Abstract

Background: There are many causes of thrombosis in cancer, including cancer itself, the release of TNF, IL-1 &IL-6 causing endothelial damage, the interaction between tumor cells and macrophages activates platelets, factors X11 &X. Cysteine proteases &tissue factor, in the tumor cells have pro-coagulant activity (Bick, R. New Engl J of Med. Volume 349. July 2003). Chemotherapy, hormonal therapy and indwelling central venous catheters also increase the risk of thrombosis. There is a RR of 4.1 for patients with cancer who did not have chemotherapy and 6.5 for patients with cancer who had chemotherapy (

Heit et al.
Arch Intern Med
.
2000
;
160
:
809
–815
).

Factor V Leiden mutation causes partial resistance to the inactivating effects of activated protein C. 5% of the population carries this mutation and it is present in 20% of patients with a 1st venous thrombotic episode. The risk of venous thrombosis is 3–8 fold. The prothrombin mutation is less common and the relative risk of thrombosis is about 2.0. In a large case control study it was found that carriers of the Factor V Leiden or the prothrombin mutation who also had cancer had an approximately 12–17 times increased risk of thrombosis; compared to an overall 7 times risk in patients with malignancy alone (Blom et al. JAMA. Feb 9, 2005. Vol 293, No 6).

Case history: A 54 year old caucasion female was diagnosed with stage 1 infiltrating ductal carcinoma after palpating a lump in her left breast. The tumor was 1.6 cm, ER negative, PR negative and HER-2 negative. Lumpectomy and axillary node dissection revealed no residual carcinoma in the breast and no involvement of eleven lymph nodes. She completed 4 cycles of Cytoxan and Adriamycin successfully and was to start radiation therapy. 1 week after completing chemotherapy she had a focal seizure with tonicclonic movements of her right arm and no loss of consciousness. An MRI showed cortical infarcts, which were originally thought to be metastatic hemorrhages, in the left parietal and frontal areas and right parietal area. A follow up MRI showed considerable improvement of the cortical lesions, with no evidence of any metastatic cancer. Subsequently, she developed bilateral DVTs for which an IVC filter was placed as it was felt that she was not a candidate for anticoagulation given her recent CNS hemorrhage. She was also found to have bilateral pulmonary emboli on CT scan of the chest. Two other underlying disorders predisposing to thrombosis were found- Factor V Leiden mutation and the prothrombin gene mutation. Further imaging confirmed a thrombotic etiology for her CNS event, and coumadin was started.

Conclusion: This case demonstrates the magnitude of the effect of cancer on thrombosis. This patient had 2 prothrombotic mutations, was a smoker, who had been on the OCP for 10 years prior to menopause, yet had no thrombotic episodes until she developed cancer. Also of interest is that the thrombotic episodes occurred shortly after completion of chemotherapy- another prothrombotic factor.

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