Prevention of Venous Thromboembolism in Pancreatic Cancer: Breaking Down a Complex Clinical Dilemma

Abstract

Venous thromboembolism (VTE) frequently occurs in patients with cancer, and particularly those with pancreatic ductal adenocarcinoma (PDAC). Therapeutic anticoagulation with either low‐molecular‐weight heparin or a direct oral anticoagulant is clearly beneficial in patients who develop a VTE. However, whether thromboprophylaxis improves patient outcomes remains unclear. Studies assessing this risk show a 10%–25% risk of VTE, with reduction to 5%–10% with thromboprophylaxis but no impact on survival. To aid in the risk stratification of patients, several tools have been developed to identify those at highest risk for a VTE event. However, the clinical application of these risk stratification models has been limited, and most patients, even those at the highest risk, will never have a VTE event. New oral anticoagulants have greatly improved the feasibility of prophylaxis but do show increased risk of bleeding in patients with the underlying gastrointestinal dysfunction frequently found in patients with pancreatic cancer. Recently, several completed clinical trials shed new light on this complicated risk versus benefit decision. Here, we present this recent evidence and discuss important considerations for the clinician in determining whether to initiate thromboprophylaxis in patients with PDAC. Implications for Practice Given the high risk of venous thromboembolism in patients with pancreatic adenocarcinoma (PDAC), whether to initiate prophylactic anticoagulation is a complex clinical decision. This review discusses recent evidence regarding the risk stratification and treatment options for thromboprophylaxis in patients with PDAC, with the goal of providing practicing clinicians with updates on recent developments in the field. This article also highlights important considerations for individualizing the treatment approach for a given patient given the lack of general consensus of uniform recommendations for this patient population.

Incidence, timing and risk factors of venous thromboembolic events in patients with pancreatic cancer

“…Dallos and colleagues showed an overview of all recent randomized controlled trials with thromboprophylaxis in pancreatic cancer patients. [38] Overall incidences of general bleeding events were between 0.4 and 4.4%, and not significantly different in patients using thromboprophylaxis versus placebo.…”

Discordant reporting of VTE in pancreatic cancer: A systematic review and meta‐analysis of thromboprophylaxis versus chemotherapeutic trials

“…Based on randomized phase 3 data showing benefit of primary thromboprophylaxis including pancreatic cancer, 10,11 current clinical practice guidelines recommend the administration of primary thromboprophylaxis with low molecular weight heparin or direct oral anticoagulants for ambulatory patients with pancreatic cancer receiving chemotherapy in the absence of contraindications 41‐44 . Under appreciation of VTE incidence in pancreatic cancer could contribute to the low utilization of primary thromboprophylaxis 45 …”

“…[41][42][43][44] Under appreciation of VTE incidence in pancreatic cancer could contribute to the low utilization of primary thromboprophylaxis. 45…”

Patterns of Thromboembolism in Patients with Advanced Pancreatic Cancer Undergoing First-Line Chemotherapy with FOLFIRINOX or Gemcitabine/nab-Paclitaxel

“…Further, initiation of antineoplastic therapy might be an additional trigger for activating the clotting system by various mechanisms including the induction of endothelial damage (33). Whether permanent prophylactic anticoagulation should be routinely performed in patients with advanced pancreatic cancer remains a matter of debate (34). Current guidelines from the American Society of Clinical Oncology (ASCO) and the International Initiative on Thrombosis and Cancer (ITAC) recommend to consider VTE prophylaxis in ambulatory cancer patients with a Khorana score of 2 or higher in the absence of significant bleeding risk (15,16).…”

“…31 Whether permanent prophylactic anticoagulation should be routinely performed in patients with aPC remains a matter of debate. 32 Current guidelines from the American Society of Clinical Oncology (ASCO) and the International Initiative on Thrombosis and Cancer (ITAC) recommend to consider VTE prophylaxis in ambulatory cancer patients with a Khorana score of 2 or higher in the absence of significant bleeding risk. 15,16 However, the adoption of this approach in clinical practice remains still low.…”