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British Journal of Clinical Pharmacology Jun 2024Bleeding events are common in patients prescribed anticoagulants and can have devastating consequences. Several specific and nonspecific agents have been developed to... (Review)
Review
Bleeding events are common in patients prescribed anticoagulants and can have devastating consequences. Several specific and nonspecific agents have been developed to reverse the effects of anticoagulant drugs or toxins. Vitamin K, as the oldest of these antidotes, specifically counteracts the effects of pharmaceuticals and rodenticides designed to deplete stores of vitamin K-dependent factors. In cases of life-threatening bleeding, the addition of prothrombin complex concentrates (PCCs) allows for the immediate replacement of coagulation factors. While the use of PCCs has been extended to the non-specific reversal of the effects of newer direct oral anticoagulants, the specific agents idarucizumab, targeting dabigatran and andexanet-α, binding factor Xa inhibitors, have recently been developed and are being preferentially recommended by most guidelines. However, despite having rapid effects on correcting coagulopathy, there is to date a lack of robust evidence establishing the clear superiority of direct oral anticoagulant-specific reversal agents over PCCs in terms of haemostatic efficacy, safety or mortality. For andexanet-α, a potential signal of increased thromboembolic risks, comparatively high costs and low availability might also limit its use, even though emerging evidence appears to bolster its role in intracranial haemorrhage. Protamine is the specific agent for the reversal of unfractionated heparin anticoagulation used mainly in cardiovascular surgery. It is much less effective for low molecular weight heparin fragments and is usually reserved for cases with life-threatening bleeding.
PubMed: 38926082
DOI: 10.1111/bcp.16142 -
BMJ Open Jun 2024Left ventricular assist devices (LVADs) have emerged as a successful treatment option for patients with end-stage heart failure. Compared with the best medical therapy,...
BACKGROUND
Left ventricular assist devices (LVADs) have emerged as a successful treatment option for patients with end-stage heart failure. Compared with the best medical therapy, LVADs improve survival and enhance functional capacity and quality of life. However, two major complications compromise this patient population's outcomes: thrombosis and bleeding. Despite technological innovations and better hemocompatibility, these devices alter the rheology, triggering the coagulation cascade and, therefore, require antithrombotic therapy. Anticoagulation and antiplatelet therapies represent the current standard of care. Still, inconsistency in the literature exists, especially whether antiplatelet therapy is required, whether direct oral anticoagulants can replace vitamin K antagonists and even whether phosphodiesterase type 5 inhibitors with their antithrombotic effects could be added to the regimen of anticoagulation.
METHODS AND ANALYSIS
We will perform a living systematic review with network meta-analysis and indirect comparison between current antithrombotic therapies, which have and have not been directly compared within clinical trials and observational studies. We will systematically search the following electronic sources: Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica Database (EMBASE). We will exclusively examine studies published in English from 2016 to the present. Studies conducted before 2016 will be omitted since our primary focus is evaluating continuous flow devices. Two independent reviewers will assess the articles by title, abstract and full text; any disagreement will be resolved through discussion, and a third reviewer will be involved if necessary. The Cochrane Risk of Bias tool will be used to assess the risk of bias. We will then conduct a pairwise meta-analysis; if the assumption of transitivity is satisfied, we will proceed with network meta-analysis using Bayesian methodology.
ETHICS AND DISSEMINATION
Formal ethical approval is not required as no primary data are collected. This systematic review and network meta-analysis will delineate the risks of stroke, thromboembolic events, pump thrombosis, gastrointestinal bleeding and mortality in patients equipped with LVADs who are subjected to various antithrombotic regimens. The findings will be disseminated via a peer-reviewed publication and presented at conference meetings. This will enhance clinical practice and guide future research on anticoagulation strategies within this distinct patient cohort.
PROSPERO REGISTRATION NUMBER
CRD42023465288.
