Hallmarks for Thrombotic and Hemorrhagic Risks in Chronic Kidney Disease Patients.

Chronic kidney disease (CKD) is a global health issue causing a significant health burden. CKD patients develop thrombotic and hemorrhagic complications, and cardiovascular diseases are associated with increased hospitalization and mortality in this population. The hemostatic alterations are multifactorial in these patients; therefore, the results of different studies are varying and controversial. Endothelial and platelet dysfunction, coagulation abnormalities, comorbidities, and hemoincompatibility of the dialysis membranes are major contributors of hypo- and hypercoagulability in CKD patients. Due to the tendency of CKD patients to exhibit a prothrombotic state and bleeding risk, they require personalized clinical assessment to understand the impact of antithrombotic therapy. The evidence of efficacy and safety of antiplatelet and anticoagulant treatments is limited for end-stage renal disease patients due to their exclusion from major randomized clinical trials. Moreover, designing hemocompatible dialyzer membranes could be a suitable approach to reduce platelet activation, coagulopathy, and thrombus formation. This review discusses the molecular mechanisms underlying thrombotic and hemorrhagic risk in patients with CKD, leading to cardiovascular complications in these patients, as well as the evidence and guidance for promising approaches to optimal therapeutic management.

New-onset organ dysfunction as a screening tool for the identification of sepsis and outcome prediction in dogs with systemic inflammation.

Introduction: Sepsis in people is defined as a life-threatening organ dysfunction (OD) caused by a dysregulated host response to infection. In veterinary medicine, sepsis is still defined by the presence of systemic inflammation plus the evidence of infection. Based on recent veterinary studies, multiorgan dysfunction syndrome (MODS) has been associated with a worse outcome in sepsis. Thus, the screening for OD is warranted to identify the most critically ill patients. The aim of this study was to investigate the diagnostic value of new-onset OD for the prediction of sepsis and outcome in a population of critically ill dogs with systemic inflammation. Materials and methods: Dogs admitted to the Emergency Room and/or the Intensive Care Unit with systemic inflammation, defined by a serum C-reactive protein concentration > 1.6 mg/dL, were retrospectively included. Enrolled dogs were categorized according to the presence of sepsis or non-infectious systemic inflammation. The presence of newly diagnosed OD was assessed based on criteria adapted from human literature and previously reported canine criteria. Results: 275 dogs were included: 128 had sepsis and 147 had non-infectious systemic inflammation. The frequency of new-onset OD was not different between these groups. Only the presence of fluid-refractory hypotension was significantly associated with a diagnosis of sepsis (OR 10.51, 3.08-35.94; p < 0.0001). The frequency of at least two ODs was significantly higher in non-survivors compared to survivors, according to both the human and the veterinary criteria considered for the study (p = 0.0001 and p = 0.0004, respectively). Specifically, the presence of acute kidney injury, stupor or coma, prolonged Prothrombin Time and decreased Base Excess were associated with a higher risk of death in the multivariate binary logistic regression. Discussion: In this population of critically ill dogs with systemic inflammation, the detection of newly diagnosed ODs was not able to predict sepsis diagnosis, other than the presence of fluid-refractory hypotension. However, given the strong prognostic significance associated with ODs, our results support the early screening for ODs in any severe inflammatory critical care condition to identify high-risk patients and optimize their management.

The clinical efficacy of pentoxifylline and l-glutamine on ischemia and reperfusion injury in cattle with displaced abomasum: a longitudinal study.

