From the Journals

Impaired clot lysis associated with mild bleeding symptoms



Patients with self-reported mild bleeding symptoms may have impaired clot lysis, according to investigators. This finding is remarkable because it contrasts with known bleeding disorders, such as hemophilia, which are associated with enhanced clot lysis, reported lead author Minka J.A. Vries, MD, of the Cardiovascular Research Institute Maastricht (CARIM) at Maastricht (the Netherlands) University and her colleagues.


The observational study, which included 335 patients undergoing elective surgery at Maastricht University Medical Center, was conducted to better understand lysis capacity, which is challenging to assess in a clinical setting. Although the Euglobulin Lysis Time (ELT) is often used in the clinic, it cannot determine the influence of hemostatic proteins or formation of a fibrin clot under physiological conditions.

“In the more recently developed lysis assays,” the investigators wrote in Thrombosis Research, “the turbidity lysis assay and the tissue plasminogen activator–rotational thromboelastometry (tPA-ROTEM) [assay], all plasma proteins are present and fibrin is formed under more physiological conditions for the measurement of fibrinolysis.” These two tests were used in the present study.

Of the 335 adult patients, 240 had self-reported mild bleeding symptoms, and 95 did not. Patients with bleeding disorders, thrombocytopenia, or anemia were excluded, as were pregnant women and those taking blood thinners or NSAIDs. Along with assessing time parameters of fibrinolysis, clot-associated proteins were measured for possible imbalances.

“We hypothesized that clot lysis capacity is enhanced in patients with mild bleeding symptoms,” the investigators wrote, based on other bleeding disorders. Surprisingly, the results told a different story.

After adjusting for sex, BMI, and age, patients with bleeding symptoms had lower tPA-ROTEM lysis speed (beta −0.35; P = .007) and longer tPA-ROTEM lysis time (beta 0.29; P = .022) than did patients without bleeding symptoms. The investigators found that tPA-ROTEM measurements depended on factor II, factor XII, alpha2-antiplasmin, plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI), and plasminogen activator inhibitor–1 (PAI-1) level. In contrast, turbidity lysis assay measurements were not significantly different between groups. This latter assay was influenced by alpha2-antiplasmin, TAFI, and PAI-1.

“We did not find evidence for systemic hyperfibrinolytic capacity in patients reporting mild bleeding symptoms in comparison to patients not reporting bleeding symptoms,” the investigators concluded. “tPA-ROTEM even suggested a slower clot lysis in these patients. Though this may appear counterintuitive, our results are in line with two papers assessing systemic clot lysis in mild bleeders.”

While this phenomenon gains supporting evidence, it remains poorly understood.

“We have no good explanation for these findings,” the investigators noted.

This study was funded by the Sint Annadal Foundation Maastricht, Maastricht University Medical Centre, CTMM INCOAG Maastricht, Cardiovascular Research Institute Maastricht, and the British Heart Foundation. No conflicts of interest were reported.

SOURCE: Vries MJA et al. Thromb Res. 2018 Dec 4. doi: 10.1016/j.thromres.2018.12.004.

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