Long term treatment Martinez Zapata 2017Results from a systematic review and meta-analysis found that both short- and long-term treatments with tinzaparin were found to be superior to vitamin K antagonists for avoiding recurrences of venous thromboembolism (VTE). Tinzaparin was associated with a significantly lower risk of recurrent VTE at the end of treatment and at longest follow-up. Tinzaparin also showed a lower risk of clinically relevant non-major bleeding at the end of treatment. No significant between-treatment differences were found for all-cause mortality or fatal and non-fatal major bleeding events.

Patients with cancer are at increased risk of recurrent VTE and bleeding. This makes long-term treatment with anticoagulants for secondary prevention challenging. Multiple factors have been reported to increase the risk of venous thrombosis in patients with cancer including chemotherapy, use of erythropoietin agents, and use of certain anticancer therapies such as thalidomide, high-dose steroids, and antiangiogenic therapy. In addition, the risk of VTE is higher in patients with coexisting chronic medical illnesses. Moreover, the risk of recurrent VTE seems to be higher in patients with metastatic versus localized malignancy. It has also been reported that the risk of recurrence is increased by factors such as interim hospitalizations, central venous catheter, and respiratory infection. A meta-analysis of 5 randomized controlled trials (RCTs) in patients with and without cancer found that tinzaparin may be a valuable option for long-term VTE treatment in patients who have a contraindication for vitamin K antagonists or when monitoring is difficult. The objective of this review was to evaluate current evidence on the safety and clinical efficacy of tinzaparin for VTE treatment in patients with cancer.

In this analysis 3 open-label RCTs evaluating 1.169 patients with cancer were included. Subcutaneous tinzaparin (175 IU/kg) was compared with oral anticoagulants or any other heparin for at least 3 months after an episode of acute deep vein thrombosis (DVT), pulmonary embolism (PE), and underlying malignancy of any type. Pooled data from all 3 trials demonstrated that tinzaparin was associated with a significantly lower risk of recurrent VTE at the end of treatment (relative risk [RR], [95% confidence interval] 0.67 [0.46-0.99]) and at longest follow-up (RR: 0.58 [0.39-0.88]) and showed a lower risk of clinically relevant non-major bleeding at the end of treatment (RR: 0.71 [0.51-1.00]). No significant between-treatment differences were found for all-cause mortality (RR: 1.09 [0.91-1.30]) or fatal and non-fatal major bleeding events (RR: 1.06 [0.56-1.99]).

In conclusion, this retrospective review demonstrated a risk reduction of recurrent symptomatic VTE in patients with cancer-associated thrombosis managed with long-term tinzaparin compared to vitamin K antagonist therapy. It also showed that tinzaparin and vitamin K antagonist therapy have a similar effect on all-cause mortality, on major (fatal and non-fatal) bleeding, clinically relevant non-major bleeding, minor bleeding, and recurrent symptomatic PE. However, the overall quality of the available evidence was deemed moderate. This suggests the need for more confirmatory trials, especially with a longer follow-up.

Reference

Martinez-Zapata MJ, Mathioudakis AG, Mousa SA, et al. Tinzaparin for long-term treatment of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. Am J Med 2017;130:337-347.


Once vs twice Trujillo Santos Thromb Haem 2017In patients with acute venous thromboembolism (VTE), it is uncertain whether enoxaparin should be administered twice or once daily. A single daily injection of low-molecular-weight heparin (LMWH) is more convenient for people and may optimize home therapy. However, twice daily administration may result in a more stable level of anticoagulation with fewer complications. Therefore, a comparison was made between 15- and 30-day outcomes in VTE patients on enoxaparin twice versus once daily.

The study included 4.730 patients of which 3.786 (80%) received enoxaparin twice daily and 944 once daily. The RIETE Registry data was used to compare the 15- and 30-day rates of VTE recurrence, major bleeding and death between patients receiving enoxaparin twice daily and those receiving it once daily. The propensity score matching was used to adjust for confounding variables.

During the first 15 days, patients treated with enoxaparin once daily had a trend towards more VTE recurrences (odds ratio [OR], 1.79), fewer major bleeds (OR, 0.42) and fewer deaths (OR, 0.32) compared to patients treated twice daily. At day 30, patients on enoxaparin once daily had more VTE recurrences (OR, 2.5), fewer major bleeds (OR, 0.40) and fewer deaths (OR, 0.58; 0.33–1.00). On propensity analysis, patients on enoxaparin once daily had fewer major bleeds at 15 (hazard ratio [HR], 0.30) and at 30 days (HR, 0.16) and also fewer deaths at 15 (HR, 0.37) and at 30 days (HR, 0.19) compared to patients on enoxaparin twice daily.

This lower bleeding rate in patients treated with enoxaparin once daily may be because they received lower daily doses (151.5 ± 15.4 IU kg-1 day-1) than patients treated twice daily (195.6 ± 16.5 IU kg-1 day-1). Certainly, patients receiving once daily enoxaparin had a higher rate of VTE recurrences, although these differences disappeared on multivariable analysis. Most importantly, the mortality rate at 15 and at 30 days was significantly lower in patients treated with enoxaparin once daily. Results of this study confirmed that enoxaparin prescribed once daily results in fewer major bleeds and deaths than enoxaparin twice daily, as suggested in a meta-analysis of controlled clinical trials.

Reference

Trujillo-Santos J, Bergmann JF, Bortoluzzi C, et al. Once versus twice daily enoxaparin for the initial treatment of acute venous thromboembolism. J Thromb Haemost 2017;15(3):429-438.


