Endothelial Activation, FVW and ADAMTS 13 imbalance and Fibrinolysis Impairment in Adults with Dengue Fever with Bleeding Complications,

Abstract Abstract 3325 Dengue fever has enormous health and economic impact in Latin America, Africa, India and Southeast Asia. In Brazil, an increasing number of severe cases of dengue have been notified, especially those with bleeding complications. Classically, the bleeding episodes in dengue have been attributed to an increased vascular permeability, but in many cases there is no evidence of vascular changes that justify the clinical bleeding. Several coagulation disorders may contribute to the occurrence of bleeding complications in dengue and knowledge of these disorders can lead to more specific treatment of the disease, in addition to conventional treatment based on fluid replacement. The aim of this study is to evaluate how the different homeostatic mechanisms behave in adults with complicated dengue fever, focusing on the modulators of capillar permeability, VWF, ADAMTS 13 and fibrinolysis parameters, correlating them with the clinical presentation of disease. Patients and methods: We recruited patients with the diagnosis of complicated dengue fever between March and May 2008 in the General Hospital of Ipanema, in Rio de Janeiro, and in the Clinical Hospital of UNICAMP, in Campinas. Alongside healthy individuals were recruited as controls. The analysis of plasma levels of VWF, tPA, D-dimer, TNF-alpha, thrombomodulin and PAI-1 were performed by ELISA. The ADAMTS 13 activity was quantified by residual binding of VWF to collagen. Results: We included 35 adult patients with dengue complicated by bleedings (DCB) and 50 controls. The diagnosis of dengue hemorrhagic fever (DHF) was done only in three patients who had pleural effusion, the other cases had no clinical signs of increased vascular permeability, the criteria for the diagnosis of DHF. The group of patients with DCB presented,comparing to controls, increased levels of VWF (median = 244.1 vs. 136.9 U/ml, P <0.0001), decreased ADAMTS13 activity (median = 72.4 vs. 125 7%, P <0.0001), increased TNF-alpha (median 2.35 vs. 1.90 pg/ml, P = 0.038), increased thrombomodulin (median 6.15 vs. 4.79 ng/ml, P = 0.0003), increased tPA antigen (median 10.8 vs. 4.2 ng/ml, P <0.0001) and increased D-dimer plasma levels (median 1745 versus 478ng/ml, P <0.0001). There was no statistical difference between patients and controls with regard to the serum levels of VEGF (median = 34.8 vs. 19.1 pg/ml) and plasma levels of PAI-1 (median = 7.4 vs. 6.5 U/ml). We also performed correlation analyzes between the different parameters studied. Thus, we found that the platelet count was indirectly correlated with plasma levels of tPA (r = −0.3432, 95% CI = −0.5921 to −0.03451, P = 0.0261) and D-dimer (r = −0.3996, 95% CI = −0.6381 to −0.09112, P = 0.0106). Conclusion: The increased plasma levels of VWF, tPA and thrombomodulin suggest a possible endothelial activation in patients with DCB, followed by stimulation of fibrinolysis. The activation of fibrinolysis in dengue fever have been described in children patients previously. Interestingly, normal levels of VEGF in these patients with DCB suggest that there is no impairment in vascular permeability in these cases. Then, fibrinolysis and thrombocytopenia seems to be the main causes of bleeding in this study. Patients with moderate to severe thrombocytopenia had the highest plasma levels of tPA and D-dimer, thus suggesting that increased levels of these proteins could be related to disease severity in adult patients. Disclosures: No relevant conflicts of interest to declare.

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Abstract P663: Polygenic Risk Scores for Plasma Levels of Fibrin D-Dimer and Tissue Plasminogen Activator Are Associated With Non-Lacunar Stroke

Stroke ◽

10.1161/str.52.suppl_1.p663 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Yonit A Addissie ◽

Brady Gaynor ◽

Thomas Jaworek ◽

Huichun Xu ◽

Colin O Stine ◽

...

