Fatal bleeding is a serious consequence of anticoagulant therapy, but factors associated with fatal bleeding during the first 3 months of treatment of venous thromboembolism (VTE) are uncertain.
...Using data from RIETE, an ongoing registry of consecutive patients with acute VTE, we assessed risk factors for fatal bleeding among all patients. We then used this information to derive a clinical model that would stratify a patient's risk of fatal bleeding during the first 3 months of treatment.
Of 24 395 patients, 546 (2.24%) had a major bleed and 135 (0.55%) had a fatal bleed. The gastrointestinal tract was the most common site (40% of fatal bleeds), followed by intracranial bleeding (25%). Fatal bleeding was independently associated with the following factors at the time of VTE diagnosis: age >75 years (OR, 2.16), metastatic cancer (OR, 3.80), immobility > or = 4 days (OR, 1.99), a major bleed within the past 30 days (OR, 2.64), an abnormal prothrombin time (OR, 2.09), a platelet count < 100 x 10(9) L(-1) (OR, 2.23), creatinine clearance < 30 mL min(-1) (OR, 2.27), anemia (OR, 1.54), and distal deep vein thrombosis (OR, 0.39). INR at the time of bleeding is not known. A clinical prediction rule for risk of fatal bleeding that included nine baseline factors was derived. Fatal bleeding occurred in 0.16% (95% CI, 0.11-0.23) of the low-risk, 1.06% (95% CI, 0.85-1.30) of the moderate-risk, and 4.24% (95% CI, 2.76-6.27) of the high-risk category.
Patient characteristics and laboratory variables can identify patients at high risk for fatal bleeding during treatment of VTE.
We conducted a prospective, noncomparative, multicenter study to assess the safety and efficacy of doxycycline and netilmicin in the treatment of human brucellosis. The study included 64 patients who ...had acute brucellosis without endocarditis or neurobrucellosis. The treatment schedule consisted of the administration of 100 mg of doxycycline (or 5 mg/kg·d if body weight ⩽40 kg) twice a day orally for 45 days, plus 300 mg of netilmicin (6 mg/kg·d if body weight ⩽50 kg) intramuscularly once daily for 7 days. Therapeutic failure was noted in 5 patients (7.7%; 95% confidence interval CI, 2.5%–17.1%), of whom 2 had spondylitis, 1 had sacroiliitis, and 1 had a splenic abscess that required splenectomy. Relapse was noted in eight patients (12.5%; 95% CI, 5.6%–23.2%). When relapse was considered in combination with initial lack of efficacy, 13 patients (21.9%; 95% CI, 12.3%–33.9%) failed to respond to therapy. Fifteen patients (23%; 95% CI, 13.5%–35.2%) had adverse effects, and one patient (1.5%) had a treatment-limiting adverse effect. Combination therapy with netilmicinldoxycycline may be effective in treating acute brucellosis. However, prospective controlled trials must confirm these results.
Patients with major bleeding who subsequently develop clinically apparent venous thromboembolism (VTE) present a particularly difficult therapeutic dilemma.
RIETE is a prospective registry of ...consecutive patients with symptomatic, objectively confirmed, acute VTE. We retrospectively studied those who had experienced recent major bleeding (<30 days prior to VTE) to assess the influence of the site of bleeding and the time elapsed to VTE on their 3 month outcome.
Of 12,294 patients enrolled up to July 2005, 306 (2.5%) had recent major bleeding: gastrointestinal (GI) tract, 116 (38%); intracranial, 94 (31%); other, 96 (31%). During the study period, 19 patients 6.2%; 95% confidence interval (CI) 3.5-8.9 with recent bleeding rebled (eight died): 13 of them (68%) during the first 2 weeks. Multivariate analysis confirmed that patients with recent GI bleeding had an increased risk for both major rebleeding (hazard ratio 2.8; 95% CI 1.4-5.3) and death (hazard ratio 1.9; 95% CI 1.2-3.1) compared to those with no recent bleeding. Those who bled in other sites had an increased risk only for death (hazard ratio 2.0; 95% CI 1.2-3.3). An elapsed time of <2 weeks from bleeding to the index VTE event was also associated with an increased risk for major rebleeding (hazard ratio 2.4; 95% CI 1.2-5.0) and death (hazard ratio 2.8; 95% CI 1.8-4.5).
The incidence of new bleeding or death depends on the site of prior bleeding and the time elapsed until VTE. This information may help to identify the best therapeutic approach for these high-risk patients.