Meta analysis Fuentes Thromb Res 2017Venous thromboembolism (VTE) is a leading cause of morbidity and mortality among patients with cancer. In lung cancer patients, the incidence of VTE is 22 times higher than the general population, and 7 times higher than in patients with other malignancies. Moreover, treatment with chemotherapy increases the risk of thrombosis by 2.2-fold. Therefore, strategies targeting primary thromboprophylaxis may have a positive impact in both survival and quality of life. However, primary thromboprophylaxis is not routinely recommended for patients with lung cancer.

To measure the impact of primary VTE prevention and its effect on mortality among patients with lung cancer, a systematic review and meta-analysis of randomized control trials (RCTs) was conducted. Studies encompassing patients with lung cancer undergoing chemotherapy and prophylactic anticoagulation were included. For the analysis 11 studies with in total 5.107 patients were covered. Clinical outcomes of these studies were VTE occurrence, all-cause mortality, major and clinically relevant non-major bleeding.

Among the studies using low molecular weight heparin (LMWH) for prevention, a 50% lower VTE occurrence was observed in the prophylaxis group (OR: 0.50; 95%CI: 0.38-0.66; I2: 0%) compared to the control group, without a significantly increased bleeding risk (OR: 2.03; 95%CI: 0.78-5.25; I2: 71.1%). There was an overall 25% reduction in mortality when all VTE prevention modalities (LMWH, unfractionated heparin [UFH] and warfarin) were grouped (OR: 0.75; 95%CI: 0.58-0.96; I2: 18.4%), but no significant difference when LMWH (OR: 0.74; 95%CI: 0.49-1.11; I2: 56.9%) and warfarin were analyzed individually (OR: 0.75; 95%CI: 0.47-1.21; I2: 0%). However, a higher total bleeding was seen when combining all treatment modalities (OR: 3.06; 95% CI: 1.64-5.72; I2: 64.4%), with the greatest occurrence in the warfarin group (OR: 5.42; 95% CI: 3.48-8.45; I2: 45.7%).

In summary, primary VTE prophylaxis with LMWH reduces the occurrence of VTE among ambulatory patients with lung cancer, without an apparent increase in bleeding risk. There is a mortality benefit when all three thromboprophylaxis modalities are grouped. However, the mortality benefit did not persist when warfarin and LMWH were analyzed independently.

Reference

Fuentes HE, Oramas DM, Paz LH, et al. Meta-analysis on anticoagulation and prevention of thrombosis and mortality among patients with lung cancer. Thromb Res 2017;154:28-34.


Clinical course Mahe Am J Med 2017In recent years the progress in the screening and treatment of cancer has resulted in improved survival of cancer patients and an increasing number of living patients. However, the incidence of venous thromboembolism (VTE) progressively increases in cancer patients, in contrast to the general population without cancer. Previous studies have shown that the more biologically active the cancers are, the higher the risk of developing VTE. It has also been shown that the risk of VTE per site of cancer is highly different, with relative low risk of VTE for breast and prostate cancer as compared to lung and pancreas cancer.

Current guidelines recommend using low-molecular-weight heparins as a first-line treatment for cancer-associated thrombosis. However, little data is available about long-term treatment in those patients while life expectancy is increasing. The authors of this study hypothesized that the clinical course of VTE in patients with active cancer may differ according to the specificities of primary tumor site. If this hypothesis is confirmed, it would suggest that cancer patients might benefit from different anticoagulant strategies according to primary tumor site.

Data from the international registry of patients with VTE (RIETE) was used to compare the clinical VTE-related outcomes during the course of anticoagulation in patients with one of the 4 more frequent cancers (breast, prostate, colorectal, or lung cancer). As of September 2014, a total of 3.947 patients were included in the study of which 55% had metastatic disease. During the course of anticoagulant therapy, the rate of thromboembolic recurrences was similar to the rate of major bleeding in patients with breast (5.6 versus 4.1 events respectively per 100 patient-years) or colorectal cancer (10 versus 12 events respectively per 100 patient-years). In contrast, the rate of venous thromboembolic recurrences in patients with prostate cancer was half the rate of major bleeding (6.9 versus 13 events respectively per 100 patient-years), whereas in those with lung cancer the rate of thromboembolic recurrences was twofold higher than the rate of major bleeding (27 versus 11 event respectively per 100 patient-years).

Thus, this study showed significant differences in the clinical profile of venous thromboembolic-related outcomes of patients while on anticoagulant treatment according to the site of cancer. This suggests that the development of cancer-specific anticoagulant strategies might be an area for further research.

Reference

Mahé I, Chidiac J, Bertoletti L, et al. The Clinical Course of Venous Thromboembolism May Differ According to Cancer Site. Am J Med 2017;130(3):337-347.


HaemoscoreEvidence based medicine provides guidelines to physicians aimed at improving efficacy and safety of patient management. As such, clinical scores and algorithms derived from evidence-based medicine play a central role in modern patient care. An international expert panel has developed this application that compiles, in a clear and simple way, most recognized and useful clinical scores and diagnosis algorithms in the field of Thrombosis and Haemostasis.

The use of score calculators and algorithms can facilitate decision making in both diagnosis and treatment of thrombotic and bleeding problems and improve diagnosis accuracy and patient stratification. Each algorithm includes the indication and a brief interpretation emphasizing the most relevant aspects of each one, followed by some representative references.


WTDRecognized on 13 October, World Thrombosis Day (WTD) focuses attention on the often overlooked and misunderstood condition of thrombosis. With thousands of educational events in countries around the world, WTD and its partners place a global spotlight on thrombosis as an urgent and growing health problem.

WTD’s mission is to increase global awareness of thrombosis, including its causes, risk factors, signs/symptoms and evidence-based prevention and treatment. Ultimately, they strive to reduce death and disability caused by the condition.