Reversal of rivaroxaban-induced alterations on hemostasis by different coagulation factor concentrates ­ in vitro studies with steady and circulating human blood.

BACKGROUND: Despite the good safety of rivaroxaban, there is limited information on strategies for urgent reversal of its antihemostatic effects. METHODS AND RESULTS: Alterations of hemostasis induced by rivaroxaban (230 ng/ml) were assessed by using several tests applied to steady and circulating human blood. Effects on thrombin generation (TG) and thromboelastometry (TEM) parameters were measured. Modifications in platelet adhesive, aggregating and procoagulant activities were evaluated in studies with circulating blood. The potential reversal of prothrombin complex concentrates (PCCs; 50 IU/kg), activated PCCs (aPCCs; 75 IU/kg), or recombinant factor VIIa (rFVIIa; 270 µg/kg) was evaluated. Impairment of TG parameters induced by rivaroxaban were corrected by the different concentrates (aPCC≥PCC>rFVIIa). Prolonged clotting times and reduced clot firmness caused by rivaroxaban on TEM tests were improved by different concentrates (rFVIIa≥aPCC>PCC). Rivaroxaban significantly reduced platelets and fibrin interactions with damaged vascular surfaces in perfusion studies. While alterations of platelet interactions were favourably counteracted by rFVIIa or aPCCs, reductions in fibrin formation were only partially restored by the different factor concentrates (rFVIIa>aPCC≥PCC). CONCLUSIONS: Rivaroxaban-induced alterations on coagulation parameters measured through assays performed under static conditions were easily reversed by the different concentrates. Studies under flow conditions revealed that these concentrates normalized the action of rivaroxaban on platelets, and significantly improved fibrin formation; although in the later case, levels were not restored to the pre-treatment value.

Fever and deep venous thrombosis. Findings from the RIETE registry.

Fever is a presenting sign in some patients with acute deep venous thrombosis (DVT), but its influence on outcome has not been thoroughly investigated. RIETE is an ongoing, international, observational registry of consecutive patients with symptomatic, objectively confirmed, acute venous thromboembolism. The aim of the present study was to assess the prevalence of fever in patients with acute DVT, and to compare their outcome during the first month of therapy, according to the presence or absence of fever. As of September 2009, 14,480 patients with symptomatic DVT have been enrolled in RIETE. Of these, 707 (4.9%) had fever at presentation. During the 30-day study period, 448 patients (3.1%) died, 171 (1.2%) developed DVT recurrences, 376 (2.6%) had pulmonary embolism, and 384 (2.6%) had a major bleeding. Patients initially presenting with fever had a higher mortality (5.8% vs. 2.9%; odds ratio: 2.6; 95% CI 1.9-3.5) than those without fever. Among the causes of death, pulmonary embolism (0.7% vs. 0.1%) and infection (1.1% vs. 0.3%) were significantly more common in patients presenting with fever. Multivariate analysis confirmed that DVT patients with fever had an increased mortality (hazard ratio: 2.00; 95% CI 1.44-2.77) irrespectively of the patient's age, body weight, and risk factors for VTE. Fever is not uncommon in patients with DVT, and carries a worse outcome.

Prior thromboprophylaxis and outcome in patients experiencing acute venous thromboembolism after an acute medical illness.

BACKGROUND: Even despite the use of thromboprophylaxis, some patients with an acute medical illness develop symptomatic venous thromboembolism (VTE). It is unclear whether the outcome in these patients is different in those in whom prophylaxis was not prescribed. PATIENTS AND METHODS: We used the RIETE (Registro Informatizado Enfermedad TromboEmbolica) database to compare the 3-month outcome (death, fatal pulmonary embolism, VTE recurrences, major bleeding) of patients with acute VTE after immobilization for an acute medical disease, according to the use of prophylaxis. RESULTS: Thromboprophylaxis was prescribed in 1313 (37%) of the 3527 patients included in August 2014. Acute infection was the most frequent cause of immobilization. Patients who received prophylaxis were more frequently immobilized in hospital than at home (70% vs. 22%), and fewer patients were immobilized for cancer (13% vs. 22%). During the first 3months of treatment, the rates of all-cause death (23 vs. 21%), fatal PE (2.6 vs. 3.1%), VTE recurrences (2.4% vs. 2.8%), and major bleeding (4.2% for both) did not differ between the two groups. Thromboprophylaxis was not associated with each outcome in multivariate analysis. CONCLUSIONS: The outcome in patients with VTE provoked by medical immobilization was not influenced by the use of thromboprophylaxis during the period of immobility.

