| 1. |
- Heenkenda, Menikae Kanchena, et al.
(författare)
-
Assessment of genetic and non-genetic risk factors for venous thromboembolism in glioblastoma - The predictive significance of B blood group
- 2019
-
Ingår i: Thrombosis Research. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0049-3848 .- 1879-2472. ; 183, s. 136-142
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Venous thromboembolism (VTE) is a common problem among patients with glioblastoma multi-forme (GBM) and with some other cancers. Here, we evaluated genetic and non-genetic potential risk factors for VTE among GBM patients. Materials and methods: A cohort of 139 patients treated with concomitant radiotherapy and temozolomide were included in the study. Next generation sequencing and genotyping approaches were applied to assess genetic risk factors in the haemostatic system. Clinical data including surgery, reoperation as well as blood group and patient information such as age and gender were available from patient records. Logistic regression analysis was performed to asses VTE risk. Results: In the study 47 patients (34%) were diagnosed for VTE during the course of their disease. When genetic and non-genetic potential risk factors were evaluated, only B blood group was found to be significantly associated with VTE incidence (odds ratio [OR] = 6.91; confidence interval [CI] = 2.19-24.14; P = 0.001). In contrast, A and O blood groups did not correlate with VTE risk. Frontal lobe tumor location also seemed to slightly increase VTE risk compared to other brain sites (OR = 3.14; CI = 1.1-10.7) although the significance level was at borderline (P = 0.05). Current study identified B blood group as the component in non-O blood groups that is responsible for increased VTE risk. Conclusion: In conclusion, these results suggest for the first time that B blood group is predictive for VTE incidence among patients with glioblastoma, information that may be potentially valuable when selecting GBM patients who are at risk for VTE for anticoagulant prophylaxis.
|
|
| 2. |
- Heenkenda, Menikae Kanchena, 1982-
(författare)
-
Understanding and Managing Thrombotic Risks in Medical Conditions : One Size Does Not Fit All
- 2024
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hemostasis is a critical physiological process that stops bleeding at the site of an injury while ensuring normal blood flow elsewhere, thereby preventing excessive clot formation that could lead to dangerous conditions like thrombosis. This delicate balance is influenced by genetics, medical conditions such as cancer, and various medications. When a blood vessel is damaged, platelets adhere to the exposed area, become activated, and aggregate to form an initial plug. Coagulation factors, particularly thrombin, create a strong fibrin network to stabilize the clot. Disruptions in this process can result in significant bleeding or dangerous clot formation.This thesis aims to explore and understand the factors affecting coagulation and the risks of thrombotic events in different medical contexts. This includes studying genetic variability in the protease-activated receptor 4 (PAR4) gene (specifically the Ala120Thr variant) among sub-Saharan African populations, identifying genetic and non-genetic risk factors for venous thromboembolism (VTE) in patients with the brain cancer glioblastoma multiforme (GBM), and investigating the impact of intravenous morphine on platelet activity in patients with ST-elevation myocardial infarction (STEMI) treated with ticagrelor, a P2Y12 inhibitor. The A allele of the rs773902 single-nucleotide polymorphism (SNP) in the PAR4 gene (F2RL3) substitutes threonine for alanine at the 120th protein position (Thr120). This allele is more prevalent in African populations compared to Caucasian populations, although previous studies did not specify the geographic ancestry of participants. Thr120 is associated with higher PAR4-induced human platelet aggregation and Ca2+ flux. Our study found that the frequency of the A allele in the Somali population is significantly lower than previously reported for African Americans. The A allele frequency in Somalis is 38%, compared to 63% for African Americans. The A allele frequency in Somalis is closer to that of the Maasai population in Kenya (41%), but vastly different from the Esan population in Nigeria (68%). Certain cancers, such as GBM, are associated with a higher risk of VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE). Our research identified blood group B as a significant risk factor for patients with GBM (OR=6.91; 95% CI=2.2–24.1; P =0.001). Also, GBM tumors in the frontal lobe are associated with an increased risk of VTE (OR=3.14; 95% CI=1.1–10.7; P =0.05). Our study on morphine, commonly used for pain management in STEMI patients, found that morphine is associated with increased platelet aggregation one hour after percutaneous coronary intervention (PCI), impacting the efficacy of ticagrelor. Morphine delays platelet inhibition by affecting the pharmacodynamics of antiplatelet therapy, likely by delaying gastric emptying. However, this effect is short-lived, as platelet reactivity returns to similar levels in both groups 12 hours post-PCI. Despite this immediate impact on platelet function, our research found no significant differences in biomarkers of platelet activity, coagulation, or inflammation between the morphine and non-morphine groups. Additionally, all patients in our study were administered unfractionated heparin injections or bivalirudin infusion during primary PCI, which may help control the risk of blood clot formation. These studies collectively emphasize the need for individualized strategies to manage thrombotic risks and coagulation. The significant genetic variability among sub-Saharan African populations highlights the need for precise genetic research to understand how genetics influence coagulation and develop personalized medical strategies. The increased risk of cancer-associated thrombosis, particularly in patients with GBM, calls for individualized anticoagulant therapies based on unique risk profiles, such as blood group typing and tumor location. Incorporating these insights into clinical practice can help healthcare providers better identify high-risk patients and tailor thromboprophylaxis strategies accordingly. Similarly, the impact of morphine on patients with STEMI treated with ticagrelor requires careful consideration. In conclusion, these findings underscore the importance of a personalized approach in managing coagulation and thrombotic risks. The studies show that genetic variability, specific medical conditions, and medication effects are crucial in thrombotic risk. Therefore, customized strategies based on individual patient profiles and contexts are essential for effectively managing and preventing thrombotic events.
|
|
