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1.
J Extra Corpor Technol ; 53(3): 170-176, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34658407

RESUMO

Systemic anticoagulation with heparin during cardiopulmonary bypass (CPB) should be neutralized by protamine administration to restore normal hemostasis. However, protamine has potentially serious side effects and excessive protamine can cause increased postoperative bleeding. Thus, our goal is to appropriately dose protamine at the completion of CPB to neutralize heparin so that neither residual heparin nor excessive protamine is present. We performed a retrospective study of 216 patients who underwent cardiac surgery to search for a safe minimum protamine dose (PD) when measuring heparin concentration (HC). In addition, we developed a formula to determine PD using total heparin dose (THD) and CPB time without measuring HC. When protamine-to-heparin ratio (P-to-H) is set at 1 mg protamine to 100 international unit (IU) heparin in HMS Plus Hemostasis Management System (HMS), we determined that 75% of the calculated total PD is a safe minimum PD to sufficiently neutralize circulating heparin after CPB. On average, this translates into either .37 mg protamine/100 IU heparin of THD or .54 mg/100 IU of the first heparin bolus. The formula we developed to calculate PD without measuring HC can provide a PD that strongly agrees with the safe minimum PD when measuring HC. The safe minimum PD to neutralize circulating heparin after CPB can be significantly lower than conventional dosing practices. Reduction of PD may decrease the risk of postoperative bleeding and protamine-related adverse events. Based on our data, we decreased P-to-H in HMS to examine whether it is possible to reduce PD further than the safe minimum PD determined in this study.


Assuntos
Heparina , Protaminas , Ponte Cardiopulmonar , Antagonistas de Heparina , Humanos , Estudos Retrospectivos
2.
Rinsho Ketsueki ; 62(8): 1236-1246, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497212

RESUMO

In 2020, infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rapidly spread across the world to become a global pandemic. Coronavirus disease-2019 (COVID-19) is associated with a high rate of coagulopathy and thrombotic complications. The underlying mechanisms involved in these processes are complex. In addition to the low physical activity, blood coagulation activation accompanied by excessive immune/inflammatory reactions and vascular endothelialitis associated with the presence of intracellular SARS-CoV-2 and disrupted cell membranes contribute substantially to the complexity of the mechanisms. The types of thrombosis that occur include arterial thrombosis and venous thromboembolism. Microthrombi in alveolar capillaries are observed in COVID-19 patients. Considering the possible involvement of thrombosis in the worsening of COVID-19, prophylactic anticoagulant therapy, such as low-molecular-weight heparin or unfractionated heparin, is essential for patients with moderate and severe infections. Even with prophylactic anticoagulant therapy, the incidence of thrombosis remains high. Consequently, control of the underlying inflammation and vascular endothelial protection may be required in combination with anticoagulant therapy.


Assuntos
Transtornos da Coagulação Sanguínea , COVID-19 , Anticoagulantes , Heparina , Humanos , Pandemias , SARS-CoV-2
3.
Mater Sci Eng C Mater Biol Appl ; 128: 112268, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474827

RESUMO

Hydrogel coatings can improve the biocompatibility of medical devices. However, stable surface bonding and homogeneity of hydrogel coatings are often challenging. This study exploits the benefits of biohybrid hydrogels of crosslinked four-armed poly(ethylene glycol) and heparin to enhance the hemocompatibility of cobalt­chromium (CoCr) vascular stents. A bonding layer of dual silane and poly(ethylene-alt-maleic anhydride) (PEMA) treatment was applied to the stent to provide covalent immobilization and hydrophilicity for the homogeneous spreading of the hydrogel. A spray coating technology was used to distribute the aqueous solution of the reactive hydrogel precursors onto the sub-millimeter struts of the stents, where the solution polymerized to a homogeneous hydrogel film. The coating was mechanically stable on the stent after ethanol dehydration, and the stents could be stored in a dry state. The homogeneity and stability of the coating during stent expansion were verified. Quasistatic and dynamic whole blood incubation experiments showed substantial suppression of the pro-coagulant and inflammatory activity of the bare metal by the coating. Translation of the technology to industrial coating devices and future surface modification of stents with anti-inflammatory hydrogels are discussed.


