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Advanced Pharmaceutical Bulletin Nov 2023Several vaccine-induced thrombotic thrombocytopenia syndrome (VITTS) cases have been reported after the ChAdOx1 nCov-19 vaccination. The current study systematically... (Review)
Review
Several vaccine-induced thrombotic thrombocytopenia syndrome (VITTS) cases have been reported after the ChAdOx1 nCov-19 vaccination. The current study systematically reviewed the reported post-ChAdOx1 nCoV-19 vaccination thrombotic thrombocytopenia cases. Their laboratory and clinical features, as well as the diagnostic and therapeutic measures, were investigated. Online databases were searched until 25 August 2021. Studies reporting post-ChAdOx1 nCov-19 vaccination thrombotic thrombocytopenia syndrome (TTS) were included. Overall, 167 cases (21-77 years old) from 53 publications were included showing a female dominance of 1.75 times. About 85% of the cases exhibited the primary symptoms within the first two weeks post-vaccination. Headache was the most common initial symptom (>44.2%), and hemorrhage/thrombotic problems (22.46%), as well as discoordination/weakness/numbness/ hemiparesis/cyanotic toes (19.6%), were the most prevalent uncommon initial symptoms. Prothrombin time (PT), D-dimers, and C-reactive protein were the most remarkable increased laboratory parameters in 50.6%, 99.1%, and 55.6% of cases, respectively. In comparison, platelet and fibrinogen were the most remarkable decreased laboratory parameters in 92.7% and 50.5% of cases, respectively. Most VITT cases presented with cerebral venous thrombosis/cerebral venous sinus thrombosis, supraventricular tachycardia, transverse sinus/cerebral thrombosis, pulmonary embolism, and cerebral hemorrhage. Anti-PF4 antibody measurement through immunoassays and functional assays were positive in 86.2% and 73% of cases, respectively. About 31% of the cases died. Early diagnosis and proper therapeutic measures are important in ChAdOx1 nCov-19 vaccine-induced VITTS patients. Therefore, experts are recommended to know the corresponding clinical and laboratory features, as well as diagnostic methods. Elucidation of the pathophysiologic mechanism of ChAdOx1 nCov-19 vaccine-induced TTS deserves further investigation.
PubMed: 38022808
DOI: 10.34172/apb.2023.081 -
Cureus Feb 2024The conventional method of heparin and protamine management during cardiopulmonary bypass (CPB) is based on total body weight which fails to account for the... (Review)
Review
BACKGROUND
The conventional method of heparin and protamine management during cardiopulmonary bypass (CPB) is based on total body weight which fails to account for the heterogeneous response to heparin in each patient. On the other hand, the literature is inconclusive on whether individualized anticoagulation management based on real-time blood heparin concentration improves post-CBP outcomes.
METHODS
We searched databases of Medline, Excerpta Medica dataBASE (EMBASE), PubMed, Cumulative Index to Nursing and Allied Health Literature (CINHL), and Google Scholar, recruiting randomized controlled trials (RCTs) and prospective studies comparing the outcomes of dosing heparin and/or protamine based on measured heparin concentration versus patient's total body weight for CPB. Random effects meta-analyses and meta-regression were conducted to compare the outcome profiles. Primary endpoints include postoperative blood loss and the correlation with heparin and protamine doses, the reversal protamine and loading heparin dose ratio; secondary endpoints included postoperative platelet counts, antithrombin III, fibrinogen levels, activated prothrombin time (aPTT), incidences of heparin rebound, and re-exploration of chest wound for bleeding.
RESULTS
Twenty-six studies, including 22 RCTs and four prospective cohort studies involving 3,810 patients, were included. Compared to body weight-based dosing, patients of individualized, heparin concentration-based group had significantly lower postoperative blood loss (mean difference (MD)=49.51 mL, 95% confidence interval (CI): 5.33-93.71), lower protamine-to-heparin dosing ratio (MD=-0.20, 95% CI: -0.32 ~ -0.12), and higher early postoperative platelet counts (MD=8.83, 95% CI: 2.07-15.59). The total heparin doses and protamine reversal were identified as predictors of postoperative blood loss by meta-regression.
