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1.
Pilot Feasibility Stud ; 10(1): 73, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720378

RESUMO

BACKGROUND: Arterial thrombo-embolic complications (TEC) are still common during and after non-cardiac arterial procedures (NCAP). While unfractionated heparin has been used during NCAP for more than 70 years to prevent TEC, there is no consensus regarding the optimal dosing strategy. The aim of this pilot study was to test the effectiveness and feasibility of an activated clotting time (ACT)-guided heparinization protocol during open abdominal aortic aneurysm (AAA) surgery, in anticipation of a randomized controlled trial (RCT) investigating if ACT-guided heparinization leads to better clinical outcomes compared to a single bolus of 5000 IU of heparin. METHODS: A prospective multicentre pilot study was performed. All patients undergoing elective open repair for an AAA (distal of the superior mesenteric artery) between March 2017 and January 2020 were included. Two heparin dosage protocols were compared: ACT-guided heparinization with an initial dose of 100 IU/kg versus a bolus of 5000 IU. The primary outcome was the effectiveness and feasibility of an ACT-guided heparinization protocol with an initial heparin dose of 100 IU/kg during open AAA surgery. Bleeding complications, TEC, and mortality were investigated for safety purposes. RESULTS: A total of 50 patients were included in the current study. Eighteen patients received a single dose of 5000 IU of heparin and 32 patients received 100 IU/kg of heparin with additional doses based on the ACT. All patients who received the 100 IU/kg dosing protocol reached the target ACT of > 200 s. In the 5000 IU group, TEC occurred in three patients (17%), versus three patients (9.4%) in the 100 IU/kg group. Bleeding complications were found in six patients (33%) in the 5000 IU group and in 9 patients (28%) in the 100 IU/kg group. No mortality occurred in either group. CONCLUSIONS: This pilot study demonstrated that ACT-guided heparinization with an initial dose of 100 IU/kg appears to be feasible and leads to adequate anticoagulation levels. Further randomized studies seem feasible and warranted to determine whether ACT-guided heparinization results in better outcomes after open AAA repair.

2.
Cureus ; 16(5): e59933, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38726359

RESUMO

BACKGROUND: Use of unfractionated heparin (UFH) during the peripartum period is considered to be a higher risk of critical obstetric bleeding compared to low-molecular-weight heparin (LMWH). However, the evidence for the safety of using LMWH during the peripartum period is currently lacking. METHODS: This study retrospectively investigated a nationwide medical database to clarify the safety of using LMWH during childbirth. The Japanese Nationwide Diagnosis Procedure Combination database was retrospectively reviewed, and data from women with childbirth between 2018 and 2022 were collected. RESULTS: Among the overall 354,299 women with childbirth, 3,099 were with obstetric disseminated intravascular coagulation (DIC), 484 were with critical obstetric bleeding requiring massive red blood cell (RBC) transfusion ≥4,000 cc, and 38 were with maternal death. Among the overall women, each of the anticoagulants other than LMWH was associated with critical obstetrical bleeding with an adjusted odds ratio (aOR) greater than 1.0, while LMWH was not associated with critical obstetrical bleeding (aOR, 0.54 (95% confidence interval, 0.11-2.71)). This finding did not change in subgroup analyses among those with Cesarean section. Furthermore, UFH was associated with critical bleeding among the 3,099 women with obstetrical DIC (aOR, 3.91 (2.83-5.46)), while LMWH was not (aOR, 0.26 (0.03-1.37)). CONCLUSION: The use of UFH was significantly associated with an increased critical obstetric hemorrhage requiring massive RBC transfusion or total hysterectomy. Meanwhile, the use of LMWH was not associated with increased critical obstetric bleeding. LMWH would be safer than UFH to be used for women during childbirth.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38735015