Topics: Humans; Heart-Assist Devices; Systematic Reviews as Topic; Network Meta-Analysis; Fibrinolytic Agents; Anticoagulants; Thrombosis; Heart Failure; Platelet Aggregation Inhibitors; Research Design; Hemorrhage
PubMed: 38925683
DOI: 10.1136/bmjopen-2023-080110 -
Haemophilia : the Official Journal of... Jun 2024Diagnosing hemophilia B (HB) carrier status is important to manage bleeding in carriers and to prevent bleeding in potential offspring. Without a family history of...
INTRODUCTION
Diagnosing hemophilia B (HB) carrier status is important to manage bleeding in carriers and to prevent bleeding in potential offspring. Without a family history of hemophilia, diagnosing HB carrier status is challenging. Genetic testing is the gold-standard, however it is reserved for individuals with a high suspicion of carrier status.
AIMS
To describe the distribution of activated partial thromboplastin time (aPTT) and factor IX coagulant (FIX:C) levels in HB carriers and assess the ratio of FIX:C to other Vitamin K dependent factors (FII:C, FVII:C, FX:C) as an indicator of HB carrier status.
METHODS
In this retrospective, single-centre cohort study, subjects were included if they were obligate or genetically proven HB carriers. Distributions of aPTT and FIX:C were described and the relationship between FIX:C levels in carriers and severity of familial HB was analysed. Ratios of FIX:C to FII:C, FVII:C, FX:C were calculated.
RESULTS
Seventy-two female HB carriers (median age: 34 years; IQR 24-43) were included. Median aPTT and FIX:C levels were 33.0 s [IQR 30.0-37.0] and 57 IU/dL [IQR 43-74]. Fifteen carriers (21%) had mild HB (FIX:C levels of 10-40 IU/dL). FIX:C levels trended higher in carriers of mild HB versus carriers of moderate/severe HB. In six carriers, the median ratio of FIX:C to other Vitamin K dependent factors was 0.44, with 92% of ratios being ≤ 0.75.
CONCLUSION
aPTT and FIX:C levels were unreliable in diagnosing HB carrier status. A low ratio of FIX:C to other Vitamin K dependent factors may be a useful marker of HB carrier status.
PubMed: 38924261
DOI: 10.1111/hae.15068 -
Journal of Cardiovascular Pharmacology Apr 2024Current guidelines recommend that direct anticoagulants should not be used in prevention of recurrent thrombosis in patients with antiphospholipid syndrome (APS)....
Current guidelines recommend that direct anticoagulants should not be used in prevention of recurrent thrombosis in patients with antiphospholipid syndrome (APS). However, except for triple-positive APS and rivaroxaban use, little evidence supports such recommendation. In a real-life cohort study, we evaluated the risk of thromboembolism and bleeding in APS patients on apixaban versus vitamin K antagonists (VKA). We enrolled 152 APS patients (aged 44 [interquartile range 36-56], 83% women), including 66 patients treated with apixaban 5 mg bid and 86 with warfarin (target INR [international normalized ratio] 2-3). During a median follow-up of 53 months, we recorded venous thromboembolism (VTE), ischemic stroke or myocardial infarction, along with major bleeding. We observed 4 (6.1%, 3 VTE and 1 ischemic stroke) thrombotic events in patients on apixaban and 12 events (14%, 9 VTE, 2 ischemic strokes and 1 myocardial infarction) in VKA patients. APS patients on apixaban had similar risk of recurrent thromboembolism compared to those on warfarin (HR=0.327, 95% CI: 0.104-1.035). Thromboembolic events occurred less commonly in statin users (8% vs 50%, p=0.01) and more frequently in triple-positive APS (50% vs 22.1%, p=0.028) and in subjects with higher D-dimer at baseline (p=0.023); the latter difference was present in the apixaban group (p=0.02). Patients on apixaban had similar risk of major bleeding compared to warfarin (HR=0.54, 95% CI: 0.201-1.448). In real-life APS patients apixaban appears to be similar to VKA for the prevention of thromboembolism and risk of bleeding, which might suggest that some APS patients could be treated with apixaban.
