The inverted U-shaped association between blood fibrinogen and rehospitalization risk in patients with heart failure.

Fibrinogen, a biomarker of thrombosis and inflammation, is related to a high risk for cardiovascular diseases. However, studies on the prognostic value of blood fibrinogen concentrations for heart failure (HF) patients are few and controversial. We performed a retrospective analysis among acute or deteriorating chronic HF patients admitted to a hospital in Sichuan, China, between 2016 and 2019, integrating electronic health care records and external outcome data (N = 1532). During 6 months of follow-up, 579 HF patients were readmitted within 6 months, and 46 of them died. Surprisingly, we found an inverted U-shaped association of blood fibrinogen levels with risk of readmission within 6 months but not with risk of death within 6 months. It was found that HF patients had the highest risk for readmission within 6 months after reaching the turning point for blood fibrinogen (2.4 g/L). In HF patients with low fibrinogen levels < 2.4 g/L, elevated fibrinogen concentrations were still significantly associated with a higher risk for readmission within 6 months [OR = 2.3, 95% CI (1.2, 4.6); P = 0.014] after controlling for relevant covariates. There was no significant association between blood fibrinogen and readmission within 6 months [(OR = 1.0, 95% CI (0.9, 1.1); P = 0.675] in HF patients with high fibrinogen (> 2.4 g/L). The effect difference for the two subgroups was significant (P = 0.014). However, we did not observe any association between blood fibrinogen and death within 6 months stratified by the turning point, and the effect difference for the stratification was not significant (P = 0.380). We observed an inverted U-shaped association between blood fibrinogen and rehospitalization risk in HF patients for the first time. Additionally, our results did not support that elevated blood fibrinogen was related to increased death risk after discharge.

A High Fibrinogen-to-Albumin Ratio on Admission is Associated with Early Neurological Deterioration Following Intravenous Thrombolysis in Patients with Acute Ischemic Stroke.

Purpose: The fibrinogen-to-albumin ratio (FAR) is a novel inflammation marker associated with various diseases. This study aimed to investigate the correlation between FAR and early neurological deterioration (END) after intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS). Patients and Methods: From September 1, 2021, to March 31, 2023, continuously recruited AIS patients who received IVT within 4.5 hours were included in the study. Blood samples were collected in the emergency room before IVT. The National Institutes of Health Stroke Scale (NIHSS) score was assessed upon admission and after thrombolysis within the first 24 hours. END was defined as an increase in the NIHSS score by ≥ 4 points within 24 hours after thrombolysis. Multivariate logistic regression analysis was conducted to explore the relationship between FAR and END, and a receiver operating characteristic (ROC) curve was used to evaluate the predictive ability of FAR for END. Results: 343 participants were recruited, and 59 (17.2%) experienced END. Patients with END had higher FAR levels than those without END (P<0.001). Multivariate logistic regression analysis showed that FAR was independently associated with END, both as a continuous variable and as a tertile variable (P<0.005). After excluding patients with hemorrhagic transformation (HT), FAR remained independently associated with END (P<0.005). The area under the curve (AUC) of FAR for predicting END was 0.650 (95% CI=0.571-0.729, P<0.001), with an optimal cutoff of 72.367 mg/g, a sensitivity of 61.6%, and a specificity of 62.6%. Conclusion: FAR upon admission was independently associated with END after IVT and can be an effective predictor.

Clinical phenotype and laboratory characteristics of 93 patients with congenital fibrinogen disorders from unrelated 36 families.

