Assessment of Hypercoagulability in Splanchnic Vein Thrombosis by Measurement of the Hemostasis Enzymes Thrombin and Activated Protein C.

Splanchnic vein thrombosis (SVT), which is particularly prevalent in myeloproliferative neoplasms (MPNs), has a multifactorial pathomechanism involving the anticoagulant protein C (PC) pathway. To better characterize the hypercoagulable state in SVT we assessed its key enzymes thrombin and activated PC (APC). The study population included 73 patients with SVT, thereof 36 MPN+, confirmed by bone marrow biopsy, 37 MPN-, and 30 healthy controls. Direct measurement of the active enzyme forms of thrombin and APC in the circulation was achieved by using oligonucleotide-based enzyme capture assays (OECA). Additionally, activation markers of coagulation and fibrinolysis were measured. Plasma levels of free thrombin and APC were higher in the MPN+ than in the MPN- cohort, with 0.49 vs. <0.46 pmol/L (p = 0.0057), respectively, 1.23 vs. 0.58 pmol/L (p = 0.0122), and in healthy controls (vs. <0.46 pmol/L, p = 0.0012; vs. 0.54 pmol/L, p = 0.0035). The indirect activation markers prothrombin fragment 1+2, thrombin-antithrombin complex, and D-dimer did not differ between groups. Receiver operating characteristic analysis suggested that SVT patients with MPN can be better distinguished by APC than by conventional indirect thrombin markers. A potential application of these biomarkers to guide anticoagulant therapy and to investigate the role of the PC pathway in MPN-associated hypercoagulability should be further studied.