PubMed: 38922590
DOI: 10.1097/FJC.0000000000001578 -
International Journal of Systematic and... Jun 2024A Gram-stain-positive, rod-shaped, aerobic, motile bacterium, J379, was isolated from radioactive water spring C1, located in a former silver-uranium mine in the Czech...
A Gram-stain-positive, rod-shaped, aerobic, motile bacterium, J379, was isolated from radioactive water spring C1, located in a former silver-uranium mine in the Czech Republic. This slow-growing strain exhibited optimal growth at 24-28 °C on solid media with <1 % salt concentration and alkaline pH 8-10. The only respiratory quinone found in strain J379 was MK-7(H). C ω9 (60.9 %), C (9.4 %), C and alcohol-C (both 6.2 %) were found to be the major fatty acids. The peptidoglycan contained directly cross-linked -diaminopimelic acid. Phylogenetic reconstruction based on the 16S rRNA gene sequences and the core-genome analysis revealed that strain J379 forms a separate phylogenetic lineage within the recently amended order . A comparison of the 16S rRNA gene sequences between strain J379 and other members of the order showed <96 % similarity. This analysis revealed that the closest type strains were D16/0 /H6 (95.2 %), 0166_1 (94.9 %) and KV-962 (94.5 %). Whole-genome analysis showed that the closest type strain was BR7-21 with an average nucleotide identity of 78 %, average amino acid identity of 63.2 % and percentage of conserved proteins of 48.2 %. The G+C content of the J379 genomic DNA was 71.7 mol%. Based on the phylogenetic and phylogenomic data, as well as its physiological characteristics, strain J379 is proposed to represent a type strain (DSM 113746=CCM 9300) of gen. nov. sp. nov. within the family .
Topics: Phylogeny; RNA, Ribosomal, 16S; Bacterial Typing Techniques; Fatty Acids; DNA, Bacterial; Sequence Analysis, DNA; Base Composition; Mining; Czech Republic; Peptidoglycan; Diaminopimelic Acid; Vitamin K 2; Silver; Water Microbiology
PubMed: 38922323
DOI: 10.1099/ijsem.0.006432 -
Dentistry Journal May 2024This review's objective is to examine the findings from various studies on oral signs and symptoms related to vitamin deficiency. In October 2023, two electronic... (Review)
Review
This review's objective is to examine the findings from various studies on oral signs and symptoms related to vitamin deficiency. In October 2023, two electronic databases (Scopus and PubMed) were searched for published scientific articles following PRISMA principles. Articles eligible for inclusion in this review had to be published in English between 2017 and 2023, be original studies, and involve human subjects. Fifteen studies were included in this review: three examining oral symptoms of vitamin B12 deficiency; one assessing vitamin B complex and vitamin E for recurrent oral ulcers; one investigating serum vitamin D levels in recurrent aphthous stomatitis patients; three exploring hypovitaminosis effects on dental caries; two measuring blood serum vitamin D levels; one evaluating vitamin B12 hypovitaminosis; three investigating hypovitaminosis as indicative of gingival disease; one focusing on vitamin deficiencies and enamel developmental abnormalities; one assessing vitamin deficiencies in oral cancer patients; one examining vitamin K as an oral anticoagulant and its role in perioperative hemorrhage; and one evaluating vitamin effects on burning mouth syndrome. Despite some limitations, evidence suggests a correlation between vitamin deficiencies and oral symptoms. This systematic review was registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) database (202430039).
PubMed: 38920853
DOI: 10.3390/dj12060152 -
Annals of the Academy of Medicine,... Mar 2024
Topics: Warfarin; Humans; Singapore; Algorithms; Anticoagulants; Pharmacogenetics; Male; International Normalized Ratio; Female; Cytochrome P-450 CYP2C9; Middle Aged; Aged; Vitamin K Epoxide Reductases
PubMed: 38920246
DOI: 10.47102/annals-acadmedsg.2023186 -
Annals of the Academy of Medicine,... Feb 2024Few real-world studies have investigated drug-drug interactions (DDIs) involving non-vitamin-K antagonist oral anticoagulants (NOACs) in patients with nonvalvular atrial...
