Thromboprophylaxis in Generalized Pancreatic Cancer

Pancreatic Cancer and TED

The incidence of TED in this oncological disease reaches up to 20%. The tumor produces a large amount of tissue factor, which is secreted into the circulation and contributes to the development of a significant prothrombotic state. Other mechanisms potentiating thrombogenesis include, for example, the expression of negatively charged phospholipids by tumor cells or the production of pro-inflammatory cytokines and proteases, which directly activate coagulation factors. The tumor disease also induces platelet aggregation and simultaneously affects the natural balance between fibrin formation and fibrinolysis.

Given that most patients with pancreatic cancer do not ultimately develop TED, it is desirable to identify patients who are at risk in this regard. The most commonly used tools include the Khorana score and also the Vienna and PROTECHT scores. However, the scoring scales compiled for this purpose have not been very successful in stratifying patients. They do not completely include all the risk factors leading to the development of TED, especially in these oncology patients.

One of these risk factors is the presence of metastases. Given the rapid progression of the disease and often late diagnosis, the generalization of pancreatic cancer is not uncommon. Patients with metastatic disease are indicated for chemotherapy. However, chemotherapy itself is another significant risk factor for the development of TED. Its cytotoxic effect damages endothelial cells, promotes platelet aggregation, and potentiates an already present hypercoagulable state.

Patients diagnosed with pancreatic cancer at an early stage are indicated for surgery. The postoperative state after pancreatectomy is one of the highest risks for the development of TED. The benefit of thromboprophylaxis in these patients clearly outweighs the risk of postoperative bleeding. Administration of enoxaparin for 4 weeks postoperatively reduced the risk of TED by approximately 50%, without increasing the incidence of postoperative hemorrhage or other complications.

Thromboprophylaxis in Patients with Pancreatic Cancer

When indicating anticoagulation in a patient with metastatic involvement, it is necessary to carefully consider whether the patient will benefit from anticoagulant treatment. Reduced kidney and liver function can significantly increase the risk of bleeding, but on the other hand, also the risk of thrombosis. Patients also often undergo some palliative procedures, in which case any bleeding could significantly complicate the situation. Therefore, it is recommended to proceed strictly individually in deciding on the administration of thromboprophylaxis, taking into account the specific patient's needs.

The CONKO-004 study examined the use of enoxaparin in thromboprophylaxis. This study included patients with pancreatic cancer treated with chemotherapy. Participants were divided into two groups, one receiving only chemotherapy and the other also receiving enoxaparin at a dose of 1 mg/kg once daily for the first 3 months, then thromboprophylaxis continued at a fixed dose of 40 mg daily. According to the study results, the incidence of TED was 1.3% in the thromboprophylaxis group and 10.2% in the control group (patients receiving only chemotherapy). No difference in the occurrence of bleeding complications was detected between both groups. Although the study demonstrated a reduction in the risk of TED upon administration of enoxaparin, no positive effect on overall patient survival was proven.

Based on study results, thromboprophylaxis cannot be unequivocally recommended for patients with pancreatic cancer, especially its metastatic form. However, it is clear that some will significantly benefit from anticoagulation. The attending physician must individually assess the condition and identify patients at risk for the development of TED.

Conclusion

Pancreatic cancer is one of the oncological diseases with the worst prognosis. The high mortality rate is also contributed to by the frequent occurrence of significant complications. Thromboprophylaxis has been shown to reduce the incidence of TED. Whether the administration of anticoagulants could also prolong patients' lives is not yet clear, but this possibility will be subject to further research.

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Source:

Dallos M. C., Eisenberger A. B., Bates S. E. Prevention of venous thromboembolism in pancreatic cancer: breaking down a complex clinical dilemma. Oncologist 2020 Feb; 25 (2): 132-139, doi: 10.1634/theoncologist.2019-0264.