Trazodone Causes Bleeding ???

Hello, Summarians!

A few good studies make us stop and think. Hopefully, you get the chance to discuss these with colleagues as I am fortunate enough and blessed enough to be able to do.

Please give me feedback on ways I can make it more useful to you.

If it is valuable to you please consider sending it on to a friend 😄 

Golden Study and Cancer

The Golden Retriever Lifetime Study (GRLS) is a comprehensive, longitudinal health study focused on identifying factors that contribute to cancer and other diseases in dogs. It specifically aims to uncover nutritional, genetic, environmental, lifestyle, and reproductive factors that might influence these conditions. A key focus of the study is haemangiosarcoma, a common malignant cancer in dogs, arising from blood vessel cells. This study's significance lies in its potential to improve understanding of disease progression, prognosis, and early detection methods in dogs, particularly for haemangiosarcoma. 

The GRLS recruited 3,044 golden retrievers from across the United States, with specific enrollment criteria including age (less than 2 years at application), having a registered pedigree, and being microchipped. Dogs with a prior malignancy or life-threatening condition were excluded. Data collection from participating dogs includes annual questionnaires from owners and veterinarians, physical exams, sample collection (blood, urine, feces, hair, nails), biopsies of suspected malignancies, post-mortem sampling, and access to the dog's full medical history upon death. 

This study also has implications for human health, as dogs share similarities with humans in disease pathobiology, clinical manifestation, and genetics. Insights gained from the study could expedite investigations into human haemangiosarcoma, which is rare in humans. The study's data and sample repository are widely accessible to researchers, fostering further research in canine health and offering potential insights into human diseases. 

The GRLS is unique in veterinary medicine, offering a rich, accessible dataset from a longitudinal study. It enables historical cohort studies to investigate risk factors for haemangiosarcoma occurrence. This study is instrumental in generating hypotheses and providing data for future research in canine haemangiosarcoma, potentially informing studies in other mammalian species, including humans. The careful management of these data in accordance with FAIR principles will be crucial to maximize the research outcomes and fulfill the study's potential. 

Hillman A, Swafford B, Delavenne C, Fieten H, Boerkamp K, Tietje K. Descriptive analysis of haemangiosarcoma occurrence in dogs enrolled in the Golden Retriever lifetime study. Vet Comp Oncol. 2023 Dec;21(4):700-708. doi: 10.1111/vco.12933. Epub 2023 Aug 27. PMID: 37635246. 

Bottom line — Hemangiosarcoma incidence was 7.65%. Age/Sex stats are also useful…

Trazodone and Bleeding Potential in Dogs

This study investigated the effects of trazodone hydrochloride, a serotonin antagonist/reuptake inhibitor, on primary hemostasis and cardiac rhythm in healthy dogs. Trazodone is commonly used in small animals for behavioral disorders and anxiety management, but it's known to cause various adverse effects like sedation, nausea, vomiting, and diarrhea in animals, and orthostatic hypotension and priapism in humans. In this study, the researchers focused on trazodone's impact on platelet aggregation and QT interval prolongation. 

The findings revealed that trazodone significantly decreases platelet aggregation in dogs, which could be clinically relevant in cases of trauma or surgical bleeding. This effect is likely due to trazodone's antagonism of serotonin 2A receptors, which are known to enhance platelet aggregation. However, other markers of primary hemostasis were not significantly affected by trazodone. 

The study also found no impact on cardiac rhythm and QT interval, contrary to its effects in humans where it's associated with QT interval prolongation and potential arrhythmias. This could be due to the conservative dosage of trazodone used and the study's duration. 

Given these results, the authors advise caution when prescribing trazodone to dogs with impaired primary hemostasis and suggest further research on its combined effects with other medications affecting hemostasis. They also recommend reconsidering trazodone's use in dogs with unresponsive therapy or worsening clinical signs. The study acknowledges limitations like potential unblinding, variability in drug administration, and the study population's health status and breed diversity. 

Overall, while trazodone is generally effective and safe, its potential to impair platelet aggregation in dogs suggests a need for cautious use, particularly in dogs at risk of bleeding disorders. 

Benjamin, EJ, Nelson, OL, Baumwart, R, Haines, J. Adverse effects of trazodone in dogs on primary hemostasis and electrocardiogram: A single-blinded placebo-controlled crossover study. J Vet Intern Med. 2023; 37(6): 2131-2136. doi:10.1111/jvim.16841 

Bottom line — Trazodone does seem to affect platelet aggregation.

E Coli and and Antibiotic Resistance in Cats

The emergence of antimicrobial resistance (AMR) is a significant global health concern, affecting both human and veterinary medicine. This resistance arises when microorganisms adapt to survive exposure to previously effective antimicrobials, leading to severe illnesses and increased healthcare costs. The role of companion animals, particularly cats, in the spread of AMR is gaining attention due to their close contact with humans and frequent exposure to antimicrobials. 

A key bacterium in this context is Escherichia coli (E. coli), a common intestinal bacterium that can become pathogenic and cause serious infections in both humans and animals. The prevalence of AMR in E. coli varies across species and antimicrobial compounds. Studies show varying susceptibility rates to different antimicrobials among E. coli strains isolated from cats, with notable resistance to ampicillin and some cephalosporins. 

The issue is compounded by the ability of E. coli to acquire resistance genes from other bacteria, leading to multidrug resistance (MDR). This makes treating infections more difficult and raises public health concerns about the zoonotic transmission of AMR. The similarity of E. coli strains in cats and humans suggests a bidirectional transmission risk. 

This study focused on the trends in AMR among E. coli isolates from cats between 2008 and 2022, utilizing data from the Cornell University Animal Health Diagnostic Center. It used survival accelerated failure time models to assess changes in bacterial tolerance to antimicrobials over time. The study observed an increase in resistance to certain cephalosporins, a class of antimicrobials critical in human medicine. Despite this, the overall susceptibility of E. coli in cats to third-generation cephalosporins remained relatively high, though regional variations in susceptibility were noted. 

The extensive use of cephalosporins has contributed to the emergence of extended-spectrum β-lactamase bacteria and MDR, limiting treatment options in both veterinary and human medicine. Alarmingly, a significant proportion of isolates in this study were classified as MDR. 

The study also found that most E. coli isolates from cats were obtained from urinary tract infections (UTIs), with higher antimicrobial resistance compared to isolates from other body sites. Despite this, amoxicillin-clavulanic acid and trimethoprim-sulfamethoxazole were found to be generally effective for treating these infections in cats. 

However, the study acknowledges limitations such as the inability to ensure only one sample per patient and the use of breakpoints from humans and other species, which could lead to misclassification. The study underscores the importance of frequent regional data analysis for informed treatment choices and highlights the need for comprehensive one-health studies to understand the dynamics of AMR across species. 

Cobo-Angel, C., Mosaddegh, A., Aprea, M., Guarino, C., Cummings, K. J., & Cazer, C. (2023). Trends of feline Escherichia coli minimum inhibitory concentrations over 14 years illustrate the need for judicious antimicrobial use in cats. American Journal of Veterinary Research https://doi.org/10.2460/ajvr.23.09.0216 

Bottom line — More scary news for resistance

Just putting things in perspective …