RESUMO

BACKGROUND: Treating cancer-associated venous thromboembolism (CAT) with anticoagulation prevents recurrent venous thromboembolism (rVTE), but increases bleeding risk. OBJECTIVES: To compare incidence of rVTE, major bleeding, and all-cause mortality for rivaroxaban versus low molecular weight heparin (LMWH) in patients with CAT. METHODS: We developed a cohort study using Swedish national registers 2013-2019. Patients with CAT (venous thromboembolism within 6 months of cancer diagnosis) were included. Those with other indications or with high bleeding risk cancers were excluded (according to guidelines). Follow-up was from index-CAT until outcome, death, emigration, or end of study. Incidence rates (IR) per 1000 person-years with 95% confidence interval (CI) and propensity score overlap-weighted hazard ratios (HRs) for rivaroxaban versus LMWH were estimated. RESULTS: We included 283 patients on rivaroxaban and 5181 on LMWH. The IR for rVTE was 68.7 (95% CI 40.0-109.9) for rivaroxaban, compared with 91.6 (95% CI 81.9-102.0) for LMWH, with adjusted HR 0.77 (95% CI 0.43-1.35). The IR for major bleeding was 23.5 (95% CI 8.6-51.1) for rivaroxaban versus 49.2 (95% CI 42.3-56.9) for LMWH, with adjusted HR 0.62 (95% CI 0.26-1.49). The IR for all-cause mortality was 146.8 (95% CI 103.9-201.5) for rivaroxaban and 565.6 (95% CI 541.8-590.2) for LMWH with adjusted HR 0.48 (95% CI 0.34-0.67). CONCLUSIONS: Rivaroxaban performed similarly to LMWH for patients with CAT for rVTE and major bleeding. An all-cause mortality benefit was observed for rivaroxaban which potentially may be attributed to residual confounding. TRIAL REGISTRATION NUMBER: NCT05150938 (Registered 9 December 2021).

4.
ESC Heart Fail ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725133

RESUMO

AIMS: It is unclear whether activated partial thromboplastin time (aPTT) or anti-Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support (MCS) patients. This study investigates the relationship between aPTT and anti-Xa in MCS patients and identifies predictors of discordance. METHODS AND RESULTS: aPTT and anti-Xa were simultaneously measured in a prospective cohort of MCS patients receiving unfractionated heparin at a tertiary academic medical centre. Therapeutic aPTT and anti-Xa levels were 60-100 s and 0.3-0.7 IU/mL, respectively, and concordance was defined as both levels being subtherapeutic, therapeutic, or supratherapeutic. To identify predictors of discordance, both a machine learning random forest model and a multivariate regression model were applied to patient demographics, device type, and 14 laboratory variables; 23 001 pairs of simultaneously measured aPTT/anti-Xa were collected from 699 MCS patients. aPTT and anti-Xa were concordant in 35.5% of paired observations and discordant in 64.5% (aPTT > antiXa 61.5%; aPTT < antiXa 3.0%). Discordance with a high aPTT relative to anti-Xa (aPTT > antiXa) was associated with high INR, eGFR, and total bilirubin, as well as low platelets, haemoglobin, pre-albumin, white blood cell count, and haptoglobin. Total artificial heart and durable ventricular assist devices were more likely to be associated with aPTT > anti-Xa than temporary MCS devices. CONCLUSIONS: aPTT and anti-Xa were frequently discordant in MCS patients receiving heparin anticoagulation. Clinical conditions common in MCS patients such as concurrent warfarin use, malnutrition, haemolysis, and thrombocytopenia, as well as durable type of MCS devices were associated with a high aPTT relative to anti-Xa.

5.
Int J Lab Hematol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747332

RESUMO

Extracorporeal membrane oxygenation (ECMO) is a type of circulatory life support for patients with severe lung failure. The use of ECMO has increased worldwide since the pandemic of H1N1 in 2009 and more recently SARS-CoV-2 in 2020 both of which caused severe respiratory failure. ECMO patients experience both increased risk of bleeding and thrombosis. This is due to the pathological insult that damages the lungs, the ECMO circuit, coagulopathy, inflammation and anticoagulation. ECMO presents unique demands on the coagulation laboratory both in tests required to manage the patients and result interpretation. This is a personal opinion of 20 years ECMO experience as a clinical scientist and a short current review of the literature. It will focus on the laboratory coagulation tests used to manage ECMO patients, including different anticoagulants used, testing frequency and interpretation of the results.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38713345

