The Importance of Cancer - Associated Hypercoagulation as a Possible Stroke Etiology

Abstract

A causal relationship between malignant cancer and thrombosis has been known since the 19 century, when Armand Trousseau in 1865 first described migratory thrombosis as the first manifestation of occult gastric cancer. The association between cancer and excessive blood coagulation has since then attracted much attention. Today the concept of “Trousseau’s syndrome” is commonly used not only to describe migratory thrombosis that precedes the diagnosis of occult cancer, but also any “hypercoagulable state associated with malignant cancer.” Nevertheless, the importance of paraneoplastic hypercoagulability as a possible stroke etiology in patients with cancer has received relatively little attention to date. This may be because it is difficult to diagnose in patients with stroke because etiologies may concur in the usually elderly and multimorbid patients and malignancy may represent a simple coincidence. Furthermore, the underlying mechanisms of paraneoplastic hypercoagulability are complex, of high interindividual variability, and still not fully understood. A small number of earlier studies on this topic generated conflicting results. The largest study including 161 patients by Kim et al in 2010 differentiated between patients with cancer+stroke with and without conventional stroke etiologies and renewed the idea of cancerassociated hypercoagulation as an important stroke etiology. Significantly higher ddimer levels as well as a significantly higher rate of multiply affected vascular territories in the group of patients without conventional stroke etiology supported the idea of cancerassociated hypercoagulation with resulting cerebral embolism. This was promoted by a higher prevalence of Background and Purpose—The importance of cancerassociated hypercoagulability as a possible stroke etiology in patients with cancer has received relatively little attention to date. A recent study has suggested that cancerassociated hypercoagulation may be of special importance in the absence of conventional stroke mechanisms. Methods—We identified patients with ischemic stroke sequentially admitted to our stroke center with the additional diagnosis of active and malignant cancer from 2002 to 2011. By using our prospectively collected stroke, MRI, and laboratory data banks, the etiology and risk factors of stroke, types of cancer, deep vein thrombosis/pulmonary embolism, ddimer levels, and diffusionweighted imaging lesion patterns were compared to an ageand sexmatched control group. Patients with cancer with a conventional stroke etiology and patients with an unidentified and/or cancerassociated stroke etiology were analyzed separately. Results—One hundred forty patients with cancer and 140 control subjects were included. Unidentified stroke (P<0.001) and infarction in multiple vascular territories (P<0.001) were significantly more frequent and ddimer levels significantly higher (P<0.05) in patients with cancer. Vice versa, risk factors such as hypertension (P<0.05) and hyperlipidemia (P<0.01) were more prevalent in control subjects. Deep vein thrombosis and pulmonary embolism were more frequent (P<0.01) and ddimer levels higher (P<0.01) in the patients with unidentified and/or cancerassociated stroke etiology compared to the patients with cancer with a conventional stroke etiology. Lung and pancreatic cancer were significantly overrepresented and ddimer levels higher in these patients compared with other patients with cancer (P<0.01). Conclusions—Our data confirm the concept of cancerassociated hypercoagulation as a widely underestimated important stroke risk factor in patients with cancer, especially in those with severely elevated ddimer levels and in the absence of conventional risk factors. (Stroke. 2012;43:3029-3034.)

Cite this paper

@inproceedings{Schwarzbach2012TheIO, title={The Importance of Cancer - Associated Hypercoagulation as a Possible Stroke Etiology}, author={Christopher Jan Schwarzbach and Anke Schaefer and Anne D. Ebert and Manuel Bolognese and Micha Kablau and Michael Hennerici and Marc Fatar}, year={2012} }