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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 -
Journal of Clinical Medicine Apr 2024: The coagulation cascade due to tissue damage is considered to be one of the causes of poor prognostic outcomes in patients with acute exacerbations of interstitial...
Usefulness of Combined Measurement of Surfactant Protein D, Thrombin-Antithrombin III Complex, D-Dimer, and Plasmin-α2 Plasmin Inhibitor Complex in Acute Exacerbation of Interstitial Lung Disease: A Retrospective Cohort Study.
: The coagulation cascade due to tissue damage is considered to be one of the causes of poor prognostic outcomes in patients with acute exacerbations of interstitial lung disease (AE-ILD). This study aimed to confirm coagulopathy in AE-ILD by evaluating the differences in the clinical characteristics of coagulation/fibrinolysis markers between stable ILD and AE-ILD. : Overall, 81 patients were enrolled in this retrospective study and categorized into the following two groups: a chronic ILD group comprising 63 outpatients and an acute ILD group comprising 18 inpatients diagnosed with AE-ILD. Serum markers, including thrombin-antithrombin III complex (TAT), D-dimer, plasmin-α2 plasmin inhibitor complex (PIC), and surfactant protein D (SP-D), were compared between the groups. : Among the 18 patients with acute ILD, 17 did not meet the International Society of Thrombosis and Hemostasis scoring system for disseminated intravascular coagulation. In acute ILD, the SP-D levels were statistically significantly positively correlated with TAT, D-dimer, and PIC levels, while the Krebs von den Lungen 6 (KL-6) levels showed no correlation with any of these coagulation/fibrinolytic markers. A positive correlation was observed between SP-D levels and TAT, D-dimer, and PIC levels in acute ILD. Serum TAT, D-dimer, and PIC all showed good area under the receiver operating characteristic (ROC) curve (AUC) values in ROC analysis for the diagnosis of acute ILD. : In the clinical setting of AE-ILD, it may be important to focus not only on alveolar damage markers such as SP-D but also on coagulation/fibrinolytic markers including TAT, D-dimer, and PIC.
PubMed: 38673700
DOI: 10.3390/jcm13082427 -
Cureus May 2024The onset of cardiovascular complications has increased the mortality rate in rheumatoid arthritis (RA) patients. Presently, there is a need to diagnose cardiovascular...
BACKGROUND
The onset of cardiovascular complications has increased the mortality rate in rheumatoid arthritis (RA) patients. Presently, there is a need to diagnose cardiovascular co-morbidity in rheumatic disease. While biomarkers such as P-selectin glycoprotein ligand-1 (PSGL-1), fibrinogen, anti-thrombin III (AT-III), hsCRP, lipoprotein (a) (lp(a)), leptin, adiponectin, and asymmetric dimethyl arginine (ADMA) are already established as independent risk factors for the development of atherosclerosis, the association of these biomarkers with disease activity in RA patients is unclear.
METHODS
The case-control study comprised 40 cases along with age- and gender-matched controls recruited from a tertiary care hospital in southern India. Platelet activation in plasma was analyzed by flow cytometry using CD41 per CPCY 5.5 (platelet marker) and human CD62P FITC monoclonal antibody (P-selectin marker). Other parameters were quantified through nephelometry and ELISA. The association between the risk factors and RA disease severity, as per the disease activity score (DAS/DAS28), was analyzed. Furthermore, an ROC analysis was done to assess the utility of these biomarkers in the diagnosis of RA.
RESULTS
With the exception of leptin, adiponectin, and ADMA, there was a significant increase in the levels of PSGL-1, fibrinogen, AT-III, hsCRP, and lp(a) when compared to healthy controls. Conventional risk factors contributing to dyslipidemia were also assessed, in which the low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio was found to be significantly higher in RA patients compared to controls. Moreover, a significant positive correlation was identified between DAS score and activated platelets, fibrinogen, and hsCRP. ROC analysis identified that fibrinogen could predict the RA disease status with 95% accuracy, followed by activated platelets and hsCRP.
CONCLUSION
Several of the studied atherothrombotic risk factors were significantly altered in patients with RA. Activated platelets, fibrinogen, and hsCRP were associated with disease activity and also served as good diagnostic predictors for RA. Based on our findings, further studies could explore the potential of introducing anti-thrombotic agents in the treatment regimen of patients with RA.
PubMed: 38846255
DOI: 10.7759/cureus.59818 -
International Journal of Laboratory... Dec 2023
Topics: Humans; Anticoagulants; Antithrombins; Antithrombin III; Blood Coagulation; Plasma; Administration, Oral
PubMed: 37344981
DOI: 10.1111/ijlh.14120 -
Clinical Laboratory Feb 2024
Topics: Humans; Protein C; Antithrombin III; Protein Carbamylation; Anticoagulants
PubMed: 38345988
DOI: 10.7754/Clin.Lab.2023.230733 -
Artificial Organs Nov 2023Thrombosis remains a critical complication during venovenous extracorporeal membrane oxygenation (VV ECMO). The involvement of neutrophil extracellular traps (NETs) in...