Keyword(s):

Ischemic Stroke ◽

Plasma Levels ◽

Early Onset ◽

Late Onset ◽

Plasma Concentrations ◽

Risk Scores ◽

Lacunar Stroke ◽

Related Factors ◽

Pai 1 ◽

D Dimer

Introduction: Plasma concentrations of prothrombotic factors such as fibrinogen have previously been associated with ischemic stroke risk. To extend this observation, we examined the association of polygenic risk scores (PRS) for increased plasma levels of thrombosis-related factors with ischemic stroke. Our hypotheses were that these PRS would be more associated with early than late onset stroke and with non-lacunar than lacunar stroke. Methods: We identified 9053 late onset (≥ 60 years) stroke cases from the NINDS International Stroke Genetics Consortium (SiGN) with 24804 controls and 6594 early onset (< 60 years) stroke cases from the Genetics of Early Onset Ischemic Stroke Consortium with 30561 controls. We identified previously known loci associated with plasma levels of four thrombosis-related factors: fibrinogen, fibrin D-dimer, tPA and PAI-1 from prior GWAS studies and developed genome-wide PRS for plasma concentrations of these factors. We then used logistic regression to test the association of these scores with risk of stroke and stroke subtype. Results: PRS for fibrin D dimer levels were associated with increased risk for all stroke and specifically for older (p = 0.019), but not younger (p = 0.22) onset stroke. PRS for tPA levels were also marginally associated with older (p = 0.06), but not younger (p = 0.24) onset stroke. Genetic risk scores for both D dimer and tPA were associated with non-lacunar stroke (Table 1). Further analyses stratified by age revealed PRS for D dimer to be significantly associated with non-lacunar stroke (but not lacunar stroke) in both late and early onset cohorts. PRS for fibrinogen and PAI-1 were not associated with stroke. Conclusion: Genomic risk scores for thrombosis-related factors including D dimer and tPA levels were associated with risk for ischemic stroke, and specifically, non-lacunar stroke.

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ECMO induces early alterations in coagulation and fibrinolysis profiles in COVID-19 patients with acute respiratory distress syndrome.

Thrombosis and Haemostasis ◽

10.1055/a-1529-2257 ◽

2021 ◽

Author(s):

Guillaume Hékimian ◽

Paul Masi ◽

Manon Lejeune ◽

Guillaume Lebreton ◽

Juliette Chommeloux ◽

...

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Thrombin Generation ◽

Distress Syndrome ◽

Endothelial Activation ◽

Ecmo Support ◽

Bleeding Complications ◽

Pai 1 ◽

Coagulation And Fibrinolysis

Hemostatic changes induced by extracorporeal membrane oxygenation (ECMO) support have been yet poorly documented in COVID-19 patients who have a baseline complex hypercoagulable state. In this prospective monocentric study of patients with severe acute respiratory distress syndrome (ARDS) rescued by ECMO, we performed longitudinal measurements of coagulation and fibrinolysis markers throughout the course of ECMO support in 20 COVID-19 and 10 non-COVID-19 patients. Blood was sampled before and then 24 hours, 7 and 14 days after ECMO implantation. Clinical outcomes were prospectively assessed until discharge from the intensive care unit or death. The median age of participants was 47 (35-56) years, with a median body mass index of 30 (27-35) kg/m², and a SOFA score of 12 (8-16). Baseline levels of von Willebrand factor, fibrinogen, factor VIII, prothrombin F1+2, thrombin-antithrombin, D-Dimers and PAI-1 were elevated in both COVID-19 and non-COVID-19 ARDS patients, indicating that endothelial activation, endogenous thrombin generation and fibrinolysis shut-down occur in all ARDS patients before ECMO implantation. From baseline to day 7, thrombin generation (prothrombin F1+2, p<0.01) and fibrin formation markers (fibrin monomers, p<0.001) significantly increased, further resulting in significant decreases in platelet count (p<0.0001) and fibrinogen level (p<0.001). PAI-1 levels significantly decreased from baseline to day 7 (p<0.0001) in all ARDS patients. These changes were more marked in COVID-19 patients, resulting in 14 non-fatal and 3 fatal bleeding. Additional studies are warranted to determine whether monitoring of thrombin generation and fibrinolysis markers might help to early predict bleeding complications in COVID-19 patients supported by ECMO.

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Intracardiac Fibrinolysis and Endothelium Activation Related to Atrial Fibrillation Ablation with Different Techniques

Cardiology Research and Practice ◽

10.1155/2020/1570483 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Orsolya Hajas ◽

Zsuzsa Bagoly ◽

Noémi K Tóth ◽

Réka Urbancsek ◽

Alexandra Kiss ◽

...