[Factors predicting a short length of stay for acute exacerbations of chronic obstructive pulmonary disease]. / Factores predictivos de un ingreso corto en pacientes con enfermedad pulmonar obstructiva crónica agudizada.

BACKGROUND AND OBJECTIVE: We intended to identify the factors predicting a short length of stay in patients with chronic obstructive pulmonary disease (COPD) and acute exacerbations in order to select those who are tributary to be admitted in a short stay unit. PATIENTS AND METHOD: Several clinical and biochemical characteristics were compared in a group of patients with COPD admitted in a short stay unit during an acute exacerbation, classified as lasting 4 days or > 4 days of hospital stay. RESULTS: A comorbidity index of 2 [1-2] vs 3 [2-3.5], a number of breaths per minute of 29.0 (6.5) vs 33.6 (6.8) and a pCO2 value on admission of 39.1 (5.3) vs 50.7 (12.0) mmHg were factors independently associated with a shorter stay (p < 0.001 in all). CONCLUSIONS: Some clinical characteristics of COPD patients are predictive of a short length of stay during acute exacerbations.

Coagulation Factor Concentrates Fail to Restore Alterations in Fibrin Formation Caused by Rivaroxaban or Dabigatran in Studies With Flowing Blood From Treated Healthy Volunteers.

We evaluated the hemostatic alterations in blood from healthy individuals treated for 5 days with direct oral anticoagulants (DOACs) rivaroxaban (20 mg/d) or dabigatran (150 mg/12 h) in a single-blind clinical trial with crossover assignment (NCT01478282). We assessed the potential of prothrombin complex concentrates, activated prothrombin complex concentrates, or recombinant activated factor VII, when added ex vivo, to reverse the alterations caused by these DOACs. Blood was drawn at maximum plasma concentration after the last dose of each DOAC, and modifications in coagulation biomarkers were evaluated using a series of tests performed under steady conditions including routine coagulation, thrombin generation, and thromboelastometry assays. Additional studies in standardized flow devices were applied to evaluate alterations on platelet deposition and fibrin formation on damaged vascular surfaces exposed to flowing blood. Both DOACs caused important modifications of all coagulation biomarkers and significantly reduced fibrin formation in flow studies. Alterations in biomarkers observed in steady laboratory tests were normalized and occasionally overcompensated by procoagulant strategies. In contrast, reductions in fibrin formation observed in studies with flowing blood were improved, although never completely restored to baseline levels. Effects of dabigatran in flow studies appeared more resistant to reversal strategies than those of rivaroxaban. Inconsistencies between results of coagulation studies in steady or flowing assays not only raise concerns about the adequacy of the earlier tests to predict the restoration of the coagulopathy induced by DOACs but also suggest limitations of nonspecific procoagulant strategies to control severe coagulopathy in patients inadvertently overexposed these agents.

[Appropriateness of hospitalization in a short stay unit of a teaching hospital. A controlled study]. / Adecuación de la hospitalización en una unidad de estancia corta de un hospital universitario. Un estudio controlado.

BACKGROUND AND OBJECTIVE: Our aim was to evaluate the rate and the reasons for inappropriate hospital use in a medical Short Stay Unit (SSU) in comparison with conventional hospitalization. PATIENTS AND METHOD: The Appropriateness Evaluation Protocol was applied to 352 patients admitted in the SSU and to 203 patients admitted in a department of internal medicine (control group). RESULTS: The rates of inappropriate hospital admissions (0.6% vs 3%; p = 0.023) and stays (6.9% vs 18.7%; p < 0.001) were significantly lower in the SSU with respect to the control group. Main causes of inappropriateness were also lower: conservative physician's attitude (9.4% vs 41.4%; p = 0.001), delay in diagnostic procedures (3.4% vs 11.3%; p < 0.001), and social and familiar factors (2.8% vs 9.4%; p = 0.001). CONCLUSIONS: A SSU is useful for the appropriateness of hospital use, due to its capacity to minimize the number and causes of inappropriate stays.

