fibrin clot
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Aim. To study the blood coagulation status by various laboratory methods in patients after pulmonary embolism (PE) receiving long-term anticoagulant therapy.Material and methods. The blood of 23 patients with pulmonary embolism, who received long-term anticoagulant therapy, was studied. The study of coagulation profile, D-dimer, thrombodynamics, thromboelastography and thrombin generation test were carried out.Results. The thrombin generation test shows a significant increase in the time of its formation, while the maximum amount of thrombin formed is half that of the reference values. There is a slightly increased median fibrin clot growth rate in the thrombodynamics test — 30,4 gm/min with a normal coagulation rate of 20-29 gm/min. The result of thromboelastography also reflects the blood hypocoagulation, in terms of R, Angle a and CI.Conclusion. Integral methods for assessing the thrombotic readiness in combination with a routine coagulation panel demonstrate a complete picture of blood coagulation potential in patients after pulmonary embolism requiring long-term anticoagulant therapy.

Mechanical properties have been extensively studied in pure elastic or viscous materials; however, most biomaterials possess both physical properties in a viscoelastic component. How the biomechanics of a fibrin clot is related to its composition and the microenvironment where it is formed is not yet fully understood. This review gives an outline of the building mechanisms for blood clot mechanical properties and how they relate to clot function. The formation of a blood clot in health conditions or the formation of a dangerous thrombus go beyond the mere polymerization of fibrinogen into a fibrin network. The complex composition and localization of in vivo fibrin clots demonstrate the interplay between fibrin and/or fibrinogen and blood cells. Studying these protein–cell interactions and clot mechanical properties may represent new methods for the evaluation of cardiovascular diseases (the leading cause of death worldwide), creating new possibilities for clinical diagnosis, prognosis, and therapy. Expected final online publication date for the Annual Review of Biophysics, Volume 51 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Objectives: thromboembolic complications are a major cause of morbidity and mortality following Fontan (FO) surgery. It is also well established that altered FO circulation results in systemic complications, including liver and endothelium damage. We sought to evaluate whether dysfunctions of these sources of hemostatic factors may result in changes of fibrin clot properties. Methods: a permeation coefficient (Ks) and clot lysis time (CLT) were assessed in 66 FO patients, aged 23.0 years [IQR 19.3–27.0], and 59 controls, aged 24.0 years [IQR 19.0–29.0]. Ks was determined using a pressure-driven system. CLT value was measured according to assay described by Pieters et al. Endothelium and liver-derived hemostatic factors along with liver function parameters were evaluated. The median time between FO operation and investigation was 20.5 years [IQR 16.3–22.0]. Results: FO patients had lower Ks (p = 0.005) and prolonged CLT (p < 0.001) compared to that of controls. Ks correlated with CLT (r = −0.28), FVIII (r = −0.30), FIX (r = −0.38), fibrinogen (r = −0.41), ALT (r = −0.25), AST (r = −0.26), GGTP (r = −0.27) and vWF antigen (r = −0.30), (all p < 0.05). CLT correlated with the time between FO operation and investigation (r = 0.29) and FIX (r = 0.25), (all p < 0.05). After adjustment for potential cofounders, TAFI antigen and GGTP were independent predictors of reduced Ks (OR 1.041 per 1% increase, 95% CI 1.009–1.081, p = 0.011 and OR 1.025 per 1 U/L increase, 95% CI 1.005–1.053, p = 0.033, respectively). Protein C and LDL cholesterol predicted prolonged CLT (OR 1.078 per 1% increase, 95% CI 1.027–1.153, p = 0.001 and OR 6.360 per 1 μmol/L increase, 95% CI 1.492–39.894, p = 0.011, respectively). Whereas elevated tPA was associated with lower risk of prolonged CLT (OR 0.550 per 1 ng/mL, 95% CI 0.314–0.854, p = 0.004). GGTP correlated positively with time between FO surgery and investigation (r = 0.25, p = 0.045) and patients with abnormal elevated GGTP activity (n = 28, 42.4%) had decreased Ks, compared to that of the others (5.9 × 10−9 cm2 vs. 6.8 × 10−9 cm2, p = 0.042). Conclusion: our study shows that cellular liver damage and endothelial injury were associated with prothrombotic clot phenotype reflected by Ks and CLT.

