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- Karlsson, Anna, 1985-, et al.
(author)
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The effect of tinzaparin on biomarkers in FIGO stages III-IV ovarian cancer patients undergoing neoadjuvant chemotherapy – the TABANETOC trial: study protocol for a randomized clinical multicenter trial
- 2024
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In: Acta Oncologica. - Uppsala : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 580-585
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Journal article (peer-reviewed)abstract
- Background: Tinzaparin, a low-molecular weight heparin (LMWH), has shown anti-neoplastic properties in animal models and in in vitro studies of human cancer cell lines. The reduction of CA-125 levels during neoadjuvant chemotherapy (NACT) in patients with epithelial ovarian cancer (EOC) co-varies with the prognosis; the larger the decrease in CA-125, the better the prognosis.Purpose: This study aims to evaluate the potential anti-neoplastic effects of tinzaparin by investigating changes in serum CA-125 levels in advanced EOC patients who receive NACT.Material and methods: This is an open randomized multicenter pilot trial. Forty patients with EOC selected to receive NACT will be randomized 1:1 to receive daily addition of tinzaparin or no tinzaparin. The processing and treatment of the patients will otherwise follow the recommendations in the Swedish National Guidelines for Ovarian Cancer. Before every cycle of chemotherapy, preoperatively, and 3 weeks after the last cycle of chemotherapy, a panel of biomarkers, including CA-125, will be measured.Patients: Inclusion criteria are women aged 18 years or older, World Health Organization performance status 0–1, histologically confirmed high-grade serous, endometrioid or clear cell EOC, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV. In addition, a CA-125 level of ≥ 250 kIE/L at diagnosis. Exclusion criteria are contraindications to LMWH, ongoing or recent treatment with unfractionated heparin, LMWH, warfarin or non-vitamin K antagonist oral anticoagulants.Interpretation: This study will make an important contribution to the knowledge of the anti-neoplastic effects of tinzaparin in EOC patients and may thus guide the planning of a future study on the impact of tinzaparin on survival in EOC.
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| 2. |
- af Geijerstam, Peder, Doktorand, 1983-, et al.
(author)
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P-selectin and C-reactive protein in relation to home blood pressure and coronary calcification: a SCAPIS substudy
- 2024
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In: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 42:7, s. 1226-1234
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Journal article (peer-reviewed)abstract
- Background: Soluble P-selectin (sP-selectin) and high-sensitivity C-reactive protein (hsCRP) have previously been associated with hypertension, but the relation with out-of-office blood pressure (BP) and coronary artery calcification score is unknown. We aimed to examine the relationship between sP-selectin, hsCRP and home BP, as well as coronary artery calcification score and carotid artery plaques.Methods: In the Swedish CArdioPulmonary bioImage Study (SCAPIS), 5057 randomly selected participants were evaluated with office and home BP using the semi-automatic Omron M10-IT device. For this cross-sectional study, participants with sP-selectin <4 standard deviations above mean and hsCRP <5 mg/l, representing low-grade inflammation, were included. Using generalized linear models, these inflammatory markers were evaluated in relation to BP classifications, as well as coronary artery calcification score and carotid artery plaques.Results: Of participants, 4548 were included in the analyses. The median age was 57.2 (53.4–61.2) years, and 775 (17.0%) reported taking medication for hypertension. Participants in the highest quartile of sP-selectin [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.40–1.98, P < 0.001] and hsCRP [OR 2.25, (95% CI 1.89–2.60), P < 0.001] were more likely to have sustained hypertension. Participants in the highest quartile of hsCRP were also more likely to have masked hypertension, OR (95% CI) 2.31 (1.72–3.10), P < 0.001 and carotid artery plaques, OR (95% CI) 1.21 (1.05–1.38), P = 0.007.Conclusion: Increased sP-selectin and hsCRP were independently associated with sustained hypertension. These findings indicate an association between hypertension and platelet activity, as expressed by sP-selectin.
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| 3. |
- Arbring, Kerstin, 1961-
(author)
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Two worlds, one goal : A Clinician’s Perspective on Laboratory Analyses in Anticoagulant Treatment
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Almost precisely a century ago, in the 1920s and 1930s, cattle bled to death in North America after being fed moldy hay containing sweet clover, the yellow Melilotus officinalis, and the white Melilotus albus. The toxic substance in the hay inhibiting blood coagulation was identified and named dicumarol. Further development resulted in warfarin, an oral anticoagulant that has been used for over 70 years and still is, even though newer direct-acting oral anticoagulants (DOACs) are mainly replacing it. For some patients, warfarin is still the drug of choice. A safe warfarin treatment needs repeated blood sample analysis (PT-INR), and with the new DOACs come new laboratory challenges. The aim of this thesis was to investigate ways laboratory methods can contribute to improving oral anticoagulant treatment. Paper I explores genetic variants of the enzyme targeted by warfarin, VKORC1. The result shows that the haplotype VKORC1*2 is the most important of the VKORC1 haplotypes for warfarin dosage, with a lower dose requirement. The VKORC1*2 haplotype was also related to more unstable PT-INR levels. Paper II describes a cross-section study comparing warfarin treatment control, as PT-INRs within the intended therapeutic range, in primary health care centers (PHCCs) and specialized anticoagulation clinics (ACCs). Both settings showed good therapeutic control, with at least as good therapeutic control in the PHCCs as in the ACCs. Today, almost all warfarin treatment in our region is centralized to ACCs. Paper III focuses on the modification of a point-of-care PT method. A ratio of PT from two different dilutions of each patient sample was calculated and used as an indirect measure of DOAC activity. There were close correlations between the PT ratio and drug concentrations measured at the hospital laboratory. The detection level varies between DOACs and may limit its use in some situations. Paper IV evaluated the MRX PT DOAC, an assay based on the PT ratio principle. It was found to be able to detect potentially interfering DOAC levels in plasma samples. Confirmatory testing is recommended, as is sensitivity improvement for the detection of specific interferences.
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| 4. |
- Bian, Li, et al.
(author)
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Rutinmässig screening med APTT är inte indicerad före operation : [Routine screening with APTT is not indicated before surgery
- 2022
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In: Läkartidningen. - : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 119
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Research review (peer-reviewed)abstract
- Activated partial thromboplastin time (APTT) is widely practiced in preoperative screening. The value of using this test to predict the risk of perioperative bleeding is not well documented in Sweden. In this article, a literature review is performed to determine whether unselected APTT testing can predict abnormal perioperative bleeding. The current literature does not support coagulation screening with APTT in routine perioperative bleeding assessment, as preoperative screening with APTT has a low sensitivity for detection of clinically significant bleeding disorder. While a comprehensive bleeding history is crucial, the APTT test should only be performed on patients with a history of increased bleeding tendency. The conclusion of this literature review is that patients with a negative bleeding history do not require routine screening with APTT prior to surgery, which, if implemented, would lead to a more cost-effective perioperative routine.
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| 5. |
- Heenkenda, Menikae Kanchena, 1982-
(author)
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Understanding and Managing Thrombotic Risks in Medical Conditions : One Size Does Not Fit All
- 2024
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Doctoral thesis (other academic/artistic)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.
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