Increased levels of cHK in plasma from patients with cancer. (A) HK cleavage in plasma from patients with pancreatic cancer and healthy donors (normal) was determined by immunoblotting using antibody to HK domain 5. (B) The same plasmas as in (A) were analyzed using an antibody specific for the C terminus of the free HK heavy chain (HC) after reduction (HKa1; supplemental Figure 1). (C) Ratio of cHK/HK in plasma from healthy individuals and patients with pancreatic cancer (PANC) (n = 26), determined by Wes capillary immunoblotting. (D) Ratio of cHK/HK in healthy individuals and patients presenting to the cancer thrombosis clinic (n = 21) with symptoms of VTE, as determined by Wes capillary immunoblotting. Bars represent means ± SEM. ***P < .001, ****P < .0001, unpaired Student t test with Welch’s correction. (E) Log relative hazard of VTE or death vs cHK/total HK ratio from the Cox proportional hazard modeling of patients with different types of cancer. Each red dot indicates a VTE or death event, and each black dot indicates a censored event; the shaded area is the 95% confidence interval for the log hazard. (F) Log relative hazard of VTE only (censored at death) vs cHK/total HK ratio from the Cox proportional hazard modeling of patients with different types of cancer. Each red dot indicates a VTE event, and each black dot indicates a censored event; the shaded area is the 95% confidence interval for the log hazard. (G) FXII activation by EVs immunopurified from a healthy donor or from patients with pancreatic or colon cancer. Data are means ± SEM. *P < .05, ***P < .001, 1-way ANOVA with a unpaired Student t test with multiple comparisons.