The Relationship of Soluble Fibrin and Cross-linked Fibrin Degradation Products to the Clinical Course of Myocardial Infarction

SummaryIn 12 patients treated with 100 mg rt-PA/3 h for acute myocardial infarction (AMI), serial fibrinogen levels were measured with the Clauss clotting rate assay (“functional fibrinogen”) and with a new enzyme immunoassay for immunologically intact fibrinogen (“intact fibrinogen”). Levels of functional and “intact fibrinogen” were strikingly different: functional levels were higher at baseline; showed a more pronounced breakdown during rt-PA therapy; and a rebound phenomenon which was not seen for “intact fibrinogen”. The ratio of functional to “intact fibrinogen” was calculated for each individual patient and each time point. The mean ratio (n = 12) was 1.6 at baseline, 1.0 at 90 min, and increased markedly between 8 and 24 h to a maximum of 2.1 (p <0.01), indicating that functionality of circulating fibrinogen changes during AMI and subsequent thrombolytic therapy. The increased ratio of functional to “intact fibrinogen” seems to reflect a more functional fibrinogen at baseline and following rt-PA infusion. This is in keeping with data that the relative amount of fast clotting “intact HMW fibrinogen” of total fibrinogen is increased in initial phase of AMI. The data suggest that about 20% of HMW fibrinogen are converted to partly degraded fibrinogen during rt-PA infusion. The rebound phenomenon exhibited by functional fibrinogen may result from newly synthesized fibrinogen with a high proportion of HMW fibrinogen with its known higher degree of phosphorylation. Fibrinogen- and fibrin degradation products were within normal range at baseline. Upon infusion of the thrombolytic agent, maximum median levels of 5.88 μg/ml and 5.28 μg/ml, respectively, were measured at 90 min. Maximum plasma fibrinogen degradation products represented only 4% of lost “intact fibrinogen”, but they correlatedstrongly and linearly with the extent of “intact fibrinogen” degradation (r = 0.82, p <0.01). In contrast, no correlation was seen between breakdown of “intact fibrinogen” and corresponding levels of fibrin degradation products. We conclude from our data that the ratio of functional to immunologically “intact fibrinogen” may serve as an important index for functionality of fibrinogen and select patients at high risk for early reocclusion. Only a small proportion of degraded functional and “intact fibrinogen”, respectively, is recovered as fibrinogen degradation products. There seems to be a strong correlation between the degree of elevation of fibrinogen degradation products and the intensity of the systemic lytic state, i.e. fibrinogen degradation.

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COVID-19 in children: Pathogenesis and current status

Allergy and Asthma Proceedings ◽

10.2500/aap.2020.42.200104 ◽

2020 ◽

Author(s):

Lawrence Frenkel ◽

Fernando Gomez ◽

Joseph A Bellanti

Keyword(s):

Respiratory Disease ◽

Respiratory Symptoms ◽

Distress Syndrome ◽

Clinical Course ◽

Current Status ◽

Current Evidence ◽

Initial Description ◽

Relationship Of ◽

Inflammatory Syndrome ◽

The Relationship

Background: Since its initial description in December 2019 in Wuhan, China, coronavirus disease 2019 (COVID-19) has rapidly progressed into a worldwide pandemic, which has affected millions of lives. Unlike the disease in adults, the vast majority of children with COVID-19 have mild symptoms and are largely spared from severe respiratory disease. However, thereare children who have significant respiratory disease, and some may develop a hyperinflammatory response similar to thatseen in adults with COVID-19 and in children with Kawasaki disease (KD), which has been termed multisystem inflammatory syndrome in children (MIS-C).Objective: The purpose of this report was to examine the current evidence that supports the etiopathogenesis of COVID-19 in children and the relationship of COVID-19 with KD and MIS-C as a basis for a better understanding of the clinical course, diagnosis, and management of these clinically perplexing conditions.Results: The pathogenesis of COVID-19 is carried out in two distinct but overlapping phases of COVID-19: the first triggered by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) itself and the second by the host immune response. Children with KD have fewer of the previously described COVID-19–associated KD features with less prominent acute respiratory distress syndrome and shock than children with MIS-C.Conclusion: COVID-19 in adults usually includes severe respiratory symptoms and pathology, with a high mortality. Ithas become apparent that children are infected as easily as adults but are more often asymptomatic and have milder diseasebecause of their immature immune systems. Although children are largely spared from severe respiratory disease, they canpresent with a SARS-CoV-2–associated MIS-C similar to KD.