CONCLUSIONS
There was a significant correlation between the doses of heparin and protamine with postoperative blood loss; therefore, précised dosing of both could be critical for reducing bleeding and transfusion requirements. Data from the enrolled studies indicated that compared to conventional weight-based dosing, individualized, blood concentration-based heparin and protamine dosing may have outcome benefits reducing postoperative blood loss. The dosing calculation of heparin based on the assumption of a one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model and linear relationship between the calculated dose and blood heparin concentration may be inaccurate. With the recent advancement of the technologies of machine learning, individualized, precision management of anticoagulation for CPB may be possible in the near future.
PubMed: 38357407
DOI: 10.7759/cureus.54144 -
Phlebology Apr 2024The study employed meta-analysis to provide a comprehensive synthesis of evidence regarding the association between the prothrombin A19911G polymorphism and the risk of... (Review)
Review
BACKGROUND
The study employed meta-analysis to provide a comprehensive synthesis of evidence regarding the association between the prothrombin A19911G polymorphism and the risk of venous thromboembolism (VTE).
METHOD
The databases were searched to identify studies investigating the association between the prothrombin A19911G polymorphism and the risk of VTE. Meta-analysis was conducted using Stata 14.0 software.
RESULTS
A total of five literature studies were included, involving 14,001 participants. Meta-analysis demonstrated that prothrombin A19911G polymorphism increased the risk of VTE (G vs A: OR = 1.17, 95% CI = 1.11-1.22, < .00001; GG + AG vs AA: OR = 1.22, 95% CI = 1.13-1.31, < .00001; GG vs AG + AA: OR = 1.23, 95% CI = 1.14-1.33, < .00001; AG vs AA: OR = 1.15, 95% CI = 1.06-1.25, = .0006; GG vs AA: OR = 1.34, 95% CI = 1.22-1.48, < .00001).
CONCLUSION
The polymorphism of prothrombin A19911G enhances the susceptibility to VTE.
PubMed: 38616379
DOI: 10.1177/02683555241247095 -
Cureus Sep 2023The coronavirus disease 2019 (COVID-19) is associated with prolonged prothrombin time (PT), active partial thromboplastin time (aPTT), and increased D-dimer levels.... (Review)
Review
The coronavirus disease 2019 (COVID-19) is associated with prolonged prothrombin time (PT), active partial thromboplastin time (aPTT), and increased D-dimer levels. Therefore, we aim to investigate if anticoagulants (AC) and antiplatelet (AP) therapy play a role in mitigating COVID-19 and its associated thrombosis along with its effect on the mortality rate, the need for mechanical ventilation, and the risk of hospital admission. Electronic databases were searched from their inception to July 19, 2022. The studies were divided into two groups: Group A (any dose of AC/AP versus no AC/AP) and Group B (therapeutic dose of AC (tAC)/AP versus prophylactic dose of AC (pAC)/AP). Review Manager (RevMan) version 5.4.1 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) was used for all statistical analyses. Adjusted data ratios were extracted from all included studies and pooled using the random effects model. A total of 33 studies were taken for the analysis of two groups (Group A: 285,065 COVID-19-positive patients, Group B: 2,421 COVID-19-positive patients). Overall analysis in Group A showed that the AC/AP group had a low risk of mortality in COVID-19 patients compared to the control group (risk ratio (RR): 0.77, 95% confidence interval (CI): 0.69-0.86). There was no significant difference in the need for mechanical ventilation (RR: 0.80, 95% CI: 0.60-1.08) and hospital admission (RR: 1.12, 95% CI: 0.78-1.59) between the AC/AP and no AC/AP group. Alongside, in Group B, tAC/AP did not demonstrate a significant decrease in mortality as compared to pAC/AP (RR: 0.62, 95% CI: 0.37-1.06). Treatment with AC and AP drugs can significantly decrease the mortality rate in COVID-19-infected patients, while AC also significantly reduces the need for mechanical ventilation.
PubMed: 37872904
DOI: 10.7759/cureus.45749 -
Journal of Chest Surgery Jan 2024Prothrombin complex concentrate (PCC) and fresh frozen plasma (FFP) are commonly used to manage bleeding in patients during cardiac surgery. However, the relative... (Review)
Review
BACKGROUND
Prothrombin complex concentrate (PCC) and fresh frozen plasma (FFP) are commonly used to manage bleeding in patients during cardiac surgery. However, the relative efficacy and safety of these 2 strategies remain uncertain.