Background: Congenital fibrinogen disorders (CFDs) are rare bleeding disorders (RBDs) caused by mutations in 1 of the 3 fibrinogen genes (FGA, FGB, and FGG). Objectives: To investigate the clinical phenotype, laboratory features, diagnosis, treatment, and prognosis of CFDs. Methods: Clinical data of 93 subjects with CFDs identified from June 2018 to December 2023 were retrospectively analyzed. Results: Among the 93 patients, there were 46 males (49.5%) and 47 females (50.5%), with a median age of 23 years. Fifty-three of 93 (57%) subjects experienced bleeding, 3/93 (3.2%) experienced thrombosis, and 37/93 (39.8%) were asymptomatic. Females were more prone to experience bleeding (P < .0001). The 93 patients exhibited prolonged thrombin time, significantly decreased fibrinogen activity (Fg:C), and normal or decreased fibrinogen antigen. The 93 patients included 3 with hypofibrinogenemia, 16 with hypodysfibrinogenemia, and 74 with dysfibrinogenemia. Among the 53 patients with bleeding, bleeding episodes were identified in 3.8% (2/53), 20.8% (11/53), and 75.5% (40/53) patients with hypofibrinogenemia, hypodysfibrinogenemia, and dysfibrinogenemia, respectively. Genetic analysis was performed on 22 cases from 8 pedigrees, revealing 10 mutations, including 1 novel splice mutation. Twenty-eight (30.1%) subjects received replacement therapy to treat or prevent bleeding, consisting of 8 fresh frozen plasma transfusions, 3 packing and suture treatment, and 61 fibrinogen infusions. Conclusion: Most patients with CFDs have mild or no bleeding symptoms. Fg:C combined with fibrinogen antigen and pedigree investigation can improve the feasibility and accuracy of diagnosis of CFDs. The severity of bleeding symptoms was negatively correlated with Fg:C.

Fibrinogen: connecting the blood circulatory system with CNS scar formation.

Wound healing of the central nervous system (CNS) is characterized by the classical phases of 'hemostasis', 'inflammation', 'proliferation', and 'remodeling'. Uncontrolled wound healing results in pathological scar formation hindering tissue remodeling and functional recovery in the CNS. Initial blood protein extravasation and activation of the coagulation cascade secure hemostasis in CNS diseases featuring openings in the blood-brain barrier. However, the relevance of blood-derived coagulation factors was overlooked for some time in CNS wound healing and scarring. Recent advancements in animal models and human tissue analysis implicate the blood-derived coagulation factor fibrinogen as a molecular link between vascular permeability and scar formation. In this perspective, we summarize the current understanding of how fibrinogen orchestrates scar formation and highlight fibrinogen-induced signaling pathways in diverse neural and non-neural cells that may contribute to scarring in CNS disease. We particularly highlight a role of fibrinogen in the formation of the lesion border between the healthy neural tissue and the fibrotic scar. Finally, we suggest novel therapeutic strategies via manipulating the fibrinogen-scar-forming cell interaction to improve functional outcomes.

Association of results of the glutaraldehyde coagulation test with plasma acute phase protein concentrations and hematologic findings in hospitalized cows.

Introduction: The glutaraldehyde test (GAT) allows for animal-side semi-quantitative estimation of fibrinogen and gamma-globulin concentrations in blood samples of adult cattle and therefore detection of inflammatory disease conditions. However, the test has potential limitations, especially due to the latency period until sufficiently high fibrinogen and/or gamma-globulin concentrations are reached. The aim of the present study was therefore to assess the association between results of GAT with other inflammatory markers including hematologic variables, fibrinogen, plasma haptoglobin and serum amyloid A (SAA) concentrations. Methods: For the purpose of this prospective observational study, a convenience sample of 202 cows with a broad range of inflammatory and non-inflammatory clinical conditions was included. The GAT was run on EDTA blood, fibrinogen was measured using the Clauss and the heat precipitation method, and commercially available ELISA tests were used for determination of plasma haptoglobin and SAA concentrations. Results: Shortened GAT coagulation times were more closely correlated to serum globulin (rs = -0.72) than to plasma fibrinogen concentrations measured with the heat precipitation (rs = -0.64) and the Clauss method (rs = -0.70). Cows with a markedly (≤3 min) or moderately (4-6 min) shortened coagulation time had higher (p < 0.001) plasma haptoglobin and SAA concentrations than cows with a negative test result. Total leukocyte, monocyte and neutrophil concentrations did not differ significantly between groups. An identified cut-off for the GAT coagulation time of ≤14 min had a sensitivity and specificity of 54.4 and 100%, respectively, for the prediction of an inflammatory state based on clinical findings and/or increased plasma haptoglobin or SAA concentrations. Discussion: In conclusion, this study demonstrates considerable diagnostic agreement between positive GAT results and increased plasma concentrations of haptoglobin and SAA. Despite high specificity, the test lacks sensitivity in case of acute inflammatory conditions indicating that plasma acute phase protein concentrations and hematologic findings can provide additional diagnostic information if the GAT is negative.

Implementation and early outcomes with Pathogen Reduced Cryoprecipitated Fibrinogen Complex.