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The relationship of markers of systemic inflammatory response and myocardial necrosis in patients with acute myocardial infarction complicated by ventricular arrhythmia

Problems of Uninterrupted Medical Training and Science ◽

10.31071/promedosvity2017.04.024 ◽

2017 ◽

Vol 27 (4) ◽

pp. 24-29

Author(s):

I. M. Fushtey ◽

◽

Mohamed Fedi ◽

E.V. Sid’ ◽

◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Inflammatory Response ◽

Ventricular Arrhythmia ◽

Myocardial Necrosis ◽

Systemic Inflammatory Response ◽

Relationship Of ◽

The Relationship

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Triiodothyronine (T3), inflammation and mortality risk in patients with acute myocardial infarction

European Thyroid Journal ◽

10.1530/etj-21-0085 ◽

2022 ◽

Author(s):

Salman Razvi ◽

Avais Jabbar ◽

Arjola Bano ◽

Lorna Ingoe ◽

Peter Carey ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Confidence Interval ◽

Mortality Risk ◽

Fold Increase ◽

Lower Serum ◽

Reactive Protein ◽

All Cause Mortality ◽

Relationship Of ◽

The Relationship

Objectives: To study the relationship between serum free T3 (FT3), C-reactive protein (CRP), and all-cause mortality in patients with acute myocardial infarction (AMI). Design: Prospective multicentre longitudinal cohort study. Methods: Between December 2014 and December 2016, thyroid function and CRP were analysed in AMI (both ST- and non-ST-elevation) patients from the ThyrAMI-1 study. The relationship of FT3 and CRP at baseline with all-cause mortality up to June 2020 was assessed. Mediation analysis was performed to evaluate if CRP mediated the relationship between FT3 and mortality. Results: In 1919 AMI patients [29.2% women, mean (SD) age 64.2 (12.1) years and 48.7% STEMI] followed over a median (inter-quartile range) period of 51 (46 to 58) months, there were 277 (14.4%) deaths. Overall, lower serum FT3 and higher CRP levels were associated with higher risk of mortality. When divided into tertiles based on levels of FT3 and CRP, the group with the lowest FT3 and highest CRP levels had 2.5-fold increase in mortality risk [adjusted hazard ratio (95% confidence interval) of 2.48 (1.82 to 3.16)] compared to the group with the highest FT3 and lowest CRP values. CRP mediated 9.8% (95% confidence interval 6.1 to 15.0%) of the relationship between FT3 and mortality. Conclusions: In AMI patients, lower serum FT3 levels on admission are associated with a higher mortality risk, which is partly mediated by inflammation. Adequately designed trials to explore potential benefits of T3 in AMI patients are required.

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D-Dimer and Fibrin Degradation Products Impair Platelet Signaling: Plasma D-Dimer Is a Predictor and Mediator of Platelet Dysfunction During Trauma

The Journal of Applied Laboratory Medicine ◽

10.1093/jalm/jfaa047 ◽

2020 ◽

Vol 5 (6) ◽

pp. 1253-1264

Author(s):

Christopher C Verni ◽

Antonio Davila ◽

Carrie A Sims ◽

Scott L Diamond

Keyword(s):