Assuntos
Heparina , Hidrogéis , Interações Hidrofóbicas e Hidrofílicas , Polietilenoglicóis , Stents
4.
Mater Sci Eng C Mater Biol Appl ; 128: 112301, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474852

RESUMO

Intimal hyperplasia, thrombosis formation, and delayed endothelium regeneration are the main causes that restrict the clinical applications of PTFE small-diameter vascular grafts (inner diameter < 6 mm). An ideal strategy to solve such problems is to facilitate in situ endothelialization. Since the natural vascular endothelium adheres onto the basement membrane, which is a specialized form of extracellular matrix (ECM) secreted by endothelial cells (ECs) and smooth muscle cells (SMCs), functionalizing PTFE with an ECM coating was proposed. However, besides ECs, the ECM-modified PTFE improved SMC growth as well, thereby increasing the risk of intimal hyperplasia. In the present study, heparin was immobilized on the ECM coating at different densities (4.89 ± 1.02 µg/cm2, 7.24 ± 1.56 µg/cm2, 15.63 ± 2.45 µg/cm2, and 26.59 ± 3.48 µg/cm2), aiming to develop a bio-favorable environment that possessed excellent hemocompatibility and selectively inhibited SMC growth while promoting endothelialization. The results indicated that a low heparin density (4.89 ± 1.02 µg/cm2) was not enough to restrict platelet adhesion, whereas a high heparin density (26.59 ± 3.48 µg/cm2) resulted in decreased EC growth and enhanced SMC proliferation. Therefore, a heparin density at 7.24 ± 1.56 µg/cm2 was the optimal level in terms of antithrombogenicity, endothelialization, and SMC inhibition. Collectively, this study proposed a heparin-immobilized ECM coating to modify PTFE, offering a promising means to functionalize biomaterials for developing small-diameter vascular grafts.


Assuntos
Heparina , Politetrafluoretileno , Prótese Vascular , Células Endoteliais , Endotélio Vascular , Matriz Extracelular
5.
F1000Res ; 10: 469, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394916

RESUMO

Background: COVID-19 disease is accompanied by derangement of coagulation with a risk of fatal thromboembolic formation. COVID-19 patients are among those indicative for heparin treatment. Increased heparin administration among COVID-19 patients increased heparin induced-thrombocytopenia's risk with/without thrombocytopenia. Case presentation: We present a 71-year-old male patient who came to the emergency department (ED) with a COVID-19 clinical manifestation that PCR nasopharyngeal swab confirmed. He was assessed to have acute respiratory distress syndrome (ARDS), as shown by rapid progression of hypoxemic respiratory failure and bilateral pulmonary infiltrate. He was then treated with moxifloxacin, remdesivir, dexamethasone, heparin pump, and multivitamins. During admission, his respiratory symptoms got worse, so he transferred to the ICU for NIV support. On the ninth day of admission, he had gross hematuria followed by a rapid fall of platelet count. We used two different scoring systems (4Ts and HEP scoring system) to confirm the diagnosis of heparin-induced thrombocytopenia (HIT). Following the discontinuation of heparin injection, the thrombocyte continued to rise, and hematuria disappeared. Conclusion: Heparin-induced thrombocytopenia is associated with an increased risk of severe disease and mortality among COVID-19 patients. The differential diagnosis of HIT could be difficult among COVID-19 patients as thrombocytopenia can also be caused by infection progression. We use two scoring systems, 4Ts and HEP scoring, that can help us to manage the patient. With good management, we can avoid patient morbidity and mortality.