OBJECTIVES: Cryoprecipitated antihemophilic factor (cryo) has been used for fibrinogen replacement in actively bleeding patients, dysfibrinogenemia, and hypofibrinogenemia. Cryo has a shelf life of 4 to 6 hours after thawing and a long turnaround time in issuing the product, posing a major limitation of its use. Recently, the US Food and Drug Administration approved Pathogen Reduced Cryoprecipitated Fibrinogen Complex (INTERCEPT Fibrinogen Complex [IFC]) for the treatment of bleeding associated with fibrinogen deficiency, which can be stored at room temperature and has a shelf life of 5 days after thawing. METHODS: We identified locations and specific end users with high cryoprecipitate utilization and waste. We partnered with our blood supplier to use IFC in these locations. We analyzed waste and turnaround time before and after implementation. RESULTS: Operative locations had a waste rate that exceeded nonoperative locations (16.7% vs 3%) and were targeted for IFC implementation. IFC was added to our inventory to replace all cryo orders from adult operating rooms, and waste decreased to 2.2% in these locations. Overall waste of cryoprecipitated products across all locations was reduced from 8.8% to 2.4%. The turnaround time for cryoprecipitated products was reduced by 58% from 30.4 minutes to 14.6 minutes. CONCLUSIONS: There has been a substantial decrease in waste with improved turnaround time after IFC implementation. This has improved blood bank logistics, improved efficiency of patient care, and reduced costly waste.

Childhood Adversity and Adult Inflammation: Exploring the Mediating Role of Emotion Regulation in the MIDUS II Study.

The present study furthers understanding of how childhood adversity connects to inflammation and, in turn, poor health. Using the publicly available Midlife in the United States II (MIDUS II) dataset, we test a recent theoretical model that suggests emotion regulation is a potential mechanism of associations between adversity and inflammation. We examined the indirect effects of various types of adversity (e.g., stressful events, maltreatment, threat, and deprivation) on inflammation via two emotion regulation strategies (i.e., expressive suppression and reappraisal). Participants included 1096 adults without a history of cancer or HIV/AIDS who had completed the initial MIDUS II follow up and a sub-study examining biomarkers. Participants completed self-report measures inquiring about psychosocial factors including stressful life events, childhood trauma, and emotion regulation as well as provided blood samples. Bivariate correlation indicated that multiple forms of childhood adversity were associated with both C-reactive protein and fibrinogen. Deprivation, as measured by a stressful life events scale, was positively associated with both reappraisal and suppression. Tests of indirect effects indicated that deprivation was positively associated with fibrinogen through both emotion regulation strategies, particularly for female participants. Our findings partially support recent theory positing emotion regulation as a pathway through which childhood adversity may impact inflammation in adulthood. Further, deprivation may be particularly critical in understanding how adversity is connected to maladaptive emotion regulation and inflammation. Emotion regulation may be an important treatment target to mitigate the negative impact of childhood adversity on health and well-being. Supplementary Information: The online version contains supplementary material available at 10.1007/s40653-023-00594-2.

The Relationship between the Laboratory Biomarkers of SARS-CoV-2 Patients with Type 2 Diabetes at Discharge and the Severity of the Viral Pathology.

In this study, we evaluated the discharge status of patients with type 2 diabetes mellitus and SARS-CoV-2 infection, focusing on the inflammatory profile through biomarkers such as procalcitonin, CRP, LDH, fibrinogen, ESR, and ferritin, as well as electrolyte levels and the prior diagnosis of diabetes or its identification at the time of hospitalization. We assessed parameters at discharge for 45 patients admitted to the Clinical Hospital "Gavril Curteanu" Oradea between 21 October 2021, and 31 December 2021, randomly selected, having as the main inclusion criteria the positive RT-PCR rapid antigen test for viral infection and the diagnosis of type 2 diabetes. At discharge, patients with type 2 diabetes registered significantly lower mean procalcitonin levels among those who survived compared to those who died from COVID-19. In our study, ferritin and hemoglobin values in individuals with type 2 diabetes were outside the reference range at discharge and correlated with severe or moderate forms of COVID-19 infection. Additionally, elevated ferritin levels at discharge were statistically associated with hypokalemia and elevated levels of ESR at discharge. Another strong statistically significant correlation was identified between high CRP levels at discharge, strongly associated (p < 0.001) with elevated LDH and fibrinogen levels in patients with type 2 diabetes and SARS-CoV-2 viral infection. The increase in CRP was inversely statistically associated with the tendency of serum potassium to decrease at discharge in patients with type 2 diabetes and COVID-19. Identifying type 2 diabetes metabolic pathology at the time of hospitalization for SARS-CoV-2 infection, compared to pre-infection diabetes diagnosis, did not significantly influence the laboratory parameter status at the time of discharge. At the discharge of patients with type 2 diabetes and viral infection with the novel coronavirus, procalcitonin was significantly reduced in those who survived COVID-19 infection, and disease severity was significantly correlated with hyperferritinemia and decreased hemoglobin at discharge. Hyperferritinemia in patients with type 2 diabetes and COVID-19 at discharge was associated with hypokalemia and persistent inflammation (quantified by ESR at discharge). The low number of erythrocytes at discharge is associated with maintaining inflammation at discharge (quantified by the ESR value).

