Sevestre1-350Cancer is associated with venous thromboembolism in 20% of patients. In such patients, thrombosis is difficult to treat, associated with bleeding, recurrence, and death. Specific treatments for venous thromboembolism in cancer are recommended. Guidelines have been implemented in many countries and international guidelines have been recently developed. A recently published study evaluated the adhesion to national French guidelines via a survey of cancer patients treated for venous thromboembolism.

The national, cross-sectional, observational CARMEN study evaluated the adhesion to guidelines in hospitalized patients. Good clinical practice was defined as initial 10-day treatment with injectable molecules followed by long-term treatment with low molecular weight heparin for at least 3 months. In total, 500 patients were evaluated of whom a majority had metastatic disease (64%). Cancer sites were gastro-intestinal (25%), gynecologic (23%), pulmonary (21%), hematological (14%), urologic (10%), or other (8%). The overall adhesion to guidelines was present in 59% of the evaluated patients (295/500). Of note, the compliance to the recommendations was particularly high during initial treatment (487/496; 98%) but significantly dropped (296/486; 62%) during the long-term maintenance. In patients with renal insufficiency, only a fourth of them received the adequate treatment.

As such, this analysis clearly shows that adhesion to practice guidelines for treatment of venous thromboembolism in cancer is not optimal. A good compliance is observed during the initial treatment, but drops after 10 days. This observation underlines the need for further education to achieve a better implementation of national and international treatment guidelines in the daily clinical practice

Reference

Selvestre M, et al. Compliance with recommendations of clinical practice in the management of venous thromboembolism in cancer: The CARMEN study. J Mal Vasc 2014; Epub ahead of print.

See also:
JTH  ISTH

Farge D, Debourdeau P, Beckers M, et al. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. J Thromb Haemost. 2013 Jan;11(1):56-70. doi: 10.1111/jth.12070.

And:

Debourdeau P, Farge D, Beckers M, et al. International clinical practice guidelines for the treatment and prophylaxis of thrombosis associated with central venous catheters in patients with cancer. J Thromb Haemost. 2013 Jan;11(1):71-80.


 

Tagalakis2To date, results for dabigatran, rivaroxaban, apixaban, and, most recently, edoxaban, for the treatment of acute VTE have been published. With predictable pharmacological profiles these agents could form an attractive alternative to LMWHs and VKAs. In particular, they are associated with minimal food and drug interactions, and can be taken orally in fixed-doses without the need for routine coagulation laboratory monitoring. However, generalizing these findings to cancer patients with VTE is difficult since very few cancer patients were included. In a recent review in Blood Reviews, it was concluded that, because of the lack of sufficient evidence in support of these new agents in the management of VTE in cancer patients, low molecular weight heparins should remain the cornerstone in the management of these patients.

Wharin C, et al. very recently published this comprehensive review, providing an overview of the current treatment of VTE, exploring anticoagulant thromboprophylaxis in ambulatory cancer patients, and summarizing existing evidence on the efficacy and safety of the new oral anticoagulants for the management of VTE in both non-cancer and cancer populations. However, there appears to be insufficient data in support of these new agents in the management of VTE in cancer patients, according to the authors. Primarily, there have been no studies specifically investigating the role of these agents in the treatment of cancer-associated VTE. Moreover, all trials to date included very few patients with malignant disease: RE-COVER study of dabigatran: 4.8%, RE-MEDY: 2.1%, EINSTEIN trials of rivaroxaban: 6% (DVT), 4.6% (PE), and 4.5% (extended VTE treatment), AMPLIFY study of apixaban: 2.7%, AMPLIFY-EXT trial of apixaban: 1.8% (2.5 mg) and 1.1% (5 mg), and HOKUSAI-VTE: 2.5%. While cancer subgroup analyses suggest clinical benefit for rivaroxaban, dabigatran and edoxaban, the small sample size and exploratory nature of these analyses limit any definitive conclusions. The strict inclusion criteria in these trials limited patients with end-organ dysfunction (e.g., renal and liver dysfunction) and elevated risk of bleeding from enrolling, resulting in an overall study population likely not-representative of patients with advanced cancer who - compared to the general population - have a higher risk of recurrent thrombosis and major bleeding with anticoagulation. Last, while the new agents demonstrated non-inferiority against warfarin, this does not necessarily equate to non-inferiority against LMWHs, which are the preferred VTE treatment method in cancer patients. As a result, the efficacy and safety of the new oral anticoagulants in cancer patients has not been adequately assessed to date in this population.

In conclusion, the new oral anticoagulants are promising for the treatment of VTE in the general population, but there are limited data on the use of these agents in cancer patients to determine their efficacy and safety in the management of cancer-associated VTE. Dedicated studies of cancer patients with VTE are needed in order to clarify the role of the new oral anticoagulants before these agents can be recommended for treatment and possibly prevention of VTE in this important patient population. Till that day, low molecular weight heparins should remain the cornerstone in the management of these patients.

Reference

Wharin C, Takalakis V. Management of venous thromboembolism in cancer patients and the role of the new oral anticoagulants. Blood Reviews 2014;28:1-8.