Assuntos
COVID-19 , Sepse , Trombocitopenia , Idoso , Anticoagulantes/efeitos adversos , Surtos de Doenças , Heparina/efeitos adversos , Humanos , Masculino , SARS-CoV-2 , Sepse/diagnóstico , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico
6.
Zh Nevrol Psikhiatr Im S S Korsakova ; 121(8. Vyp. 2): 41-46, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34553580

RESUMO

OBJECTIVE: To evaluate the effectiveness and safety of various heparin therapy regimens for venous thromboembolic complications in patients with acute cerebral circulatory disorders of the hemorrhagic type. MATERIAL AND METHODS: In a prospective single-center study, treatment results of 62 patients with hypertensive brain hematoma were analyzed. All patients were divided into two comparable groups: the group of «very early¼ prophylactic heparin therapy or the first 48 hours from the moment of the disease (n=35) and the group of «early¼ prophylactic heparin therapy, or later than 48 hours from the moment of the intracerebral hematoma development (n=27). The end points of the study were: venous thrombosis, pulmonary embolism (fatal and non-fatal), recurrent intracerebral hemorrhage, other clinically significant hemorrhagic complications, and intrahospital mortality. RESULTS: In the group of «very early¼ and «early¼ prophylactic heparin therapy, the results were as follows: venous thrombosis 22.9% vs. 29.6% (p=0.36), total rate of PE 2.9% vs. 11.1% (p=0.03), nonfatal PE 0% vs. 7.4% (p=0.007), fatal PE 2.9% vs. 3.7% (p=0.76), recurrent intracerebral hemorrhage and other hemorrhagic complications 0% in both groups, intrahospital mortality was 54.3% versus 48.1% (p=0.54). CONCLUSION: The earliest administration of direct anticoagulants in prophylactic doses in patients with hemorrhagic stroke leads to the decrease in the frequency of venous thrombosis and thromboembolic complications, without being accompanied by the development of repeated intracranial and other hemorrhagic events.


Assuntos
Anticoagulantes , Embolia Pulmonar , Anticoagulantes/efeitos adversos , Hemorragia Cerebral/complicações , Heparina , Humanos , Estudos Prospectivos
7.
J Trauma Nurs ; 28(5): 323-331, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34491950

RESUMO

BACKGROUND: Appropriate venous thromboembolism (VTE) chemoprophylaxis in trauma and emergency general surgery (EGS) patients is crucial. OBJECTIVE: The purpose of this study is to review the recent literature and offer recommendations for VTE chemoprophylaxis in trauma and EGS patients. METHODS: We conducted a literature search from 2000 to 2021 for articles investigating VTE chemoprophylaxis in adult trauma and EGS patients. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. RESULTS: Our search resulted in 34 articles. Most studies showed low-molecular-weight heparin (LMWH) is similar to unfractionated heparin (UFH) for VTE prevention; however, LMWH was more commonly used. Adjusted chemoprophylaxis dosing did not change the VTE rate but the timing did. Direct oral anticoagulants (DOACs) have been shown to be safe and effective in trauma and traumatic brain injury (TBI)/spinal cord injury (SCI). Studies showed VTE prophylaxis in EGS can be inconsistent and improves with guidelines that lower VTE events. CONCLUSIONS: There may be no benefit to receiving LMWH over UFH in trauma patients. In addition, different drugs under the class of LMWH do not change the incidence of VTE. Adjusted dosing of enoxaparin does not seem to affect VTE incidence. The use of DOACs in the trauma TBI and SCI setting has been shown to be safe and effective in reducing VTE. One important consideration with VTE prophylaxis may be the timing of prophylaxis initiation, specifically as it relates to TBI, with a higher likelihood of developing VTE as time progresses. EGS patients are at a high risk of VTE. Improved compliance with clinical guidelines in this population is correlated with decreased thrombotic events.


