Combined thrombogenic effects of vessel injury, pregnancy and procoagulant immune globulin administration in mice

Xu, Yanqun; Liang, Yideng; Parunov, Leonid A.; Despres, Daryl; Eckhaus, Michael; Scott, Dorothy E.; Ovanesov, Mikhail V.; Struble, Evi

doi:10.1186/s12959-020-00245-8

Cited by 3 publications

(5 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We used pooled plasma to model the average population response, but we lacked information about possible subject-to-subject variability in TG sensitivity, which will need to be obtained in future studies that utilize single donor samples for each species. Our TG results appear consistent with previous studies of individual animal donors [8][9][10][15][16][17][18][19]. Consistent with previous reports [9,17,18], we observed that rat, mouse, and rabbit samples had smaller thrombin signals and lower TPT and clot times than human plasmas.…”

Section: Discussionsupporting

confidence: 93%

“…Our study may assist in the preclinical evaluation of these inhibitors in animal species. To our knowledge, only two studies have previously observed TG triggered by FXIa in the plasma of animals, and both were performed in mice [ 16 , 35 ]. In the present study, we obtained results analogous to the study [ 16 ] in murine plasma, and we added a comparison to other species.…”

Section: Discussionmentioning

confidence: 99%

“…Despite this, TG is widely used for evaluation of coagulation in animal models, often without a side-by-side comparison between the animal and the human plasma samples under study. Moreover, there is a limited amount of studies that compare TG between various species [ 8 , 10 , 15 , 16 ]. When interspecies differences were evaluated [ 9 , 17 , 18 , 19 ], the authors suggested that while some animals might have TG similar to humans, others might not.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Comparative Thrombin Generation in Animal Plasma: Sensitivity to Human Factor XIa and Tissue Factor

Liang,

Tarandovskiy,

Surov

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

Preclinical evaluation of drugs in animals helps researchers to select potentially informative clinical laboratory markers for human trials. To assess the utility of animal thrombin generation (TG) assay, we studied the sensitivity of animal plasmas to triggers of TG, human Tissue Factor (TF), and Activated Factor XI (FXIa). Pooled human, mouse, rat, guinea pig, rabbit, bovine, sheep, and goat plasmas were used in this study. TF- or FXIa-triggered TG and clotting were measured via fluorescence and optical density, respectively. Thrombin peak height (TPH) and time (TPT), clot time (CT), and fibrin clot density (FCD) were all analyzed. The trigger low and high sensitivity borders (LSB and HSB) for each assay parameter were defined as TF and FXIa concentrations, providing 20 and 80% of the maximal parameter value, unless the baseline (no trigger) value exceeded 20% of the maximal, in which case, LSB was derived from 120% of baseline value. Normal human samples demonstrated lower TPH HSB than most of the animal samples for both TF and FXIa. Animal samples, except mice, demonstrated lower TPT LSB for FXIa versus humans. Most rodent and rabbit samples produced baseline TG in the absence of TG triggers that were consistent with the pre-activation of blood coagulation. FCD was not sensitive to both TF and FXIa in either of the plasmas. Animal plasmas have widely variable sensitivities to human TF and FXIa, which suggests that optimization of trigger concentration is required prior to test use, and this complicates the extrapolation of animal model results to humans.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comparative Thrombin Generation in Animal Plasma: Sensitivity to Human Factor XIa and Tissue Factor

Liang,

Tarandovskiy,

Surov

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Decreased lumen area of placental arteries and artery wall thickening occur in SARS-CoV-2-positive women independent of symptoms. The overlap of vessel wall abnormalities, blood flow abnormalities, and hypercoagulable state increases the risk of thrombosis while gradually diminishing placental functions (Khalil and Granger, 2002;Xu et al, 2020). SARS-CoV-2 damages the placenta by inducing inflammation in the villous chamber (Bouachba et al, 2021).…”