Brucellosis is a common zoonosis in many parts of the world; the best regimen for the treatment of brucellosis has not been clearly determined. We have carried out a multicenter, open, controlled ...trial in five general hospitals in Spain to compare the efficacy and safety of doxycycline and rifampin (DR) versus doxycycline and streptomycin (DS) for the treatment of human brucellosis. The study included 194 ambulatory or hospitalized patients with acute brucellosis, without endocarditis or neurobrucellosis. The diagnostic criterion was isolation of Brucella species from blood or other tissues (n = 120) or a standard tube agglutination titer of 1/160 or more for anti-Brucella antibodies with compatible clinical findings (n = 74). Patients were randomly assigned to receive either 100 mg of doxycycline twice daily plus rifampin, 900 mg/day, in a single morning dose for 45 days (DR group) or the same dose of doxycycline for 45 days plus streptomycin, 1 g/day, intramuscularly for 14 days (DS group). A lack of therapeutic efficacy developed in 8 of the 100 patients in the DR group (8%) and in 2 of the 94 patients in the DS group (2%) (P = 0.10). Relapses occurred in 16 of the 100 patients in the DR group (16%) but in only 5 of the 94 patients in the DS group (5.3%) (P = 0.02). When relapse was considered in combination with initial lack of efficacy, 26 patients in the DR group (24%) and 7 patients in the DS group (7.45%) failed to respond to therapy (P = 0.0016). In general, therapy was well tolerated, and only four patients (4%) in the DR group and two (2%) in the DS group had episodes of adverse effects necessitating discontinuation of treatment (P > 0.2). We conclude that a doxycycline-and-rifampin regimen is less effective than the doxycycline-and-streptomycin regimen in patients with acute brucellosis.
Background: The biologic agents causing leukoaraiosis are unknown. Our aim was to study the genetic basis of leukoaraiosis.
Methods: We analyzed 212 single nucleotide polymorphisms (SNPs) in 142 ...patients with ischaemic stroke, generating a total of 30 104 genotypes. Seventy‐nine subjects (55.6%) presented leukoaraiosis measured by the Fazekas scale and 69 (48.6%) by ARWMC scale. We analyzed the presence of synergic associations between SNPs using the hfcc software. Finally, functional studies were performed in 56 subjects. The Ingenuity Pathways software (ipa) was used to examine the role of the identified genes.
Results: Six SNPs were associated with leukoaraiosis using both measuring scales. After logistic regression adjusted for leukoaraiosis risk factors, the rs2252070 of MMP13 (OR = 4.9, 95%CI: 1.34–17.9, P = 0.016), rs662 of PON1 (OR = 0.37, 95%CI: 0.15–0.87, P = 0.024) and rs1800779 of NOS3 (OR = 3.9, 95%CI: 1.38–11.38, P = 0.01) were independently associated with leukoaraiosis under a dominant/recessive model and the rs2290608 of IL5RA (OR = 0.46, 95%CI: 0.25–0.85, P = 0.013) and rs669 of A2M (OR = 2.5, 95%CI: 1.36–4.83, P = 0.004) under an additive model. Computational analysis showed a synergic association of rs10497212‐AA of ITGB6 and rs2290608‐GG of IL5RA with leukoaraiosis using both scales. (i) ARWMC (P = 1.3 × 10−4) and (ii) Fazekas (P = 4.5 × 10−5). Functional studies showed that the rs669 SNP was associated with plasma levels of A2M (P = 0.012) and A2M levels with leukoaraiosis in Fazekas scale (P = 0.02). ipa analysis revealed that the genes associated with leukoaraiosis were involved in blood–brain barrier (BBB) homeostasis.
Conclusions: Amongst patients with ischaemic stroke, several genes associated with BBB homeostasis could be involved with a higher risk of leukoaraiosis.
To asses the association of acute reactants and interleukin 6 and 8 (IL-6 & IL-8) at diagnosis of venous thromboembolic disease (VTD) and clinical outcome.
100 patients were diagnosed of VTD by image ...tests. Acute reactants (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen), D-dimer and IL-6 and IL-8 we measured at the moment of diagnosis. We made a 12 month follow-up of these patients to notice any clinical evolution outcomes (recurrences, bleeding, post-phlebitic syndrome, death).
IL-6 was increased in 9 patients and IL-8 in 3. The risk factors, time to diagnosis and pulmonary embolism rate were similar in both interleukin groups (normal and high levels). Fibrinogen levels were significantly increased in high IL-6 group (585 +/- 179 vs. 485 +/- 154 mgr/dl; p = 0.05). During follow-up there were 5 deaths, 3 recurrences, 11 bleedings and 43 postphlebitic syndromes. Normal ESR level was associated to postphlebitic syndrome (17.8 +/- 14.5 vs. 31.4 +/- 27.4 mm/1st h; p = 0.016). Patients who had high levels of IL-6 had worse survival than these with normal levels (p = 0.015).
IL-6, ESR, and CPR at diagnosis of VTD could be useful to identified patients with higher risks of death and postphlebitic syndrome during the first year after diagnosis.
Objectives: Registro Informatizado de Enfermedad TromboEmbólica (RIETE) database was used to investigate whether neurosurgical patients with venous thromboembolism (VTE) were more likely to die of ...bleeding or VTE and the influence of anticoagulation on these outcomes. Methods: Clinical characteristics, treatment details, and 3-month outcomes were assessed in those who developed VTE after neurosurgery. Results: Of 40 663 patients enrolled, 392 (0.96%) had VTE in less than 60 days after neurosurgery. Most patients in the cohort (89%) received initial therapy with low-molecular-weight heparin, (33% received subtherapeutic doses). In the first week, 10 (2.6%) patients died (8 with pulmonary embolism PE, no bleeding deaths; P = .005). After the first week, 20 (5.1%) patients died (2 with fatal bleeding, none from PE). Overall, this cohort was more likely to develop a fatal PE than a fatal bleed (8 vs 2 deaths, P = .058). Conclusions: Neurosurgical patients developing VTE were more likely to die from PE than from bleeding in the first week, despite anticoagulation.
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