Thrombosis Prediction Based on Reference Ranges of Coagulation-Related Markers in Different Stages of Pregnancy

Abstract

Introduction: Careful monitoring of the hypercoagulable state is required during pregnancy. However, coagulation and fibrinolysis markers are not fully utilized because there are no reference values reflective of coagulation and fibrinolysis dynamics during pregnancy, which differ from the nonpregnant state. Methods: Changes in antithrombin (AT), fibrinogen (Fbg), prothrombin fragment 1þ2 (F 1þ2 ), thrombin-antithrombin complex (TAT), soluble fibrin (SF), D-dimer (DD), and protein S (PS) were investigated in healthy pregnant women, and reference ranges in the early, mid, late, and end stages of pregnancy were established. Results: The AT was essentially constant throughout pregnancy. The Fbg, F 1þ2 , TAT, and DD increased significantly as pregnancy progressed. In contrast, SF did not show a significant increase throughout the entire pregnancy period. Total PS antigen and total PS activity showed a corresponding decrease from early gestation. When test data in 3 cases in which deep vein thrombosis or intrauterine fetal death occurred during pregnancy were compared to the established reference ranges, all of the cases had multiple markers with values that exceeded the reference ranges. Conclusion: Establishing reference ranges for each week could potentially make it possible to evaluate abnormalities of the coagulation and fibrinolysis systems during pregnancy. Of note, SF might be a useful marker that reflects thrombus formation during pregnancy. Larger-scale studies will be required to establish reference ranges for every gestational week.

Thrombogenicity assessment of Pipeline Flex, Pipeline Shield, and FRED flow diverters in an in vitro human blood physiological flow loop model

“…We utilized two fundamental markers of thrombosis as end points in this study. The increase of TAT above baseline indicates progressive thrombin formation and the consumption of anti‐thrombin, and is therefore widely accepted as a clinical biomarker for intravascular generation of thrombin . Similarly, βTG is a measure of platelet degranulation (alpha‐granule release) which is a direct consequence of platelet activation .…”

“…The increase of TAT above baseline indicates progressive thrombin formation and the consumption of anti-thrombin, and is therefore widely accepted as a clinical biomarker for intravascular generation of thrombin. 21,22 Similarly, βTG is a measure of platelet degranulation (alpha-granule release) which is a direct consequence of platelet activation. 23 Both these markers were similar to negative control (empty loop) for the Pipeline Shield device post-experiment.…”

Changes in levels of coagulation parameters in different trimesters among Chinese pregnant women

“…5 However, these biochemical parameters during pregnancy are different from those under non-pregnant conditions for physiological changes in different trimesters. 6 It indicates that routinely used reference intervals cannot be applied for pregnant women; otherwise, it may affect the clinical diagnosis and treatment. In addition, there have been several studies on the coagulation function of healthy pregnant women, but most of them are based on Western population.…”

“…Most reference samples were based on samples obtained from healthy non‐pregnant women 5 . However, these biochemical parameters during pregnancy are different from those under non‐pregnant conditions for physiological changes in different trimesters 6 . It indicates that routinely used reference intervals cannot be applied for pregnant women; otherwise, it may affect the clinical diagnosis and treatment.…”

Thrombogenicity assessment of Pipeline, Pipeline Shield, Derivo and P64 flow diverters in an in vitro pulsatile flow human blood loop model

“…Both TAT [29,30] and βTG [31] are widely accepted as indicators of clinical thrombosis and were therefore used as end-points for thrombogenicity measurements in this study. TAT and βTG measures post experiment for Pipeline Shield were statistically similar to the Negative Control.…”