Anemia and bleeding in patients receiving anticoagulant therapy for venous thromboembolism.

In patients receiving anticoagulant therapy for venous thromboembolism (VTE), the important issue of anemia influence on the risk of bleeding has not been consistently studied. We used the large registry data RIETE (Registro Informatizado Enfermedad Tromboembólica) to compare the rate of major bleeding in patients receiving anticoagulant therapy for VTE according to the presence or absence of anemia at baseline. Patients with or without cancer were separately studied. Until August 2016, 63492 patients had been enrolled. Of these, 21652 (34%) had anemia and 14312 (23%) had cancer. Anemia was found in 57% of the patients with cancer and in 28% without (odds ratio 3.46; 95% CI 3.33-3.60). During the course of anticoagulant therapy, 680 patients with cancer had a major bleeding event (gastrointestinal tract 43%, intracranial 14%, hematoma 12%). Cancer patients with anemia had a higher rate of major bleeding (rate ratio [RR]: 2.52; 95% CI 2.14-2.97) and fatal bleeding (RR 2.73; 95% CI 1.95-3.86) than those without anemia. During the course of anticoagulation, 1133 patients without cancer had major bleeding (gastrointestinal tract 32%, hematoma 24%, intracranial 21%). Patients with anemia had a higher rate of major bleeding (RR 2.84; 95% CI 2.52-2.39) and fatal bleeding (RR 2.76; 95% CI 2.07-3.67) than those without. On a multivariable analysis, anemia independently predicted the risk for major bleeding in patients with and without cancer (hazard ratios: 1.66; 95% CI 1.40-1.96 and 1.95; 95% CI 1.72-2.20, respectively). During anticoagulation for VTE, both cancer- and non-cancer anemic patients had a higher risk for major bleeding than those without anemia. In anemic patients (with or without cancer), the rate of major bleeding during the course of anticoagulant therapy exceeded the rate of VTE recurrences. In patients without anemia the rate of major bleeding was lower than the rate of VTE recurrences.

Form of presentation, natural history and course of postoperative venous thromboembolism in patients operated on for pelvic and abdominal cancer. Analysis of the RIETE registry. / Forma de presentación, historia natural y evolución de la enfermedad tromboembólica venosa postoperatoria en pacientes operados por cáncer abdominal y pélvico. Análisis del registro RIETE.

INTRODUCTION: Venous thromboembolism (VTE) represents a serious complication after oncologic surgery. Recent studies have shown that the risk of VTE persists several weeks after surgery. This study assesses the form of presentation and time course of VTE after abdominal and pelvic cancer surgery. METHODS: Prospective, multicenter, observational study that analyzes data from an international registry (RIETE) that includes consecutive patients with symptomatic VTE. Our study assesses the form and time of presentation of postoperative VTE, as well as main outcomes, in patients operated for abdominopelvic cancer 8 weeks prior to VTE diagnosis. Variables related to the presentation of VTE after hospital discharge are identified. RESULTS: Out of the 766 analyzed patients with VTE, 395 (52%) presented pulmonary embolism (PE). Most VTE cases (84%) were detected after the first postoperative week, and 38% after one month. Among patients with VTE in the first postoperative week, 70% presented PE. VTE presented after hospital discharge in 54% of cases. Colorectal, urologic, and gynecologic tumors, the use of radiotherapy, and blood hemoglobin levels were independently associated with VTE diagnosis after hospital discharge. Complications (thrombosis recurrence, bleeding, and death) occurred in 34% of patients with VTE detected before hospital discharge, compared to 24% in VTE after hospital discharge (P<0.01). CONCLUSIONS: VTE occurs after hospital discharge in most patients, particularly in those operated for colorectal, urologic, and gynecologic cancer. Pulmonary embolism is more frequent in patients who develop early VTE, who also have worse prognosis.

Analysis of noncatheter-associated upper extremity deep venous thrombosis from the RIETE registry.

OBJECTIVE: We sought to determine the risk factors for subsequent bleeding and recurrent venous thromboembolism (VTE) events following isolated noncatheter-associated upper extremity deep venous thrombosis (non-CA-UEDVT) to better inform future treatment decisions for this group of patients. METHODS: The RIETE registry (Registro Informatizado de Enfermedad TromboEmbólica [Computerized Registry of Patients with Venous Thromboembolism]) is a prospective international registry of patients with objectively confirmed symptomatic VTE. Patients with a symptomatic, isolated, proximal UEDVT from March 2001 through March 2015 were analyzed. Any patient with an indwelling catheter or pacemaker lead at the DVT site and at the time of thrombosis was considered to have a CA-UEDVT and was excluded. Patient and treatment characteristics such as age, gender, comorbidities, VTE risk factors, treatment drug, and duration were collected. Outcomes examined included recurrent DVT, subsequent pulmonary embolism (PE), and hemorrhage. Multivariate analysis was performed using stepwise logistic regression. RESULTS: Of the 1100 patients who met the study criteria, 580 (53%) were male. The mean age of the patients was 50 ± 20 years, and overall patient survival at 1 year was 85%. Recurrent VTE occurred in 59 patients (5.4%). Of these, 46 patients (4%) had recurrent DVT, 10 (0.9%) had a PE following UEDVT diagnosis, and 3 (0.3%) had both. PE was fatal in three patients (0.3%). Bleeding occurred in 50 patients (4.5%), major bleeding in 19 patients (1.7%), and fatal bleeding in 6 patients (0.5%). On multivariate analysis, malignant disease was associated with VTE recurrence (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.04-3.45; P < .04), whereas hemorrhage was associated with age (OR, 1.03; 95% CI, 1.01-1.05; P = .002) and malignant disease (OR, 2.53; 95% CI, 1.34-4.76; P < .005). Hemorrhage and recurrent VTE were also significantly associated (OR, 2.79; 95% CI, 1.16-6.76; P < .03). CONCLUSIONS: PE following non-CA-UEDVT is rare. Malignant disease was associated with VTE recurrence. Age and malignant disease were associated with hemorrhage, and VTE recurrence was associated with hemorrhage. Further prospective studies should be undertaken to best determine length of anticoagulation treatment for the varied populations of patients with UEDVT.

