Publications by authors named "Cihan Ay"
Hemophilia is a rare X-linked bleeding disorder caused by mutations in the F8 or F9 gene (hemophilia A or B), leading to deficient factor VIII or IX proteins, respectively. Hemophilia-related complications caused by bleeding into the joints (the hallmark of hemophilia) and age-related comorbidities occur frequently and impact the functionality and quality of life of persons with hemophilia (PwH). Given the chronic nature of hemophilia, we hypothesized that hemophilia has an association with accelerated biological aging.
View Article and Find Full Text PDFBackground: The hemostatic system is tightly interconnected with cancer. Research has focused predominantly on thrombotic complications, but less is known about bleeding and bleeding risk prediction. Growth differentiation factor (GDF)-15 has previously emerged as a prognostic biomarker for bleeding.
View Article and Find Full Text PDFVenous thromboembolism (VTE) is a common and serious complication among cancer patients. Mitochondrial DNA (mtDNA) copy number is known to influence various cellular pathways involved in cancer development. While an association between reduced mtDNA and VTE risk in non-cancer patients was previously reported, its relationship with VTE in cancer patients remains unclear.
View Article and Find Full Text PDFBackground: The sensitivity of the platelet function analyzer (PFA-100, Dade Behring Inc) was shown to be high for the detection of von Willebrand disease (VWD), but limited for platelet function defects.
Objectives: To study the diagnostic utility of PFA-100 in mild-to-moderate bleeding disorders and bleeding disorder of unknown cause (BDUC).
Methods: PFA-100 closure times (CTs) were measured with collagen-epinephrine (EPI) and collagen-adenosine diphosphate (ADP) cartridges in 818 patients with mild bleeding disorders from the Vienna Bleeding Biobank.
Background: Epidemiological data on acute pulmonary embolism among children and adolescents are sparse and only date back to the 2000s. We aimed to establish annual estimates and age-stratified and sex-stratified indicators of acute pulmonary embolism among children and adolescents aged 0-19 years.
Methods: We did a retrospective, nationwide, patient-level analysis of the Kids' Inpatient Database, including 5733 patients with acute pulmonary embolism aged 0-19 years admitted to hospital in the USA in 2016 and 2019.
Venous thromboembolism remains a major cause of morbidity and mortality among ambulatory cancer patients, necessitating effective risk assessment and prevention strategies. Despite the availability of risk assessment models and guidelines recommending primary thromboprophylaxis with low-molecular-weight heparins or direct oral anticoagulants, the application of these strategies is inconsistent. This review provides an overview of the current state-of-the-art venous thromboembolism risk assessment and thromboprophylaxis in ambulatory patients with cancer, focusing on existing risk assessment models and the latest guideline recommendations.
View Article and Find Full Text PDFImproved efficacy has been shown for amivantamab and amivantamab-based combination therapies in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) compared to established treatment options in clinical trials. However, a high risk of venous thromboembolism (VTE) was observed in patients treated with amivantamab-based therapies, with considerable differences in VTE risk according to the line of systemic treatment, concomitant treatment with lazertinib, and intravenous vs. subcutaneous amivantamab administration.
View Article and Find Full Text PDFBiological Aging and Venous Thromboembolism: A Review of Telomeres and Beyond.
Biomedicines
December 2024
Although venous thromboembolism (VTE) is the third most common cardiovascular disease, and the risk of VTE increases sharply with advancing age, approximately 40% of VTE cases are currently classified as unprovoked, highlighting the importance of risk factor research. While chronological aging is associated with the risk of VTE, the association with biological aging remains unclear. Biological aging is highly complex, influenced by several dysregulated cellular and biochemical mechanisms.
View Article and Find Full Text PDFBackground: The benefits and risks of extending anticoagulant treatment beyond the first 3 to 6 months in patients with venous thromboembolism (VTE) in clinical practice are not well understood.
Methods: ETNA-VTE Europe is a prospective, noninterventional, post-authorization study in unselected patients with VTE treated with edoxaban in eight European countries for up to 18 months. Recurrent VTE, major bleeding, and all-cause death were the primary study outcomes.
Introduction: Factor XI/XIa (FXI/XIa) has emerged as a potential target for antithrombotic therapy, driven by preclinical evidence showing the role of FXI/XIa inhibition for preventing thrombosis without impeding hemostasis. This is particularly promising for patients at high risk of both thromboembolic events and bleeding, such as patients with end-stage kidney disease (ESKD) on hemodialysis (HD).
Methods: We systematically searched Embase, MEDLINE, and ClinicalTrials.
Background: Patients with cancer treated with immune-checkpoint inhibitors (ICIs) have a substantial risk of venous thromboembolism (VTE). The association between ICI-induced inflammation and hypercoagulability is unclear, and no biomarkers currently exist to stratify VTE risk.
Objectives: The authors sought to determine the association between the early changes in C-reactive protein (CRP) after ICI initiation and the risk of VTE.
Treatment of VTE in the thrombocytopenic cancer patient.
Hematology Am Soc Hematol Educ Program
December 2024
Thrombocytopenia is a frequent complication in patients with cancer, mostly due to the myelosuppressive effects of antineoplastic therapies. The risk of venous thromboembolism (VTE) in patients with cancer is increased despite low platelet counts. The management of cancer-associated VTE in patients with thrombocytopenia is challenging, as the risk of both recurrent VTE and bleeding complications is high.