METHODS
MEDLINE, Embase, and Cochrane were searched for studies comparing PCC and FFP in patients who underwent cardiac surgery complicated by bleeding. Review Manager (RevMan) ver. 5.4 (Nordic Cochrane Centre, The Cochrane Collaboration) was used for statistical analysis. Binary and continuous outcomes were compared using pooled risk ratios and mean differences, respectively. The meta-analysis protocol was registered in the International Prospective Register of Systematic Reviews under protocol number CRD42022379144.
RESULTS
We included 8 studies with 1,500 patients, of whom 613 (40.9%) received PCC. The mean follow-up period ranged from 28 to 90 days. The PCC group had significantly lower chest tube drainage at 24 hours (mean difference [MD], -148.50 mL; 95% CI, -253.02 to -43.99 mL; p=0.005; I=42%). Fewer units of red blood cells (RBCs) were transfused within the first 24 hours (MD, -1.02 units; 95% CI, -1.81 to -0.24 units; p=0.01; I=56%), and fewer patients required RBC transfusion within the first 24 hours (risk ratio, 0.85; 95% CI, 0.78-0.93; p<0.007; I=45%) in the PCC group. There were no statistically significant differences in secondary outcomes. Nonetheless, a subgroup analysis of randomized controlled trials failed to corroborate the results obtained from the main analysis.
CONCLUSION
Our findings suggest that PCC can be effective, without increased adverse events, when compared with FFP in patients undergoing cardiac surgery complicated by bleeding.
PubMed: 37994088
DOI: 10.5090/jcs.23.081 -
BMC Pregnancy and Childbirth May 2024Preeclampsia (PE), an obstetric disorder, remains one of the leading causes of maternal and infant mortality worldwide. In individuals with PE, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preeclampsia (PE), an obstetric disorder, remains one of the leading causes of maternal and infant mortality worldwide. In individuals with PE, the coagulation-fibrinolytic system is believed to be among the most significantly impacted systems due to maternal inflammatory responses and immune dysfunction. Therefore, this systematic review and meta-analysis aimed to assess the association of prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT) levels with preeclampsia.
METHODS
This systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. Articles relevant to the study, published from July 26, 2013, to July 26, 2023, were systematically searched across various databases including PubMed, Scopus, Embase, and Hinari. The methodological quality of the articles was evaluated using the Joanna Briggs Institute critical appraisal checklist. Utilizing Stata version 14.0, a random-effects model was employed to estimate the pooled standardized mean difference (SMD) along with the respective 95% CIs. The I statistics and Cochrane Q test were utilized to assess heterogeneity, while subgroup analyses were performed to explore its sources. Furthermore, Egger's regression test and funnel plot were employed to assess publication bias among the included studies.
RESULTS
A total of 30 articles, involving 5,964 individuals (2,883 with PE and 3,081 as normotensive pregnant mothers), were included in this study. The overall pooled SMD for PT, APTT, and TT between PE and normotensive pregnant mothers were 0.97 (95% CI: 0.65-1.29, p < 0.001), 1.05 (95% CI: 0.74-1.36, p < 0.001), and 0.30 (95% CI: -0.08-0.69, p = 0.11), respectively. The pooled SMD indicates a significant increase in PT and APTT levels among PE patients compared to normotensive pregnant mothers, while the increase in TT levels among PE patients was not statistically significant.
CONCLUSIONS
The meta-analysis underscores the association between PE and prolonged PT and APTT. This suggests that evaluating coagulation parameters like PT, APTT, and TT in pregnant women could offer easily accessible and cost-effective clinical indicators for assessing PE. However, multicenter longitudinal studies are needed to evaluate their effectiveness across various gestational weeks of pregnancy.
Topics: Humans; Pregnancy; Female; Pre-Eclampsia; Partial Thromboplastin Time; Prothrombin Time; Thrombin Time; Blood Coagulation
PubMed: 38741046
DOI: 10.1186/s12884-024-06543-7 -
Brazilian Journal of Cardiovascular... Apr 2024The purpose of present study was to comprehensívely explore the efficacy and safety of prothrombín complex concentrate (PCC) to treat massíve bleedíng in patíents... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The purpose of present study was to comprehensívely explore the efficacy and safety of prothrombín complex concentrate (PCC) to treat massíve bleedíng in patíents undergoing cardiac surgery.
