HemosIL ThromboPath assay an economical, sensitive option for venous thromboembolism screening
The HemosIL ThromboPath assay is highly sensitive to abnormalities in the protein C (PC) pathway in unselected patients, according to a new study presented at the recent American Heart Association Scientific Session 2018 (AHA 2018), held in Chicago, Illinois.
“The high negative predictive value (NPV) associated with normal test results suggests the potential interest of that assay as part of the screening strategy of PC pathway abnormalities in which that assay would be used as a first-step screening test,” said researchers.
Plasma samples of 597 patients (mean age 45.6 years; range, 15–100 years; 388 females) were screened for biological risk factors for venous thromboembolism. A hundred patients (16.8 percent) were positive for any abnormality in the PC pathway: 45 had congenital and acquired protein S (PS) deficiency, 33 had Factor V (FV) Leiden mutations, 14 had PC deficiency, and eight had lupus anticoagulant (LA). [AHA 2018, abstract 101]
The Protac-Induced Coagulation Inhibition percentage (PICI%) were significantly lower in participants who demonstrated any abnormality in the PC pathway than in those who did not (69.0 percent vs 89.8 percent; p<0.0001).
Moreover, all carriers of FV Leiden mutations (one homozygote, 32 heterozygotes) had PICI% values below the 88.5-percent cutoff level determined from healthy controls. The median PICI% was 67.1 percent (range, 15.3–84.5 percent).
Similarly, 100 percent of participants who presented with PC deficiency (median, 40.3 percent; range, 31.5–88.2 percent), PS deficiency (median, 76.5 percent; range, 32.0–88.3 percent) or LA (median, 79.0 percent; range, 69.0–83.1 percent) failed to meet the predetermined PICI% cutoff value.
In contrast, only 41.5 percent (n=206) of patients without any PC pathway abnormalities fell short of this target. The median PICI% in this subgroup was 89.8 percent [range, 35.8–98.0 percent).
In terms of performance, the sensitivity of the HemosIL ThromboPath assay for detecting any abnormalities in the PC pathway was 100 percent (95 percent CI, 96.4–100 percent), while its specificity was 58.6 percent (54.1–62.9 percent).
In addition, the positive predictive value was determined to be 32.7 percent (27.5–38.3 percent), and the NPV was calculated to be 100 percent (98.7–100 percent).
Researchers then proposed a screening strategy where the HemosIL ThromboPath assay would be used as a first-step screen, and that tests for the four pathways (ie, FV Leiden mutation, PC deficiency, PS deficiency, LA) would be recommended only when initial results showed abnormalities.
In this scenario, there would be a 27.8-percent drop in the total number of tests performed (2,172 vs 2,985), resulting in a 34.5-percent decrease in screening costs.
The excellent sensitivity and NPV of the assay, taken with its corresponding economic benefits and global scope, suggest that the HemosIL ThromboPath may prove to be a simple and practical addition to the current screening regimen for the biological risk factors for venous thromboembolism.
“However, these results deserve to be confirmed in larger scale studies involving populations of different origins and/or in different technical conditions,” said researcher.
A chromogenic thrombin generation assay, the HemosIL ThromboPath assay used in the present study uses optical density to measure thrombin concentration after the addition of a specific chromogenic substance in the presence of absence of Protac. The addition of Protac activates PC to activated PC which, in turn, reduces the production of thrombin.