Total Content and Composition of Phenolic Compounds from Filipendula Genus Plants and Their Potential Health-Promoting Properties.

This current article was dedicated to the determination of the composition of phenolic compounds in extracts of four species of the genus Filipendula in order to establish a connection between the composition of polyphenols and biological effects. A chemical analysis revealed that the composition of the extracts studied depended both on the plant species and its part (leaf or flower) and on the extractant used. All four species of Filipendula were rich sources of phenolic compounds and contained hydrolyzable tannins, condensed tannins, phenolic acids and their derivatives, and flavonoids. The activities included data on those that are most important for creating functional foods with Filipendula plant components: the influence on blood coagulation measured by prothrombin and activated partial thromboplastin time, and on the activity of the digestive enzymes (pancreatic amylase and lipase). It was established that plant species, their parts, and extraction methods contribute meaningfully to biological activity. The most prominent result is as follows: the plant organ determines the selective inhibition of either amylase or lipase; thus, the anticoagulant activities of F. camtschatica and F. stepposa hold promise for health-promoting food formulations associated with general metabolic disorders.

Bioinspired, surfactant-free, dual-layer asymmetric structures based on polysaccharides, gelatin, and tannic acid for potential applications in biomedicine.

The formation of dual-layer asymmetric porous structures in surfactant-based systems is significantly influenced by emulsions. Surfactants self-assemble to alter the conformational arrangement of polysaccharides, while gravity disrupts the initial uniformity of the established equilibrium droplet concentration gradient in the emulsion, thus achieving delamination. Specifically, high-speed rotation and non-instantaneous freezing allow the gelatin solution to form two different states of foam layers. The integrated dual-layer asymmetric porous structure, composed of polysaccharides and tannic acid, is constructed with gelatin as a skeleton and surfactant. This innovative approach eliminates the need to consider the toxicity of chemically synthesized surfactants and expands the concept of gelatin utilization. This intriguing structure exhibits a variety of desirable characteristics within 30 days (e.g., tailorable performance, ultrarapid antioxidant activity, efficient antibacterial activity, low differential blood clotting index, and good hemocompatibility and cytocompatibility), suggesting its potential as a valuable reference for applying hierarchical porous structures, thereby offering more formulation flexibility for biomaterials with adjustable properties.

The breast cancer coagulome in the tumor microenvironment and its role in prognosis and treatment response to chemotherapy.

BACKGROUND: The procoagulant phenotype in cancer is linked to thrombosis, cancer progression, and immune response. A novel treatment that reduces the risk of both thrombosis and cancer progression without excess bleeding risk remains to be identified. OBJECTIVES: Here, we aimed to broadly investigate the breast tumor coagulome and its relation to prognosis, treatment response to chemotherapy, and the tumor microenvironment. METHODS: Key coagulation-related genes (n = 35) were studied in a Norwegian cohort with tumor (n = 134) and normal (n = 189) tissue and in the Cancer Genome Atlas (n = 1052) data set. We performed gene set variation analysis in the Norwegian cohort, and in the Cancer Genome Atlas cohort, associations with the tumor microenvironment and prognosis were evaluated. Analyses were performed with cBioPortal, Estimation of Stromal and Immune cells in Malignant Tumors Using Expression Data, Tumor Immune Estimation Resource, the integrated repository portal for tumor-immune system interactions, Tumor Immune Single-cell Hub 2, and the receiver operating characteristic plotter. Six independent breast cancer cohorts were used to study the tumor coagulome and treatment response to chemotherapy. RESULTS: Twenty-two differentially expressed coagulation-related genes were identified in breast tumors. Several coagulome factors were correlated with tumor microenvironment characteristics and were expressed by nonmalignant cells in the tumor microenvironment. PLAT and F8 were independent predictors of better overall survival and progression-free survival, respectively. F12 and PLAU were predictors of worse progression-free survival. The PROCR-THBD-PLAT signature showed a promising predictive value (area under the curve, 0.75; 95% CI, 0.69-0.81; P = 3.6 × 10-17) for combination chemotherapy with fluorouracil, epirubicin, and cyclophosphamide. CONCLUSION: The breast tumor coagulome showed potential in prediction of prognosis and chemotherapy response. Cells within the tumor microenvironment are sources of coagulome factors and may serve as therapeutic targets of coagulation factors.