METHODS
PubMed®, Embase, and Cochrane Líbrary databases were searched for studíes ínvestigating PCC administratíon duríng cardiac surgery published before September 10, 2022. Mean dífference (MD) wíth 95% confidence interval (CI) was applíed to analyze continuous data, and dichotomous data were analyzed as risk ratio (RR) with 95% CI.
RESULTS
Twelve studies were included in the meta-analysis. Compared with other non-PCC treatment regimens, PCC was not assocíated with elevated mortality (RR=1.18, 95% CI=0.86-1.60, P=0.30, I2=0%), shorter hospital stay (MD=-2.17 days; 95% CI=-5.62-1.28, P=0.22, I2=91%), reduced total thoracic drainage (MD=-67.94 ml, 95% CI=-239.52-103.65, P=0.44, I2=91%), thromboembolíc events (RR=1.10, 95% CI=0.74-1.65, P=0.63, I2=39%), increase ín atríal fibríllatíon events (RR=0.73, 95% CI=0.52-1.05, P=0.24, I2=29%), and myocardial infarction (RR=1.10, 95% CI=0.80-1.51, P=0.57, I2=81%). However, PCC use was associated with reduced intensive care unit length of stay (MD=-0.81 days, 95% CI=-1.48- -0.13, P=0.02, I2=0%), bleeding (MD=-248.67 ml, 95% CI=-465.36- -31.97, P=0.02, I2=84%), and intra-aortic balloon pump/extracorporeal membrane oxygenation (RR=0.65, 95% CI=0.42-0.996, P=0.05, I2=0%) when compared with non-PCC treatment regimens.
CONCLUSION
The use of PCC in cardiac surgery did not correlate with mortality, length of hospítal stay, thoracic drainage, atríal fibríllatíon, myocardíal ínfarction, and thromboembolíc events. However, PCC sígnificantly improved postoperatíve intensíve care unít length of stay, bleedíng, and intra-aortic balloon pump/ extracorporeal membrane oxygenation outcomes ín patients undergoing cardíac surgery.
Topics: Humans; Atrial Fibrillation; Cardiac Surgical Procedures; Hemorrhage; Myocardial Infarction; Hemostasis; Blood Coagulation Factors
PubMed: 38568885
DOI: 10.21470/1678-9741-2023-0076 -
Scientific Reports May 2024Malaria infection leads to hematological abnormalities, including deranged prothrombin time (PT). Given the inconsistent findings regarding PT in malaria across... (Meta-Analysis)
Meta-Analysis
Malaria infection leads to hematological abnormalities, including deranged prothrombin time (PT). Given the inconsistent findings regarding PT in malaria across different severities and between Plasmodium falciparum and P. vivax, this study aimed to synthesize available evidence on PT variations in clinical malaria. A systematic literature search was performed in PubMed, Embase, Scopus, Ovid, and Medline from 27 November 2021 to 2 March 2023 to obtain studies documenting PT in malaria. Study quality was evaluated using the Joanna Briggs Institute checklist, with data synthesized through both qualitative and quantitative methods, including meta-regression and subgroup analyses, to explore heterogeneity and publication bias. From 2767 articles, 21 studies were included. Most studies reported prolonged or increased PT in malaria patients compared to controls, a finding substantiated by the meta-analysis (P < 0.01, Mean difference: 8.86 s, 95% CI 5.32-12.40 s, I: 87.88%, 4 studies). Severe malaria cases also showed significantly higher PT than non-severe ones (P = 0.03, Hedges's g: 1.65, 95% CI 0.20-3.10, I: 97.91%, 7 studies). No significant PT difference was observed between P. falciparum and P. vivax infections (P = 0.88, Mean difference: 0.06, 95% CI - 0.691-0.8, I: 65.09%, 2 studies). The relationship between PT and malaria-related mortality remains unclear, underscoring the need for further studies. PT is typically prolonged or increased in malaria, particularly in severe cases, with no notable difference between P. falciparum and P. vivax infections. The inconsistency in PT findings between fatal and non-fatal cases highlights a gap in current understanding, emphasizing the need for future studies to inform therapeutic strategies.
