Jara Palomares Throms Res 2017 2The relationship between venous thromboembolism (VTE) and cancer is well-established. The absolute incidence of cancer-associated thrombosis (CAT) varies widely depending on the type of tumor, the stage of the cancer and the oncologic treatment received. CAT is associated with a higher incidence of recurrence and bleeding, and these complications are independent risk factors of death. 

The administration of low-molecular-weight heparin (LMWH) during 3 to 6 months has shown to be effective and safe in patients with CAT. The CATCH trial showed that the administration of tinzaparin versus vitamin K antagonists (VKA) during 6 months led to a significant reduction in clinically relevant non-major bleeding. However, data related to the use of LMWH beyond 6 months are limited. The aim of the TiCAT study (Tinzaparin in Cancer-Associated Thrombosis) was to evaluate the safety and efficacy of long-term tinzaparin treatment in patients with CAT.

The study included 247 patients with active cancer diagnosed with symptomatic or asymptomatic VTE: deep vein thrombosis (DVT) or pulmonary embolism (PE). All patients received tinzaparin (175 IU/kg) subcutaneously once a day. The rate of clinically relevant bleeding events (major and non-major clinically relevant bleeding) and venous thromboembolism (VTE) recurrence was evaluated, comparing the 2 initial periods of follow-up: 1 to 6 months and 7 to 12 months.

The patients recruited had a crude incidence of major bleeding of 4.9% (12/247). The rate of clinically relevant bleeding during months 1-6 and 7-12, was 0.9% per patient and month [95% CI: 0.5% - 1.6%] and 0.6% (95% CI: 0.2% - 1.4%) (p=0.5) per patient and month, respectively. Male patients had a higher risk for clinically relevant bleeding with a hazard ratio (HR) of 2.97 (95% CI: 1.01 - 8.1; p=0.02). During months 7–12, 2 patients had a VTE recurrence, with an incidence of 1.1% (95% CI: 0.1% - 3.9%), while during months 1–6, 11 patients had a VTE recurrence with an incidence of 4.5% (95% CI: 2.2% - 7.8%) (p =0.08). One patient died due to VTE recurrence and 2 patients because of severe bleeding.

In line with previous studies with LMWH up to 6 months after CAT, the TiCAT study demonstrated that treatment with tinzaparin from months 7–12 after the diagnosis of VTE has a good safety profile with a low incidence of clinically relevant bleedings and VTE recurrences.

Reference

Jara-Palomares L, Solier-Lopez A, Elias-Hernandez T, et al. Tinzaparin in cancer associated thrombosis beyond 6months: TiCAT study. Thromb Res 2017 Sep; 157: 90-6.


Mitsis J Cancer 2017 1Colon cancer is the most common form of colorectal cancer representing about 72% of all cases. For these patients surgery with a curative intention is the standard of care. Nevertheless, even after an apparently curative tumor resection a significant proportion of patients develop local or distant recurrence of the disease. VEGF-A165 (VEGF) is a direct acting angiogenic protein, and plays a pivotal role in many normal physiological functions including wound healing. Preoperative levels of VEGF in colon cancer patients are a strong and sensitive predictor for disease recurrence and overall survival.

Elevated postoperative VEGF levels could have undesirable effects by enhancing tumor growth and metastasis formation. Several studies have suggested that thromboprophylaxis with a Low Molecular Weight Heparin (LMWH) in surgical cancer patients, in addition to thromboembolic protection, may exert some anti-neoplastic properties. The aim of this study was to assess the potential impact of the LMWH tinzaparin at different doses and for different perioperative periods, upon the post-operative variability of serum VEGF levels in surgical colon cancer patients.

For this study 54 consecutive colon cancer patients who underwent a curative resection were randomized in 4 groups according to their peri-operative thromboprophylaxis scheme. This scheme was based on administrating tinzaparin in different doses and at different periods:

  • Group I: 3,500 IU for 10 days
  • Group II: 3,500 IU for 30 days
  • Group III: 4,500 IU for 10 days
  • Group IV: 4,500 IU for 30 days

Serum VEGF concentrations were evaluated on the pre-operative day (day 0) and on the 10th and 30th post-operative days (day 10 and day 30, respectively).

The results showed that serum VEGF concentrations didn't differ between groups I, II, III and IV on day 0 (p>0.05, for every comparison). However, on day 10 serum VEGF concentration was increased in all groups. Between day 10 and day 30 serum VEGF concentrations remained stable in groups I (p=0.031) and II (p=1.000) and increased significantly in group III (p=0.005). On the contrary, serum VEGF concentrations decreased significantly in group IV (p<0.001). In groups I, II and III serum VEGF concentrations on day 30 remained significantly higher compared to day 0 (p<0.001, p=0.041 and p<0.001, respectively). In contrast the serum VEGF concentration on day 30 in group IV, which consisted of extended-duration with the highest dose of 4,500 IU of tinzaparin, was comparable to day 0 (p=1.000).

The authors of this study concluded that in surgical colon cancer patients only the recommended thromboprophylaxis scheme with the highest prophylactic dose of tinzaparin (4,500 IU) for extended-duration (30 days) normalizes VEGF levels at the end of the first post-operative month by reducing them to the pre-operative levels. As previous studies have suggested that VEGF in colon cancer patients directly mediates colon cancer growth and metastasis, a possible normalization of VEGF concentrations during the immediate post-op period could be a promising finding. Even though the results indicate a normalization of VEGF levels in group IV, chance findings could not be excluded given the small sample size. Further research, with larger sample sizes is needed to validate these findings.