Sodium dehydroacetate-induced disorder of coagulation function in broiler chickens and the protective effect afforded by vitamin K.

Sodium dehydroacetate (S-DHA) is used widely as a preservative in several products, including poultry feed. The anticoagulation effect of 200 mg/kg S-DHA in rats has been reported to accompany a reduction in hepatic expression of vitamin K epoxide reductase complex 1 (VKORC1). Poultry and mammals have different physiology and coagulation systems, and species differences in VKORC1 expression have been found. The effect of S-DHA on blood clotting of poultry has not been studies deeply. S-DHA was given to yellow-plumage broilers (YBs) as single and multiple administrations. Vitamin K3 (VK3) was injected into YBs 2 wk after S-DHA administration. Then, the prothrombin time (PT), partial activated prothrombin time (APTT), plasma levels of vitamin K (VK), factor IX (FIX), and S-DHA, and hepatic expression of VKORC1 were obtained. Chicken hepatocellular carcinoma (LMH) cells were also exposed to S-DHA, and the cell activity, VK level, and FIX level were measured. S-DHA prolonged the PT or APTT significantly, decreased levels of VK and FIX in blood, and inhibited hepatic expression of VKORC1. The maximum changes were 1.15-fold in the PT, 1.42-fold in the APTT, 0.8-fold in the VK level, 0.7-fold in the FIX level, and 0.35-fold in VKORC1 expression compared with controls. The cell activity, VK level, FIX level, and VKORC1/VKORC1L1 expression of LMH cells were reduced significantly at S-DHA doses of 2.0 to 10.0 mM. Prolongation of the PT/APTT and lower levels of VK/FIX in YBs or the lower cell activity and VK/FIX levels in LMH cells induced by S-DHA therapy were resisted significantly by VK3 treatment. We demonstrated that S-DHA could induce a disorder in coagulation function in YBs or in LMH cells via reduction of VKORC1/VKORC1L1 expression, and that VK could resist this anticoagulation effect.

Protective effects of rivaroxaban against cisplatin-induced testicular damage in rats: Impact on oxidative stress, coagulation, and p-NF-κB/VCAM-1 signaling.

Coagulation is a main pathway in various diseases pathogenesis including testicular damage. This study evaluated rivaroxaban (RVX) protective effects in testicular impairment by cisplatin (CP). Rats were randomly allocated into five groups: Control, RVX (7 mg/kg/day), CP (10 mg/kg), RVX 5 mg + CP and RVX 7 mg + CP. Serum testosterone and testicular ALT, AST, and ALP were assessed. Testicular oxidative stress and antioxidant parameters and inflammatory indicators including interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were assessed. qRT-PCR was used to determine mRNA expression of 3ß-hydroxysteroid dehydrogenase (3ß-HSD), 17ß-hydroxysteroid dehydrogenase (17ß-HSD), and steroidogenic acute regulatory protein (stAR). Protein expressions of p-Nuclear factor kappa B (p- NF-κB) and vascular cell adhesion protein-1 (VCAM-1) were analyzed by Western blot analysis. Tissue factor (TF) expression was immunohistochemically analyzed. Results revealed that RVX significantly increased serum testosterone and sperm count while significantly reduced IL-1ß and TNF-α. It significantly decreased tissue MDA and NO contents while increased SOD and GPx. In addition, RVX attenuated CP-induced histopathological aberrations and normalized TF. It also decreased the VCAM-1 and p-NF-κB expression and showed strong expression of 3ß-HSD, 17ß-HSD, and stAR, indicating improvement of steroidogenesis. In conclusion, RVX counteracted testicular damage by CP via suppressing oxidative stress, inflammation, and coagulation and downregulating p-NF-κB/VCAM-1 signaling.