Assuntos
Tromboembolia Venosa , Adulto , Anticoagulantes/efeitos adversos , Quimioprevenção , Heparina , Heparina de Baixo Peso Molecular , Humanos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
8.
Trials ; 22(1): 639, 2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34538275

RESUMO

BACKGROUND: Heparin is used worldwide for 70 years during all non-cardiac arterial procedures (NCAP) to reduce thrombo-embolic complications (TEC). But heparin also increases blood loss causing possible harm for the patient. Heparin has an unpredictable effect in the individual patient. The activated clotting time (ACT) can measure the effect of heparin. Currently, this ACT is not measured during NCAP as the standard of care, contrary to during cardiac interventions, open and endovascular. A RCT will evaluate if ACT-guided heparinization results in less TEC than the current standard: a single bolus of 5000 IU of heparin and no measurements at all. A goal ACT of 200-220 s should be reached during ACT-guided heparinization and this should decrease (mortality caused by) TEC, while not increasing major bleeding complications. This RCT will be executed during open abdominal aortic aneurysm (AAA) surgery, as this is a standardized procedure throughout Europe. METHODS: Seven hundred fifty patients, who will undergo open AAA repair of an aneurysm originating below the superior mesenteric artery, will be randomised in 2 treatment arms: 5000 IU of heparin and no ACT measurements and no additional doses of heparin, or a protocol of 100 IU/kg bolus of heparin and ACT measurements after 5 min, and then every 30 min. The goal ACT is 200-220 s. If the ACT after 5 min is < 180 s, 60 IU/kg will be administered; if the ACT is between 180 and 200 s, 30 IU/kg. If the ACT is > 220 s, no extra heparin is given, and the ACT is measured after 30 min and then the same protocol is applied. The expected incidence for the combined endpoint of TEC and mortality is 19% for the 5000 IU group and 11% for the ACT-guided group. DISCUSSION: The ACTION-1 trial is an international RCT during open AAA surgery, designed to show superiority of ACT-guided heparinization compared to the current standard of a single bolus of 5000 IU of heparin. A significant reduction in TEC and mortality, without more major bleeding complications, must be proven with a relevant economic benefit. TRIAL REGISTRATION {2A}: NTR NL8421 ClinicalTrials.gov NCT04061798 . Registered on 20 August 2019 EudraCT 2018-003393-27 TRIAL REGISTRATION: DATA SET {2B}: Data category Information Primary registry and trial identifying number ClinicalTrials.gov : NCT04061798 Date of registration in primary registry 20-08-2019 Secondary identifying numbers NTR: NL8421 EudraCT: 2018-003393-27 Source(s) of monetary or material support ZonMw: The Netherlands Organisation for Health Research and Development Dijklander Ziekenhuis Amsterdam UMC Primary sponsor Dijklander Ziekenhuis Secondary sponsor(s) N/A Contact for public queries A.M. Wiersema, MD, PhD Arno@wiersema.nu 0031-229 208 206 Contact for scientific queries A.M. Wiersema, MD, PhD Arno@wiersema.nu 0031-229 208 206 Public title ACT Guided Heparinization During Open Abdominal Aortic Aneurysm Repair (ACTION-1) Scientific title ACTION-1: ACT Guided Heparinization During Open Abdominal Aortic Aneurysm Repair, a Randomised Trial Countries of recruitment The Netherlands. Soon the recruitment will start in Germany Health condition(s) or problem(s) studied Abdominal aortic aneurysm, arterial disease, surgery Intervention(s) ACT-guided heparinization 5000 IU of heparin Key inclusion and exclusion criteria Ages eligible for the study: ≥18 years Sexes eligible for the study: both Accepts healthy volunteers: no Inclusion criteria: Study type Interventional Allocation: randomized Intervention model: parallel assignment Masking: single blind (patient) Primary purpose: treatment Phase IV Date of first enrolment March 2020 Target sample size 750 Recruitment status Recruiting Primary outcome(s) The primary efficacy endpoint is 30-day mortality and in-hospital mortality during the same admission. The primary safety endpoint is the incidence of bleeding complications according to E-CABG classification, grade 1 and higher. Key secondary outcomes Serious complications as depicted in the Suggested Standards for Reports on Aneurysmal disease: all complications requiring re-operation, longer hospital stay, all complications.


