- Case report
- Open Access
Ventricular metastasis resulting in disseminated intravascular coagulation
© John and Davis; licensee BioMed Central Ltd. 2005
- Received: 01 March 2005
- Accepted: 24 May 2005
- Published: 24 May 2005
Disseminated Intravascular Coagulation (DIC) complicates up to 7% of malignancies, the commonest solid organ association being adenocarcinoma. Transitional Cell Carcinoma (TCC) has rarely been associated with DIC.
A 74-year-old woman with TCC bladder and DIC was found to have a cardiac lesion suspicious for metastatic disease. The DIC improved with infusion of plasma and administration of Vitamin K, however the cardiac lesion was deemed inoperable and chemotherapy inappropriate; given the patients functional status. We postulate that direct activation of the coagulation cascade by the intraventricular metastasis probably triggered the coagulopathy in this patient.
Cardiac metastases should be considered in cancer patients with otherwise unexplained DIC. This may influence treatment choices.
- Factor VIIa
- Tissue Factor
- Disseminate Intravascular Coagulation
- Transitional Cell Carcinoma
- Disseminate Intravascular Coagulation
DIC is characterised by the widespread activation of coagulation. This in turn results in intravascular formation of fibrin and ultimately thrombotic occlusion of small to medium sized vessels . The commonest causes are sepsis and trauma. Malignancy is a well recognised cause of a prothrombotic state, with DIC occurring in up to 7% of solid organ tumours. It is most frequently associated with adenocarcinomas such as pancreatic, breast and prostate cancer. Transitional cell carcinoma is rarely associated with DIC, with very few reports in the literature.
A 74 year old woman presented with a two day history of haematuria and increasing lethargy one month following palliative radiotherapy to the bladder for a T4 Grade III urothelial carcinoma. Clinical examination revealed large ecchymoses over both upper and lower limbs as well as oral mucosal bleeding without any evidence of petechiae. The patient was apyrexial and vital signs were all within normal limits. There were no other significant findings on cardiovascular, respiratory and abdominal examination.
Although a hypercoagulable state exists in virtually all patients with malignancy, the incidence of overt DIC is much lower . The aetiology of the activation of coagulability in malignancy is multifactorial and poorly understood. Molecular changes which may influence hypercoagulability include the expression of tissue factor (TF) as well as the proteases hepsin and cancer procoagulant by circulating tumour cells .
TF assembles with factor VIIa to activate factors IX and X thereby triggering thrombin formation. TF has been demonstrated to exist in normal vascular endothelial cells suggesting a role in initiating rapid activation of coagulation. It is rarely expressed in normal epithelial tissue but has been found to be expressed in malignant tissue such as breast cancer, whilst not being present in patients with benign fibrocystic disease . The degree of tissue factor expression has been shown to correlate with metastatic potential and histological differentiation such that increased TF expression results an increased potential to metastasise and a more undifferentiated histological appearance [6, 7]. Cancer procoagulant has been found in malignant and foetal tissue, but not in normally differentiated tissue[8, 9]. Its only known property is the calcium and vitamin K dependent conversion of factor X into Xa, independent of the TF / factor VIIa complex. Hepsin, a protease found on hepatocyte surface membranes but also in several tumour cell lines, has been shown to initiate coagulation by activating factor VIIa independent of TF .
The heart is an under-recognised site of metastatic disease in patients with cancer. In one series, the incidence at autopsy was 1.25%. The commonest types of malignancy to spread to the heart in this series were lung and oesophageal cancers as well as lymphomas . This reflects the direct proximity of these tumours to the heart, with direct invasion being the likely pathogenesis. Lung, breast, soft tissue carcinomas, renal cell carcinomas, lymphomas and melanoma are most frequently associated with cardiac involvement. This usually results in pericardial or epicardial disease, with endocardial metastases being less common. There are reports of cardiac metastases from metastatic TCC in the literature, however we could find only one other report of a patient with a cardiac metastases presenting with DIC  and this was associated with cervical carcinoma.
