Collagen-Induced Platelet Aggregates, Diabetes, and Aspirin Therapy Predict Clinical Outcomes in Acute Ischemic Stroke

Harima, Kaho; Honda, S; Mikami, Kasumi; Kitajima, Maiko; Urushizaka, Mayumi; Tomisawa, Toshiko; Hagii, Joji; Makino, Hírofumi; Yasujima, Minoru; Osanai, Tomohiro

doi:10.1016/j.jstrokecerebrovasdis.2019.05.021

Cited by 4 publications

(5 citation statements)

References 36 publications

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“…Those with poor glycemic control have higher baseline platelet activity and incomplete suppression of platelet activity. 11 13 14 Furthermore, individuals on LDA with increased levels of glycosylated hemoglobin across gestation had higher rates of aspirin resistance compared with those with decreasing levels of glycosylated hemoglobin. Accumulating clinical and laboratory evidence in the nonpregnant population suggests a reduced efficacy of aspirin in patients with diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…This phenomenon has been well described in the literature outside of pregnancy; wherein, elevated levels of hemoglobin A1C have been associated with an increased risk for aspirin resistance that may be overcome by higher aspirin doses. [9][10][11][12][13][14][15] Pregestational diabetes is considered a high-risk factor for the development of PEC. 4 While the exact mechanism for this clinical link between diabetes and PEC is unknown, diabetic patients with poor glycemic control have been shown to have higher rates of PEC.…”

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confidence: 99%

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Glycemic Control and Aspirin Resistance in Patients Taking Low-Dose Aspirin for Pre-eclampsia Prevention

et al. 2021

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Objectives To assess the association between aspirin and glycemic control in diabetic, pregnant patients, and the risk for aspirin resistance in those with poor glycemic control across gestation taking low-dose aspirin (LDA) for pre-eclampsia (PEC) prevention. Study Design We performed a secondary analysis of samples collected during the Maternal-Fetal Medicine Units trial of LDA for PEC prevention. A subset of insulin-controlled diabetic patient samples on placebo or 60 mg aspirin daily were evaluated. Glycosylated hemoglobin was measured at randomization, mid-second trimester, and third trimester time points. Thromboxane B2 (TXB2) measurements were previously assessed as part of the original study. Primary outcome was the effect of LDA on glycosylated hemoglobin levels compared with placebo across gestation. Results Levels of glycosylated hemoglobin increased across gestation in the placebo group (2,067.7 [interquartile range, IQR: 1,624.6–2,713.5 µg/mL] vs. 2,461.9 [1,767.0–3,209.9 µg/mL] vs. 3,244.3 [2,691.5–4,187.0 µg/mL]; p < 0.01) compared with no difference in levels of glycosylated hemoglobin across gestation in the LDA group (2,186.4 [IQR: 1,462.3–3,097.7 µg/mL] vs. 2,337.1 [1,327.7–5,932.6 µg/mL] vs. 2,532.9 [1,804.9–5,511.8 µg/mL]; p = 0.78). Higher levels of glycosylated hemoglobin were associated with increased TXB2 levels prior to randomization (r = 0.67, p < 0.05). Incomplete TXB2 was higher in pregnancies with increasing levels of glycosylated hemoglobin compared with those with decreasing levels of glycosylated hemoglobin across gestation (69.2 vs. 18.1%, p = 0.02). Conclusion LDA exposure may be beneficial to glycemic control in this patient population. Additionally, poor glycemic control is associated with a higher level of TXB2 in diabetic pregnant patients on LDA. Higher doses of aspirin may be required in these patients to prevent development of PEC. Key Points

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Glycemic Control and Aspirin Resistance in Patients Taking Low-Dose Aspirin for Pre-eclampsia Prevention

et al. 2021

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“…In turn, the high functional activity of platelets in this disease was determined by increased sensitivity to aggregation inducers (ADP, thrombin, collagen, etc. ), but also metabolic disorders (violation of carbohydrate and lipid metabolism) [ 50 , 51 , 52 ]. Accordingly, ASA resistance in T2DM patients is of considerable concern, as it reduces the effectiveness of prevention of cardiovascular complications in them [ 53 , 54 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

