How to Prevent and Treat Thromboembolic Disease in Cancer Patients
Malignancy is one of the risk factors for the development of thromboembolic disease (TED). Venous thromboembolism is considered the second most common cause of death in cancer patients, with the top cause being the cancer itself. Therefore, optimal treatment and timely prevention of these complications is very important.
Malignancy as an Ideal Environment for Thrombus Formation
The pathogenetic mechanisms of thrombosis formation are generally summarized as the so-called Virchow's triad: endothelial damage, blood stasis, and hypercoagulable state.
The endothelium of blood vessels in malignancies is often damaged due to chemotherapy. The highest risk has been observed in patients with gastric and pancreatic cancer, and among the substances with the highest thrombogenic potential is the frequently used cisplatin.
Blood stasis in the vessels can occur due to dehydration and as a result of surgical procedures and the necessary immobilization of patients related to these procedures.
Malignant tumors also produce a number of cytokines and other agents that affect the function of the coagulation cascade. Tissue factor is more highly expressed by tumor cells, especially in pancreatic or ovarian carcinoma. Physiologically, it does not appear on endothelial cells, but in the event of cancer, it becomes one of the most significant procoagulant factors. Malignant tumors also produce increased amounts of plasminogen activator inhibitor 1 (PAI-1), resulting in reduced fibrinolytic activity of the plasma. Other factors influencing coagulation include adhesive molecules and inflammatory cytokines.
Other Risk Factors
The risk of TED increases with the patient's age and is also higher in women. The location and histological type of the tumor, as well as the disease stage, also affect the risk of TED. The highest risk is associated with adenocarcinomas of the pancreas, lungs, and gastrointestinal tract. The presence of long-term venous catheters also increases the incidence of thrombosis. Patients with a history of a previous thromboembolic episode have a 6–7× higher risk of these complications during malignancy.
Prevention of TED Development
The benefit of thromboprophylaxis was clearly demonstrated in cancer patients undergoing surgery, with the risk of deep vein thrombosis halved. Other studies have shown the benefit of extended thromboprophylaxis (2–6 weeks) during surgeries for malignant diseases in the abdominal and pelvic areas. The advantages of thromboprophylaxis in outpatient cancer patients undergoing chemotherapy have not been clearly proven.
Prophylaxis is administered through subcutaneous low-molecular-weight heparins (LMWH), with enoxaparin being a frequently used representative of this drug group. Risk stratification can estimate the individual risk of thromboembolism. For patients with intermediate risk, a dose of 2000 IU once daily for 7–10 days is recommended, while for patients at high risk, a dose of 4000 IU once daily is recommended. Administration should begin 12 hours before surgery, and for patients undergoing abdominal and pelvic surgeries, prophylaxis should last at least 4 weeks.
Treatment of Thromboembolism in Cancer Patients
In the treatment of acute thromboembolic complications, LMWH is usually initially administered, such as enoxaparin in the usual dose of 150 IU/kg once daily or 100 IU/kg twice daily. For patients with recurrent thromboembolism during anticoagulant therapy, it is recommended to replace the oral anticoagulant, if used, with LMWH or, if LMWH is already used, increase its dose by 20–25%. Compared to warfarin, LMWH was associated with a lower risk of bleeding events and recurrent thrombosis. New, or direct anticoagulants (DOACs), have shown approximately the same efficacy as LMWH in studies, but more bleeding complications were observed during their use, particularly gastrointestinal bleeding. Detailed comparison of the effects and risks of NOACs versus LMWH will be the subject of further studies.
Conclusion
Thromboembolic disease significantly increases the morbidity and mortality of cancer patients, undoubtedly affecting the overall prognosis of the disease. Therefore, prevention and timely therapy should be a fundamental part of the care for these patients. Currently, low-molecular-weight heparins are the most commonly used drugs for the prevention and treatment of TED. Comparing NOACs with LMWH and determining suitable and safe drugs for specific patient groups will be the subject of further research.
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Sources:
1. Abdol Razak N. B., Jones G., Bhandari M. et al. Cancer-associated thrombosis: an overview of mechanisms, risk factors, and treatment. Cancers (Basel) 2018; 10 (10): 380, doi: 10.3390/cancers10100380.
2. Wang T.-F., Li A., Garcia D. Managing thrombosis in cancer patients. Res Pract Thromb Haemost 2018; 2 (3): 429–438, doi: 10.1002/rth2.12102.
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