Search Results (51)

Background and Objectives: Inflammation contributes to plaque rupture and thrombosis in ST-elevation myocardial infarction (STEMI). The Aggregate Index of Systemic Inflammation (AISI) is a novel biomarker that reflects innate immune and thrombotic activation. Due to the connection between inflammation and thrombosis, higher AISI values could indicate a greater thrombus burden and the necessity of glycoprotein IIb/IIIa inhibitors. The aim of this study was to assess the relationship between AISI and tirofiban use during primary percutaneous coronary intervention (PCI) in STEMI patients. Materials and Methods: This retrospective study included 2624 STEMI patients who underwent primary PCI at a tertiary heart center between 2019 and 2024. Patients with pre-hospital fibrinolysis, missing laboratory data, or rescue PCI were excluded. AISI was calculated as (neutrophil × monocyte × platelet)/lymphocyte. The primary outcome was tirofiban use during PCI. Univariate and multivariable logistic regression analyses were performed to identify independent predictors, and receiver operating characteristic (ROC) curve analysis was used to evaluate AISI performance. Statistical significance was defined as p < 0.05. Results: Among the 2624 patients with STEMI undergoing primary PCI, tirofiban was administered in 23.5% of cases. Patients receiving tirofiban had significantly higher AISI values (p < 0.001). ROC analysis demonstrated that AISI predicted tirofiban use with a modest discriminative performance (AUC = 0.566; 95% CI 0.536–0.596; p < 0.001). In multivariable logistic regression, younger age (OR 0.98; p < 0.001), higher AISI (per 100-unit increase; OR 1.01; p = 0.037), and lower LVEF (OR 0.98; p < 0.001) independently predicted tirofiban use, whereas admission glucose showed only borderline significance (p = 0.089). Conclusions: Elevated AISI was independently associated with tirofiban use during primary PCI, indicating that systemic inflammatory status parallels intraprocedural decision-making in STEMI. Although its discriminative performance was modest, AISI reflects systemic inflammatory–thrombotic activation in this clinical setting. Full article

Background and Objectives: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is standard in ST-segment elevation myocardial infarction (STEMI). Guidelines favor ticagrelor over clopidogrel, but their effect on infarct artery flow prior to percutaneous coronary intervention (PCI) remains debated. Objective was to compare the effects of aspirin + clopidogrel versus aspirin + ticagrelor pretreatment on infarct artery Thrombolysis in Myocardial Infarction (TIMI) flow in STEMI patients. Materials and Methods: This retrospective cohort study included first-time STEMI patients ≥ 18 years admitted to the Military Medical Academy, Belgrade (January 2016–January 2022), who received pretreatment with aspirin + clopidogrel or aspirin + ticagrelor and underwent PCI. TIMI flow was graded before and after PCI. Primary outcomes were pre- and post-PCI TIMI flow; secondary outcome was in-hospital mortality. Results: Of 299 STEMI patients, 174 received aspirin + ticagrelor and 125 received aspirin + clopidogrel. Pre-PCI TIMI flow was significantly higher in the ticagrelor group (p < 0.001), while post-PCI TIMI flow (p = 0.056) and in-hospital mortality (p = 0.083) did not significantly differ between groups. After exclusion of patients receiving glycoprotein IIb/IIIa inhibitors, the difference in PCI TIMI flow grade after PCI became statistically significant (p = 0.007), favoring the aspirin + ticagrelor group. In multivariate analysis, male gender, drug-eluting stent implantation, and glycoprotein IIb/IIIa inhibitor use were independently associated with reduced in-hospital mortality. Conclusions: In STEMI patients, ticagrelor-based DAPT was associated with better initial coronary flow compared to clopidogrel. However, this advantage was not evident after PCI. Male gender, drug-eluting stent implantation, and glycoprotein IIb/IIIa inhibitor use were associated with improved survival. Full article