Click here for PDF of full article


 

GomesWhile it is generally acknowledged that patients with malignancy are at a substantially high risk for venous thromboembolism (VTE) as compared with the general population, the incidence of VTE varies significantly between subgroups of cancer patients. Even within the same patient over the natural history of their malignancy. As such, it is important to have tools to assess the risk of VTE in individual cancer patients. A very recent review article, published in Seminars in Thrombosis and Haemostasis that was entirely dedicated to VTE and cancer, discusses the risk factors, predictive biomarkers and new guidelines, which recommend risk assessment of VTE for cancer patients.

The risk in the general cancer population has been estimated to be 13 per 1000 person years. However, this does not accurately reflect the prevalence of clinical events observed in cancer patients on active treatment, where the incidence can be much higher. Because of this wide variation in risk, a recent update by the American Society of Clinical Oncology (ASCO) VTE guidelines panel recommends that patients with cancer should be assessed for VTE risk at the time of initiation of chemotherapy and periodically thereafter.

The risk of VTE varies depending upon individual patient specific, disease specific and treatment specific clinical risk factors (Table 1). In addition to this, studies in cancer patients have identified several novel biomarkers as predictors of VTE events. These include pre-chemotherapy elevated platelet count, elevated leukocyte count, elevated D-dimer, elevated pro-thrombin split products, elevated soluble P-selectin, peak thrombin generation, and elevated levels of tissue factor (TF)-bearing microparticles (TFMP). Cancer patients with any of these biomarkers have a several fold, increased risk of VTE when compared to other cancer patients.

As this long list of risk factors and biomarkers indicates, the etiology of cancer-associated VTE is multifactorial. Multiple large trials have attempted to identify patients at high risk for VTE based on one or two risk factors. However, event rates in such studies have been quite low indicating that a high-risk population was not selected. Based on these data, the 2013 updated ASCO guidelines and the recent NCCN and ESMO guidelines recommend against the use of single risk factors or biomarkers to identify high-risk patients. The panel rather recommends the use of a (high) risk-assessment score that incorporates multiple variables (i.e. site of cancer, pre-chemotherapy platelet count, hemoglobin level, pre-chemotherapy leukocyte count and body mass index). This risk score was initially derived from a cohort of 2,701 patients and was later validated in several studies and can identify patients at high risk for cancer-associated VTE.

Reference

Gomes M, Khorana AA. Risk assessment for thrombosis in cancer. Semin Thromb Hemost 2014;40:319-24.

 

Click here for full article as PDF

 

Table 1. Clinical risk factors for VTE in cancer patients

Tabel1

 


 

App1-350Whether you are a cardiologist seeing new-onset atrial fibrillation, an orthopedic surgeon prescribing DVT prophylaxis after a hip replacement, an emergency room physician encountering a bleeding diathesis in the setting of a supratherapeutic INR, an intensivist treating a pulmonary embolus in the ICU, or a neurologist medically optimizing a stroke patient, it is critical to have a strong understanding of “blood thinners,” or various antiplatelet and anticoagulant agents. In this light, the ClotRx app attempts to “provide the busy practitioner with quick access to information on the use of antithrombotic agents.”

In short, the main features of this app are:

  • Easy navigation by disease state and medication
  • Tables, algorithms, and brief synopses of critical information provide efficiency in data access
  • Treatment and prevention of arterial and venous thromboembolic events are covered
  • Contains also medication indication, dosing, mechanism of action, contraindications/precautions, and common adverse effects
  • Evidence-based information on latest body of literature, consensus guidelines, and manufacturer labeling

Browsing by medication offers three categories: antiplatelet medications (aspirin, aggrenox, plavix, and prasugrel), anticoagulant medications (pradaxa, arixtra, heparin, LMWHs, and warfarin), and mechanism of action (antiplatelet or anticoagulant medications). Clicking on a specific medication, renders links to concise information on dosing, adverse events, precautions/contraindications and mechanism of action of specific drugs.

Alternatively, browsing by disease from the ‘Table of Contents’ offers a look at atrial fibrillation (a-fib), coronary artery disease (CAD), stroke or transient ischemic attack (TIA), peripheral arterial disease (PAD) and venous thromboembolism (deep venous thrombosis or pulmonary embolism (DVT or PE)).

Finally, the Card View provides a list of “cards” with densely-packed, but useful information related to antithrombotic therapy. These cards would be excellent as pocket cards to print and stick inside one’s white coat (or easily access on one’s iPhone!). For example, topics covered include an overview of VTE, DVT and PE prophylaxis and anticoagulant reversal, treatment of VTE, stroke prevention, a warfarin overview and warfarin drug-interactions.

Some screenshots of the app:

App1   App2  ClotRx3

The ClotRx app costs USD 1,99 and can be downloaded in the app store at https://itunes.apple.com/us/app/clot-rx/id408979176?mt=8

ClotRx

  • This app is designed for both iPhone and iPad
  • Updated: Nov 21, 2013
  • Version: 1.6
  • Size: 11.2 MB
  • Language: English
  • Seller: Insight Therapeutics, LLC




 

videoWatch here a videoclip of an interview with Prof. Dr. Christian Chatelain, Chef de Clinique Hématologie, CHU Dinant Godinne, UCL Namur, on the management of thromboembolism in cancer patients with renal impairment. Featuring many practical insights, personal tips and advice for your day-to-day clinical practice.