A RIETE registry analysis of recurrent thromboembolism and hemorrhage in patients with catheter-related thrombosis.

BACKGROUND: Few studies have investigated the treatment and the outcomes of patients with catheter-related thrombosis (CRT). METHODS: The RIETE registry (Registro Informatizado de Enfermedad TromboEmbólica [Computerized Registry of Patients with Venous Thromboembolism]) is a prospective international registry of consecutive patients with objectively confirmed venous thromboembolism (VTE). We analyzed the characteristics, treatment, and outcomes of patients with CRT. RESULTS: Of 558 patients with CRT, 45 (8%) presented with a pulmonary embolism (PE) concomitantly. More patients had central line-associated thrombosis compared with port systems, but catheter type did not influence the risk of presenting with a PE. Patients with only CRT were more often prescribed low-molecular-weight heparin for the duration of their anticoagulant treatment compared with patients presenting with concomitant PE. VTE recurrences and major bleeding events occurred frequently during treatment with anticoagulation (7 per 100 patient-years and 8.9 per 100 patient years, respectively). The rates of fatal PE recurrences (1.85 per 100 patient-years) and fatal bleeding (2.32 per 100 patient-years) were similar. Patients with an additional transient risk factor for VTE had the lowest risk for VTE recurrences (odds ratio [OR], 0.07; 90% confidence interval [CI], 0.01-0.45) compared with patients with CRT and no additional transient risk factors. PE at presentation increased the risk of recurrent thrombosis by 2.4 times. Renal insufficiency was also an independent predictor of recurrent thrombosis (OR, 3.93; 90% CI, 2.0-7.7). The odds of recurrent thrombosis was decreased by 77% in patients who received anticoagulation therapy for >90 days compared with patients with a shorter treatment (OR, 0.23; 90% CI, 0.1-0.56). CONCLUSIONS: Concomitant PE occurs less frequently in CRT than lower extremity deep venous thrombosis, but it is associated with a worse outcome. CRT occurs in high-risk patients, and duration of anticoagulation must be predicated on balancing these risks.

Bemiparin in oncology.

An association between cancer and thrombosis has been recognized since 1865. It is considered to be a two-way association; cancer is associated with an increased risk of venous thromboembolism (VTE), whereas activation of the coagulation cascade enhances the proliferation, angiogenesis potential and metastasis of tumour cells. A sizeable proportion of VTE events in cancer patients undergoing major surgery occur after discharge from hospital, suggesting that extended thromboprophylaxis beyond the normal 7-10 days is warranted in these patients. Studies have demonstrated reduced incidences of VTE with extended thromboprophylaxis using low molecular weight heparins (LMWH) and guidelines recommend continuing thromboprophylaxis after discharge in patients who have undergone major cancer surgery, but the evidence is still considered limited and of low quality, and the recommendations have not been widely implemented in clinical practice. Extended prophylaxis with bemiparin was shown to reduce significantly the incidence of major VTE in patients undergoing major cancer surgery in the Cancer, Bemiparin and Surgery Evaluation study, providing further support for the routine use of extended thromboprophylaxis with LMWH in cancer patients. Heparins, particularly LMWH, in addition to preventing VTE in cancer patients, can block tumour cell growth, invasion, metastasis and angiogenesis. As with other LMWH, bemiparin and its ultra-low molecular weight derivative, RO-14, appear to be effective in preventing angiogenesis in in-vitro models. Recent clinical studies have demonstrated significant survival advantages when LMWH have been added to chemotherapy in cancer patients. This could be partly due, not only to the prevention of thromboembolic diseases in these patients, but also to 'direct' antineoplastic properties of LMWH. The survival benefits appeared greater in patients with limited cancer, especially limited small cell lung cancer. The Adjuvant Bemiparin in Small Cell Lung Cancer study is assessing the effect of bemiparin on survival in patients with limited small cell lung cancer, and although results are not yet available, preliminary data appear very promising.