The mechanism of DIC in the described case is speculative but may relate to the activation of coagulation pathways directly by the interaction of tumour antigens with plasma . The postulated mechanism of DIC in this case is the direct exposure of tumour cells within the right ventricle to circulating plasma, thus triggering direct activation of the coagulation cascade through mechanisms mentioned above. Although we are unable to prove causality, given that TCC is rarely associated with DIC and that this phenomenon only developed when the tumour metastasised to the patient's heart; this explanation appears more plausible than the assumption that the patients malignancy alone resulted in DIC.
This case demonstrates that cardiac metastases should be considered in all cancer patients with otherwise unexplained DIC and that this may influence treatment choices.
The author(s) declare that they have no competing interests.
Permission was obtained through University of Melbourne Human Research and Ethics Committee for publication of this case report as due to death of the patient her consent could not be obtained.
- Levi M, Ten Cate H: Disseminated intravascular coagulation. N Engl J Med. 1999, 341: 586-592. 10.1056/NEJM199908193410807.View ArticlePubMedGoogle Scholar
- Sallah S, Wan JY, Nguyen NP, Hanrahan LR, Sigounas G: Disseminated intravascular coagulation in solid tumors: clinical and pathologic study. Thromb Haemost. 2001, 86: 828-833.PubMedGoogle Scholar
- Colman RW, Rubin RN: Disseminated intravascular coagulation due to malignancy. Semin Oncol. 1990, 17: 172-186.PubMedGoogle Scholar
- Sampson MT, Kakkar AK: Coagulation proteases and human cancer. Biochem Soc Trans. 2002, 30: 201-207. 10.1042/BST0300201.View ArticlePubMedGoogle Scholar
- Contrino J, Hair G, Kreutzer DL, Rickles FR: In situ detection of tissue factor in vascular endothelial cells: correlation with the malignant phenotype of human breast disease. Nat Med. 1996, 2: 209-215. 10.1038/nm0296-209.View ArticlePubMedGoogle Scholar
- Kakkar AK, Chinswangwatanakul V, Lemoine NR, Tebbutt S, Williamson RC: Role of tissue factor expression on tumour cell invasion and growth of experimental pancreatic adenocarcinoma. Br J Surg. 1999, 86: 890-894. 10.1046/j.1365-2168.1999.01153.x.View ArticlePubMedGoogle Scholar
- Kakkar AK, Lemoine NR, Scully MF, Tebbutt S, Williamson RC: Tissue factor expression correlates with histological grade in human pancreatic cancer. Br J Surg. 1995, 82: 1101-1104.View ArticlePubMedGoogle Scholar
- Gordon SG, Mielicki WP: Cancer procoagulant: a factor X activator, tumor marker and growth factor from malignant tissue. Blood Coagul Fibrinolysis. 1997, 8: 73-86.View ArticlePubMedGoogle Scholar
- Gordon SG, Franks JJ, Lewis B: Cancer procoagulant A: a factor X activating procoagulant from malignant tissue. Thromb Res. 1975, 6: 127-137. 10.1016/0049-3848(75)90018-3.View ArticlePubMedGoogle Scholar
- Kazama Y, Hamamoto T, Foster DC, Kisiel W: Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation. J Biol Chem. 1995, 270: 66-72. 10.1074/jbc.270.1.66.View ArticlePubMedGoogle Scholar
- Lam KY, Dickens P, Chan AC: Tumors of the heart. A 20-year experience with a review of 12,485 consecutive autopsies. Arch Pathol Lab Med. 1993, 117: 1027-1031.PubMedGoogle Scholar
- Harvey RL, Mychaskiw G, Sachdev V, Heath BJ: Isolated cardiac metastasis of cervical carcinoma presenting as disseminated intravascular coagulopathy. A case report. J Reprod Med. 2000, 45: 603-606.PubMedGoogle Scholar
- Sutherland DE, Weitz IC, Liebman HA: Thromboembolic complications of cancer: epidemiology, pathogenesis, diagnosis, and treatment. Am J Hematol. 2003, 72: 43-52. 10.1002/ajh.10263.View ArticlePubMedGoogle Scholar
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