INTRODUCTION
Few real-world studies have investigated drug-drug interactions (DDIs) involving non-vitamin-K antagonist oral anticoagulants (NOACs) in patients with nonvalvular atrial fibrillation (NVAF). The interactions encompass drugs inducing or inhibiting cytochrome P450 3A4 and permeability glycoprotein. These agents potentially modulate the breakdown and elimination of NOACs. This study investigated the impact of DDIs on thromboembolism in this clinical scenario.
METHOD
Patients who had NVAF and were treated with NOACs were selected as the study cohort from the National Health Insurance Research Database of Taiwan. Cases were defined as patients hospitalised for a thromboembolic event and who underwent a relevant imaging study within 7 days before hospitalisa-tion or during hospitalisation. Each case was matched with up to 4 controls by using the incidence density sampling method. The concurrent use of a cytochrome P450 3A4/permeability glycoprotein inducer or inhibitor or both with NOACs was identified. The effects of these interactions on the risk of thromboembolic events were examined with univariate and multivariate conditional logistic regressions.
RESULTS
The study cohort comprised 60,726 eligible patients. Among them, 1288 patients with a thromboembolic event and 5144 matched control patients were selected for analysis. The concurrent use of a cytochrome P450 3A4/permeability glycoprotein inducer resulted in a higher risk of thromboembolic events (adjusted odds ratio [AOR] 1.23, 95% confidence interval [CI] 1.004-1.51).
CONCLUSION
For patients with NVAF receiving NOACs, the concurrent use of cytochrome P450 3A4/ permeability glycoprotein inducers increases the risk of thromboembolic events.
Topics: Humans; Atrial Fibrillation; Drug Interactions; Thromboembolism; Anticoagulants; Male; Female; Aged; Administration, Oral; Taiwan; Middle Aged; Case-Control Studies; Aged, 80 and over; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 CYP3A; Factor Xa Inhibitors; Pyridones
PubMed: 38920231
DOI: 10.47102/annals-acadmedsg.2023137 -
Annals of the Academy of Medicine,... Feb 2024
Topics: Humans; Anticoagulants; Administration, Oral; Factor Xa Inhibitors; Atrial Fibrillation
PubMed: 38920229
DOI: 10.47102/annals-acadmedsg.202413 -
Journal of Medical Case Reports Jun 2024Acute hepatitis A infection is common among children in developing nations. The clinical presentation in children is usually asymptomatic and anicteric, and it is a...
BACKGROUND
Acute hepatitis A infection is common among children in developing nations. The clinical presentation in children is usually asymptomatic and anicteric, and it is a self-limiting infection. Rarely, it can be associated with extrahepatic complications such as pleural effusion, acalculous cholecystitis, and ascites.
CASE PRESENTATION
An 8-year-old middle eastern child presented with abdominal pain, jaundice in the sclera, yellowish color of urine, and poor appetite. In the last two days, abdominal distension developed. After conducting diagnostic investigations, the child was diagnosed with HAV hepatitis associated with bilateral pleural effusion, acalculous cholecystitis, and ascites. He was managed conservatively with vitamin K supplementation and supportive parenteral fluids. After 4 days, clinical improvement was observed.
CONCLUSION
Hepatitis A infections presented with extrahepatic manifestations like pleural effusion, acalculous cholecystitis, and ascites are very rare, especially in children. There have been some reports of these manifestations occurring in isolation, but for them to co-exist to our knowledge, this has only been reported in two cases in the literature, and this is the third case with all these three rare complications being presented simultaneously in a single child. Although HAV infection is an asymptomatic and self-limiting viral disease in childhood, it can manifest with rare extrahepatic complications, so pediatricians should be aware of this rare association to avoid unnecessary investigations.
Topics: Humans; Acalculous Cholecystitis; Hepatitis A; Ascites; Child; Pleural Effusion; Male; Vitamin K; Abdominal Pain
PubMed: 38918800
DOI: 10.1186/s13256-024-04627-8