Dabigatran does not affect performance of coagulation tests

The analytical performances of laboratory coagulation tests in patients treated with the direct oral anticoagulant (DOAC) dabigatran are comparable to those in a healthy population, according to a recent study (J Appl Lab Med 2024; doi: 10.1093/jalm/jfae116).

DOACs are preferred treatments for venous thrombosis and atrial fibrillation (AF). In recent years, their use has soared in patients with these diagnoses, despite unclear biological variation of hemostatic markers among them. Ideally, biological variance should be measured in patient populations for whom these tests are ordered, but underlying data are mostly from healthy individuals.

To fill in this gap, researchers determined the biological variance of activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen, and trough dabigatran levels in AF patients treated with dabigatran long-term.

In a prospective cohort study, the researchers followed 18 patients with AF treated with dabigatran for more than 3 months. The researchers determined the biological variation of APTT, PT, fibrinogen, and dabigatran levels during a follow-up of more than 1 year and calculated within-subject, between-subject, and analytical variation. In up to 10 monthly blood collections, the researchers measured APTT, PT, fibrinogen, and trough dabigatran levels and calculated between-subject variance (CVG), within-subject variance (CVI), and analytical variance (CVA). In all, they measured and made calculations using 130 samples. Ten patients (55.6%) completed the full follow-up of 10 samples. Eight participants did not complete the follow-up protocol.

For APTT, CVG was 11.5%, the CVI 8.8%, and the CVA 1.1%. For PT, these values were 5.2%, 4.0%, and 1.0%; and for fibrinogen, 13.6%, 11.8%, and 1.6%, respectively. For dabigatran levels, the values were 37.9%, 33.0%, and 3.4%, respectively.

In healthy individuals, previous research had shown CVG of 7.2% and CVI of 2.8% for APTT. For PT, these previously recorded values in healthy individuals were 5.1% and 2.6%. For fibrinogen, they were 17.1% and 10.2%, respectively, according to the paper.

Study limitations include the small sample size and the use of reagents and instruments that differ from those in related previous research, the researchers noted.

New colorectal cancer screening tests fail to measure up

New blood screening tests for colorectal cancer (CRC) are more expensive and less effective than colonoscopy and stool tests, according to recent research (Ann Intern Med 2024; doi:10.7326/ANNALS-24-00910).

About 40% of people ages 50 to 75 are not up to date with U.S. Preventive Services Task Force colorectal cancer screening recommendations, which call for stool tests, colonoscopy, CT colonography, or flexible sigmoidoscopy. Medicare covers CRC screening every 3 years with Food and Drug Administration-approved blood-based tests with sufficient sensitivity and specificity. An approved cell-free.

DNA (cf-DNA) blood test, Guardant Shield, costs $1,495, and has high sensitivity for CRC stages II to IV but not stage I nor CRC precursors, the study said.

In this changing landscape, tradeoffs have emerged between tests’ abilities to detect CRC and CRC precursors, their specificity, their uptake, and their cost. The researchers aimed to estimate the clinical and economic costs of new CRC blood screening tests, compared with commercially available, established alternatives, in average-risk adults aged 45 and older.

Those established tests were colonoscopy, a fecal immunochemical test (FIT), and a multitarget stool DNA test (MT-sDNA, Exact Sciences’ Cologuard). The four emerging screening methods were the cf-DNA tests Guardant Shield and Freenome, as well as the next-generation multitarget stool test (ngMT-sDNA) and a new FIT-RNA test, Geneoscopy ColoSense.

The researchers modeled the relative rate of colorectal cancer and deaths among 100,000 average-risk people using various screening approaches. They found that colonoscopy and FIT would reduce incidence of CRC by 70% and mortality by 75%, versus no screening. The MT-sDNA test would reduce CRC incidence by 68% and mortality by 73%, with similar rates for the ngMT-sDNA and FIT-RNA tests, versus no screening. The cf-DNA tests yielded CRC incidence and mortality reductions of only 42% and 56%, respectively, the researchers wrote.

They also found that colonoscopy and FIT were more effective and less expensive than the cf-DNA and MT-sDNA tests. Meanwhile, the MT-sDNA test was more effective and less expensive than the cf-bDNA test.

The blood tests were better than no screening at all. Otherwise, substituting blood tests would lead to worse outcomes on a population level, the researchers commented.

PIGF May Spot High Risk of Preterm Birth

Mid-pregnancy placental growth factor (PlGF) testing may be a potential tool for identifying pregnancies at highest risk of early preterm birth, researchers reported (JAMA Netw Open 2024; doi: 10.1001/jamanetworkopen.2024.44454).

Preterm birth is defined as prior to 37 weeks of gestation. One-quarter of these births occur before 34 weeks, constituting early preterm birth. These are associated with the greatest risk of adverse infant and childhood outcomes, at tremendous societal cost.

To determine whether PlGF testing at the time of gestational diabetes screening finds pregnancies at higher risk for early preterm birth, the researchers conducted a prospective cohort study at a tertiary care center. The study involved 9,037 singleton pregnancies. Unselected participants had PlGF tests at 24 to 28 weeks’ gestation. The primary outcome was all early preterm birth, while secondary outcomes included iatrogenic preterm birth, spontaneous preterm birth, preeclampsia, stillbirth, and small-for-gestational-age birth weight.

PlGF levels less than 100 pg/mL were associated with a 79.4-fold increased likelihood of early preterm birth. Low PlGF level was present in more than half of iatrogenic early preterm births and about one-third of all antepartum stillbirths.

These findings suggest that PlGF screening timed with routine gestational diabetes screening may be a powerful clinical tool to identify pregnancies at risk of early preterm birth, especially iatrogenic birth. Strategically redirecting healthcare resources to this high-risk group could improve maternal and perinatal outcomes, the researchers said.