Safety of Fibrinogen Concentrate in Non-Trauma and Non-Obstetric Adult Patients during Perioperative Care: Systematic Review and Meta-Analysis.

Background: Low fibrinogen levels are associated with an increased risk of perioperative bleeding. However, there is an ongoing debate over the ideal treatment threshold, the benefits of prophylactic supplementation with fibrinogen concentrate, and the best source of fibrinogen. While fibrinogen concentrate supplementation is being widely used to treat bleeding related to acquired haemostatic deficiencies, there is a lack of evidence regarding its dosage, effectiveness, and safety. This systematic review provides an up-to-date summary of the relationship between fibrinogen concentrate supplementation and safety measures in the perioperative care of non-trauma, non-obstetric adult patients. Methods: A comprehensive online search was conducted on PubMed/Medline, EMBASE, Scopus, Web of Science, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials. Results: This systematic review and meta-analysis encompasses ten studies involving 1391 patients. There was a decreased risk of total thromboembolic events in patients treated with fibrinogen compared to the control (OR 0.65, 95% CI 0.43 to 0.98, I2 = 0%). In addition, when fibrinogen was used prophylactically, it resulted in shorter ICU stays (MD -1.50, 95% CI -2.64 to -0.36), when set against its therapeutic use. A sensitivity analysis on cardiovascular surgery studies did not reveal any statistically significant difference. Conclusions: The use of fibrinogen concentrate in the perioperative care of non-trauma and non-obstetric adult patients may lead to potential benefits.

The Impact of Cytokines on Coagulation Profile in COVID-19 Patients: Controlled for Socio-Demographic, Clinical, and Laboratory Parameters.

Background: Severe coagulation abnormalities are common in patients with COVID-19 infection. We aimed to investigate the relationship between pro-inflammatory cytokines and coagulation parameters concerning socio-demographic, clinical, and laboratory characteristics. Methods: Our study included patients hospitalized during the second wave of COVID-19 in the Republic of Serbia. We collected socio-demographic, clinical, and blood-sample data for all patients. Cytokine levels were measured using flow cytometry. Results: We analyzed data from 113 COVID-19 patients with an average age of 58.15 years, of whom 79 (69.9%) were male. Longer duration of COVID-19 symptoms before hospitalization (B = 69.672; p = 0.002) and use of meropenem (B = 1237.220; p = 0.014) were predictive of higher D-dimer values. Among cytokines, higher IL-5 values significantly predicted higher INR values (B = 0.152; p = 0.040) and longer prothrombin times (B = 0.412; p = 0.043), and higher IL-6 (B = 0.137; p = 0.003) predicted longer prothrombin times. Lower IL-17F concentrations at admission (B = 0.024; p = 0.050) were predictive of higher INR values, and lower IFN-γ values (B = -0.306; p = 0.017) were predictive of higher aPTT values. Conclusions: Our findings indicate a significant correlation between pro-inflammatory cytokines and coagulation-related parameters. Factors such as the patient's level of education, gender, oxygen-therapy use, symptom duration before hospitalization, meropenem use, and serum concentrations of IL-5, IL-6, IL-17F, and IFN-γ were associated with worse coagulation-related parameters.

U-Shaped Relationship Between Fibrinogen Level and 10-year Mortality in Patients With Acute Coronary Syndrome: Prospective Cohort Study.

