In:
Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 3226-3226
Abstract:
Introduction: Venous thromboembolism (VTE) is common in patients with active malignancy. While thromboprophylaxis can mitigate this risk, current guidelines do not support routine use as the benefit is modest and maybe negated by an increase in bleeding complications. However, there is significant variation in VTE risk within the cancer population, thus prophylaxis can be considered in high-risk patients. The Khorana score (KS) is validated to predict chemotherapy-associated VTE; however, it has several limitations including variable performance based on tumor type as well as a static risk categorization, based on pre-chemotherapy laboratory data, rather than a continuous assessment. Thrombin generation (TG) is an emerging biomarker that assesses global coagulation activation and predicted increased VTE risk in cancer patients in the Vienna Cancer and Thrombosis Study (PMID: 21464402). This study enrolled a heterogeneous cancer population, however, peak TG was not reported by tumor type nor were the TG levels monitored over time in response to systemic therapy. The primary aim of this study was to assess the relationship between TG (both peak TG and endogenous thrombin potential, ETP) and KS. Secondary outcomes were to evaluate the impact of systemic therapy on peak TG and ETP levels over time and to assess the relationship between TG and clinical outcomes. Methods: This was a prospective study that enrolled adults with newly diagnosed, locally advanced or metastatic adenocarcinoma of the lung or pancreas. All patients received their care at Dartmouth Hitchcock Medical Center. Those with a history of active VTE or use of full dose anticoagulant within 30 days prior to enrollment were excluded. After informed consent, KS was calculated and blood was collected in sodium citrate tubes at 3 different time points (at initiation of therapy, and at the beginning of the 2 nd and 3 rd cycles of systemic therapy). Platelet-poor plasma was prepared by centrifugation and stored at - 80°C until analysis by calibrated automated thrombogram (CAT; Thrombinoscope BV, Maastricht, Netherlands) using 1 pM tissue factor and 4 uM phospholipids to trigger coagulation reactions. Measurements were performed in triplicate for each specimen, and raw data were converted to peak TG and ETP. Information about VTE events, response to treatment and survival was obtained by chart review. Mean and standard deviation were calculated for continuous variables and unpaired T test was used for statistical analysis. Results: We report the results from 32 participants (17 lung, 15 pancreas). The majority of patients had metastatic disease (94%) and all received systemic therapy. The median age was 67 and 56% of participants were male. The KS breakdown for the cohort was: KS1, 25%; KS2, 53%; KS3, 19%; KS4, 3%. Mean peak TG was 279, 352, 487 and 325 nmole and mean ETP was 1320, 1653, 2252, 1726 nmole/min for KS 1, 2, 3 and 4, respectively. Initial peak TG and ETP levels were significantly higher in the KS ≥2 group compared to those with KS=1 (peak TG: 384 ±135 vs 279 ±82, p 0.047; Initial ETP: 1806 ±632 vs 1320 ±286, p 0.045). There were 8 VTE events (25%) with all but one occurring in the pancreatic cancercohort; all events occurred in KS 2 and 3 groups (75% and 25% respectively). No statistically significant difference was observed for initial peak TG or ETP in those with VTE vs those without (Peak TG: 342 ±171 vs 363 ±119, p 0.701; ETP: 1736 ±720 vs 1667 ±571, p 0.783). Both peak TG and ETP decreased in response to systemic therapy (initial peak TG vs final: 376 ±115 vs 225 ±125, p 0.0001; initial ETP vs final: 1799 ±498 vs 1254 ±423, p 0.0003). No significant difference in survival was noted based on initial ETP level of & lt;1500 nmole/min vs ≥1500 nmole/min (574 ±620 vs 287 ±227, p 0.069). Conclusions: There appears to be an association between KS and peak TG and ETP. In addition, both peak TG and ETP declined in response to systemic therapy, suggesting that the degree of coagulation activation is related to tumor burden. Our findings in this small study support further investigation of TG for VTE risk assessment in cancer patients. Future strategies incorporating TG into risk stratification models may allow oncologists to better identify the population that may benefit most from pharmacologic thromboprophylaxis. Funding: Northern New England Clinical Oncology Disclosures No relevant conflicts of interest to declare.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood-2021-154333
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2021
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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