Assuntos
Aneurisma da Aorta Abdominal , COVID-19 , Adolescente , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Heparina/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Método Simples-Cego , Resultado do Tratamento
9.
Molecules ; 26(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34500644

RESUMO

The linear anionic class of polysaccharides, glycosaminoglycans (GAGs), are critical throughout the animal kingdom for developmental processes and the maintenance of healthy tissues. They are also of interest as a means of influencing biochemical processes. One member of the GAG family, heparin, is exploited globally as a major anticoagulant pharmaceutical and there is a growing interest in the potential of other GAGs for diverse applications ranging from skin care to the treatment of neurodegenerative conditions, and from the treatment and prevention of microbial infection to biotechnology. To realize the potential of GAGs, however, it is necessary to develop effective tools that are able to exploit the chemical manipulations to which GAGs are susceptible. Here, the current knowledge concerning the chemical modification of GAGs, one of the principal approaches for the study of the structure-function relationships in these molecules, is reviewed. Some additional methods that were applied successfully to the analysis and/or processing of other carbohydrates, but which could be suitable in GAG chemistry, are also discussed.


Assuntos
Glicosaminoglicanos/química , Polissacarídeos/química , Animais , Anticoagulantes/química , Heparina/química , Humanos , Relação Estrutura-Atividade
10.
Mater Sci Eng C Mater Biol Appl ; 129: 112405, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34579917

RESUMO

Due to the uncontrollable anticoagulant activity and limited source, Heparin, which is commonly used in clinical anticoagulation therapies, faces the risk of spontaneous bleeding and thrombocytopenia. Herein, a series of anionic poly(amino acid) s poly (l-Serine-ran-L-Glutamic acid-ran-L-Cysteine-SO3) (PSEC-SO3) were prepared by the controlled Ring Opening Polymerization (ROP) of N-Carboxyanhydrides (NCAs). The anticoagulant activities of PSEC-SO3 can be regulated by simply adjusting the feeding ratio of monomers. In vitro tests show that these polypeptides can effectively prolong the Activated Partical Thromboplastin Time (APTT) and inhibit Factor IIa and Factor Xa, but has no significant effect on Prothrombin Time (PT) and Thrombin Time (TT), which indicates that PSEC-SO3 mainly act on the intrinsic pathway. In summary, the activity-tunable heparin-like polypeptides are expected to have good application prospects in the anticoagulant field.


Assuntos
Anticoagulantes , Heparina , Anticoagulantes/farmacologia , Heparina/farmacologia , Tempo de Tromboplastina Parcial , Peptídeos/farmacologia , Solubilidade
12.
Phys Chem Chem Phys ; 23(36): 20406-20418, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34494046

RESUMO

Abnormal aggregation of proteins into pathological amyloid fibrils is implicated in a wide range of devastating human neurodegenerative diseases. Intracellular fibrillary inclusions formed by Tau protein are characterized as the hallmark of tauopathies, including Alzheimer's disease and frontotemporal dementia. Heparin has been often used to trigger Tau aggregation in in vitro studies. However, the conformational changes induced by heparin and the underlying mechanism of promotion of Tau aggregation by heparin are not well understood. Structural characterization of Tau oligomers in the early stage of fibrillation is of great importance but remains challenging due to their dynamic and heterogeneous nature. R3, the third microtubule-binding repeat of Tau, contains the fibril-nucleating core (PHF6) and is crucial for Tau aggregation. In this study, utilizing extensive all-atom replica-exchange molecular dynamic simulations, we explored the conformational ensembles of R3 monomer/dimer in the absence and presence of heparin. Our results show that without heparin, both monomeric and dimeric R3 preferentially adopt collapsed ß-sheet-containing conformations and PHF6 plays an important role in the formation of interchain ß-sheet structures, while in the presence of heparin, R3 can populate relatively extended disordered states where chain dimension is similar to that of R3 in Tau filaments. Through electrostatic, hydrogen-bonding and hydrophobic interactions, heparin has a preference for interacting with residues V306/Q307/K317/K321/H329/H330/K331 which distribute throughout the entire sequence of R3, in turn acting as a template to extend R3 conformations. More importantly, heparin alters intramolecular/intermolecular interaction patterns of R3 and increases the intermolecular contact regions. Our results suggest that heparin remodels the conformations of R3 towards fibril-prone structures by increasing chain dimension and intermolecular contact regions, which may shed light on the atomic mechanism of heparin-induced amyloid fibrillization of Tau protein.