This study demonstrated that fibrinogen is an independent risk factor for 10-year mortality in patients with acute coronary syndrome (ACS), with a U-shaped nonlinear relationship observed between the two. These findings underscore the importance of monitoring fibrinogen levels and the consideration of long-term anti-inflammatory treatment in the clinical management of patients with ACS.

Soluble Fibrinogen-Like Protein 2 Downregulation and Th17/Treg Imbalance in a Taurocholate-Induced Murine Experimental Model of Severe Acute Pancreatitis.

BACKGROUND: Severe acute pancreatitis (SAP) is associated with tremendous systemic inflammation, T-helper 17 (Th17) cells, and regulatory T (Treg) cells play an essential role in the inflammatory responses. Meanwhile, soluble fibrinogen-like protein 2 (Sfgl2) is a critical immunosuppressive effector cytokine of Treg cells and modulates immune responses. However, the impact of SAP induction on Sfgl2 expression and the role of Sfgl2 in immunomodulation under SAP conditions are largely unknown. METHODS: A taurocholate-induced mouse SAP model was established. The ratios of CD4+CD25+Foxp3+ Treg cells or CD4+IL-17+ Th17 cells in blood and pancreatic tissues as well as surface expression of CD80, CD86, and major histocompatibility complex class II (MHC-II) were determined by flow cytometry. Gene mRNA expression was determined by qPCR. Serum amylase and soluble factors were quantitated by commercial kits. Bone marrow-derived dendritic cells (DCs) were generated, and NF-κB/p65 translocation was measured by immunofluorescence staining. RESULTS: SAP induction in mice decreased the Th17/Treg ratio in the pancreatic tissue and increased the Th17/Treg ratio in the peripheral blood. In addition, SAP was associated with a reduced level of Sfgl2 in the pancreatic tissue and blood: higher levels of serum IL-17, IL-2, IFN-α, and TNF-α, and lower levels of serum IL-4 and IL-10. Furthermore, the SAP-induced reduction in Sfgl2 expression was accompanied by dysregulated maturation of bone marrow-derived DCs. CONCLUSIONS: SAP causes reduced Sfgl2 expression and Th17/Treg imbalance, thus providing critical insights for the development of Sfgl2- and Th17/Treg balance-targeted immunotherapies for patients with SAP.

Fibrinogen to albumin ratio's prognostic value in ischemic stroke patients who underwent mechanical thrombectomy.

Background and purpose:

Fibrinogen to albumin ratio (FAR) is thought to have a predictive effect in diseases such as cancer and myocardial infarction. We aimed to elucidate the prognostic value of FAR in ischemic stroke patients who underwent mechanical thrombectomy.

A total of 103 patients hospita­lized for acute stroke who underwent me­cha­nical thrombectomy within 6 hours of symp­toms’ outset have been analyzed retro­spectively. Stroke severity was interpreted via the National Institutes of Health Stroke Scale (NIHSS) score during the neurological examination. Recanalization success after mechanical thrombectomy was evaluated with the TICI score (Thrombolysis in Cerebral Infarction scale), and 2b – 3 patients were recorded as those with recanalization. The patients’ modified Rankin scale (mRS) at discharge and at the end of the third month were recorded. 

 Statistically significant differen­ces were observed in age, admission blood glucose, glomerular filtration rate and FAR according to the mRS scores of the patients in the third month (p<0.05). Significant va­riab­les in the risk factor analysis were re-evaluated in the multivariate model. The best model was determined using the backward Wald method in the multivariate model, and it was determined that differences in age, admission blood glucose, and FAR were significant.

FAR can be used as a novel, effective, economical, and practical biomarker in patient with acute ischemic stroke who underwent mechanical thrombectomy.

Challenging the current hypothesis that thrombosis is responsible for the post-COVID-19 condition.

People with the post-COVID-19 condition suffer symptoms that persist beyond 12 weeks following acute COVID-19 infection. Fatigue, shortness of breath, and cognitive dysfunction ("brain fog") are common. Scientists, clinicians, and patients debate the pathophysiology. One pathophysiological hypothesis is that prothrombotic changes associated with acute COVID-19 persist, causing clots that lead to symptoms. This theory, arising from a research team in South Africa and supported by a paper in Nature Medicine, has been widely disseminated on social media and entered the public narrative as a cause of the post-COVID-19 condition. We describe the development of this theory, examine the findings of a Cochrane review that critically appraises the "microclot" beliefs, and critically appraise the influential study relating clotting biomarkers to cognitive deficits. We conclude the inferences for the hypothesis are not based on evidence, unlicensed use of antithrombotic medication is not justified, and apheresis should not be considered outside of a well-designed clinical trial.

