Thromb Haemostasis
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Multicenter Study Clinical Trial
Safety and efficacy of sucrose-formulated full-length recombinant factor VIII: experience in the standard clinical setting.
The safety of full-length sucrose-formulated recombinant factor VIII (rFVIII-FS; Kogenate FS) for up to 24 months of use was evaluated in a postmarketing observational study in Europe. Long-term safety and efficacy data were available for 212 patients with severe haemophilia A, including 13 previously untreated patients (PUPs) and 12 patients with 1-19 exposure days (EDs). Patients accumulated a mean (+/- SD) of 187 (121) EDs to rFVIII-FS and received a total of 39,627 infusions, mainly for prophylaxis and for the treatment of 4,283 spontaneous or trauma-related bleeds during an average observation time of 710 (136) days. ⋯ Four of the five patients who reported possible drug-related adverse effects developed inhibitors. The results of this observational study demonstrate the efficacy and safety of rFVIII-FS during normal clinical use in the treatment of patients with severe haemophilia A. Furthermore, these findings are consistent with those of previous phase III clinical studies with rFVIII-FS, particularly with regard to its efficacy and low incidence of inhibitor formation.
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Multicenter Study
Further validation and simplification of the Wells clinical decision rule in pulmonary embolism.
The Wells rule is a widely applied clinical decision rule in the diagnostic work-up of patients with suspected pulmonary embolism (PE). The objective of this study was to replicate, validate and possibly simplify this rule. We used data collected in 3,306 consecutive patients with clinically suspected PE to recalculate the odds ratios for the variables in the rule, to calculate the proportion of patients with PE in the probability categories, the area under the ROC curve and the incidence of venous thromboembolism during follow-up. ⋯ The venous thromboembolism incidence at three months in the group of patients with a Wells score < or = 4 and a normal D-dimer was 0.5%, versus 0.3% with a modified rule and 0.5% with a simplified rule. The proportion of patients safely excluded for PE was 32%, versus 31% and 30%, respectively. This study further validates the diagnostic utility of the Wells rule and indicates that the scoring system can be simplified to one point for each variable.
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Clinical Trial
Increased thrombin generation and fibrinogen level after therapeutic plasma transfusion: relation to bleeding.
In a clinical setting, fresh frozen plasma (FFP) is transfused to diluted patients with complicated surgery or trauma, as guided by prolonged conventional coagulation times or low fibrinogen levels. However, the limited sensitivity of these coagulation tests may restrict their use in measuring the effect of transfusion and hence predicting the risk of perioperative bleeding. We used the more sensitive, calibrated automated thrombogram (CAT) method to evaluate the result of therapeutic FFP transfusion to 51 patients with dilutional coagulopathy. ⋯ Plasmas from 15 of the 19 patients with ongoing bleeding were markedly low in either thrombin generation or fibrinogen level. We conclude that the thrombin generation method detects improved haemostatic activity after plasma transfusion. Furthermore, the data suggest that thrombin generation and fibrinogen are independent determinants of the risk of perioperative bleeding in this patient group.
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Clinical Trial
Fondaparinux for the treatment of patients with acute heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) is a life-threatening immune response to heparin that is associated with a high risk of thromboembolic complications. We prospectively treated seven subjects with acute HIT with fondaparinux and compared the results to a similar historical control population from the same hospital. Six of the seven fondaparinux-treated subjects were transitioned to warfarin, beginning after platelet count recovery occurred. ⋯ No new thromboembolic complications or major bleeds occurred but limb gangrene occurred in four controls. The development of limb gangrene in the historical controls may have been a result of delayed recognition of HIT and/or inappropriately early institution of warfarin in the historical controls. This pilot study suggests that fondaparinux may be useful in patients with acute HIT.
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We sought to assess the effect of clopidogrel on in-hospital events in unselected patients with acute ST elevation myocardial infarction (STEMI). In a retrospective analysis of consecutive patients enrolled in the Acute Coronary Syndromes (ACOS) registry with acute STEMI we compared outcomes of either adjunctive therapy with aspirin alone or aspirin plus clopidogrel within 24 hours after admission. A total of 7,559 patients were included in this analysis, of whom 3,541 were treated with aspirin alone, and 4,018 with dual antiplatelet therapy. ⋯ There was a significant increase in major bleeding complications with clopidogrel (7.1% vs. 3.4%, p<0.001). In clinical practice early adjunctive therapy with clopidogrel in addition to aspirin in patients with STEMI is associated with a significant reduction of in-hospital MACCE regardless of the initial reperfusion strategy. This advantage was associated with an increase in major bleeding complications.