Assuntos
Amiloide/química , Heparina/química , Simulação de Dinâmica Molecular , Proteínas tau/química , Humanos , Agregados Proteicos
13.
Int J Mol Sci ; 22(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34576237

RESUMO

Previous studies reported on the broad-spectrum antiviral function of heparin. Here we investigated the antiviral function of magnesium-modified heparin and found that modified heparin displayed a significantly enhanced antiviral function against human adenovirus (HAdV) in immortalized and primary cells. Nuclear magnetic resonance analyses revealed a conformational change of heparin when complexed with magnesium. To broadly explore this discovery, we tested the antiviral function of modified heparin against herpes simplex virus type 1 (HSV-1) and found that the replication of HSV-1 was even further decreased compared to aciclovir. Moreover, we investigated the antiviral effect against the new severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and measured a 55-fold decreased viral load in the supernatant of infected cells associated with a 38-fold decrease in virus growth. The advantage of our modified heparin is an increased antiviral effect compared to regular heparin.


Assuntos
Antivirais/farmacologia , Heparina/farmacologia , Cloreto de Magnésio/farmacologia , Aciclovir/farmacologia , Adenovírus Humanos/efeitos dos fármacos , Adenovírus Humanos/fisiologia , Animais , Antivirais/química , Células CHO , Linhagem Celular Tumoral , Chlorocebus aethiops , Cricetulus , Avaliação Pré-Clínica de Medicamentos , Fibroblastos , Heparina/química , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/fisiologia , Humanos , Cloreto de Magnésio/química , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Cultura Primária de Células , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologia , Relação Estrutura-Atividade , Células Vero , Carga Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
14.
Biosens Bioelectron ; 194: 113612, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34507094

RESUMO

We have reported an optical indicator displacement assay (IDA) for heparin with a UV-vis absorbance and fluorescence dual-readout based on pyranine/methyl viologen (MV2+). Upon introducing heparin, pyranine/MV2+ shows a clearly observable increase in UV-vis absorbance and a turn-on of the fluorescence signal. We have demonstrated that the ionic nature of buffers significantly affects the pyranine displacement and the zwitterionic HEPES was most suitable for heparin sensing. After careful screening of experimental conditions, the pyranine/MV2+-based optical chemosensor exhibits a fast, sensitive, and selective response toward heparin. It shows dynamic linear concentration of heparin in the ranges of 0.1-40 U·mL-1 and 0.01-20 U·mL-1 for the absorptive and fluorescent measurements, respectively, which both cover the clinically relevant levels of heparin. As with the animal experiments, the optical chemosensor has been demonstrated to be selective and effective for heparin level qualification in rat plasma. The chemosensor is readily accessible, cost-effective, and reliable, which holds a great promise for potential application on clinical and biological studies. Furthermore, this IDA system can serve as an IMPLICATION logic gate with a reversible and switchable logical manner.