RESUMO

Heparin-binding protein 17 (HBp17), first purified in 1991 from the conditioned medium of the human A431 squamous cell carcinoma (SCC) cell line, was later renamed fibroblast growth factor-binding protein 1 (FGFBP-1). HBp17/FGFBP-1 is specifically expressed and secreted by epithelial cells, and it reversibly binds to fibroblast growth factor (FGF)-1 and FGF-2, as well as FGFs-7, -10, and -22, indicating a crucial involvement in the transportation and function of these FGFs. Our laboratory has investigated and reported several studies to elucidate the function of HBp17/FGFBP-1 in SCC cells and its potential as a molecular therapeutic target. HBp17/FGFBP-1 transgene exoression in A431-4 cells, a clonal subline of A431 that lacks tumorigenicity and does not express HBp17/FGFBP-1, demonstrated a significantly enhanced proliferation in vitro compared with A431-4 cells, and it acquired tumorigenicity in the subcutis of nude mice. Knockout (KO) of the HBp17/FGFBP-1 by genome editing significantly suppressed tumor growth, cell motility, and tumorigenicity compared with control cells. A comprehensive analysis of expressed molecules in both cell types revealed that molecules that promote epithelial cell differentiation were highly expressed in HBp17/FGFBP-1 KO cells. Additionally, we reported that 1α,25(OH)2D3 or eldecalcitol (ED-71), which is an analog of 1α,25(OH)2D3, suppresses HBp17/FGFBP-1 expression and tumor growth in vitro and in vivo by inhibiting the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway. Here, we discuss the prospects of molecular targeted therapy targeting HBp17/FGFBP-1 with 1α,25(OH)2D3 or ED71 in SCC and oral SCC.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38724407

RESUMO

BACKGROUND: Finding the balance between the reduction in ischemic events and bleeding complications is crucial for the success of percutaneous coronary intervention (PCI). The activated clotting time (ACT) is used routinely worldwide to monitor and titrate anticoagulation therapy with unfractionated heparin (UFH) during the procedure. OBJECTIVES: We aimed to test the accuracy of ACT measurements from the guiding catheter compared to the arterial access sheath. METHODS: Patients undergoing PCI with UFH therapy were prospectively enrolled. Blood samples were drawn from the coronary guide catheter and the arterial access sheath. ACT values were determined in the same ACT machine, and potential interactions with clinical variables were analyzed. RESULTS: The study included 331 patients with post PCI ACT measurements. The mean ACT value of the catheter samples was statistically higher than the arterial access sample [294 ± 77 s Vs. 250 ± 60 s, p < 0.001]. The mean difference between the guiding catheter and the arterial line sheath samples was 43 ± 27 s (P < 0.001). We found that in 101/331 [30 %] patients the ACT from the guiding catheter was above 250 s, while from the access sheath it was below 250 s. Notably, in 40/331 [12 %] the ACT from the guiding catheter was above 200 s, while from the access sheath it was below 200 s. CONCLUSIONS: Large proportion of patient may be considered to have therapeutic ACT if measured from guide catheter during PCI, while the corresponding ACT from arterial sheath is subtherapeutic. This difference may have clinical and safety significance.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38705748

RESUMO

INTRODUCTION: The possible use of dalbavancin as a catheter lock solution was previously demonstrated by our study group. However, it was needed to assess whether heparin could affect dalbavancin bioactivity during freezing storage. METHODS: We tested the bioactivity of a dalbavancin+heparin (DH) vs. dalbavancin (D) against Staphylococcal biofilms comparing DH median value of cfu counts and metabolic activity with that obtained for D before and during storage under freezing up to 6 months. RESULTS: Despite there was a slight decrease in the median percentage reduction of metabolic activity at month 3 in Staphylococcus epidermidis between DH and D (97.6 vs. 100, p=0.037), considering the clinical criteria, no significant reduction in any of the variables tested was observed at the end of the experiment between D and DH solutions. CONCLUSION: The addition of heparin to a dalbavancin lock solution did not affect its bioactivity against staphylococcal biofilms irrespective of its preservation time under freezing.