Effects of subclinical hypothyroidism in type II diabetes mellitus patients on biochemical, coagulation, and fibrinolysis status.

The aim of the currnet study to examine the effect of subclinical hypothyroidism (SCH) in diabetic patients on coagulation parameters. This retrospective case-control study involves 130 patients diagnosed with type 2 diabetes mellitus (T2DM), divided into 65 T2DM with newly diagnosed SCH and 65 euthyroid (EUT) T2DM patients without SCH. Fibrinogen (FIB) was significantly higher in SCH (508.2 ± 63.0 mg/dL) than EUT (428.1 ± 44.8 mg/dL). In the SCH patients, FIB correlated with several parameters, such as age (ß = 0.396), body mass index (ß = 0.578), glycated hemoglobin (ß = 0.281), and activated partial thromboplastin time (ß = 0.276). In conclusion SCH in DM patients appears to increase the magnitude of coagulopathy.

Fibrinogen binding to activated platelets and its biomimetic thrombus-targeted thrombolytic strategies.

Thrombosis is associated with various fatal arteriovenous syndromes including ischemic stroke, myocardial infarction, and pulmonary embolism. However, current clinical thrombolytic treatment strategies still have many problems in targeting and safety to meet the thrombolytic therapy needs. Understanding the molecular mechanism that underlies thrombosis is critical in developing effective thrombolytic strategies. It is well known that platelets play a central role in thrombosis and the binding of fibrinogen to activated platelets is a common pathway in the process of clot formation. Based on this, a concept of biomimetic thrombus-targeted thrombolytic strategy inspired from fibrinogen binding to activated platelets in thrombosis was proposed, which could selectively bind to activated platelets at a thrombus site, thus enabling targeted delivery and local release of thrombolytic agents for effective thrombolysis. In this review, we first summarized the main characteristics of platelets and fibrinogen, and then introduced the classical molecular mechanisms of thrombosis, including platelet adhesion, platelet activation and platelet aggregation through the interactions of activated platelets with fibrinogen. In addition, we highlighted the recent advances in biomimetic thrombus-targeted thrombolytic strategies which inspired from fibrinogen binding to activated platelets in thrombosis. The possible future directions and perspectives in this emerging area are briefly discussed.

Guideline-Optimised Treatment in Heart Failure-Do Higher Doses Reduce Systemic Inflammation More Significantly?

Background: Chronic inflammation is a constant phenomenon which accompanies the heart failure pathophysiology. In all phenotypes of heart failure, irrespective of the ejection fraction, there is a permanent low-grade activation and synthesis of proinflammatory cytokines. Many classes of anti-remodelling medication used in the treatment of chronic heart failure have been postulated to have an anti-inflammatory effect. Methods: This retrospective study enrolled 220 patients and focused on evaluating the effect of the most used active substances from these classes in reducing the level of inflammatory biomarkers (C reactive protein, erythrocyte sedimentation rate and fibrinogen) after initiation or up-titration. Our research is evaluating if this anti-inflammatory effect intensifies while raising the dose. The evaluation was performed at two visits with an interval between them of 6 months. Results: From the beta-blockers class, carvedilol showed a reduction in erythrocyte sedimentation rate (ESR), in low (6.25 mg, bi daily) and medium (12.5 mg, bi daily) doses. At the same time, sacubitril/valsartan showed a reduction in CRP levels. This effect was obtained only in the medium (49/51 mg, bi daily) and high (97/103 mg, bi daily) doses, with the maximum reduction being observed in the high dose. Conclusions: From the classes of medication evaluated, the study showed a significant reduction in ESR levels in the low and medium doses of carvedilol and a reduction in CRP values in the cases of medium and high doses of ARNI.

Monoclonal whole IgG impairs both fibrin and thrombin formation: hemostasis and surface plasmon resonance studies.

