On my hematology oncology rotation recently, I learned that pancreatic adenocarcinomas have an increased risk of hypercoagulability in comparison to other cancers.The relationship between hypercoagulability and malignancy is something that most medical students are fairly familiar with.  However, while most students may be familiar with the topic, some of the nuances that surround it are a little less clear.  What exactly is causing the issues with hypercoagulability?   Why do some cancers have a higher risk of hypercoagulability than others?  These are the questions I hope to answer in this blog post.

How do we know that there is a relationship between cancer and clotting?  Well, some studies have been done that have demonstrated the relationship between cancer and thrombosis.  We have seen prolonged survival among patients with small cell lung cancer who were receiving warfarin.   Similarly there are lower mortality rates among cancer patients who received unfractionated or low-molecular weight heparin.  Both of these findings suggest that some of the mortality risk with cancer results from clotting and thrombotic events.  It was further found that in cancer patients without obvious thrombosis it was not uncommon to see abnormal laboratory coagulation tests, characterizing a subclinical hypercoagulable state.

The mechanisms that contribute to the development of a hypercoagulable state in cancer are varied.   Tumor cells are well known to contribute to the development of hypercoagulability both through the production of procoagulant and fibrinolytic substances in addition to inflammatory cytokines.  These substances are likely produced to facilitate the growth and invasion of the cancer.  Tumor cells also may be mediating hypercoagulability through their physical interaction between the tumor cells and blood or vascular cells.  Malignancy may also contribute to a hypercoagulable state through the generation of nonspecific factors such as acute phase reactants, necrosis, abnormal protein metabolism or hemodynamic compromise.  What may come as a surprise is that anticancer therapies themselves may similarly increase the risk of thromboembolic events through similar mechanisms. That includes surgery, chemotherapy or even hormone therapy.

While the above factors may be contributing to a hypercoagulable state, why do some malignancies, like pancreatic adenocarcinoma, have a higher prevalence of VTE than others?  This likely falls within the realm of understanding that different cancers behave differently.  All of the dysregulation that may occur in the coagulation system may occur to varying degrees depending on the type of cancer, and that means that not all malignancies will have the same thrombotic risk.

Reference:

Caine GJ, Stonelake PS, Lip GY, Kehoe ST. The hypercoagulable state of malignancy: pathogenesis and current debate. Neoplasia. 2002 Nov-Dec;4(6):465-73. doi: 10.1038/sj.neo.7900263. PMID: 12407439; PMCID: PMC1550339.

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