Direct Oral Anticoagulants for the Treatment of Cancer-Associated Venous Thromboembolism: A Latin American Perspective.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with cancer. On the basis of results from randomized controlled trials, direct oral anticoagulants (DOACs) are now recommended for the treatment of cancer-associated VTE. The decision to use a DOAC requires consideration of bleeding risk, particularly in patients with gastrointestinal (GI) malignancies, the cost-benefit and convenience of oral therapy, and patient preference. While efficacy with apixaban, edoxaban, and rivaroxaban versus dalteparin has been consistent in the treatment of cancer-associated VTE, heterogeneity is evident with respect to major GI bleeding, with an increased risk with edoxaban and rivaroxaban but not apixaban. Although cost and accessibility vary in different countries of Latin America, DOACs should be considered for the long-term treatment of cancer-associated VTE in all patients who are likely to benefit. Apixaban may be the preferred DOAC in patients with GI malignancies and LMWH may be preferred for patients with upper or unresected lower GI tumors. Vitamin K antagonists should only be used for anticoagulation when DOACs and low molecular weight heparin are inaccessible or unsuitable.

Effect of Therapeutically Related Drugs on Coagulation-Anticoagulation Balance in Acute Promyelocytic Leukemia.

Acute promyelocytic leukemia (APL) usually presents with a series of coagulation-anticoagulation disturbance. Early administration of All-trans retinoic acid (ATRA) can reduce the risk of bleeding, but the potential for thrombosis needs to be addressed in some cases. The role of arsenic agent in correcting coagulation disorder remains to be studied, but oral arsenic agent shows potential advantages in coagulation recovery compared with intravenous agent, and chemotherapy can aggravate the progress of coagulation disease. In addition to early application of ATRA, avoiding invasive procedures and transfusion support can reduce the risk of bleeding. Whether the administration of heparin, thrombomodulin, recombinant factor VIIa or antifibrinolytics reduces the risk of bleeding and thrombosis associated with APL remains to be further explored, and their routine use outside of clinical trials is not recommended. This article reviews the effects of related drugs on coagulation-anticoagulation balance in APL patients.

Diindolylmethane ameliorates platelet aggregation and thrombosis: In silico, in vitro, and in vivo studies.

Diindolylmethane (DIM), a major metabolite of indole-3-carbinol (I3C), plays a vital role in the pharmacological actions of I3C. The role of DIM in the inhibition of platelet aggregation and thrombus generation is yet to be revealed. However, how DIM and I3C modulate the interaction of platelets with the glycoproteinVI (GPVI) and purinergic receptor Y12 (P2Y12) receptors is unknown. In silico studies revealed that the indole group of DIM and indole and the hydroxyl group of I3C are responsible for modulating platelet interaction with GPVI and P2Y12 receptors. In silico studies further predicted that DIM more superiorly modulates platelet interaction with GPVI and P2Y12 receptors than I3C. In vitro studies identified that DIM significantly inhibited platelet aggregation induced by adenosine diphosphate (ADP), collagen, thrombin, and arachidonic acid, increasing the thrombin-induced clot retraction size and clot retraction weight. Moreover, in vivo results of ferric chloride (FeCl3) induced carotid artery thrombus generation indicate that DIM significantly reduced the reactive oxygen species (ROS), hydrogen peroxide (H2O2), thromboxane 2 (TXB2), cyclooxygenase 1 (COX-1), prostaglandin E2 (PGE2), thrombus weight, increased the cyclic adenosine monophosphate (cAMP), and extended the time to occlusion (TTO). Furthermore, DIM did not show thrombolytic activity. Therefore, DIM acts as an antiplatelet aggregation and antithrombotic agent. Moreover, DIM is responsible for the antiplatelet aggregation and antithrombotic activity of I3C. Therefore, DIM could be used to treat thrombotic diseases.

Extracellular Vesicles Derived from 3T3-L1 Adipocytes Enhance Procoagulant Activity.

Obesity is associated with the risk of venous thromboembolism. Thrombi are constantly formed via the coagulation cascade and degraded by the fibrinolytic system, so they tend to form in obese individuals. Adipocytes are involved in thrombus formation in obesity, but it is not clear whether bioactive factors from adipocytes directly initiate or enhance coagulation and thrombosis. In this study, we confirmed that adipocyte-derived extracellular vesicles (ADEVs) enhance procoagulant activity in vitro. ADEVs prepared from the culture supernatant of mature 3T3-L1 adipocytes shortened plasma clotting times. Moreover, the effect of ADEVs on clotting time was weakened when using plasma lacking factors of the extrinsic pathway, but not the intrinsic pathway. ADEVs contain tissue factors and phosphatidylserine, which are involved in the extrinsic pathway, and blockade of these molecules diminished the effects of ADEVs on plasma clotting time. Additionally, the effect of ADEVs on plasma clotting time was further enhanced when cells were stimulated with the proinflammatory cytokine tumor necrosis factor-α. Thus, ADEVs may be a factor in thrombus formation in obesity.

