Background: Changes in the intrinsic coagulation pathway during aortic arch surgery in patients with acute aortic dissection (AAD) have not yet been reported. The aim of this study is to describe the changes in intrinsic coagulation factor XII, explore its function and find a new target for the treatment of coagulopathy during surgery.
Methods: Eighty-eight patients undergoing emergent surgery for AAD were enrolled. Changes in the intrinsic and extrinsic coagulation pathways were evaluated at 5 different timepoints during the perioperative period by measuring intrinsic coagulation factor XII, extrinsic coagulation factor VII and some intrinsic upstream stimulating factors. The 88 patients were also divided into two groups according to whether reoperation for coagulopathy was required after surgery.
Results: Both coagulation factors XII and VII demonstrated a significant and similar change during the perioperative period. These factors decreased significantly during hypothermia circulation arrest (P<0.001) and recovered to normal levels by 24 hours after surgery. Among the intrinsic upstream stimulating factors, bradykinin (BK) demonstrated a similar changing trend with coagulation factors XII and VII, while other stimulating factors did not. However, compared with factor VII, factor XII demonstrated a greater decline during surgery. The proportion of decline of factor XII from anesthesia induction to hypothermia circulation arrest was 42%, whereas the proportion of decline of factor VII during the same period was 20% (P<0.001). Moreover, factor VII recovered to preoperative levels 4 hours after surgery with a relatively faster speed (P<0.001) while factor XII had not recovered (P=0.010). The independent -test and Wilcoxon test showed that coagulation factor XII levels during hypothermia circulation arrest (P=0.002), total dosage of fibrinogen (P=0.027), total dosage of packed red blood cells (PRBCs) (P=0.006) and total dosage of fresh frozen plasma (FFP) (P=0.022) during the perioperative period were significantly different between the patients who did or did not require reoperation for coagulopathy. Multivariable logistic regression analysis suggested that the factor XII level during hypothermia circulation arrest was an independent risk factor for reoperation for coagulopathy [odds ratio (OR): 1.342, 95% confidence interval (CI): 1.058-1.570; P=0.012].
Conclusions: Factor XII levels are more influenced by surgery and require a longer period of time to recover to preoperative levels compared with factor VII, and the level of factor XII during hypothermia circulation arrest might be an independent risk factor for reoperation for coagulopathy. Therefore, supplementation of coagulation factor XII and its upstream stimulating factors might be a promising therapeutic modality in the future.
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http://dx.doi.org/10.21037/jtd.2018.06.127 | DOI Listing |
Proc Natl Acad Sci U S A
February 2025
SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon 16419, Republic of Korea.
The design of organic-peptide hybrids has the potential to combine our vast knowledge of protein design with small molecule engineering to create hybrid structures with complex functions. Here, we describe the computational design of a photoswitchable Ca-binding organic-peptide hybrid. The designed molecule, designated Ca-binding switch (CaBS), combines an EF-hand motif from classical Ca-binding proteins such as calmodulin with a photoswitchable group that can be reversibly isomerized between a spiropyran (SP) and merocyanine (MC) state in response to different wavelengths of light.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Pathology, 906 Hospital of Joint Logistic Support Force of PLA, Ningbo, Zhejiang, China.
Objective: To investigate the effects and mechanisms of miRNA 221 on myocardial ischemia/reperfusion injury (MIRI) in mice through the regulation of phospholamban (PLB) expression.
Methods: The MIRI mouse model was created and mice were divided into sham, MIRI, MIRI+ 221, and MIRI+ scr groups, with miRNA 221 overexpression induced in the myocardium of MIRI mice by targeted myocardial injection. Quantitative RT-PCR analysis was performed to observe the variation in miRNA 221, PLB, SERCA2, RYR2, NCX1, Cyt C and caspase 3 mRNA levels in myocardium, while Western blot assessed the levels of PLB, p-PLB (Ser16), p-PLB (Thr17), SERCA2, RYR2, NCX1, Cyt C and caspase 3 proteins.
Am J Clin Pathol
January 2025
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, US.
Objective: Hemostatic abnormalities, including disseminated intravascular coagulation (DIC), are often cited as a common finding in patients following Loxosceles spider envenomation (ie, loxoscelism). The prevalence and severity of coagulopathy, however, particularly following L reclusa (ie, brown recluse) envenomation, is not well described. This study aimed to characterize coagulation laboratory parameters and coagulopathy in patients following L reclusa envenomation.
View Article and Find Full Text PDFJ Gen Physiol
March 2025
Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Voltage-gated Ca2+ channels (VGCCs) are highly expressed throughout numerous biological systems and play critical roles in synaptic transmission, cardiac excitation, and muscle contraction. To perform these various functions, VGCCs are highly regulated. Inactivation comprises a critical mechanism controlling the entry of Ca2+ through these channels and constitutes an important means to regulate cellular excitability, shape action potentials, control intracellular Ca2+ levels, and contribute to long-term potentiation and depression.
View Article and Find Full Text PDFPlatelets
December 2025
Cyrus Tang Medical Institute, The Fourth Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China.
Recent studies have shown that anti-ERp5 antibodies inhibit platelet activation and thrombus formation; Moreover, ERp5-deficient platelets exhibit enhanced platelet reactivity via regulation of endoplasmic reticulum (ER) stress. In this study, we used a new ERp5-knockout mouse model as well as recombinant ERp5 (rERp5) protein, to examine the role of ERp5 in platelet function and thrombosis. Although platelet-specific ERp5-deficient mice had decreased platelet count, the mice had shortened tail-bleeding times and enhanced platelet accumulation in FeCl-induced mesenteric artery injury, compared with wild-type mice.
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