Objective: Stent-assisted treatments for intracranial aneurysms, including stent-assisted coiling (SAC) and flow diversion (FD), are associated with an increased thrombotic risk despite dual antiplatelet therapy (DAPT). Recently, intravenous prophylactic protocols incorporating glycoprotein IIb/IIIa antagonists, adapted from cardiology practices, have been introduced. This study evaluates the safety and efficacy of prophylactic low-dose intra-arterial Eptifibatide for cerebral aneurysm management using SAC or FD. Methods: This single-center, single-arm, retrospective study included 99 patients who underwent endovascular treatment with stent-assisted coiling (SAC) or flow diversion (FD) between 2017 and 2023. All patients were initiated on dual antiplatelet therapy (DAPT) 7 days prior to the procedure. Prophylactic intra-arterial Eptifibatide (2–3 mg) was administered intra-procedurally, immediately after stent deployment. Complications were recorded and categorized as periprocedural (occurring during or within 24 h of the procedure) or postprocedural (occurring between 24 and 72 h after the procedure), and included both thrombotic and hemorrhagic events. Results: Among the 99 patients (mean age 57.0 ± 10.8 years), periprocedural complications included three cases of ischemic-related neurological deficits, with no evidence of stent thrombosis or intracranial branch occlusion. All deficits were resolved within 48 h. An additional two patients developed ischemic-related neurological deficits post-procedural. One patient fully recovered following a short rehabilitation period, while the other was left with mild permanent deficits. Overall, any complications following Eptifibatide administration were observed in 5.1% of patients. No hemorrhagic complications were recorded. Conclusions: Prophylactic low-dose intra-arterial Eptifibatide demonstrated a favorable safety profile, potentially reducing thrombotic complications without substantially increasing hemorrhagic risk. Full article

Background/Objectives: Patients that undergo percutaneous coronary intervention (PCI) require effective antiplatelet therapies to minimize the risk of thrombotic cardiovascular events. Oral P2Y12 inhibitors are often utilized, however co-administered opioids may lead to gastric absorption issues in these patients, affecting the efficacy of oral inhibitors. Cangrelor is an intravenous, direct-acting, reversible P2Y12 inhibitor that could be explored as a potential treatment option for patients with gastric absorption issues during ST-elevation myocardial infarction. The objective was to estimate the UK budget impact of introducing cangrelor for ST-elevation myocardial infarction (STEMI) patients with gastric absorption issues undergoing PCI. Methods: A budget impact model was developed to calculate the impact of introducing cangrelor to treat STEMI patients with gastric absorption issues undergoing PCI, to the UK National Health Service and personal social services, over 5 years. Oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor), glycoprotein IIb/IIIa inhibitors (eptifibatide and tirofiban), and aspirin and heparin alone were included as base case comparators. Cangrelor uptake ranged from 10% to 30% in years 1–5. The cangrelor-eligible population was estimated at 10,903 patients per year. Results: Over 5 years, cangrelor leads to a small cost saving (0.29%), varying from −GBP 261,989 in year 1 to GBP 174,778 in year 5. The introduction of cangrelor is estimated to lead to 314 fewer hospital days and 190 clinical events avoided over 5 years. Conclusions: Introducing cangrelor to STEMI patients with gastric absorption issues undergoing PCI in the UK is estimated to generate a small cost saving and reduced length of stay for some patients. Full article

Platelet satellitism (PS) is an in vitro phenomenon of platelets adhering around white blood cells, especially in blood samples anticoagulated with K₃EDTA. This, in some cases, can lead to spurious thrombocytopenia, without platelet dysfunction or bleeding events. Diagnosis is made by peripheral blood smear examination. The potential mechanism for PS remains largely unknown; however, it possibly involves the formation of IgG antibodies against the platelet glycoprotein receptor IIb/IIIa (GPIIb/IIIa). PS has been observed in various medical conditions, including infectious, autoimmune, and lymphoproliferative disorders, without an obvious causative relationship. Here, we describe a case of PS in a patient who presented with infection in the setting of underlying Immune Thombocytopenic Purpura and Multiple Sclerosis. Full article

Bleeding complications are a significant concern in the management of acute coronary syndromes (ACS). The evidence from clinical trials demonstrates the need for balancing efficacy in reducing ischemic events with safety concerns, as bleeding events adversely affect prognosis and mortality. Pharmacological agents like aspirin, P2Y12 inhibitors (e.g., prasugrel, ticagrelor), glycoprotein IIb/IIIa inhibitors, and heparins are fundamental to ACS treatment but carry varying bleeding risks depending on individual patient profile. Recent advancements in risk stratification tools have enabled tailored approaches to dual antiplatelet therapy (DAPT), optimizing its duration based on bleeding and thrombotic risks. Further Emerging therapies, including shortened DAPT protocols and P2Y12 inhibitor monotherapy, have shown promise in minimizing bleeding while maintaining clinical efficacy. The findings underscore the importance of personalized antithrombotic regimens in ACS management, emphasizing precise risk assessment to enhance outcomes and mitigate adverse events. This review examines the mechanisms, risk factors, and strategies to mitigate bleeding associated with anticoagulant and antiplatelet therapies in ACS. Full article