Resistance to Acetylsalicylic Acid in Patients with Coronary Heart Disease Is the Result of Metabolic Activity of Platelets

et al. 2020

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Sensitivity to acetylsalicylic acid (ASA) is important in the treatment of patients with coronary heart disease (CHD) after coronary artery bypass grafting (CABG). Patients were divided into ASA sensitive (sASA) and ASA resistant (rASA) by the activity of platelet aggregation induced arachidonic acid (ARA) together with ASA. Induced platelet aggregation activity was studied in sASA and rASA patients with CHD before and after CABG. The level of synthesis of primary and secondary reactive oxygen species (ROS) by platelets was determined using chemiluminescent analysis. The activity of NAD- and NADP-dependent dehydrogenases in platelets was determined by the bioluminescent method. It was found that the aggregation activity of platelets depended on the sensitivity of CHD patients to ASA and decreased during postoperative ASA therapy. The most pronounced differences in metabolic parameters of platelets in sASA and rASA patients were detected by Nox2 activity. The synthesis of secondary ROS by platelets of CHD patients did not depend on the sensitivity of patients to ASA but increased during postoperative treatment with ASA. The activity of NAD(P)-dependent dehydrogenases in platelets did not differ in sASA and rASA patients with CHD.

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“…Mutações no colágeno IV foram descritas como causais para AVC isquêmico em indivíduos jovens, porém sua influência na gravidade do evento ou recuperação pós AVC ainda é controverso (178)(179)(180). O colágeno também é relevante para a adesão plaquetária e inflamação nos processos isquêmicos, estando associado com o prognóstico do evento (181,182). O polimorfismo rs4103, presente no gene COL4A2, foi significativamente associado com a etiologia lacunar nos pacientes com AVC isquêmico na China (183).…”

Section: Discussionunclassified

“…Com essa estratégia, identificamos variantes em genes de interesse para o AVC, como COL4A3, COL6A3, FGFR2, FVIII, HLA-B. Esses genes integram, individualmente, vias moleculares de interesse, como biossíntese de colágeno, angiogênese, integridade vascular, coagulação sanguínea e processos inflamatórios (172,182,183,205,207). Contudo, com uma análise de rede utilizando os genes alterados na análise de exoma, observamos a maioria das vias alteradas associadas ao sistema imune e sinalização celular.…”

Section: Discussão Geralunclassified

Identificação de variantes genéticas para pacientes com acidente vascular cerebral isquêmico

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Agradeço à minha orientadora Dra. Íscia Lopes-Cendes pela oportunidade de desenvolver este trabalho sob sua orientação em seu laboratório, pelos ensinamentos e valores que me foram passados e pelo grande exemplo profissional que se tornou para mim. Agradeço a todos os coautores deste trabalho por toda amizade, dedicação e colaboração no desenvolvimento e discussão do projeto e resultados. Sem vocês este trabalho não teria sido concretizado. Ao Dr. Jørgen Kjems pelo aceite de supervisão durante meu estágio de pesquisa no exterior, no qual parte deste trabalho foi realizado, e por todos os ensinamentos e experiências profissionais que me proporcionou.

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Collagen-Induced Platelet Aggregates, Diabetes, and Aspirin Therapy Predict Clinical Outcomes in Acute Ischemic Stroke

Cited by 4 publications

References 36 publications

Glycemic Control and Aspirin Resistance in Patients Taking Low-Dose Aspirin for Pre-eclampsia Prevention

Glycemic Control and Aspirin Resistance in Patients Taking Low-Dose Aspirin for Pre-eclampsia Prevention

Resistance to Acetylsalicylic Acid in Patients with Coronary Heart Disease Is the Result of Metabolic Activity of Platelets

Identificação de variantes genéticas para pacientes com acidente vascular cerebral isquêmico

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