9.
Artif Organs ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38716639

RESUMO

BACKGROUND: Regional anticoagulation in hemodialysis avoids the use of heparin, which is responsible for both hemorrhagic and non-hemorrhagic complications. Typically, blood is decalcified by injecting citrate into the arterial line of the extracorporeal circuit. Calcium-free dialysate improves anticoagulation efficacy but requires injection of a calcium-containing solution into the venous line and strict monitoring of blood calcium levels. Recent improvements have made regional anticoagulation with calcium-free dialysate safer and easier. OBSERVATIONS: (1) Adjusting the calcium injection rate to ionic dialysance avoids the risk of dyscalcemia, thus making unnecessary the monitoring of blood calcium levels. This adjustment could be carried out automatically by the hemodialysis monitor. (2) As calcium-free dialysate reduces the amount of citrate required, this can be supplied by dialysate obtained from currently available concentrates containing citric acid. This avoids the need for citrate injection and the risk of citrate overload. (3) Calcium-free dialysate no longer needs the dialysate acidification required for avoiding calcium carbonate precipitation in bicarbonate-containing dialysate. CONCLUSIONS: Regional anticoagulation with calcium-free dialysate enables an acid- and heparin-free procedure that is more biocompatible and environmentally friendly than conventional bicarbonate hemodialysis. The availability of specific acid-free concentrates and adapted hemodialysis monitors is required to extend this procedure to maintenance hemodialysis.

10.
Res Pract Thromb Haemost ; 8(3): 102395, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38699410

RESUMO

The University of North Carolina Symposia on Hemostasis began in 2002, with The First Symposium on Hemostasis with a Special Focus on FVIIa and Tissue Factor. They have occurred biannually since and have maintained the primary goal of establishing a forum for the sharing of outstanding advances made in the basic sciences of hemostasis. The 2024 11th Symposium on Hemostasis will bring together leading scientists from around the globe to present and discuss the latest research related to coagulation factors and platelet biology. In keeping with the tradition of the conference, we expect novel cross-disciplinary collaborations to result from bringing together fundamental scientists and physician-scientists from different backgrounds and perspectives. The aim of these collaborations is to springboard the next generation of important advances in the field. This year's program was designed to discuss Coagulation and Platelet Biology at the Intersection of Health and Disease. The goal is to develop a better understanding of the pathophysiologic mechanisms leading to hemostatic and thrombotic disorders as this understanding is critical for the continued development of safe and efficacious therapeutics. Included in this review article are illustrated capsules provided by our speakers that highlight the main conclusions of the invited talks.

11.
SAGE Open Med ; 12: 20503121241247471, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711468

RESUMO

Objectives: Heparin-induced thrombocytopenia can occur in obese subjects. The medical comorbidities associated with obesity may contribute to the pathogenesis of this disease. It is unknown, however, which specific medical comorbidities and if higher odds of thrombosis are present in obese heparin-induced thrombocytopenia patients. We sought to determine whether obese heparin-induced thrombocytopenia subjects had higher odds of both comorbidities and thrombosis, hypothesizing that this patient population would have higher odds of both these conditions. Methods: This was a multi-center retrospective study utilizing TriNetX©, an electronic health record database, in subjects aged 18-99 years diagnosed with heparin-induced thrombocytopenia. The cohort was divided into two groups (1) non-obese (body mass index < 30 kg/m2) and (2) obese (body mass index ⩾ 30 kg/m2). We evaluated patient characteristics, diagnostic, laboratory, medication, and procedure codes. Results: A total of 1583 subjects (696 (44.0%) non-obese and 887 (56.0%) obese) were included. Obese subjects had higher odds of diabetes with complications (OR = 1.73, 95% CI = 1.35-2.22, p < 0.001) and without complications (OR = 1.81, 95% CI = 1.47-2.22, p < 0.001). This association was still present after correcting for demographic and clinical factors. There were no increased odds of thrombosis observed in the obesity group. Conclusions: Our study found that obese heparin-induced thrombocytopenia subjects had higher odds of having a diabetes mellitus comorbidity, but did not have higher odds of thrombosis. Given obesity is considered a hypercoagulable state, further study may be needed to understand why obese subjects diagnosed with heparin-induced thrombocytopenia do not have higher rates of thrombosis.