Topics: Humans; Malaria, Vivax; Malaria, Falciparum; Plasmodium vivax; Plasmodium falciparum; Prothrombin Time; Severity of Illness Index
PubMed: 38698102
DOI: 10.1038/s41598-024-60170-y -
Phytomedicine : International Journal... Mar 2024Panax notoginseng saponins (PNS) are the primary active components of an ancient Chinese herb Panax notoginseng. Hypercoagulable state of blood (HCS) is an independent... (Meta-Analysis)
Meta-Analysis
Clinical efficacy and safety of Panax notoginseng saponins in treating chronic obstructive pulmonary disease with blood hypercoagulability: A meta-analysis of randomized controlled trials.
BACKGROUND
Panax notoginseng saponins (PNS) are the primary active components of an ancient Chinese herb Panax notoginseng. Hypercoagulable state of blood (HCS) is an independent risk factor and a cause of death in chronic obstructive pulmonary disease (COPD). Several vivo studies have demonstrated the use of PNS preparations for treating COPD with HCS.
PURPOSE
This study aimed to systematically evaluate the clinical efficacy and safety of PNS preparations in treating COPD with HCS.
STUDY DESIGN
Meta-analysis of the randomized controlled trials (RCTs) was conducted to review data.
METHODS
RCTs on the treatment of COPD with HCS and PNS preparations were searched from PubMed, Cochrane Library, Embase, Web of Science, Chinese National Knowledge Infrastructure, Vip Information Database, Wanfang data, and Chinese Biomedical Literature Database. Relevant data were extracted from the included studies and methodological quality evaluation was performed. R language (version 4.2.3) was applied for the meta-analysis.
RESULTS
Twenty RCTs involving 1831 patients were analyzed. The results revealed that PNS preparations considerably increased the total clinical efficiency, improved forced expiratory volume in one second percent of predicted, and forced expiratory volume/forced vital capacity ratio. Further, PNS preparations improved fibrinogen, plasma d-dimer, whole blood viscosity at high cut, whole blood viscosity at low cut, and plasma viscosity levels. The results obtained for activated partial thromboplastin and prothrombin times were not statistically significant. Finally, PNS preparations increased partial pressure of oxygen and decreased carbon dioxide pressure.
CONCLUSION
This is the first relatively comprehensive systematic review of the clinical efficacy and safety of PNS preparations for treating COPD with HCS. The study revealed that PNS preparations considerably improve lung function, hypoxia, and blood hypercoagulability in patients with COPD and HCS without increasing the risk of hemorrhage and has a good safety profile; therefore, it can be used as a new modulating agent and anticoagulant.
Topics: Humans; Panax notoginseng; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Saponins; Thrombophilia; Treatment Outcome
PubMed: 38216446
DOI: 10.1016/j.phymed.2023.155244 -
Seminars in Thrombosis and Hemostasis Apr 2024Venous thromboembolism (VTE) is a main contributor to morbidity and mortality in cancer patients. Biomarkers with the potential to predict cancer-associated VTE are...
Venous thromboembolism (VTE) is a main contributor to morbidity and mortality in cancer patients. Biomarkers with the potential to predict cancer-associated VTE are continually sought. Of these, markers of thrombin generation present a likely option. The present systematic review examines the ability of three widely used biomarkers of thrombin generation: prothrombin fragment 1.2 (F1.2), thrombin-antithrombin complex (TAT), and ex vivo thrombin generation, to predict VTE in both solid and hematologic adult cancer patients. Relevant studies were identified in the PubMed and Embase databases, and the review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Each study was evaluated using the quality assessment tool from the National Heart, Lung, and Blood Institute. The review protocol was published on PROSPERO with identifier CRD42022362339. In total, 24 papers were included in the review: 11 reporting data on F1.2, 9 on TAT, and 12 on ex vivo thrombin generation. The quality ratings of the included studies varied from good ( = 13), fair ( = 8), to poor ( = 3) with a high heterogenicity. However, F1.2, TAT complex, and ex vivo thrombin generation were all found to be associated with the development of VTE. This association was most pronounced for F1.2. Furthermore, the determination of F1.2 was able to improve the precision of several established risk assessment scores. In conclusion, markers of thrombin generation were found to be elevated in cancer patients with VTE, and particularly, F1.2 was found to be a promising predictor of cancer-associated VTE.
Topics: Adult; Humans; Thrombin; Venous Thromboembolism; Biomarkers; Risk Factors; Neoplasms
PubMed: 37813372
DOI: 10.1055/s-0043-1775856