Sex differences in patients receiving anticoagulant therapy for venous thromboembolism.

In patients with venous thromboembolism (VTE), the outcome during the course of anticoagulant therapy may differ according to the patient's sex. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of VTE recurrences, major bleeding, and mortality due to these events according to sex.As of August 2013, 47,499 patients were enrolled in RIETE, of whom 24,280 (51%) were women. Women were older, more likely presented with pulmonary embolism (PE), and were more likely to have recent immobilization but less likely to have cancer than men. During the course of anticoagulation (mean duration: 253 d), 659 patients developed recurrent deep vein thrombosis (DVT), 576 recurrent PE, 1368 bled, and 4506 died. Compared with men, women had a lower rate of DVT recurrences (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.67-0.91), a similar rate of PE recurrences (HR: 0.98; 95% CI: 0.83-1.15), a higher rate of major bleeding (HR: 1.21; 95% CI: 1.09-1.35), and higher mortality due to PE (HR: 1.24; 95% CI: 1.04-1.47). On multivariable analysis, any influence of sex on the risk for recurrent DVT (HR: 0.88; 95% CI: 0.75-1.03), major bleeding (HR: 1.10; 95% CI: 0.98-1.24), or fatal PE (HR: 1.01; 95% CI: 0.84-1.22) was no longer statistically significant.In conclusion, women had fewer DVT recurrences and more bleeds than men during the course of anticoagulation. These differences were not due to sex, but very likely to other patient characteristics more common in female patients and differences in treatment choice.

Prothrombotic platelet phenotype in major depression: downregulation by antidepressant treatment.

BACKGROUND: Serotonergic mechanisms have been suggested as a link between major depression and cardiovascular risk. We investigated the existence of a prothrombotic condition in depressed patients and its possible modulation during treatment with a selective serotonin-reuptake inhibitor (SSRI). METHODS: Modifications in a series of biomarkers of platelet and coagulation activation were evaluated in blood from 19 patients with a major depression disorder (MDD) at the time of diagnosis, and at 8 and 24 weeks of treatment with escitalopram. Response of blood aliquots recirculated through a thrombogenic surface was assessed in a thrombosis model. Results were compared with those of 20 healthy-matched controls. RESULTS: In comparison with controls, platelets from MDD patients showed elevated volumes (p<0.01), significantly enhanced aggregating response to arachidonic acid and augmented expression of GPIb, fibrinogen, factor V, and anionic phospholipids by flow cytometry (p<0.05). Clot firmness and procoagulant activity of platelet-associated tissue factor were also significantly elevated (p<0.05). Studies with circulating blood revealed increased fibrin formation in early diagnosed patients (71.1±9.5% vs. 45.8±5.3%; p<0.05 vs. controls). After 24 weeks of treatment with escitalopram, the majority of the alterations observed were normalized, except for a residual increased expression of GPIIbIIIa (p<0.05) and persistent alterations in thromboelatometic parameters. LIMITATIONS: Despite the reduced number of followed-up patients our findings were consistent reaching statistical significance. CONCLUSIONS: Our results reveal a prothrombotic phenotype in MDD patients. While continuous treatment with an SSRI downregulated the majority of the biomarkers analyzed, alterations in viscoelastic parameters of clot formation remained unaffected by the antidepressant treatment.

