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Prothrombotic fibrin clot properties associated with increased endogenous thrombin potential and soluble P‐selectin predict occult cancer after unprovoked venous thromboembolism
Author(s) -
Mrozinska Sandra,
Cieslik Joanna,
Broniatowska Elżbieta,
Malinowski Krzysztof Piotr,
Undas Anetta
Publication year - 2019
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.14579
Subject(s) - medicine , venous thromboembolism , fibrin , thrombin generation , cardiology , thrombin , occult , fibrinogen , thrombosis , platelet , pathology , immunology , alternative medicine
Background Compact fibrin clots relatively resistant to lysis are observed in patients at increased risk of venous thromboembolism ( VTE ) including malignancy. The citrullinated histone H3 (H3Cit) predicts VTE in cancer patients. Objectives We performed a cohort study to investigate whether abnormal clot properties predict cancer diagnosis following unprovoked VTE . Methods In 369 consecutive patients aged <70 years without malignancy detected during routine screening, we determined plasma clot permeability (K s ) and clot lysis time ( CLT ), along with several prothrombotic markers and H3Cit after 2 to 8 months since VTE . Results During follow‐up (median, 37; interquartile range, 33‐39 months), malignancy was diagnosed in 22 patients (6%), who were older. This group had denser fibrin networks (−13% K s ), impaired fibrinolysis (+25.5% CLT ), increased endogenous thrombin potential ( ETP ,+7%), soluble P‐selectin (+40.3%), and H3Cit (+169.2%) measured off anticoagulation after median 4 months since VTE . The K s and CLT correlated with H3Cit ( r = −.58 and r = .31, P < .05, respectively). The Kaplan–Meier survival analysis showed that reduced K s (the first quartile, ≤6.2 × 10 −9 cm 2 ), prolonged CLT (the top quartile, >106 min), and higher ETP (the top quartile, >1657 nM × min) were predictors of cancer diagnosed during follow‐up. The multivariable Cox proportional hazards model showed that patients with the prothrombotic clot phenotype (low K s and long CLT ) had the highest risk of cancer diagnosis [ hazard ratio(HR) , 23.4; 95% confidence interval (CI) , 6.67‐82.15]. Conclusions Prothrombotic clot properties following unprovoked VTE might help identify patients at risk of a diagnosis of cancer within the first 3 years of follow‐up.