Coagulopathy and Venous Thromboembolic Events Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Abstract

Background Coagulopathy after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is recognized but few details have been studied. Objectives The aim of this study was to investigate changes in coagulation biomarkers and their predictive ability for venous thromboembolism (VTE). Methods Patients undergoing CRS and HIPEC at Uppsala University Hospital, Sweden, from 2004 to 2014 were included in a prospective study of coagulation biomarkers. Prothrombin time international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), fibrinogen, antithrombin, D-dimer, and platelets were sampled on postoperative days 1, 2, 5, and 10. Logistic regression analysis was used to evaluate predictive capacity for coagulation-related complications. Results Overall, 380 patients were included (214 females, mean age 56 years); 38 patients had a history of thromboembolism and 57 were active smokers. Mean perioperative blood loss was 1228 mL and 231 (61%) received perioperative blood transfusions. PT-INR and APTT were elevated directly after surgery but returned to normal levels on postoperative day 5. Conversely, fibrinogen, platelet count, D-dimer, and antithrombin increased by postoperative day 5 and continued to increase up to day 10. There were 23 radiologically verified cases of VTE within 6 months. The multivariate analysis identified a completeness of cytoreduction score of 2–3 (p = 0.047) and day 2 D-dimer (p = 0.0082) as independent risk factors for postoperative VTE. Conclusion Significant postoperative changes in coagulation biomarkers occur with dynamic changes over 10 days postoperatively. The incidence of symptomatic VTE was low. Residual tumor at completion of surgery and elevated D-dimer on day 2 were independent risk factors for postoperative VTE.

Changes in Coagulation in Cancer Patients Undergoing Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy Treatment (HIPEC)—A Systematic Review

“…15 24 35 36 37 38 39 41 43 44 45 46 47 The HIPEC method was reported in 13 out of 15 studies. 15 24 35 36 38 39 40 41 43 44 45 46 47 Six studies used the open abdomen method, 24 35 38 39 40 44 45 four used the closed abdomen method, 41 43 46 47 and two used both methods for HIPEC. 15 36 Intraperitoneal chemotherapy solutions were reported in 13 of 15 studies, 15 24 35 36 38 39 40 41 43 44 45 46 47 with oxaliplatin utilized in four studies 15 24 39 41 and mitomycin-c in eight studies.…”

“…15 24 35 36 38 39 40 41 43 44 45 46 47 Six studies used the open abdomen method, 24 35 38 39 40 44 45 four used the closed abdomen method, 41 43 46 47 and two used both methods for HIPEC. 15 36 Intraperitoneal chemotherapy solutions were reported in 13 of 15 studies, 15 24 35 36 38 39 40 41 43 44 45 46 47 with oxaliplatin utilized in four studies 15 24 39 41 and mitomycin-c in eight studies. 15 24 36 40 43 44 45 47 Cisplatin was also used in eight studies, 15 24 40 43 44 45 46 47 either as monotherapy or in combination with mitomycin-c 15 40 43 44 or doxorubicin.…”

“…Changes in secondary hemostasis from postoperative day 2 to 10 were reported in 10 studies. 15 24 37 38 39 40 41 43 45 47 Prolonged INR 37 39 40 45 47 and aPTT 15 24 39 40 43 45 47 indicated impaired secondary hemostasis. However, Dranichnikov et al reported both INR and aPTT within reference ranges from postoperative day 5 to 10.…”

“…24 Also, Dranichnikov et al demonstrated that elevated d-dimer at postoperative day 5 and 10 was not significantly associated with an increased risk for venous thromboembolism. 24…”

Thrombotic Events in Cancer Patients

“…• Time after cancer diagnosis: 3-6 months after cancer diagnosis is highest risk full time for thrombotic events. Although, some other research suggest that greatest risk of thromboembolism is within the first year following diagnosis [8][9][10].…”