Comunicación urgente del laboratorio de anemias potencialmente graves en pacientes ambulatorios / Urgent laboratory notifications on potential serious anemias in outpatients

Introducción. La notificación urgente al clínico del diagnóstico de laboratorio de anemias potencialmente graves en pacientes ambulatorios puede influir en la decisión de derivación de estos pacientes a los servicios de urgencias. Material y métodos. Mediante un protocolo basado en pruebas de laboratorio de hematología y bioquímica habitual, se procedió al diagnóstico en el mismo día de la extracción de la muestra de todas las anemias con hemoglobina (Hb) inferior a 80g/l durante un año. En el mismo día se informó al clínico del diagnóstico de la anemia y del valor de la Hb (grupo de estudio) o únicamente del valor de la Hb (grupo control). Resultados. Se envió a urgencias a 18 de 89 pacientes del grupo de estudio (20%) y a 42 de 91 pacientes del grupo control (46%) (p=0,0003). Los pacientes enviados a urgencias del grupo de estudio tenían una Hb de 69±1,1g/l y los del grupo control de 60±1,0g/l (p<0,001). Conclusiones. La comunicación urgente al clínico del diagnóstico de laboratorio de anemias potencialmente graves facilita la adecuada derivación a urgencias de los pacientes ambulatorios en comparación con la comunicación aislada del valor de la Hb (AU)

Introduction. Urgent notification to clinicians of the laboratory diagnosis of potentially serious anaemias in outpatients may influence the decision to refer these patients to emergency units. Material and methods. Using a protocol based on routine haematology and biochemical lab analyses, we made, on the same day the sample was obtained, the diagnosis of any anaemia with a Hb<80g/L, over one year. The clinician was informed of the anaemia diagnosis and the Hb value on the same day (study group) or the Hb value only (control group). Results. A total of 18 of the 89 (20%) patients in the study group and 42 of the 91 (46%) patients in the control group were referred to emergency units (P=0.0003). Patients from the study group who were sent to emergency units had a Hb of 69±1.1g/L, while those of the control group had a Hb of 60±1.0g/L (P<0.001). Conclusions. Urgently notifying the clinician of the laboratory diagnosis of potentially serious anaemias makes referrals of outpatients to emergency units easier compared to the communication of the Hb value only (AU)

Factores predictivos de un ingreso corto en pacientes con enfermedad pulmonar obstructiva crónica agudizada / Factors predicting a short lenght of stay for acute exacerbations of chronic obstructive pulmonary disease

Fundamento y objetivo: Identificar los factores predictivos de una estancia hospitalaria más reducida en pacientes con enfermedad pulmonar obstructiva crónica (EPOC) agudizada, con el fin de seleccionar a aquellos tributarios de ingreso en una unidad de estancia corta. Pacientes y método: Se compararon diversos aspectos clínicos en un grupo de pacientes con EPOC agudizada que habían permanecido ingresados 4 días o menos, respecto a otro grupo de ingreso más prolongado. Resultados: El índice de comorbilidad (2 [extremos: 1-2] frente a 3 [extremos: 2-3,5]), el número de respiraciones/min (media [desviación estándar] de 29,0 [6,5] frente a 33,6 [6,8]) y la presión arterial de anhídrido carbónico en el momento del ingreso (media de 39,1 [5,3] frente a 50,7 [12,0] mmHg) se relacionan de forma independiente con una hospitalización de más corta duración (p < 0,001, en ambos casos). Conclusiones: Algunas características clínicas permiten identificar a los pacientes con EPOC agudizada que requieren un ingreso hospitalario corto

Background and objective: We intended to identify the factors predicting a short length of stay in patients with chronic obstructive pulmonary disease (COPD) and acute exacerbations in order to select those who are tributary to be admitted in a short stay unit. Patients and method: Several clinical and biochemical characteristics were compared in a group of patients with COPD admitted in a short stay unit during an acute exacerbation, classified as lasting 4 days or > 4 days of hospital stay. Results: A comorbidity index of 2 [1-2] vs 3 [2-3.5], a number of breaths per minute of 29.0 (6.5) vs 33.6 (6.8) and a pCO2 value on admission of 39.1 (5.3) vs 50.7 (12.0) mmHg were factors independently associated with a shorter stay (p < 0.001 in all). Conclusions: Some clinical characteristics of COPD patients are predictive of a short length of stay during acute exacerbations