Regression Analysis to Estimate the Factor VIII Activity of Patients with Hemophilia A Without Inhibitor who Received Emicizumab Therapy.

BACKGROUND: Emicizumab, a bispecific monoclonal antibody for hemophilia A (HA), has strong pharmacodynamic effects in several coagulation assays resulting in dosing difficulties with Factor VIII (FVIII) concentrates during bleeding emergencies. MATERIALS AND METHODS: Single and multiple regression models were studied to estimate FVIII activity using 27 archived plasma samples from three patients with HA without inhibitor under emicizumab treatment. Explanatory variables were FVIII chromogenic assay (CSA), Ad|min1|, Ad|min2|, the number of seconds of APTT, and the FVIII one-stage assay (OSA), which were measured without idiotype antibodies. The response variable was FVIII OSA measured with idiotype antibodies. RESULTS: In the simple linear model, the FVIII CSA regression coefficient was 1.04 and the intercept was -14.55 (r2 = 0.95; p < 0.001). In the multiple regression model, FVIII OSA and FVIII CSA were selected based on the Akaike Information Criterion, with regression coefficients of 1.74 and 1.15, respectively, and an intercept of -92.03 (r2 = 0.96, p < 0.001). CONCLUSIONS: The regression models can estimate the FVIII:C levels in patients with HA receiving emicizumab and would be useful in a bleeding emergency and/or surgery.

The effects of fructose diphosphate on routine coagulation tests in vitro.

To evaluate the effects of fructose diphosphate (FDP) on routine coagulation tests in vitro, we added FDP into the mixed normal plasma to obtain the final concentration of 0, 1, 2, 3, 4, 5, 6, 10, 15, 20, 25, 30 and 35 mg/mL of drug. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen (FBG) and thrombin time (TT) of samples were analyzed with blood coagulation analyzers from four different manufacturers(Sysmex, Stago, SEKISUI and Werfen) and their corresponding reagents, respectively. Before the experiment, we also observed whether there were significant differences in coagulation test results of different lots of reagents produced by each manufacturer. At the same time as the four routine clotting tests, the Sysmex blood coagulation analyzer and its proprietary analysis software were used to detect the change of maximum platelet aggregation rate in platelet-rich plasma after adding FDP (0, 1, 2, 3, 4, 5 and 6 mg/mL). The results of PT, aPTT and TT showed a FDP (0-35 mg/mL) concentration-dependent increase and a FBG concentration-dependent decrease. The degree of change (increase or decrease) varied depending on the assay system, with PT and aPTT being more affected by the Sysmex blood coagulation testing instrument reagent system and less affected by CEKISUI, TT less affected by CEKISUI and more affected by Stago, and FBG less affected by Stago and more affected by Sysmex. The results of PT, aPTT and TT were statistically positively correlated with their FDP concentrations, while FBG was negatively correlated. The correlation coefficients between FDP and the coagulation testing systems of Sysmex, Stago, Werfen and SEKISUI were 0.975, 0.988, 0.967, 0.986 for PT, and 0.993, 0.989, 0.990 and 0.962 for aPTT, 0.994, 0.960, 0.977 and 0.982 for TT, - 0.990, - 0.983, - 0.989 and - 0.954 for FBG, respectively. Different concentrations of FDP (0, 1, 2, 3, 4, 5 and 6 mg/mL) had different effects on the maximum aggregation rate of platelet induced by the agonists of adenosine diphosphate (ADP, 5 µmol/L), arachidonic acid (Ara, 1 mmol/L), collagen (Col, 2.5 µg/mL) and epinephrine (Epi,10 µmol/L), but the overall downward trend was consistent, that is, with the increase of FDP concentration, the platelet aggregation rate decreased significantly. Our experimental study demonstrated a possible effect of FDP on the assays of coagulation and Platelet aggregation, which may arise because the drug interferes with the coagulation and platelet aggregation detection system, or it may affect our in vivo coagulation system and Platelet aggregation function, the real mechanism of which remains to be further verified and studied.

