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

Abstract

Venous thromboembolism and postoperative bleeding are complications of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this systematic review was to summarize current knowledge on the effect of cytoreductive surgery with HIPEC on coagulation and fibrinolysis within 10 days after surgery. Studies were identified in PubMed, Embase, and Web of Science on December 12, 2022. Data on biomarkers of coagulation and fibrinolysis measured preoperatively up to the 10th postoperative day were extracted. Among 15 included studies, 13 studies reported markers of primary hemostasis. Eleven studies found reduced platelet count following cytoreductive surgery with HIPEC and two studies reported reduced platelet function. Twelve studies reported impaired secondary hemostasis until postoperative day 10 indicated by prolonged international normalized ratio, prothrombin time, and activated partial thromboplastin time. Fibrinogen was decreased in three studies from preoperative to postoperative day 3 switching to increased levels until postoperative day 10. In accordance, three studies found reduced maximum amplitude and maximum clot firmness by thromboelastography/thromboelastometry (ROTEM/TEG) on the first postoperative day indicating impaired clot strength. Four studies demonstrated increased d-dimer, factor (F) VIII, and thrombin generation during the 10 postoperative days. Four studies investigated fibrinolysis by ROTEM/TEG and plasminogen activator inhibitor-1 (PAI-1) after cytoreductive surgery with HIPEC reporting contradictive results. In conclusion, a decrease in platelet count and subtle changes in secondary hemostasis were found following cytoreductive surgery with HIPEC. Data on the effect of cytoreductive surgery with HIPEC on fibrinolysis are sparse and this needs to be further investigated.

Cancer-Associated Thrombosis and Beyond: Biomarkers, Treatments, and Cancer-Hemostasis Interactions

“…21 The next paper in the present issue by Lundbech et al aims to get behind the potential increased VTE risk in HIPEC and reviews the effect of HIPEC on hemostatic activation. 22 The authors conclude that possible mechanisms behind increased VTE risk are an increased acute response, indicated by increased factor VIII and fibrinogen, and possibly impaired fibrinolysis. HIPEC did not greatly influence standard coagulation markers or platelet count, while dynamic assays of platelet activation, thrombin generation, or fibrin formation have only been sparsely researched.…”