Reference

Mitsis M, Koliou P, Bali C, et al. In Surgical Colon Cancer Patients Extended-Duration Thromboprophylaxis (30 days) with the Highest Dose of Tinzaparin (4,500 IU s.c./q.d.) Normalizes the Postoperative VEGF Levels. J Cancer 2017 Aug 25;8(15):2899-906.


Van Rien J Thromb Haemost 2017Low-molecular-weight-heparins (LMWH) are widely used for the treatment and prevention of venous thrombosis and are on the List of High-Alert Medications issued by the Institute for Safe Medication Practices. LMWHs are considered members of a class of drugs with similar anticoagulant properties. However, pharmacodynamics and pharmacokinetics between LMWHs differ, which may result in different bleeding risks. As these agents are used by many patients, small differences may lead to a large effect on numbers of major bleeding events.

To determine major bleeding risks for different LMWH agents and dosing schedules a cohort study was conducted including 12.934 patients with acute venous thrombosis, with a mean age of 59 years. Of this cohort 6.218 (48%) were men. These patients used a LMWH and a vitamin K antagonist and were followed until they ceased LMWH treatment or until major bleeding. Exposures were classified according to different types of LMWHs and frequency of use: ‘twice a day’ or ‘once daily’. Cumulative incidences for major bleeding per 1000 patients and risk ratios were calculated and adjusted for study center.

Results showed that the cumulative incidence of major bleeding was 2.5 per 1000 patients (95% confidence interval [CI]: 1.7-3.5). Enoxaparin once and twice daily was associated with a relative bleeding risk of 1.7 (95% CI: 0.2-17.5) compared with nadroparin once daily. In addition, a nadroparin twice daily dosing schedule was associated with a two-fold increased major bleeding risk (95% CI: 0.8-5.1) as compared with a nadroparin once daily dosing schedule.

In conclusion, absolute major bleeding rates were low for all LMWH agents and dosing schedules in a large unselected cohort. Nevertheless, twice-daily dosing with nadroparin appeared to be associated with an increased major bleeding risk as compared with once-daily dosing, as also suggested in a meta-analysis of controlled clinical trials.

Reference

Van Rein N, Biedermann JS, van der Meer FJM, et al. Major bleeding risks of different low-molecular-weight heparin agents: a cohort study in 12 934 patients treated for acute venous thrombosis. J Thromb Haemost. 2017 Jul; 15(7): 1386-1391.


Elalamy J Thromb Haem 2017Cancer-associated thrombosis (CAT) accounts for almost one-fifth of all cases of venous thromboembolism (VTE) and is a leading cause of death, morbidity, delays in care, and increased costs. It often involves potentially-fatal blockage of a lung artery (pulmonary embolism) and of veins in the leg (deep vein thrombosis). Patients with CAT carry a higher risk of recurrence, bleeding and mortality as compared with non-cancer patients. Thus, the specific profiles of cancer patients, combining frequent co-morbidities, the use of anti-tumoral therapies and the cancer progression itself, represent a major therapeutic challenge for choosing a long-term anticoagulant treatment.

In this review the practical basis of making a choice between the available drugs for a long-term antithrombotic strategy is discussed, linked to their pharmacology, mechanism of action, evidence of clinical benefits, and advantages and limitations in such a complex clinical context.

Low-molecular-weight heparins (LMWHs) are the preferred option for the secondary prevention of venous thromboembolism in patients with cancer because they have been shown to be superior to vitamin K antagonists (VKAs). However, even though LMWHs are effective and safe in cancer patients they require daily subcutaneous injections, which may be inconvenient for some patients, especially for those patients needing long-term therapy that may exceed 6 months' duration.

Compared to VKAs, direct oral anticoagulants (DOACs) are more target specific and do not require laboratory monitoring, whereas the oral route of administration makes them potentially attractive alternatives to LMWH. Studies in randomized controlled trials in the general population have shown that DOACs are non-inferior to VKAs in terms of efficacy with a lower rate of clinically relevant or major bleeding. However, given the limited number of cancer patients enrolled in these studies (which also included patients with poorly defined active cancer), available trials are inconclusive regarding the usefulness of DOACs in the cancer setting. Therefore, ongoing head-to-head comparisons versus LMWH in patients with CAT may allow an informed choice to be made regarding the DOAC option.

Reference

Elalamy I, Mahé I, Ageno W, et al. Long-term treatment of cancer-associated thrombosis: the choice of the optimal anticoagulant. J Thromb Haemost. 2017 May; 15(5): 848-857.


app200 200The BridgeAnticoag app supports clinicians across specialties in managing anticoagulation around an invasive procedure for NVAF patients. The app assesses procedural and patient risk to provide individualized advice that balances bleed and stroke risk.

Use the app to assess whether and how to:
- Interrupt anticoagulation
- Bridge anticoagulation
- Restart anticoagulation

 

Advice from the app is derived from the 2017 ACC Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients with Nonvalvular Atrial Fibrillation.

 


WTDOn October 25th a paper was released in Research and Practice in Thrombosis and Haemostasis (RPTH) by the World Thrombosis Day campaign, led by the International Society on Thrombosis and Haemostasis (ISTH). This paper revealed that global public awareness of atrial fibrillation (AFib) is low at 48 percent worldwide compared with other medical conditions. In addition, only 36 percent of the survey respondents were aware of the connection between AFib and stroke. Click here to read more about the paper.