Tyrosine Kinase Inhibitor Sunitinib Delays Platelet-Induced Coagulation: Additive Effects of Aspirin.

BACKGROUND: Sunitinib is a multitarget tyrosine kinase inhibitor (TKI) used for cancer treatment. In platelets, sunitinib affects collagen-induced activation under noncoagulating conditions. We investigated (1) the effects of sunitinib on thrombus formation induced by other TK-dependent receptors, and (2) the effects under coagulating conditions. Cardiovascular disease is a comorbidity in cancer patients, resulting in possible aspirin treatment. Sunitinib and aspirin are associated with increased bleeding risk, and therefore we also investigated (3) the synergistic effects of these compounds on thrombus and fibrin formation. METHODS: Blood or isolated platelets from healthy volunteers or cancer patients were incubated with sunitinib and/or aspirin or vehicle. Platelet activation was determined by TK phosphorylation, flow cytometry, changes in [Ca2+]i, aggregometry, and whole blood perfusion over multiple surfaces, including collagen with(out) tissue factor (TF) was performed. RESULTS: Sunitinib reduced thrombus formation and phosphatidylserine (PS) exposure under flow on collagen type I and III. Also, sunitinib inhibited glycoprotein VI-induced TK phosphorylation and Ca2+ elevation. Upon TF-triggered coagulation, sunitinib decreased PS exposure and fibrin formation. In blood from cancer patients more pronounced effects of sunitinib were observed in lung and pancreatic as compared to neuroglioblastoma and other cancer types. Compared to sunitinib alone, sunitinib plus aspirin further reduced platelet aggregation, thrombus formation, and PS exposure on collagen under flow with(out) coagulation. CONCLUSION: Sunitinib suppresses collagen-induced procoagulant activity and delays fibrin formation, which was aggravated by aspirin. Therefore, we urge for awareness of the combined antiplatelet effects of TKIs with aspirin, as this may result in increased risk of bleeding.

Iron-Driven Alterations on Red Blood Cell-Derived Microvesicles Amplify Coagulation during Hemolysis via the Intrinsic Tenase Complex.

Hemolytic disorders characterized by complement-mediated intravascular hemolysis, such as autoimmune hemolytic anemia and paroxysmal nocturnal hemoglobinuria, are often complicated by life-threatening thromboembolic complications. Severe hemolytic episodes result in the release of red blood cell (RBC)-derived proinflammatory and oxidatively reactive mediators (e.g., extracellular hemoglobin, heme, and iron) into plasma. Here, we studied the role of these hemolytic mediators in coagulation activation by measuring factor Xa (FXa) and thrombin generation in the presence of RBC lysates. Our results show that hemolytic microvesicles (HMVs) formed during hemolysis stimulate thrombin generation through a mechanism involving FVIII and FIX, the so-called intrinsic tenase complex. Iron scavenging during hemolysis using deferoxamine decreased the ability of the HMVs to enhance thrombin generation. Furthermore, the addition of ferric chloride (FeCl3) to plasma propagated thrombin generation in a FVIII- and FIX-dependent manner suggesting that iron positively affects blood coagulation. Phosphatidylserine (PS) blockade using lactadherin and iron chelation using deferoxamine reduced intrinsic tenase activity in a purified system containing HMVs as source of phospholipids confirming that both PS and iron ions contribute to the procoagulant effect of the HMVs. Finally, the effects of FeCl3 and HMVs decreased in the presence of ascorbate and glutathione indicating that oxidative stress plays a role in hypercoagulability. Overall, our results provide evidence for the contribution of iron ions derived from hemolytic RBCs to thrombin generation. These findings add to our understanding of the pathogenesis of thrombosis in hemolytic diseases.

Interplay between coagulation and inflammation in cancer: Limitations and therapeutic opportunities.