12.
EJIFCC ; 35(1): 10-22, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38706733

RESUMO

BACKGROUND: BD Barricor™ tubes have been proposed to decrease laboratory turnaround time (TAT). We analytically validated and then clinically verified these tubes for use with Abbott Alinity™ and Siemens Atellica® highly sensitive cardiac troponin I (hs-cTnI) assays. METHODS: hs-cTnI measurements were undertaken in paired Barricor™ and in-use PSTII™ tubes on both systems. 359 matched samples with hs-cTnI levels between 3 and 15,000 ng/L (Atellica® values) were used to assess the hemolysis rate and make method comparisons. 599 paired patient samples were collected on emergency department (ED) admission to compare the performance of the rapid acute myocardial infarction (AMI) rule-out strategy based on hs-cTnI concentrations lower than recommended thresholds (<4 ng/L Alinity™; <5 ng/L Atellica®) when different tubes and systems were employed. RESULTS: No between-tube differences in hemolysis rate were seen when free hemoglobin concentrations in plasma samples were ≥0.25 g/L, even if PSTII™ showed a significant increase of hemolysis rate vs. Barricor™ (31% vs. 22%, p=0.007) when a lower cut-off for hemolysis (≥0.11 g/L) was employed on the Atellica® detection system. The alternate use of these tubes did not influence the hs-cTnI results obtained from either of the two assays, which remained markedly biased (~40%) irrespective of the tube used. The expected optimal ability of very low hs-cTnI values on ED admission for ruling out AMI was confirmed by using both systems regardless of the tube type. CONCLUSIONS: Barricor™ and PSTII™ tubes can provide analytically equivalent hs-cTnI results when used on either Alinity™ or Atellica® hs-cTnI assays.

13.
Chem Asian J ; : e202400291, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695635

RESUMO

Recently, anionic bio-templates have emerged as promising platforms for designing dynamic and stimuli-responsive chromophoric assemblies capable of light harvesting in aqueous media thereby mimicking natural photosynthesis. Here, we present multi-metal ion-responsive luminescent co-assemblies between cationic pyrene-imidazolium amphiphile and anionic bio-templates (ATP, heparin, and DNA) in aqueous media. The anionic bio-templates enhance Förster resonance energy transfer (FRET) in the co-assemblies, with pyrene serving as an excellent donor for generating tunable multi-luminescent materials with embedded acceptor dyes. However, a significant loss in energy transfer towards acceptor dyes was observed in the presence of various metal ions, attributed to excimeric emission quenching facilitated by electron transfer between the pyrene chromophore and metal ions. Interestingly, detailed studies revealed that only ATP-based co-assemblies exhibited quenching phenomena in the presence of metal ions, contrasting with heparin and ctDNA co-assemblies. Additionally, label-free detection of multi-metal ions in aqueous environments, such as Fe2+, Fe3+, and Cu2+ ions, was successfully achieved with lower detection limits of 0.01 µM (3 ppb), 0.12 µM (30 ppb), and 0.58 µM (150 ppb) respectively. These co-assemblies hold significant promise for practical applications in environmental and biomedical sensing, enabling sensitive monitoring of metal ion concentrations.