Degradation Products ◽

Calcium Mobilization ◽

Factor Xiiia ◽

Platelet Glycoprotein ◽

Trauma Patients ◽

Platelet Dysfunction ◽

Soluble Fibrin ◽

Glycoprotein Vi ◽

Fibrin Degradation Products ◽

D Dimer

Abstract Background Platelet dysfunction often accompanies trauma-induced coagulopathy. Because soluble fibrin impairs platelet glycoprotein VI (GPVI) signaling and platelets of trauma patients can display impaired calcium mobilization, we explored the role of fibrinolysis on platelet dysfunction during trauma. Methods Convulxin-induced GPVI calcium mobilization was investigated in healthy platelet-rich plasma (PRP) pretreated with thrombin and tissue plasminogen activator (tPA). Blood samples from healthy participants (n = 7) and trauma patients (n = 22) were tested for platelet calcium mobilization, plasma D-dimer, platelet D-dimer binding (via flow cytometry), and platelet lumi-aggregometry. Results For healthy platelets, maximal platelet dysfunction was observed when cross-linked soluble fibrin (no tPA) or cross-linked fibrin degradation products (FDPs) were generated in suspension before convulxin stimulation. Lack of fibrin polymerization (inhibited by Gly-Pro-Arg-Pro [GPRP]) or lack of factor XIIIa cross-linking (T101-inhibited) restored GPVI signaling, whereas non–cross-linked FDPs only partially blocked signaling induced by convulxin. In addition, D-dimer added to healthy PRP impaired platelet aggregation and dense granule release induced by various agonists. Plasma D-dimer level was strongly correlated (R = 0.8236) with platelet dysfunction as measured by platelet calcium mobilization induced with various agonists. By 48 to 120 h after trauma, plasma D-dimer levels declined, and platelet function increased significantly but not to healthy levels. Trauma platelets displayed elevated D-dimer binding that was only partially reduced by αIIbβ3-inhibitor GR144053. After 60-minute incubation, washed healthy platelets resuspended in plasma from trauma patients captured approximately 10 000 D-dimer equivalents per platelet. Conclusions During trauma, D-dimer and FDPs inhibit platelets, potentially via GPVI and integrin αIIbβ3 engagement, contributing to a fibrinolysis-dependent platelet loss-of-function phenotype.

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Fibrin fragment D-dimer and fibrinogen B beta peptides in plasma as markers of clot lysis during thrombolytic therapy in acute myocardial infarction

Blood ◽

10.1182/blood.v76.7.1341.1341 ◽

1990 ◽

Vol 76 (7) ◽

pp. 1341-1348 ◽

Cited By ~ 29

Author(s):

CM Lawler ◽

EG Bovill ◽

DC Stump ◽

DJ Collen ◽

KG Mann ◽

...

Keyword(s):

Myocardial Infarction ◽

Degradation Product ◽

Degradation Products ◽

Tissue Type ◽

Clot Lysis ◽

Fibrin Degradation Product ◽

Fibrin Degradation Products ◽

Group 2 ◽

D Dimer ◽

Group 1

Abstract The validity of markers in plasma of in vitro thrombolysis was investigated in 12 patients with extensive fibrinogen breakdown (greater than 80%, group 1) and in 12 patients with minimal breakdown (less than 20%, group 2). The patients were treated with 100 mg of recombinant tissue-type plasminogen activator (rt-PA) in the “Thrombolysis in Myocardial Infarction II” (TIMI II) trial. Cross- linked fibrin degradation product levels were measured with two variant enzyme-linked immunosorbent assays (ELISAs), both using a fibrin fragment D-dimer specific capture antibody. In one instance, a tag antibody was used that cross-reacts with fibrinogen (pan-specific tag ELISA); in the other, the tag antibody was specific for fibrin fragment D (fibrin-specific tag ELISA). Apparent concentrations of cross-linked fibrin degradation products at baseline were within normal limits with both assays in most patients. At 8 hours after rt-PA infusion, the measured cross-linked fibrin degradation products were increased about twofold to fourfold in group 2 with both assays. However, in group 1, levels were significantly higher with the pan-specific tag ELISA (5.8 +/- 4.2 micrograms/mL) compared with the fibrin-specific tag ELISA (1.5 +/- 1.3 micrograms/mL). This observation was most likely a result of detection of fibrinogen degradation products in the pan-specific ELISA. Apparent levels of fibrinopeptide B beta 1–42, a marker of fragment X formation, increased during thrombolysis from 4.2 +/- 2.8 pmol/mL to 2,000 +/- 230 pmol/mL in group 1 and from 4.1 +/- 2.1 pmol/mL to 300 +/- 43 pmol/mL in group 2, and were correlated significantly with the extent of fibrinogen breakdown (r = -0.8). Fibrinopeptide beta 15–42 levels increased from 4.3 +/- 3 pmol/mL to 70 +/- 19 pmol/mL in group 1, but did not increase in group 2. The apparent increase in group 1 could be explained by cross-reactivity of fibrinopeptide B beta 1–42 in the fibrinopeptide beta 15–42 assay. We conclude that cross-linked fibrin degradation product levels as measured with a pan-specific tag ELISA and fibrinopeptide beta 15–42 levels as measured with certain monoclonal antibody-based ELISA are influenced by the extent of fibrinogen degradation. Fibrinopeptide B beta 1–42 is a marker specific for fibrinogen breakdown. Cross-linked fibrin degradation product levels, measured with a fibrin-specific tag ELISA, appear to be markers specific for thrombolysis. Consequently, assays similar to the fibrin- specific tag ELISA may provide more accurate information when correlated with clinical endpoints.

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