, it can be difficult to make decisions on an individual patient basis. In this article, data from important and illustrative trials have been extracted and compared and controversies highlighted. The conclusions drawn should help clinicians make balanced decisions on the optimal duration of anticoagulation after an episode of VTE.
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