Advances in understanding the molecular mechanisms of tumor progression have achieved impressive progress in the treatment of cancer and so-called immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. Indeed, antibody-based drugs blocking immune escape of tumor cells by modulation of T cell responses are increasingly utilized for a wide range of tumor entities. Nonetheless, response rates remain limited, and the development of secondary resistance is a common problem. In addition, by increasing the immune response a variety of severe side effects are provoked. Next to autoimmune responses, activation of the complement system and skin toxicity, an increased incidence for thrombotic complications has been observed associated with an increased mortality rate. Based on this, it can be postulated that the interplay of coagulation with inflammation in the tumor microenvironment is relevant for each step in the tumor life cycle. This review focuses on the coagulation as central player fostering mechanisms associated with tumor progression. Thus, a better understanding of the molecular pathways involved in the complex interaction of circulating tumor cells, the plasmatic coagulation and immune cells may help to improve therapeutic concepts reducing mortality and morbidity associated with cancer.

Characterization of a single-domain von Willebrand factor type C protein (HaSVC) from the salivary gland of the tick Hyalomma asiaticum.

As a widely distributed arthropod and vector for various pathogens, Hyalomma asiaticum presents great risk and potential losses in animal husbandry. Effective measures, including the use of vaccines, are necessary for controlling ticks and tick-borne diseases. A concise understanding of the tick-host interaction associated molecules and pathways is required for vaccine development. In the present study, a protein containing a single-domain von Willebrand factor type C (HaSVC) was isolated from H. asiaticum and was subjected to functional identification. As a result, the full-length sequence of the HaSVC (506 bp) gene was obtained, which putatively encodes 100 amino acids with a predicted molecular mass of 11 kDa, excluding the 23-amino acid signal peptide. HaSVC contains 8 cysteines to form 4 disulfide bonds. The native HaSVC protein was detected in multiple tick organs. HaSVC neither attenuated the anti-coagulation process nor directly affected the blood feeding of adult ticks. However, the purified recombinant protein HaSVC (rHaSVC/GST) significantly increased the proliferation of mice spleen cells. This might suggest a regulatory function for HaSVC on inflammation, thus providing new information that may explain the "crosstalk" between ticks and hosts.

Divergent impacts of tocilizumab and colchicine in COVID-19-associated coagulopathy: the role of alpha-defensins.

Patients who are severely affected by coronavirus disease 2019 (COVID-19) may develop a delayed onset 'cytokine storm', which includes an increase in interleukin-6 (IL-6). This may be followed by a pro-thrombotic state and increased D-dimers. It was anticipated that tocilizumab (TCZ), an anti-IL-6 receptor monoclonal antibody, would mitigate inflammation and coagulation in patients with COVID-19. However, clinical trials with TCZ have recorded an increase in D-dimer levels. In contrast to TCZ, colchicine reduced D-dimer levels in patients with COVID-19. To understand how the two anti-inflammatory agents have diverse effects on D-dimer levels, we present data from two clinical trials that we performed. In the first trial, TCZ was administered (8 mg/kg) to patients who had a positive polymerase chain reaction test for COVID-19. In the second trial, colchicine was given (0·5 mg twice a day). We found that TCZ significantly increased IL-6, α-Defensin (α-Def), a pro-thrombotic peptide, and D-dimers. In contrast, treatment with colchicine reduced α-Def and Di-dimer levels. In vitro studies show that IL-6 stimulated the release of α-Def from human neutrophils but in contrast to colchicine, TCZ did not inhibit the stimulatory effect of IL-6; raising the possibility that the increase in IL-6 in patients with COVID-19 treated with TCZ triggers the release of α-Def, which promotes pro-thrombotic events reflected in an increase in D-dimer levels.

Neutralization of toxic activities of Bothrops asper snake venom by ethnomedicinal plants used in Central America, with emphasis in Guatemala: a review / Neutralización de actividades tóxicas del veneno de la serpiente Bothrops asper por plantas etnomedicinales utilizadas en Centroamérica, con énfasis en Guatemala: Revisión

