Early changes of a novel APC-dependent thrombin generation assay during chemotherapy independently predict venous thromboembolism in cancer patients--a pilot study.
OBJECTIVE
Identifying cancer patients who are most at risk for venous thromboembolism (VTE) is essential to improve timely delivery of chemotherapy. Several studies have been performed to identify novel candidate biomarkers, but no agreement has yet been reached. In this light, we sought to analyze whether a dynamic evaluation of early changes of activated protein C (APC) function during chemotherapy could be predictive of a first VTE episode in cancer outpatients, thus improving risk stratification.


METHODS
A retrospective single-center pilot study was conducted to investigate the adequacy of a dynamic evaluation of a novel APC-dependent thrombin generation assay (HemosIL ThromboPath (ThP)) in predicting VTE in 208 ambulatory cancer patients, enrolled on the basis of tight inclusion criteria, prior to start and before the second cycle of a new chemotherapy regimen.


RESULTS
Retrospective analysis of samples showed the occurrence of an acquired APC resistance during chemotherapy, which was predictive of VTE. Univariate Cox proportional hazards survival analysis showed that early ThP changes predicted VTE (stable vs. decreasing ThP: hazard ratio (HR) 0.21; 95% CI 0.10-0.19; p < 0.0001), which was confirmed in the multivariate model (HR 0.25; CI 0.12-0.52, p < 0.0001). Stratification of patients according to a risk assessment model showed a 0.18 HR for stable vs. decreasing ThP assay results in an intermediate risk group.


CONCLUSIONS
We may thus conclude that early changes of ThP assay in patients on active chemotherapy enhance VTE risk stratification, helping in identifying a population of cancer patients who might benefit from thromboprophylaxis.
Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Via della Pisana 235, 00163, Rome, Italy. patrizia.ferroni@sanraffaele.it
Patrizia
P
Ferroni
Francesca
F
Martini
Ilaria
I
Portarena
Italia
I
Grenga
Silvia
S
Riondino
Francesca
F
La Farina
Anastasia
A
Laudisi
Fiorella
F
Guadagni
Mario
M
Roselli
D020016:Activated Protein C Resistance / Q000209:etiology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010045:Outpatients; D010865:Pilot Projects; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011486:Protein C / Q000378:metabolism*; D012189:Retrospective Studies; D012306:Risk; D018570:Risk Assessment / Q000379:methods; D016019:Survival Analysis; D013917:Thrombin / Q000378:metabolism*; D054556:Venous Thromboembolism / Q000209:etiology*
D000970:Antineoplastic Agents; D011486:Protein C; D013917:Thrombin