Tissue-type plasminogen activator-induced fibrinolysis is enhanced in patients with breast, lung, pancreas and colon cancer.

Although cancer-mediated changes in hemostatic proteins unquestionably promote hypercoagulation, the effects of neoplasia on fibrinolysis in the circulation are less well defined. The goals of the present investigation were to determine if plasma obtained from patients with breast, lung, pancreas and colon cancer was less or more susceptible to lysis by tissue-type plasminogen activator (tPA) compared to plasma obtained from normal individuals. Archived plasma obtained from patients with breast (n = 18), colon/pancreas (n = 27) or lung (n = 19) was compared to normal individual plasma (n = 30) using a thrombelastographic assay that assessed fibrinolytic vulnerability to exogenously added tPA. Plasma samples were activated with tissue factor/celite, had tPA added, and had data collected until clot lysis occurred. Additional, similar samples had potato carboxypeptidase inhibitor added to assess the role played by thrombin-activatable fibrinolysis inhibitor in cancer-modulated fibrinolysis. Rather than inflicting a hypofibrinolytic state, the three groups of cancers demonstrated increased vulnerability to tPA (e.g. decreased time to lysis, increased speed of lysis, decreased clot lysis time). However, hypercoagulation manifested as increased speed of clot formation and strength compensated for enhanced fibrinolytic vulnerability, resulting in a clot residence time that was not different from normal individual thrombi. In sum, enhanced hypercoagulability associated with cancer was in part diminished by enhanced fibrinolytic vulnerability to tPA.

Plasmatic hypercoagulation in patients with breast cancer: role of heme oxygenase-1.

Breast cancer is an important health threat to women worldwide, and is associated with a 9-14% incidence of thrombophilia. Of interest, patients with breast cancer have been noted to have an increase in endogenous carbon monoxide production via upregulation of heme oxygenase-1 activity. Given that it has been demonstrated that carbon monoxide enhances plasmatic coagulation in vitro and in vivo, we sought to determine whether patients with breast cancer had an increase in endogenous carbon monoxide and concurrent plasmatic hypercoagulability. Breast cancer patients who were not smokers scheduled to undergo partial or complete mastectomy (n = 18) had 15 ml of whole blood collected via an indwelling intravenous catheter and anticoagulated with sodium citrate. Whole blood was centrifuged and citrated plasma assessed with a thromboelastometric method to measure coagulation kinetics and the formation of carboxyhemefibrinogen. Breast cancer patients were determined to have an abnormally increased carboxyhemoglobin concentration of 2.5 ±â€Š1.3%, indicative of heme oxygenase-1 upregulation. Breast cancer patient plasma on average clotted 73% more quickly and had 32% stronger thrombus strength than normal individual (n = 30) plasma. Further, 44% of breast cancer patients had plasma clot strength that exceeded the 95% confidence interval value observed in normal individuals, and 75% of this hypercoagulable subgroup had carboxyhemefibrinogen formation. Future investigation of the role played by heme oxygenase-1-derived carbon monoxide in the pathogenesis of breast cancer-related thrombophilia is warranted.

Trends in post-mastectomy reconstruction: a SEER database analysis.

BACKGROUND AND OBJECTIVES: This study was performed to investigate recent trends and factors associated with immediate breast reconstruction (IBR) using a large population-based registry. We hypothesized that rates of IBR have increased since passage of the Women's Health and Cancer Rights Act of 1998. METHODS: The SEER (surveillance, epidemiology and end results) database was used to evaluate Stage I-III breast cancer (BC) patients who underwent total mastectomy from 1998 to 2008. Univariate and multivariate analyses were performed to study predictors of IBR. RESULTS: Of 112,348 patients with BC treated by mastectomy 18,001 (16%) had IBR. Rates of IBR increased significantly from 1998 to 2008 (P < 0.0001). Use of IBR significantly decreased as patient age increased (P < 0.0001), as stage increased (P < 0.0001), and as the number of positive lymph nodes increased (P < 0.0001). Estrogen receptor+/progesterone receptor+ (ER+/PR+) patients had significantly higher IBR rates than ER-/PR-patients (P < 0.0001). IBR was used in 3,615 of 25,823 (14.0%) of patients having post-mastectomy radiation (XRT) and in 14,188 of 86,513 (16.4%) of those not having XRT (P < 0.0001). CONCLUSIONS: The utilization of IBR has increased significantly over the last decade. IBR was found to be significantly associated with age, race, geographical region, stage, ER, grade, LN status, and XRT (P < 0.0001).