BACKGROUND
Thrombosis remains a critical complication during venovenous extracorporeal membrane oxygenation (VV ECMO). The involvement of neutrophil extracellular traps (NETs) in thrombogenesis has to be discussed. The aim was to verify NETs in the form of cell-free DNA (cfDNA) in the plasma of patients during ECMO.
METHODS
A fluorescent DNA-binding dye (QuantifFluor®, Promega) was used to detect cell-free DNA in plasma samples. cfDNA concentrations from volunteers (n = 21) and patients (n = 9) were compared and correlated with clinical/technical data before/during support, ECMO end and time of a system exchange.
RESULTS
Before ECMO, patients with a median (IQR) age of 59 (51/63) years, SOFA score of 11 (10/15), and ECMO run time of 9.0 (7.0/19.5) days presented significantly higher levels of cfDNA compared to volunteers (6.4 (5.8/7.9) ng/μL vs. 5.9 (5.4/6.3) ng/μL; p = 0.044). Within 2 days after ECMO start, cfDNA, inflammatory, and hemolysis parameters remained unchanged, while platelets decreased (p = 0.005). After ECMO removal at the end of therapy, cfDNA, inflammation, and coagulation data (except antithrombin III) remained unchanged. The renewal of a system resulted in known alterations in fibrinogen, d-dimers, and platelets, while cfDNA remained unchanged.
CONCLUSION
Detection of cfDNA in plasma of ECMO patients was not an indicator of acute and circuit-induced thrombogenesis.
Topics: Humans; Middle Aged; Extracorporeal Membrane Oxygenation; Clinical Relevance; Blood Coagulation; Thrombosis; Cell-Free Nucleic Acids; Retrospective Studies
PubMed: 37525949
DOI: 10.1111/aor.14616 -
Frontiers in Molecular Neuroscience 2023Currently, there is a shortage of the protein biomarkers for classifying spinal cord injury (SCI) severity. We attempted to explore the candidate biomarkers for...
PURPOSE
Currently, there is a shortage of the protein biomarkers for classifying spinal cord injury (SCI) severity. We attempted to explore the candidate biomarkers for predicting SCI severity.
METHODS
SCI rat models with mild, moderate, and severe injury were constructed with an electro-mechanic impactor. The behavior assessment and pathological examinations were conducted before and after SCI. Then, quantitative liquid chromatography-mass spectrometry (LC-MS/MS) was performed in spinal cord tissues with different extents of injury. The differentially expressed proteins (DEPs) in SCI relative to controls were identified, followed by Mfuzz clustering, function enrichment analysis, and protein-protein interaction (PPI) network construction. The differential changes of candidate proteins were validated by using a parallel reaction monitoring (PRM) assay.
RESULTS
After SCI modeling, the motor function and mechanical pain sensitivity of SCI rats were impaired, dependent on the severity of the injury. A total of 154 DEPs overlapped in the mild, moderate, and severe SCI groups, among which 82 proteins were classified in clusters 1, 2, 3, 5, and 6 with similar expression patterns at different extents of injury. DEPs were closely related to inflammatory response and significantly enriched in the IL-17 signaling pathway. PPI network showed that Fgg (Fibrinogen gamma chain), Fga (Fibrinogen alpha chain), Serpinc1 (Antithrombin-III), and Fgb (Fibrinogen beta chain) in cluster 1 were significant nodes with the largest degrees. The upregulation of the significant nodes in SCI samples was validated by PRM.
CONCLUSION
Fgg, Fga, and Fgb may be the putative biomarkers for assessing the extent of SCI.
PubMed: 38155913
DOI: 10.3389/fnmol.2023.1153230 -
Thrombosis Journal Nov 2023Mixed phenotype acute leukaemia (MPAL) is associated with worse overall survival, compared with other acute leukaemias in adults. Lack of clear treatment guidelines...