Increased platelet activity is a risk factor of thrombotic events in cardiovascular patients. We studied the relationship between platelet function, platelet size, and the content of reticulated platelets (RP) in patients with coronary heart disease (CHD, n = 55) and acute coronary syndrome (ACS, n = 95) receiving acetylsalicylic acid + clopidogrel or ticagrelor, respectively. The control group consisted of patients with risk factors for CHD, but with no CHD/ACS and free of antiplatelet drugs (n = 66). Platelet function was evaluated by the exposure of activated glycoprotein (GP) IIb-IIIa and P-selectin. In the control group, platelets were activated by TRAP (Thrombin Receptor Activating Peptide) 10 µM, and ADP 20, 5, 2.5 µM, and in the CHD/ACS groups, by TRAP 10 µM, and ADP 20 5 µM (±epinephrine 20 µM). Platelet size was assessed by the mean volume, % large forms, and forward scattering. RP were stained by thiazole orange. In the control group, activated GP IIb-IIIa and P-selectin correlated with platelet size and RP content after platelet activation by all agonists. Despite the decrease in platelet activity by antiplatelet drugs, most correlations (primarily for activated GP IIb-IIIa) were preserved in the CHD/ACS patients. In conclusion, increased platelet size and RP content are associated with increased platelet activity and the reduced efficacy of antiplatelet therapy. Full article

Acute myocardial infarction still represents the major cause of mortality in high-income countries. Therefore, considerable efforts have been focused on the treatment of myocardial infarctions in the acute and long-term phase, with special attention being paid to reperfusion strategies and adjunctive antithrombotic therapies. In fact, despite the successful mechanical recanalization of the epicardial conduit, a substantial percentage of patients still experience poor myocardial reperfusion or acute/subacute in-stent thrombosis. Due the delayed onset of action of currently available oral antiplatelet therapies, glycoprotein (GP) IIb–IIIa inhibitors could be expected to improve clinical outcomes, especially when administrated in the early phase of the infarction, due to the larger platelet composition of fresh thrombi, the dynamic nature of early thrombi, and the larger amount of viable myocardium existing in the early, as compared to a delayed, phase. Considerable evidence has accumulated regarding the benefits from GP IIb–IIIa inhibitors on mortality, especially among high-risk patients and when administered as an upstream strategy. Therefore, based on currently available data, GP IIb–IIIa inhibitors can be considered when the drug can be administered within the first 3 h of symptom onset and among high-risk patients (e.g., those with advanced Killip class or an anterior myocardial infarction). Even though it is not universally accepted, in our opinion, this strategy should be implemented in a pre-hospital setting (in an ambulance) or as soon as possible when arriving at the hospital (at the Emergency Room or Coronary Care Unit, irrespective of whether they are in spoke or hub hospitals). A new, second-generation GP IIb–IIIa inhibitor (zalunfiban) appears to be highly suitable as a pre-hospital pharmacological facilitation strategy at the time of first medical contact due to its favourable features, including its simple subcutaneous administration, rapid onset of action (15 min), and limited time of action (with a half-life of ~1 h), which is likely to minimize the risk of bleeding. The ongoing CELEBRATE trial, including 2499 STEMI patients, may potentially provide compelling data to support the upstream treatment of STEMI patients undergoing mechanical reperfusion. In fact, although the current therapeutic target of increased rates of timely reperfusion has been achieved, the future goal in myocardial infarction treatment should be to achieve the most rapid reperfusion prior to primary percutaneous coronary intervention, thus further minimizing myocardial damage, or, in some cases, even preventing it completely, and improving survival. Full article

Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare but severe complication following COVID-19 vaccination, marked by thrombocytopenia and thrombosis. Analogous to heparin-induced thrombocytopenia (HIT), VITT shares similarities in anti-platelet factor 4 (PF4) IgG-mediated platelet activation via the FcγRIIa. To investigate the involvement of platelet-antibodies in VITT, we analyzed the presence of platelet-antibodies directed against glycoproteins (GP)IIb/IIIa, GPV and GPIb/IX in the serum of 232 clinically suspected VITT patients determined based on (suspicion of) occurrence of thrombocytopenia and/or thrombosis in relation to COVID-19 vaccination. We found that 19% of clinically suspected VITT patients tested positive for anti-platelet GPs: 39%, 32% and 86% patients tested positive for GPIIb/IIIa, GPV and GPIb/IX, respectively. No HIT-like VITT patients (with thrombocytopenia and thrombosis) tested positive for platelet-antibodies. Therefore, it seems unlikely that platelet-antibodies play a role in HIT-like anti-PF4-mediated VITT. Platelet-antibodies were predominantly associated with the occurrence of thrombocytopenia. We found no association between the type of vaccination (adenoviral vector vaccine versus mRNA vaccine) or different vaccines (ChAdOx1 nCoV-19, Ad26.COV2.S, mRNA-1273, BTN162b2) and the development of platelet-antibodies. It is essential to conduct more research on the pathophysiology of VITT, to improve diagnostic approaches and identify preventive and therapeutic strategies. Full article

Background and Objectives: This retrospective cohort study investigates the role of genetic thrombophilia in pregnant women experiencing early pregnancy loss compared to those with late pregnancy loss. Materials and Methods: Participants were categorized into early and late pregnancy loss groups based on gestational age. A total of 156 patients were included, out of which 103 had early-trimester pregnancy losses and 96 had multiple miscarriages. Results: The study revealed a synergistic effect of Factor V Leiden (FVL G1691A) and Methylenetetrahydrofolate Reductase (MTHFR C677T) mutations (coefficient 3.42). Prothrombin (PT) G20210A and β-Fibrinogen 455 G>A mutations exhibited a significant interaction (coefficient 1.98). Additionally, MTHFR A1298C and Plasminogen Activator Inhibitor-1 (PAI-1 4G/5G) mutations showed a significant interaction (coefficient 1.65). FVL G1691A and Endothelial Protein C Receptor (EPCR) allele A1/A2 mutations also demonstrated a significant association (coefficient 2.10). Lastly, MTHFR C677T and Glycoprotein IIb/IIIa T1565C mutations interacted significantly (coefficient 1.77). Risk factor analysis identified several mutations associated with early pregnancy loss, including PAI-1 4G/5G homozygous (OR 3.01), FVL G1691A heterozygous (OR 1.85), and MTHFR A1298C heterozygous (OR 1.55). Both homozygous and heterozygous MTHFR C677T mutations were significant risk factors (OR 2.38; OR 2.06), as was PT G20210A homozygous mutation (OR 1.92). The PAI-1 4G/4G homozygous variant posed a risk (OR 1.36). Late pregnancy loss was associated with MTHFR A1298C homozygous mutation (OR 3.79), β-Fibrinogen 455 G>A heterozygous mutation (OR 2.20), and MTHFR A1298C heterozygous mutation (OR 2.65). Factor XIII G1002T heterozygous mutation (OR 1.18) and PAI-1 4G/5G homozygous mutation (OR 2.85) were also significant risk factors. EPCR allele A1/A2 (OR 1.60) and A2/A3 (OR 1.73) mutations were identified as significant risk factors for late pregnancy loss. Furthermore, FVL G1691A homozygous mutation, PT G20210A homozygous mutation, MTHFR C677T heterozygous mutation, MTHFR A1298C heterozygous mutation, and EPCR allele A1/A2 were identified as significant risk factors for multiple miscarriage. Conclusions: This study highlights significant interactions and risk factors related to genetic thrombophilia mutations in different types of pregnancy loss, contributing valuable insights for miscarriage management guidelines. Full article