OBJECTIVES: Monoclonal gammopathies frequently associate with hemostatic alterations. Thrombotic events occur with high incidence particularly upon treatment, while in rarer cases hemorrhagic diathesis can be observed. The pathology of these tendencies could be caused by thrombocytopenia or hyperviscosity burden of circulating monoclonal antibodies. Studies also suggest interference of monoclonal antibodies with primary hemostasis. We isolated monoclonal whole IgG paraproteins from two myeloma patients to observe their effect on thrombin formation and fibrin polymerization. METHODS: Monoclonal whole IgG was prepared from sera of two newly diagnosed untreated multiple myeloma patients and control normal plasma samples. Fibrin formation was measured using thrombin time and dilute prothrombin time tests and thrombin formation was detected with a fluorimetric thrombin generation assay. In addition, molecular interactions were investigated by surface plasmon resonance (SPR). RESULTS: Thrombin time was prolonged upon addition of monoclonal IgG even at 30 g/L by 12 %, increasing up to 36 % at 60 g/L concentration. Dilute prothrombin time was prolonged by 20 % even at 30 g/L. Thrombin generation assay indicated an impairment in thrombin formation at the presence of monoclonal IgG compared to polyclonal at equivalent concentration. By an SPR assay we determined that both clonality IgG preparations interacted with fibrinogen, however interaction with human thrombin was only detected with monoclonal immunoglobulins (KD=1.03 × 10-7 M). CONCLUSIONS: Here we provide evidence that isolated monoclonal whole IgG from myeloma patients can impair both fibrin and thrombin formation and we demonstrate by SPR assay that it interacts with components of the final phase of the coagulation system.

Associations of RBC counts and incidence of DVT in patients with spinal cord injury: a five year observational retrospective study.

BACKGROUND: The role of red blood cell (RBC) counts as potential independent risk factors for deep vein thrombosis (DVT) in patients with spinal cord injury (SCI) remains uncertain. This study aims to clarify the associations between RBC counts and DVT incidence among this population. METHODS: A retrospective analysis was performed on 576 patients with SCI admitted to the rehabilitation medicine department from January 1, 2017 to December 31, 2021. After exclusions, 319 patients were analyzed, among which 94 cases of DVT were identified. RESULTS: Mode of injury, D-dimer and anticoagulant therapy were significant covariates (P < 0.05). Age, fibrinogen, D-dimer, anticoagulant therapy and American Spinal Cord Injury Association impairment scale (AIS) grades were associated with RBC counts and DVT incidence (P < 0.05). Adjusting for these factors, a 1.00 × 10^12/L increase in RBC counts correlated with a 45% decrease in DVT incidence (P = 0.042), revealing a "U" shaped relationship with a pivot at 4.56 × 10^12/L (P < 0.05). CONCLUSION: RBC counts below 4.56 × 10^12/L serve as a protective factor against DVT, while counts above this threshold pose a risk. These findings could inform the development of DVT prevention strategies for patients with SCI, emphasizing the need for targeted monitoring and management of RBC counts.

An early predictive model for Kawasaki disease shock syndrome in children in central China.

Introduction: This study aims to analyze the clinical features of Kawasaki disease (KD) shock syndrome (KDSS) and explore its early predictors. Methods: A retrospective case-control study was used to analyze KD cases from February 2016 to October 2023 in our hospital. A total of 28 children with KDSS and 307 children who did not develop KDSS were included according to matching factors. Baseline information, clinical manifestations, and laboratory indicators were compared between the two groups. Indicators of differences were analyzed based on univariate analysis; binary logistic regression analysis was used to identify the risk factors for KDSS, and then receiver operating characteristic analysis was performed to establish a predictive score model for KDSS. Results: Elevated neutrophil-to-lymphocyte ratio(NLR) and decreased fibrinogen (FIB) and Na were independent risk factors for KDSS; the scoring of the above risk factors according to the odds ratio value eventually led to the establishment of a new scoring system: NLR ≥ 7.99 (6 points), FIB ≤ 5.415 g/L (1 point), Na ≤ 133.05 mmol/L (3 points), and a total score of ≥3.5 points were high-risk factors for progression to KDSS; otherwise, they were considered to be low-risk factors. Conclusion: Children with KD with NLR ≥ 7.99, FIB ≤ 5.415 g/L, and Na ≤ 133.05 mmol/L, and those with two or more of the above risk factors, are more likely to progress to KDSS, which helps in early clinical diagnosis and treatment.