Mixed phenotype acute leukaemia (MPAL) is associated with worse overall survival, compared with other acute leukaemias in adults. Lack of clear treatment guidelines makes the therapy challenging. ALL-like induction and consolidation treatment followed by allo-HSCT is the preferred first-line treatment. We present a case of a 36-year-old woman diagnosed with MPAL (EGIL Myelo/B) with KMT2A rearrangement, treated with the PALG-ALL-7 (including PEG-asparaginase) protocol. On day 25 after the induction therapy initiation, numbness of limbs and dizziness were observed. Therefore, the imaging studies (CT and MRI) were performed and a diagnosis of thrombosis of superior sagittal sinus of the brain was established. Routinely performed blood coagulation tests showed prolonged APTT and PT, decreased antithrombin III activity and decreased free protein S concentration. LMWH treatment and substitutional therapy with antithrombin III were started, which resulted in a significant reduction in the thrombosis associated symptoms and improvement of the neurological status after 3 days. After induction and consolidation therapy, the patient obtained complete haematological remission and negative measurable residual disease. Six months after the diagnosis, allo-HSCT was successfully performed. During the 4 months follow-up, the patient remained MRD negative and thrombotic symptoms free. To the best of our knowledge, our communication has been the first report of such complication in an MPAL patient treated with PEG-asparaginase containing protocol in adults. We recommend increased vigilance in patients manifesting any mild neurological symptoms and early decision about the MRI study performance.
PubMed: 37974201
DOI: 10.1186/s12959-023-00561-9 -
Journal of Ultrasound in Medicine :... Sep 2023To evaluate the risk factors of isolated distal deep vein thrombosis (IDDVT) in the lower limbs by using a combination of Doppler ultrasound and thrombus molecular...
OBJECTIVE
To evaluate the risk factors of isolated distal deep vein thrombosis (IDDVT) in the lower limbs by using a combination of Doppler ultrasound and thrombus molecular markers.
METHODS
A prospective cohort study was used. We selected 145 patients with deep vein thrombosis of the lower limbs. They were divided into the IDDVT group and the non-IDDVT group. We compared the differences in Doppler ultrasound and biochemical indexes between the two groups. The independent influencing factors of IDDVT were analyzed using logistic regression, and we plotted the receiver operating characteristic (ROC) curve.
RESULTS
We compared 47 IDDVT cases diagnosed by DSA with 47 non-IDDVT cases selected at random. The diameter of the common femoral vein (CFV) of the affected side, deep femoral vein, and the great saphenous vein, thickness of subcutaneous tissue, and serum D-dimer (D-D) and thrombin-antithrombin III complexes (TAT) were significantly higher in the IDDVT group than the non-IDDVT group (P < .05). Logistic regression analysis showed that CFV diameter, subcutaneous tissue thickening, D-D, and TAT were all independent risk factors for IDDVT (P < .05). The combined predictor had higher predictive sensitivity, specificity, and Youden's index (93.6, 87.2, and 0.808, respectively) than using thrombus molecular markers alone or Doppler ultrasound alone.
CONCLUSION
D-D and TAT, the thrombosis molecular markers, CFV diameter, and thickening of subcutaneous tissue, as well as the Doppler ultrasound, all have their own independent effects on IDDVT. When Thrombosis molecular markers and Doppler ultrasound are used in combination, they can predict which patients are at high risk of IDDVT and help doctors in making clinical decisions pertaining to prevention and treatment.
Topics: Humans; Venous Thrombosis; Prospective Studies; Risk Factors; Lower Extremity; Ultrasonography
PubMed: 37010437
DOI: 10.1002/jum.16227 -
International Journal of Molecular... Feb 2024Serine proteases are members of a large family of hydrolytic enzymes in which a particular serine residue in the active site performs an essential role as a nucleophile,... (Review)
Review
Serine proteases are members of a large family of hydrolytic enzymes in which a particular serine residue in the active site performs an essential role as a nucleophile, which is required for their proteolytic cleavage function. The array of functions performed by serine proteases is vast and includes, among others, the following: the ability to fight infections; the activation of blood coagulation or blood clot lysis systems; the activation of digestive enzymes; and reproduction. Serine protease activity is highly regulated by multiple families of protease inhibitors, known collectively as the SERine Protease INhibitor (SERPIN). The serpins use a conformational change mechanism to inhibit proteases in an irreversible way. The unusual conformational change required for serpin function provides an elegant opportunity for allosteric regulation by the binding of cofactors, of which the most well-studied is heparin. The goal of this review is to discuss some of the clinically relevant serine protease-serpin interactions that may be enhanced by heparin or other negatively charged polysaccharides. The paired serine protease-serpin in the framework of heparin that we review includes the following: thrombin-antithrombin III, plasmin-anti-plasmin, C1 esterase/kallikrein-C1 esterase inhibitor, and furin/TMPRSS2 (serine protease Transmembrane Protease 2)-alpha-1-antitrypsin, with the latter in the context of COVID-19 and prostate cancer.
Topics: Serpins; Heparin; Serine Proteases; Serine Proteinase Inhibitors; Anticoagulants; Thrombin
PubMed: 38339082
DOI: 10.3390/ijms25031804