Aim: Cutaneous T-cell lymphomas (CTCL) can be described as chronic skin inflammation lesions with the content of malignant T cells and they are considered to be T-cell-mediated skin diseases. CD147 is recognized as a 58-kDa cell surface glycoprotein of the immunoglobulin superfamily; it can induce the synthesis of MMPs (matrix metalloproteinases) on the surface of tumor cells where it was originally identified. It can also function in adjacent tumor fibroblasts using CD147–CD147 interactions. The polymorphism rs8259 T/A is situated in the untranslated region (3′UTR) of the CD147 gene. HLA DRB1*1501 takes part in the process of presentation and recognition of different antigens to T cells. It can be expressed by antigen-presenting cells—macrophages, dendritic cells, and B cells. The aim of the study is to test genotype–phenotype associations of both polymorphisms including therapy in a large cohort of CTCL patients. Materials and Methods: A final total of 104 CTCL patients were enrolled in the study. For the first remission at the clinic department, they were treated by means of local skin-directed therapy, phototherapy, and systemic therapy. Genomic DNA was isolated from peripheral blood leukocytes. A standard technique using proteinase K was applied. The polymorphisms rs8259 T/A (CD147 gene) and rs3135388 (HLA DRB1*1501) were detected through standard PCR-restriction fragment length polymorphism methods. Results: The severity of the disease (patients with parapsoriasis, stages IA and IB, vs patients with stages IIB, IIIA, and IIIB) was associated with the CD147 genotype: the AA variant was 3.38 times more frequent in more severe cases, which reflects the decision on systemic therapy (p = 0.02, specificity 0.965). The AA genotype in the CD147 polymorphism was 12 times more frequent in patients who underwent systemic therapy of CTCL compared to those not treated with this therapy (p = 0.009, specificity 0.976). The same genotype was also associated with radiotherapy—it was observed 14 times more frequently in patients treated with radiotherapy (p = 0.009, specificity 0.959). In patients treated with interferon α therapy, the AA genotype was observed to be 5.85 times more frequent compared to the patients not treated with interferon therapy (p = 0.03, specificity 0.963). The HLA DRB1*1501 polymorphism was associated with local skin-directed therapy of CTCL. The CC genotype of the polymorphism was observed to be 3.57 times more frequent in patients treated with local therapy (p = 0.008, specificity 0.948). When both polymorphisms had been calculated together, even better results were obtained: the AACC double genotype was 11 times more frequent in patients with severe CTCL (p = 0.009, specificity 0.977). The TACT double genotype was associated with local skin-directed therapy (0.09 times lower frequency, p = 0.007, sensitivity 0.982). The AACC genotype was 8.9 times more frequent in patients treated by means of systemic therapy (p = 0.02, specificity 0.976) and as many as 18.8 times more frequent in patients treated with radiotherapy (p = 0.005, specificity 0.969). Thus, the AACC double genotype of CD147 and DRB1*1501 polymorphisms seems to be a clinically highly specific marker of severity, systemic therapy and radiotherapy of patients with T-cell lymphoma. Conclusion: Although genotyping results were not known during the treatment decision and could not modify it, the clinical decision on severity and therapy reflected some aspects of the genetic background of this complicated T-cell-associated disease very well. Full article

Activated platelets are involved in blood coagulation by exposing phosphatidylserine (PS), which serves as a substrate for assembling coagulation complexes. Platelets accelerate fibrin formation and thrombin generation, two final reactions of the coagulation cascade. We investigated the effects of antiplatelet drugs on platelet impact in these reactions and platelet ability to expose PS. Washed human platelets were incubated with acetylsalicylic acid (ASA), ticagrelor, ASA in combination with ticagrelor, ruciromab (glycoprotein IIb-IIIa antagonist), or prostaglandin E1 (PGE1). Platelets were not activated or activated by collagen and sedimented in multiwell plates, and plasma was added after supernatant removal. Fibrin formation (clotting) was monitored in a recalcification assay by light absorbance and thrombin generation in a fluorogenic test. PS exposure was assessed by annexin V staining using flow cytometry. Ticagrelor (alone and in combination with ASA), ruciromab, and PGE1, but not ASA, prolonged the lag phase and decreased the maximum rate of plasma clotting and decreased the peak and maximum rate of thrombin generation. Inhibition was observed when platelets were not treated with exogenous agonists (activation by endogenous thrombin) and pretreated with collagen. Ticagrelor (alone and in combination with ASA), ruciromab, and PGE1, but not ASA, decreased PS exposure on washed platelets activated by thrombin and by thrombin + collagen. PS exposure on activated platelets in whole blood was lower in patients with acute coronary syndrome receiving ticagrelor + ASA in comparison with donors free of medications. These results indicate that antiplatelet drugs are able to suppress platelet coagulation activity not only in vitro but also after administration to patients. Full article