There are few scientific studies that explore the use of medicinal plants for snakebite envenoming in Central America, although plant-based therapies have been traditionally used in the region. This work reviews the studies conducted in Central America to assess the ability of extracts obtained from plants of local ethnomedical use to inhibit toxic activities of the venom of Bothrops asper, the snake responsible for approximately half of the snakebite envenomings in these countries. The search prioritized the description of the plants used in Guatemala, since most of the studies described in this work were conducted in that country, although references to other countries are included. Information concerning secondary metabolites and other pharmacological activities of these plant species, relevant to the treatment of snakebites, was also described. The literature search was conducted in the Google Scholar, PubMed and Scopus databases and completed with locally available literature. It was found that extracts of 12 plant species inhibited the hemorrhagic effect of the venom and three neutralized the edema-forming activity, while inhibition of proteolytic and phospholipase A2 (PLA2) activities was achieved by three and one plant species, respectively. Only Brownea rosa-de-monte was able to effectively counteract the in vitro coagulant effect of the venom. Some plant extracts screened in Guatemala demonstrated procoagulant or anti-thrombin intrinsic effects that might aggravate the coagulopathy induced by the venom. These findings underscore the need of carrying out scientific studies aimed to validate the inhibitory potential of Central American plant extracts and their metabolites against B. asper venom.

Pocos estudios científicos han explorado el uso de plantas medicinales para el tratamiento del envenenamiento ofídico en Centroamérica, a pesar de que las terapias basadas en plantas son de uso tradicional en la región. Este trabajo recopiló información sobre los estudios realizados en Centroamérica para evaluar la capacidad de extractos de plantas de uso etno-médico para inhibir las actividades tóxicas del veneno de Bothrops asper, la serpiente responsable de aproximadamente la mitad de los envenenamientos ofídicos en Centroamérica. La búsqueda priorizó la descripción de plantas utilizadas en Gua-temala, ya que la mayoría de los estudios aquí descritos fueron realizados en ese país. También se incluyó la descripción de los metabolitos secundarios y otras actividades farmacológicas de las especies evaluadas, que podrían explicar su uso como antiofídicos. La búsqueda de literatura se realizó en las bases de datos de Google Scholar, PubMed, Scopus, y se completó con literatura disponible localmente. Se determinó que 12 extractos de plantas inhibieron el efecto hemorrágico del veneno y tres el efecto edematígeno; la actividad proteolítica fue inhibida por extractos de tres especies y la fosfolipasa A2 (PLA2) por una especie. Solamente Brownea rosa-de-monte demostró inhibir efectivamente el efecto coagulante del veneno in vitro. Algunos extractos de las plantas tamizadas en Guatemala demostraron efectos procoagulantes o anti-trombina intrínsecos, que podrían agravar las alteraciones inducidas por el veneno en la coagulación. Estos hallazgos enfatizan la necesidad de validar el potencial de extractos de plantas centroamericanas y sus metabolitos secundarios para neutralizar el veneno de B. asper.

Role of acquired von Willebrand syndrome in the development of bleeding complications in patients treated with Impella RP devices.

Axial flow pumps are standard treatment in cases of cardiogenic shock and high-risk interventions in cardiology and cardiac surgery, although the optimal anticoagulation strategy remains unclear. We evaluated whether laboratory findings could predict bleeding complications and acquired von Willebrand syndrome (avWS) among patients who were treated using axial flow pumps. We retrospectively evaluated 60 consecutive patients who received Impella devices (Impella RP: n = 20, Impella CP/5.0: n = 40; Abiomed Inc., Danvers, USA) between January 2019 and December 2020. Thirty-two patients (53.3%) experienced major or fatal bleeding complications (Bleeding Academic Research Consortium score of > 3) despite intravenous heparin being used to maintain normal activated partial thromboplastin times (40-50 s). Extensive testing was performed for 28 patients with bleeding complications (87.5%). Relative to patients with left ventricular support, patients with right ventricular support were less likely to develop avWS (87.5% vs. 58.8%, p = 0.035). Bleeding was significantly associated with avWS (odds ratio [OR]: 20.8, 95% confidence interval [CI]: 3.3-128.5; p = 0.001) and treatment duration (OR: 1.3, 95% CI 1.09-1.55; p = 0.003). Patients with avWS had longer Impella treatment than patients without avWS (2 days [1-4.7 days] vs. 7.3 days [3.2-13.0 days]). Bleeding complications during Impella support were associated with avWS in our cohort, while aPTT monitoring was not sufficient to prevent bleeding complications. A more targeted anticoagulation monitoring might be needed for patients who receive Impella devices.