Prospective evaluation of protein C and factor VIII in prediction of cancer-associated thrombosis

Abstract

Venous thromboembolism (VTE) is a preventable disease, yet it is one of the leading causes of death among patients with cancer. Improving risk stratification mechanisms will allow us to personalize thromboprophylaxis strategies. We sought to evaluate Collagen and Thrombin Activated Platelets (COAT-platelets) as well as protein C and factor VIII as biomarkers predictive of cancer-associated thrombosis in a prospective cohort of patients with cancer. Protein C was selected as a candidate based on bioinformatics prediction. Blood samples were collected before chemotherapy. All specimen processing was blinded to clinical data. Surveillance and adjudication of the main outcome of VTE was performed for up to 1 year. We used Cox proportional hazard regression to measure the association of biomarkers and incident events using SAS 9.2 for all statistical analysis. Death was modeled as a competing event. Among 241 patients followed for an average of 10.4 months, 15% died and 13% developed a VTE. COAT-platelets were not predictive of VTE. Low levels of pre-chemotherapy protein C (< 118 %) (HR 2.5; 95%CI 1.1–5.5) and high baseline factor VIII (> 261 % I) (HR 3.0; 95%CI 1.1–8.0) were predictive of VTE after adjusting for age, Khorana prediction risk, metastatic disease and D dimer. In addition, low protein C was predictive of overall mortality independent of age, metastatic disease and functional status (HR 2.8; 95%CI 1.3–6.0). Addition of these biomarkers to Cancer-VTE risk prediction models may add to risk stratification and patient selection to optimize thrombo-prophylaxis.

Promising biomarkers for the prediction of catheter‐related venous thromboembolism in hospitalized children: An exploratory study

“…Similarly, FVIII has shown prospective predictive potential in a subset of adults, both in association with CVC and without CVC (adjusted OR = 3), with FVIII levels >200%. None of these studies evaluated the value of combining clinical prediction tools and biomarkers, but several compared the two approaches in the evaluation of at‐risk adults …”

“…Several adult studies demonstrated the association of elevated TG parameters with the occurrence of the first VTE event (OR = 1.7) and with recurrence of unprovoked VTE (ORs = 1.6‐4.6) . Similarly, FVIII has shown prospective predictive potential in a subset of adults, both in association with CVC and without CVC (adjusted OR = 3), with FVIII levels >200%. None of these studies evaluated the value of combining clinical prediction tools and biomarkers, but several compared the two approaches in the evaluation of at‐risk adults …”

Increased activity of procoagulant factors in patients with small cell lung cancer

“…In addition, procoagulant phospholipids (PPL), i.e. anionic phospholipids, mainly phosphatidylserine, and a high level of coagulation factor VIII (FVIII), which is an acute-phase protein, have been associated with an increased risk of thrombosis [17,18] also including cancer patients [7,[19][20][21][22]. PPL is also present on the surface of EVs in plasma.…”

Association of Coagulation Factors VIII/XI/XIII Polymorphisms With Coagulation Factor Activities and Deep Vein Thrombosis After Artificial Joints Replacement

“…10 It is reported that increased FVIII activity was a risk factor for venous thrombosis, and plasma activity of FVIII is mainly affected by genetic polymorphisms. 11 The major role of coagulation factor IX (factor X, FXA) in the coagulation process is to maintain the generation of thrombin and inhibition of fibrinolysis. 12 It is reported that people with high levels of FXI (10%) had 2.2-fold increased risk of DVT, compared with other people (90%).…”