Section: Changes In Placenta Caused By Sars-cov-2 Infectionmentioning

confidence: 99%

Mechanisms of SARS-CoV-2 Placental Transmission

Gostomczyk,

Borowczak,

Siekielska-Domanowska

et al. 2023

Archivum Immunologiae Et Therapiae Experimentalis

View full text Add to dashboard Cite

The widespread occurrence of SARS-CoV-2 infections and the diverse range of symptoms have placed significant strain on healthcare systems worldwide. Pregnancy has also been affected by COVID-19, with an increased risk of complications and unfavorable outcomes for expectant mothers. Multiple studies indicate that SARS-CoV-2 can infiltrate the placenta, breach its protective barrier, and infect the fetus. Although the precise mechanisms of intrauterine transmission remain unclear, factors such as perinatal infection, macrophages, sexual intercourse, and the virus’ interaction with host angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP-1) proteins appear to play a role in this process. The integrity of the placental barrier fluctuates throughout pregnancy and appears to influence the likelihood of fetal transmission. The expression of placental cell receptors, like ACE2, changes during pregnancy and in response to placental damage. However, due to the consistent presence of others, such as NRP-1, SARS-CoV-2 may potentially enter the fetus at different stages of pregnancy. NRP-1 is also found in macrophages, implicating maternal macrophages and Hofbauer cells as potential routes for viral transmission. Our current understanding of SARS-CoV-2's vertical transmission pathways remains limited. Some researchers question the ACE2-associated transmission model due to the relatively low expression of ACE2 in the placenta. Existing studies investigating perinatal transmission and the impact of sexual intercourse have either involved small sample sizes or lacked statistical significance. This review aims to explore the current state of knowledge regarding the potential mechanisms of COVID-19 vertical transmission, identifying areas where further research is needed to fill the gaps in our understanding.

show abstract

“…Normal pregnancy is a hypercoagulable state [1,2] with a balance between coagulation and fibrinolysis, promoting pro-coagulation and limiting fibrinolysis. Pregnancy encourages thrombosis with a reduction of hemorrhagic risk, particularly during the third trimester.…”

Section: Introductionmentioning

confidence: 99%

Plasma Plasmin Generation and its Determinants in Third Trimester of Pregnancy

Okoye

Nwagha

Enebe

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Pregnancy, especially in the third trimester, is associated with changes in the fibrinolytic system that supports clot formation and reduces hemorrhagic risk. Imbalance in the system may occur and can be assessed by plasmin generation (PG). Certain factors are known to affect PG. Aim: To assess PG and its determinants during pregnancy using plasma D dimer and plasmin antiplasmin (PAP) complex levels. Methods: Healthy pregnant women in the third trimester of pregnancy were systematically recruited. Using the ELISA method, venous blood samples were taken to assess D-Dimer and PAP complex plasma levels. IBM Statistical Package for Social Sciences (SPSS) version 21 was used for statistical analysis. Results: We studied a total of 41 subjects with a mean age (SD )and gestational age (SD )of 30.68 (4.69)years and 34.78 (3.34)weeks, respectively. The mean (SD )values of the D dimer and PAP complex were 194 ( 24 )ng/mL and 175 ( 11) ng/mL, respectively. D-Dimer and PAP complex positively correlated with age, GA, and BMI classification. However, only age was statistically significant (p value 0.032 and 0.016, respectively). In addition, the multiple linear regression model showed that with every unit increase in age, D dimer and PAP complex increased by 2.0 (95% CI 0.4 to 3.6) ng/mL and 0.8 (95% CI 0.1 to 1.5) ng/mL respectively, after controlling for GA and BMI. Conclusion: D dimer and PAP levels increased with increasing age during the third trimester of pregnancy, showing that the woman's age is an independent determinant of PG in the third trimester.

show abstract

Combined thrombogenic effects of vessel injury, pregnancy and procoagulant immune globulin administration in mice

Cited by 3 publications

References 37 publications

Comparative Thrombin Generation in Animal Plasma: Sensitivity to Human Factor XIa and Tissue Factor

Comparative Thrombin Generation in Animal Plasma: Sensitivity to Human Factor XIa and Tissue Factor

Mechanisms of SARS-CoV-2 Placental Transmission

Plasma Plasmin Generation and its Determinants in Third Trimester of Pregnancy

Contact Info

Product

Resources

About