Assuntos
Técnicas Biossensoriais , Heparina , Animais , Sulfonatos de Arila , Corantes Fluorescentes , Paraquat , Ratos
15.
Viruses ; 13(9)2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34578301

RESUMO

BACKGROUND: According to recent guidelines, all hospitalized patients with COVID-19 should receive pharmacological prophylaxis for venous thromboembolism (VTE), unless there are specific contraindications. However, the optimal preventive strategy in terms of intensity of anticoagulation for these patients is not well established. OBJECTIVES: To investigate the impact of individualized regimens of enoxaparin on the development of VTE and on the risk of major bleeding complications during hospitalization in patients with COVID-19 infection. METHODS: All consecutive patients admitted to the medical wards of six Italian hospitals between 15 September and 15 October 2020 with COVID-19 infection of moderate severity were administered enoxaparin in subcutaneous daily doses adjusted to the Padua Prediction Score stratification model: No heparin in patients scoring less than 4, 4000 IU daily in those scoring 4, 6000 IU in those scoring 5, and 8000 in those scoring six or more. Objective tests were performed in patients developing clinical symptoms of deep vein thrombosis and/or pulmonary embolism. Bleeding complications were defined according to the ISTH classification. RESULTS: From the 154 eligible patients, enoxaparin was administered in all: 4000 IU in 73 patients, 6000 IU in 53, and 8000 IU in the remaining 28. During the course of hospitalization, 27 patients (17.5%) died. VTE developed in 14 of the 154 patients (9.1%; 95% CI, 4.6% to 13.6%), and was fatal in 1. Major bleeding complications developed in 35 patients (22.7%; 95% CI, 16.1% to 29.3%), and were fatal in 8. CONCLUSIONS: Despite the use of risk-adjusted doses of enoxaparin, the rate of VTE events was consistent with that reported in contemporary studies where fixed-dose low-molecular-weight heparin was used. The unexpectedly high risk of bleeding complications should induce caution in administering enoxaparin in doses higher than the conventional low ones.


Assuntos
Anticoagulantes/administração & dosagem , COVID-19/complicações , COVID-19/virologia , Heparina/administração & dosagem , SARS-CoV-2 , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , COVID-19/epidemiologia , Feminino , Hemorragia/etiologia , Heparina/efeitos adversos , Humanos , Masculino , Prognóstico , Resultado do Tratamento
16.
Nutrients ; 13(8)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34445055

RESUMO

BACKGROUND: We previously reported that severe COVID-19 patients had higher chances of survival and a reduced risk of developing respiratory failure when administered with the probiotic formulation SLAB51. This study aimed to investigate further bacteriotherapy mechanisms and how early they are activated. METHODS: We performed an analysis on the blood oxygenation parameters collected in sixty-nine severe COVID-19 patients requiring non-invasive oxygen therapy and presenting a CT lung involvement ≥50%. Twenty-nine patients received low-molecular-weight heparin, azithromycin and Remdesivir. In addition, forty subjects received SLAB51. Blood gas analyses were performed before the beginning of treatments and at 24 h. RESULTS: The patients receiving only standard therapy needed significantly increased oxygen amounts during the 24 h observation period. Furthermore, they presented lower blood levels of pO2, O2Hb and SaO2 than the group also supplemented with oral bacteriotherapy. In vitro data suggest that SLAB51 can reduce nitric oxide synthesis in intestinal cells. CONCLUSIONS: SARS-CoV-2 infected patients may present lesions in the lungs compromising their gas exchange capability. The functionality of the organs essential for these patients' survival depends mainly on the levels of pO2, O2Hb and SaO2. SLAB51 contains enzymes that could reduce oxygen consumption in the intestine, making it available for the other organs.