Abstract Bleeding disorders with normal, borderline, or nondiagnostic coagulation tests represent a diagnostic challenge. Disorders of primary hemostasis can be further evaluated by additional platelet function testing modalities, platelet electron microscopy, repeat von Willebrand disease testing, and specialized von Willebrand factor testing beyond the usual initial panel. Secondary hemostasis is further evaluated by coagulation factor assays, and factor XIII assays are used to diagnose disorders of fibrin clot stabilization. Fibrinolytic disorders are particularly difficult to diagnose with current testing options. A significant number of patients remain unclassified after thorough testing; most unclassified patients have a clinically mild bleeding phenotype, and many may have undiagnosed platelet function disorders. High-throughput genetic testing using large gene panels for bleeding disorders may allow diagnosis of a larger number of these patients in the future, but more study is needed. A logical laboratory workup in the context of the clinical setting and with a high level of expertise regarding test interpretation and limitations facilitates a diagnosis for as many patients as possible.

Nanocomposites based on apatitic tricalcium phosphate in an autofibrin matrix were obtained by precipitation at a Ca/P ratio of 1.50, pH 9 and a maturation time from 30 min to 7–14 days. The resorbability of nanocomposites was determined by the composition of calcium phosphates, which, during long-term maturation, formed as the calcium-deficient hydroxyapatite with a Ca/P ratio of 1.66, whereas biopolymer matrix favored the formation of more soluble calcium phosphates with a Ca/P ratio of 1.53–1.59. It was found that the fibrin clot stabilized, along with apatitic tricalcium phosphate, the phase of amorphous calcium phosphate, which after 800 °C was transformed into resorbable α-tricalcium phosphate. Citrated plasma inhibited the conversion of apatitic tricalcium phosphate into stoichiometric hydroxyapatite, which also facilitated the formation of resorbable β-tricalcium phosphate after 800 °C. The combined effect of the maturation time and the biopolymer matrix determined the composition, physicochemical and morphological properties of nanocomposites and the possibililty to control its extent of resorption

The high incidence of thrombotic events suggests a possible role of the contact system pathway in COVID-19 pathology. Here, we demonstrate altered levels of factor XII (FXII) and its activation products in critically ill COVID-19 patients in comparison to patients with severe acute respiratory distress syndrome due to influenza virus (ARDS-influenza). Compatible with this data, we report rapid consumption of FXII in COVID-19, but not in ARDS-influenza, plasma. Interestingly, the lag phase in fibrin formation, triggered by the FXII activator kaolin, was not prolonged in COVID-19 as opposed to ARDS-influenza. Using confocal and electron microscopy, we showed that increased FXII activation rate, in conjunction with elevated fibrinogen levels, triggers formation of fibrinolysis-resistant, compact clots with thin fibers and small pores in COVID-19. Accordingly, clot lysis was markedly impaired in COVID-19 as opposed to ARDS-infleunza subjects. Dysregulatated fibrinolytic system, as evidenced by elevated levels of thrombin-activatable fibrinolysis inhibitor, tissue-plasminogen activator, and plasminogen activator inhibitor-1 in COVID-19 potentiated this effect. Analysis of lung tissue sections revealed wide-spread extra- and intra-vascular compact fibrin deposits in COVID-19 patients. Together, compact fibrin network structure and dysregulated fibrinolysis may collectively contribute to high incidence of thrombotic events in COVID-19.

The analysis of literature data and our own research of lungs tissues of the persons who died owing to COVID-19 caused fibrosis testify to participation in this pathology of a cascade of disturbances of molecular and cellular levels. Viral damage to endothelial cells causes systemic damage to the vascular glycocalyx, which loses its clotting properties and releases significant amounts of blood clotting factors. The fibrin clot formed under such conditions is characterized by resistance to fibrinolysis and locally blocks blood vessels with the systemic development of endogenous intoxication. Destabilized proteins of the latter form micro- and nano-sized aggregates with a significant content of β-folded structures. This contributes to the increase of fibrin resistance to the proteolytic action of plasmin, causes the development of fibrosis of the tissues affected in this way, and leads to the failure of the functions of the relevant organs.