14.
Health Sci Rep ; 7(5): e2057, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38736476

RESUMO

Background and Aim: One of the complications of using catheters is the occurrence of thrombosis, which can be dangerous for patients. The main objective of this study is to compare the effect of heparin, reteplase, and taurolock in the prevention of thrombosis in hemodialysis catheters. Methods: The present study is a clinical trial, in which the effect of three drugs, heparin, reteplase, and taurolock, in the prevention of thrombosis in hemodialysis catheters, has been investigated. The research units were studied in two intervention and control groups. The stratified random allocation method was used to assign patients to five groups (control, Heparin 50, Heparin 1000, reteplase, and taurolock), with strata based on the patient's age (20-70 years), gender, and duration of dialysis. Within each stratum, patients were also assigned to groups using the randomized block permutation method and a random number table tool. To prevent bias, this study is triple-blinded. This means that the patient, the thrombosis assessor, and the statistical analyst are unaware of the type of intervention received by the patient. Results: Gender (p < 0.999), age distribution (p = 0.774), and duration of dialysis (p = 0.875) showed no statistically significant relationship with thrombosis. However, significant differences were observed among the five groups regarding thrombosis incidence. The relative risk of thrombosis in the Heparin 50, Heparin 1000, reteplase, and taurolock groups compared to the control group was 92.5%, 92.2%, 98.2%, and 89% lower, respectively. Conclusion: Our study underscores the efficacy of heparin, reteplase, and taurolock in preventing thrombosis in hemodialysis catheters. While all three drugs demonstrated efficacy, the Heparin 50 group exhibited the highest relative risk reduction. These findings suggest that heparin, particularly at a low dose, should be considered a standard prophylactic treatment in hemodialysis patients.

15.
Cureus ; 16(4): e57987, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38738034

RESUMO

This article presents a case of a multimorbid 63-year-old woman with chronic kidney disease and heparin-induced thrombocytopenia (HIT). Following the insertion of a central venous catheter, she developed phlegmasia cerulea dolens (PCD) in her left arm, a rare and severe complication of deep vein thrombosis (DVT). Given the severity of the case, adapting to anticoagulant contraindications or unavailability, management with catheter-directed thrombolysis and mechanical thrombectomy was made. It is concluded that catheter-directed thrombolysis and mechanical thrombectomy are valuable therapeutic alternatives in critical situations where treatment options are limited.

16.
Cureus ; 16(4): e58124, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38738156

RESUMO

Development of cerebral venous sinus thrombosis (CVST) is a rare manifestation of heparin-induced thrombocytopenia (HIT). Herein, we present a case in which heparin administration for primary CVST caused paradoxical worsening of CVST secondary to HIT. A 53-year-old woman diagnosed with CVST was provided with intravenous unfractionated heparin therapy. After 12 days, the patient presented tonic convulsive seizures (TCS). Subsequent magnetic resonance image (MRI) scans revealed an exacerbation of cerebral edema with a subcortical hemorrhage on the left parietal lobe. Laboratory test results revealed a significant decline in platelet count. Heparin was immediately discontinued and replaced with argatroban. The definitive diagnosis of HIT was made through the presence of HIT antibodies. The present case, in which HIT caused the secondary CVST exacerbation, is distinctly rare. Our case provides an instructive example by highlighting the potential of TCS as the first sign of HIT development during CVST treatment.

17.
Int J Biol Macromol ; : 132181, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38740155

RESUMO

Nowadays, developing vascular grafts (e.g., vascular patches and tubular grafts) is challenging. Bacterial cellulose (BC) with 3D fibrous network has been widely investigated for vascular applications. In this work, different from BC vascular patch cultured with the routine culture medium, dopamine (DA)-containing culture medium is employed to in situ synthesize dense BC fibrous structure with significantly increased fiber diameter and density. Simultaneously, BC fibers are modified by DA during in situ synthesis process. Then DA on BC fibers can self-polymerize into polydopamine (PDA) accompanied with the removal of bacteria in NaOH solution, obtaining PDA-modified dense BC (PDBC) vascular patch. Heparin (Hep) is subsequently covalently immobilized on PDBC fibers to form Hep-immobilized PDBC (Hep@PDBC) vascular patch. The obtained results indicate that Hep@PDBC vascular patch exhibits remarkable tensile and burst strength due to its dense fibrous structure. More importantly, compared with BC and PDBC vascular patches, Hep@PDBC vascular patch not only displays reduced platelet adhesion and improved anticoagulation activity, but also promotes the proliferation, adhesion, spreading, and protein expression of human umbilical vein endothelial cells, contributing to the endothelialization process. The combined strategy of in situ densification and Hep immobilization provides a feasible guidance for the construction of BC-based vascular patches.