Assuntos
COVID-19/terapia , Oxigênio/uso terapêutico , Probióticos/uso terapêutico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Idoso , Alanina/análogos & derivados , Alanina/uso terapêutico , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Gasometria , Linhagem Celular , Feminino , Heparina , Humanos , Hipóxia , Itália , Pulmão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Bratisl Lek Listy ; 122(9): 626-630, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34463107

RESUMO

NTRODUCTION: Anticoagulant treatment approach in patients with COVID-19 is not well studied and not standardized. We aimed to compare the effects of standard prophylactic and pre-emptive therapeutic Low-Molecular-weight Heparin (LMWH) treatment approaches on mortality in patients with COVID-19. PATIENTS AND METHODS: This retrospective and single-centre study includes patients aged ≥ 18 years, who were diagnosed with COVID-19 and treated with LMWH during the hospital stay. Therapeutic dose of LMWH was defined as 1 mg/kg subcutaneously twice daily and prophylactic dose of LMWH was defined as 40 mg subcutaneously once daily. RESULTS: Among the 336 patients diagnosed with COVID-19 pneumonia, 115 patients, who received LMWH were included in the study. The mean age was 58.6 ± 13.3 and 58 (50.4 %) of the patients were male. Sixty-nine (60 %) of the patients were treated with prophylactic and 46 (40 %) therapeutic LMWH.In-hospital mortality was not different between patients treated therapeutic LMWH and prophylactic LMWH by the multivariate regression analysis (OR=2.187, 95% CI 0.484-9.880, p=0.309) and the propensity score modelling (OR=1.586, 95% CI 0.400-6.289, p=0.512.)CONCLUSION: Clinicians should consider the potential risks and benefits of standard prophylactic and pre-emptive therapeutic LMWH. Therefore, anticoagulant therapy should be individualized in patients with COVID-19 (Tab. 3, Ref. 28).


Assuntos
Anticoagulantes/administração & dosagem , COVID-19 , Heparina de Baixo Peso Molecular/administração & dosagem , COVID-19/terapia , Heparina , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
Ned Tijdschr Geneeskd ; 1652021 05 20.
Artigo em Holandês | MEDLINE | ID: mdl-34346643

RESUMO

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is diagnosed if there is venous or arterial thrombosis with thrombocytopenia caused by antibodies against platelet factor 4 (PF4) that activate thrombocytes and is confirmed by a heparin-induced platelet activation (HIPA) test, occurring 4 to 28 days after vaccination against COVID19. This extremely rare syndrome has been recognized after Astra Zeneca (reporting incidence 0.91 per 100.000) and Janssen vaccins (0.22 per 100.000). Causality with the vaccine is difficult to ascertain if the HIPA test is negative, or if there is severe thrombosis (such as cerebral sinus or splanchnic thrombosis) without thrombocytopenia. Symptoms compatible with thrombosis or bleeding occurring in a specific time window after vaccination should prompt urgent assessment of the thrombocyte count and appropriate diagnostic tests. Heparin-like anticoagulants should be avoided and central laboratory assessment is essential. Early recognition likely improves prognosis of this extremely rare but severe complication of vaccination against COVID-19.


Assuntos
COVID-19 , Trombocitopenia , Trombose , Vacinas , Anticoagulantes , Heparina , Humanos , SARS-CoV-2 , Trombocitopenia/induzido quimicamente , Vacinas/efeitos adversos
20.
J Transl Med ; 19(1): 344, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376200

RESUMO

Although reports implicate radioresistance as an important obstacle for the management of breast cancer, its molecular mechanism is elusive. Herein, we found that high HDGF levels are expressed significantly in breast cancer and exhibit a positive association with poor survival prognosis. Heparin-binding growth factor (HDGF) was upregulated in radioresistant breast cancer cells, however, its knockdown could reduce breast cancer radioresistant both in vitro and in vivo. Additionally, the binding of RXRα to HDGF promoter blocked HDGF transcriptional activity, consequently inhibiting breast cancer radioresistance. The enhanced radioresistant activity of HDGF is induced by TKT and STAT3, impacting the STAT3-Tyr705 and STAT3-Ser727 phosphorylation and STAT3 transcriptional activity. Notably, HDGF depletion renders radioresistant hypersensitive to the drug that targets STAT3 phosphorylation. This article demonstrates the novel function of HDGF as a promising molecular target for predicting radioresistance in breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Feminino , Heparina/farmacologia , Humanos , Fator de Transcrição STAT3 , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular
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