Therapeutic peptides are oligomers or short polymers of amino acids used for various medical purposes. Peptide-based treatments have evolved considerably due to new technologies, stimulating new research interests. They have been shown to be beneficial in a variety of therapeutic applications, notably in the treatment of cardiovascular disorders such as acute coronary syndrome (ACS). ACS is characterized by coronary artery wall damage and consequent formation of an intraluminal thrombus obstructing one or more coronary arteries, leading to unstable angina, non-ST elevated myocardial infarction, and ST-elevated myocardial infarction. One of the promising peptide drugs in the treatment of these pathologies is eptifibatide, a synthetic heptapeptide derived from rattlesnake venom. Eptifibatide is a glycoprotein IIb/IIIa inhibitor that blocks different pathways in platelet activation and aggregation. In this narrative review, we summarized the current evidence on the mechanism of action, clinical pharmacology, and applications of eptifibatide in cardiology. Additionally, we illustrated its possible broader usage with new indications, including ischemic stroke, carotid stenting, intracranial aneurysm stenting, and septic shock. Further research is, however, required to fully evaluate the role of eptifibatide in these pathologies, independently and in comparison to other medications. Full article

A polyphenol-rich diet has beneficial effects on cardiovascular health. However, dietary polyphenols generally have low bioavailability and reach low plasma concentrations. Small phenolic metabolites of these compounds formed by human microbiota are much more easily absorbable and could be responsible for this effect. One of these metabolites, 4-methylcatechol (4-MC), was suggested to be a potent anti-platelet compound. The effect of 4-MC was tested ex vivo in a group of 53 generally healthy donors using impedance blood aggregometry. The mechanism of action of this compound was also investigated by employing various aggregation inducers/inhibitors and a combination of aggregometry and enzyme linked immunosorbent assay (ELISA) methods. 4-MC was confirmed to be more potent than acetylsalicylic acid on both arachidonic acid and collagen-triggered platelet aggregation. Its clinically relevant effect was found even at a concentration of 10 μM. Mechanistic studies showed that 4-MC is able to block platelet aggregation caused by the stimulation of different pathways (receptors for the von Willebrand factor and platelet-activating factor, glycoprotein IIb/IIIa, protein kinase C, intracellular calcium elevation). The major mechanism was defined as interference with cyclooxygenase-thromboxane synthase coupling. This study confirmed the strong antiplatelet potential of 4-MC in a group of healthy donors and defined its mechanism of action. Full article

We have previously demonstrated that platelet-poor plasma (PPP) obtained from patients with Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is characterized by a hypercoagulable state and contains hyperactivated platelets and considerable numbers of already-formed amyloid fibrin(ogen) or fibrinaloid microclots. Due to the substantial overlap in symptoms and etiology between Long COVID/PASC and ME/CFS, we investigated whether coagulopathies reflected in Long COVID/PASC—hypercoagulability, platelet hyperactivation, and fibrinaloid microclot formation—were present in individuals with ME/CFS and gender- and age-matched healthy controls. ME/CFS samples showed significant hypercoagulability as judged by thromboelastography of both whole blood and platelet-poor plasma. The area of plasma images containing fibrinaloid microclots was commonly more than 10-fold greater in untreated PPP from individuals with ME/CFS than in that of healthy controls. A similar difference was found when the plasma samples were treated with thrombin. Using fluorescently labelled PAC-1, which recognizes glycoprotein IIb/IIIa, and CD62P, which binds P-selectin, we observed hyperactivation of platelets in ME/CFS hematocrit samples. Using a quantitative scoring system, the ME/CFS platelets were found to have a mean spreading score of 2.72 ± 1.24 vs. 1.00 (activation with pseudopodia formation) for healthy controls. We conclude that ME/CFS is accompanied by substantial and measurable changes in coagulability, platelet hyperactivation, and fibrinaloid microclot formation. However, the fibrinaloid microclot load was not as great as was previously noted in Long COVID/PASC. Fibrinaloid microclots, in particular, may contribute to many ME/CFS symptoms, such as fatigue, seen in patients with ME/CFS, via the (temporary) blockage of microcapillaries and hence ischemia. Furthermore, fibrinaloid microclots might damage the endothelium. The discovery of these biomarkers represents an important development in ME/CFS research. It also points to possible uses for treatment strategies using known drugs and/or nutraceuticals that target systemic vascular pathology and endothelial inflammation. Full article