18.
Clin Chem Lab Med ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38738903

RESUMO

OBJECTIVES: Heparin is a highly charged polysaccharide used as an anticoagulant to prevent blood coagulation in patients with presumed myocardial infarction and to prepare heparin plasma samples for laboratory tests. There are conflicting data regarding the effects of heparin on the measurement of cardiac isoforms of troponin I (cTnI) and troponin T (cTnT), which are used for the immunodiagnosis of acute myocardial infarction. In this study, we investigated the influence of heparin on the immunodetection of human cardiac troponins. METHODS: Gel filtration (GF) techniques and sandwich fluoroimmunoassay were performed. The regions of сTnI and cTnT that are affected by heparin were investigated with a panel of anti-cTnI and anti-cTnT monoclonal antibodies, specific to different epitopes. RESULTS: Heparin was shown to bind to the human cardiac full-size ternary troponin complex (ITC-complex) and free cTnT, which increased their apparent molecular weights in GF studies. Heparin did not bind to the low molecular weight ITC-complex and to binary cTnI-troponin С complex. We did not detect any sites on cTnI in the ITC-complex that were specifically affected by heparin. In contrast, cTnT regions limited to approximately 69-99, 119-138 and 145-164 amino acid residues (aar) in the ITC-complex and a region that lies approximately between 236 and 255 aar of free cTnT were prone to heparin influence. CONCLUSIONS: Heparin binds to the ITC-complex via cTnT, interacting with several sites on the N-terminal and/or central parts of the cTnT molecule, which might influence the immunodetection of analytes in human blood.

19.
Int J Mol Sci ; 25(9)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38732176

RESUMO

Platelets play an important role in hemostasis, and a low platelet count usually increases the risk of bleeding. Conditions in which thrombosis occurs despite low platelet counts are referred to as thrombosis with thrombocytopenia syndrome, including heparin-induced thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia, paroxysmal nocturnal hemoglobinuria, antiphospholipid syndrome, thrombotic microangiopathy (TMA), and disseminated intravascular coagulation. TMA includes thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (HUS), and atypical HUS. Patients with these pathologies present with thrombosis and consumptive thrombocytopenia associated with the activation of platelets and the coagulation system. Treatment varies from disease to disease, and many diseases have direct impacts on mortality and organ prognosis if therapeutic interventions are not promptly implemented. Underlying diseases and the results of physical examinations and general laboratory tests as part of a thorough workup for patients should promptly lead to therapeutic intervention before definitive diagnosis. For some diseases, the diagnosis and initial treatment must proceed in parallel. Utilization of not only laboratory tests but also various scoring systems is important for validating therapeutic interventions based on clinical information.


Assuntos
Trombocitopenia , Trombose , Humanos , Trombocitopenia/diagnóstico , Trombose/etiologia , Plaquetas/metabolismo , Contagem de Plaquetas , Heparina/uso terapêutico , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/sangue
20.
Res Pract Thromb Haemost ; 8(3): 102384, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38617049

RESUMO

Background: Inherited antithrombin (AT) deficiency (ATD) is a severe thrombophilia causing venous thromboembolism, which can be complicated by postthrombotic syndrome (PTS). Venous recanalization, used to treat PTS, often requires a temporary withdrawal of anticoagulant therapy. In ATD patients, there is a risk of insufficient perioperative anticoagulation due to altered heparin response. Key Clinical Question: There is no consensus on how to manage perioperative anticoagulation in ATD patients. Clinical Approach: Warfarin-unfractionated heparin transition could be a more reliable strategy than low-molecular-weight heparin transition because unfractionated heparin anti-Xa activity not only reflects heparin-bound AT but also AT's activity, which correlates strongly with therapeutic anticoagulation. Biological monitoring could thus decrease the number of plasma-derived AT supplementation. Conclusion: This study describes a successful perioperative management of anticoagulation for venous recanalization that could be suggested to type 1 ATD patients with PTS.

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