This study aimed to assess the clinical efficacy of pentoxifylline (PTX) and L-glutamine (L-Gln) treatment on ischemia and reperfusion (I/R) injury in the abomasal tissue, acute phase response (APR), oxidative stress (OS), cytokine response, hemostatic, and coagulation disorders in the 96-h period before and after surgery in displaced abomasum (DA) cases. The study sample consisted of 48 dairy cows with DA that were categorized into four groups as group S (Sham group) (9 Left displaced abomasum (LDA)+3 Right displaced abomasum (RDA), group P (PTX) (10 LDA+2 RDA), group G (L-Gln) (10 LDA+2 RDA), and group P+G (PTX+L-Gln) (10 LDA+2 RDA). Acute-phase protein (Haptoglobin), oxidative stress indicators (malondialdehyde, nitric oxide, and glutathione), cytokines (tumor necrosis factor (TNF)-α and interleukin-1ß (IL-1ß), coagulation factors (D-Dimer, Antithrombin (ATIII), Thrombin-antithrombin complex, Plasminogen activator inhibitor-1), and enzyme activities (lactate dehydrogenase, gamma- -glutamyl transferase, sorbitol dehydrogenase, glutamate dehydrogenase, adenosine deaminase, myeloperoxidase, and creatine phosphokinase) in blood serum samples and coagulometric analyses of blood plasma were performed in samples taken before the operation and at 30 and 60 min and 2, 5, 10, 24, 48, 72, and 96 h after the operation. In DA cases, while post-operative treatment procedures with PTX and L-Gln were effective in decreasing APR and OS, these were ineffective in prohibiting the inflammatory response coordinated by cytokines. For the treatment and prevention of I/R injury in the DA cases, PTX and L-Gln procedures hold promise with their effects on APR, OS, and hemostatic dysfunction. Additional treatment procedures are required for the suppression of inflammatory response, and the effectiveness of preconditioning treatment may be evaluated.

The evaluation of hemostatic dysfunction and disseminated intravascular coagulation in dairy cows with abomasal displacement.

Disseminated intravascular coagulation (DIC) is a complex, dynamic and hemostatic disorder which develops secondarily to a disease characterized with an imbalance in the pro-coagulant and anti-coagulant components of hemostasis. The aim of the study is to evaluate hemostatic dysfunc- tion and the DIC syndrome in cattle with displaced abomasum (DA), with using the hematologic analyses and an extensive coagulation profile in the 96 hour-period including before and after surgery. The animal material of the study consisted of 12 dairy cows diagnosed with displaced abomasum (9 LDA and 3 RDA without volvulus) in the 2-4 week period after parturation and with no other post-partum disease. In dairy cows diagnosed with DA, hematological, coagulomet- ric (PT, APTT, Fibrinogen) and coagulation factor analyses [D-Dimer, TAT (thrombin-anti- thrombin complex), ATIII (antithrombin III), PAI-1 (plazminogen activator inhibitor-1] were performed in blood samples obtained before the operation as well as 30 minutes, 60 minutes and 2, 5, 10, 24, 48, 72 and 96 hours after the operation. In the DA cases, abnormalities were found in 6 of the 8 coagulation parameters. In the LDA and RDA groups, prolonged PT (sec), PT (INR) and APTT, hypofibrinogenemia, an increase in serum D-Dimer concentration at 72 and 96 hours after the operation and an increase in serum ATIII concentrations before and 30, 60 minutes and 2, 5, 72 and 96 hours after the operation was found (p⟨0.05). Hemostatic dysfunction and the risk of DIC developing in DA cases and continuing in the post-operative period was determined.

Activation and shedding of platelet glycoprotein IIb/IIIa under non-physiological shear stress.

The purpose of this study was to investigate the influence of non-physiological high shear stress on activation and shedding of platelet GP IIb/IIIa receptors. The healthy donor blood was exposed to three levels of high shear stresses (25, 75, 125 Pa) from the physiological to non-physiological status with three short exposure time (0.05, 0.5, 1.5 s), created by a specific blood shearing system. The activation and shedding of the platelet GPIIb/IIIa were analyzed using flow cytometry and enzyme-linked immunosorbent assay. In addition, platelet P-selectin expression of sheared blood, which is a marker for activated platelets, was also analyzed. The results from the present study showed that the number of activated platelets, as indicated by the surface GPIIb/IIIa activation and P-selectin expression, increased with increasing the shear stress level and exposure time. However, the mean fluorescence of GPIIb/IIIa on the platelet surface, decreased with increasing the shear stress level and exposure time. The reduction of GPIIb/IIIa on the platelet surface was further proved by the reduction of further activated platelet GPIIb/IIIa surface expression induced by ADP and the increase in GPIIb/IIIa concentration in microparticle-free plasma with increasing the applied shear stress and exposure time. It is clear that non-physiological shear stress induce a paradoxical phenomenon, in which both activation and shedding of the GPIIb/IIIa on the platelet surface occur simultaneously. This study may offer a new perspective to explain the reason of both increased thrombosis and bleeding events in patients implanted with high shear blood-contacting medical devices.