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- Pregnant women with paroxysmal nocturnal hemoglobinuria (PNH) face high risks of serious blood clots, but eculizumab, a complement inhibitor, can help reduce these risks and improve pregnancy outcomes.
- This study examines two pregnant patients with PNH showing low-level hemolysis, managed solely with preventive anticoagulation and no complement inhibition.
- Both patients had successful pregnancies without thromboembolic issues, suggesting that careful monitoring and anticoagulation might be a viable management approach for certain PNH cases during pregnancy, though more research is necessary.
Background: Treatment sequence in primary immune thrombocytopenia (ITP) is based on national and international recommendations, treatment availability, and physician expertise.
Aim: This article aimed to provide real-world data on treatment sequence and responses to first- and second-line treatments in newly diagnosed and relapsed adult ITP patients.
Methods: We analyzed a cohort of 46 adult ITP patients from the Vienna ITP Biobank, who started first-line therapy within 1 week before their first study visit between February 2016 and March 2023.
Venous thromboembolism (VTE) is the third most common cardiovascular disease. Clonal haematopoiesis (CH) is linked to cardiovascular disease risk, but its potential association with VTE remains poorly understood. We assessed the prevalence of CH in patients with recurrent VTE (n = 107; median age [IQR] 57 [48-63] years, 44.
View Article and Find Full Text PDFIntroduction: The haemophilia joint health score (HJHS) is a tool used to assess joint changes in patients with haemophilia. There is lack of consensus on the interpretation of HJHS scores and their clinical relevance.
Aim: To evaluate available literature reporting HJHS changes over time and assess a possible cut-off value for clinically relevant outcomes and the ideal follow-up for a meaningful score change.
Article Synopsis
- Human saliva contains extracellular vesicles (EVs) that can activate blood coagulation through the presence of extrinsic tenase complexes, which include tissue factor and activated factor VII.
- Individuals with severe hemophilia A, who lack FVIII, have salivary EVs that can compensate for their condition by generating FXa, leading to infrequent oropharyngeal bleeding.
- In contrast, people with severe FVII deficiency lack these functional extrinsic tenase complexes in their saliva, resulting in more frequent oropharyngeal bleedings; however, adding recombinant FVIIa can restore coagulation potential in their saliva.
Article Synopsis
- Antiphospholipid syndrome is an autoimmune disorder that causes blood clots and pregnancy issues due to persistent antiphospholipid antibodies.
- Treatment typically involves long-term anticoagulation therapy, which only manages symptoms and doesn't cure the condition.
- A case study shows that a woman treated with CAR T-Cell therapy for lymphoma achieved a lasting reduction in all types of antiphospholipid antibodies, indicating a potential new treatment avenue using immunotherapy.
Article Synopsis
- Biological barriers pose significant challenges in the development of new therapies, as drugs must navigate various protective layers at both the tissue and cellular levels to effectively target specific cells.
- A diverse range of therapeutic options is now available, from small molecules to advanced techniques like gene therapies and monoclonal antibodies, with recent innovations rapidly transforming treatment approaches.
- Notable advancements, such as the FDA approval of new RNA-based therapies and viral-vector gene therapies for hemophilia, exemplify the potential for innovative medicines to address complex diseases and improve patient care.
Background: Patients with end-stage kidney disease (ESKD) are at very high risk for thromboembolism and bleeding. This study aimed to identify small noncoding RNAs (sncRNAs), specifically microRNAs and transfer-RNA (tRNA)-derived fragments (tRFs), as potential novel biomarkers for predicting thromboembolism and bleeding in this high-risk population.
Methods: In this sncRNA discovery research, we leveraged the VIVALDI cohort, consisting of 625 ESKD patients on hemodialysis, to conduct two nested case-control studies, each comprising 18 participants.
Introduction: Patients with chronic kidney disease, especially those with end-stage kidney disease (ESKD) on hemodialysis (HD), are at increased risk for cardiovascular disease (CVD), including myocardial infarction and ischemic stroke. A shortening in telomere length, as a parameter for accelerated vascular aging, is an established biomarker for CVD in the general population. We aimed to elucidate the role of telomere length in ESKD patient on HD and its association with cardiovascular outcomes.
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- Bleeding disorder of unknown cause (BDUC) is diagnosed after ruling out other causes, and this study analyzed data from 375 BDUC patients compared to 100 healthy controls.
- The findings revealed that BDUC patients had lower peak plasmin levels and clot density, indicating potential issues with clot structure, while still showing a higher potential for plasmin generation.
- A model including fibrinogen and plasmin generation parameters effectively distinguished BDUC patients from healthy controls, demonstrating the potential for predictive diagnostics in bleeding disorders.
Article Synopsis
- The hemostatic system and cancer are closely linked, resulting in frequent hemostatic imbalances in cancer patients, particularly concerning bleeding risks associated with therapeutic anticoagulation.
- Despite the known thrombotic risks, there is limited understanding of bleeding risk factors in cancer patients, which can vary based on factors such as hospitalization, tumor type, and medications.
- Current risk assessment models for bleeding in cancer patients on anticoagulation exist but lack validation, and the growing recognition of bleeding risks has led to more studies, although varying study designs complicate the synthesis of findings.