Venous Thromboembolism and Primary Thromboprophylaxis in Perioperative Pancreatic Cancer Care

Abstract

Recent studies have shown that patients with pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant chemo(radio)therapy followed by surgery have an improved outcome compared to patients treated with upfront surgery. Hence, patients with PDAC are more and more frequently treated with chemotherapy in the neoadjuvant setting. PDAC patients are at a high risk of developing venous thromboembolism (VTE), which is associated with decreased survival rates. As patients with PDAC were historically offered immediate surgical resection, data on VTE incidence and associated preoperative risk factors are scarce. Current guidelines recommend primary prophylactic anticoagulation in selected groups of patients with advanced PDAC. However, recommendations for patients with (borderline) resectable PDAC treated with chemotherapy in the neoadjuvant setting are lacking. Nevertheless, the prevention of complications is crucial to maintain the best possible condition for surgery. This narrative review summarizes current literature on VTE incidence, associated risk factors, risk assessment tools, and primary thromboprophylaxis in PDAC patients treated with neoadjuvant chemo(radio)therapy.

Pancreatic Cancer and Venous Thromboembolism

“…The newer direct thrombin inhibitor or factor Xa inhibitors carry less bleeding risk than older agents such as heparins and warfarin, but there are limited data regarding the use of these agents in cancer patients [ 107 , 108 ]. However, overall primary thromboprophylaxis in ambulatory cancer patients treated with chemotherapy, and in PC patients with an elevated VTE risk, is safe, effective, and advisable [ 22 ]. With regard to cancer patients, there are no relevant data for dabigatran in the primary prevention or treatment of VTE.…”

“…The metanalysis was conducted over several studies, studying the efficacy among several cancer types, with the primary safety outcome as major bleeding [ 117 ]. Overall, current guidelines suggest the use of apixaban, rivaroxaban, and LMWH in patients without critical risk factors for bleeding and without the potential for drug–drug interactions [ 22 ]. Another treatment option in thromboprophylaxis is warfarin, a vitamin K antagonist that targets a broad array of vitamin-k-dependent coagulation proteins, including Factor IIa, Factor VIIa, Factor IXa, and Factor Xa.…”

“…There is no clear evidence regarding whether thromboprophylaxis improves survival in at-risk PDAC patients. Some studies claim there is no evidence that thromboprophylaxis administration prolongs survival in patients with advanced PDAC and chemotherapy [ 22 ]. However, some other recent studies have shown improved overall survival in patients receiving warfarin compared to LMWH long term [ 119 ].…”

“…Due to advances in neoadjuvant chemotherapy options, several patients diagnosed with local, resectable pancreatic tumors are treated with chemotherapy prior to surgery [ 21 ]. Patients treated with a combination of neoadjuvant therapy and surgical resection of pancreatic tumors have lower rates of VTE compared to patients with advanced, metastatic PDAC [ 22 ]. Thus, current guidelines suggest thromboprophylaxis for patients with advanced and metastatic PDAC who are treated with chemotherapy.…”