Keyword(s):

Pulmonary Vein ◽

Endothelial Activation ◽

Ablation Catheter ◽

Antithrombotic Treatment ◽

Pulmonary Vein Ablation ◽

Fviii Activity ◽

Before And After ◽

Pai 1 ◽

D Dimer ◽

Pulmonary Vein Ablation Catheter

Objective. The effect of pulmonary vein isolation (PVI) on fibrinolytic and endothelial activation with currently applied periprocedural anticoagulation has not been explored. We measured markers of fibrinolysis and endothelium activation before and after PVI with the second-generation cryoballoon (Cryo), pulmonary vein ablation catheter (PVAC-Gold), and irrigated radiofrequency (IRF). Methods. Markers of fibrinolysis and endothelium activation in left atrial (LA) blood samples were measured in 31 patients before and after PVI (Cryo:10, PVAC-Gold: 7, IRF: 14). Periprocedural anticoagulation included uninterrupted vitamin K antagonist and iv heparin (ACT≥300 sec) during LA dwelling. Results. Levels of D-dimer (median; interquartile range, mgFEU/L) increased with all techniques (PVAC: 0.34; 0.24–0.50 versus 0.70; 0.61–1.31; p=0.0313, Cryo: 0.33; 0.28–0.49 versus 0.79; 0.65–0.93; p=0.0078; IRF 0.33; 0.21–0.44 versus 0.83; 0.56–1.21; p=0.0001). PAP complex level (ng/ml) increased after Cryo (247.3, 199.9–331.6 versus 270.9, 227.9–346.7; p=0.0020) and IRF (265.3; 202.0–800.1 versus 325.6, 250.2–701.9; p=0.0166), but not after PVAC (p=0.2969). PAI-1 activity (%) decreased with the PVAC (1.931; 0.508–3.859 versus 0.735, 0.240–2.707; p=0.0313) and Cryo (0.361; 0.080–1.575 versus 0.378; 0.111–0.915; p=0.0313). A similar trend was observed with IRF (p=0.0676). Both VWF antigen levels and FVIII activity increased after PVI with all the 3 techniques. The levels of soluble VCAM-1 (ng/ml) did not change after PVAC procedures, but increased after Cryo (542, 6; 428.5–753.1 versus 619.2; 499.8–799.0; p=0.0005) and IRF (679.3; 505.0–744.7 versus 770.9; 631.9–894.0; p<0.0001). Conclusion. PVI with contemporary ablation techniques and periprocedural antithrombotic treatment induces coagulation and endothelium activation of similar magnitude with different ablation methods.

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Hemostatic Abnormalities and Changes Following Bone Marrow Transplantation

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602960401000406 ◽

2004 ◽

Vol 10 (4) ◽

pp. 341-350 ◽

Cited By ~ 15

Author(s):

Takeshi Matsumoto ◽

Hideo Wada ◽

Hiroyoshi Nishiyama ◽

Tomomi Hirano ◽

Miho Sakakura ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Plasminogen Activator ◽

Plasma Levels ◽

Marrow Transplantation ◽

Allogeneic Bone Marrow Transplantation ◽

Allogeneic Bone ◽

Survivor Group ◽

Pai 1 ◽

D Dimer

Hemostatic parameters were examined in 39 patients who underwent allogeneic bone marrow transplantation (BMT). Twenty-six patients survived and 13 patients died within 6 months after BMT. The main causes of death were acute graft-versus-host disease (GVHD: n=6), veno-occlusive disease (VOD: n=2), and thrombotic microangiopathy (TMA: n=2). Plasma levels of D-dimer and thrombomodulin (TM) were significantly elevated in the non-survivor group. Plasma levels of soluble fibrin (SF) and Fas were significantly elevated in the non-survivor group at 1 to 4 weeks after BMT. Plasma levels of thrombin-antithrombin complex (TAT), D-dimer, and tissue plasminogen activator-plasminogen activator inhibitor-1 complex (tPA-PAI-1 complex) were significantly elevated in patients with complications after BMT. Plasma levels of TAT, D-dimer, and tPA-PAI-1 complex were significantly elevated in patients with GVHD. These results suggest that abnormalities of hemostatic parameters might predict poor outcomes or complications in patients with BMT.

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DNA-Polymorphisms and Plasma Levels of Vascular Disease Risk Factors in Greenland Inuit

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614522 ◽

1999 ◽

Vol 81 (04) ◽

pp. 547-552 ◽

Cited By ~ 9

Author(s):

Moniek P. M. de Maat ◽

Else Marie Bladbjerg ◽

Lars G. Johansen ◽

Peter de Knijff ◽

Jørgen Gram ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

High Risk ◽

Plasma Levels ◽

Disease Risk ◽

Allele Frequencies ◽

Cvd Risk ◽

Risk Alleles ◽

Pai 1 ◽

D Dimer

SummaryGreenland Inuit are a population with a low risk of cardiovascular disease. Recently, we stated that frequencies of potentially high risk alleles of the apolipoproteins, fibrinogen, factor V, glycoprotein IIIa and factor VII (FVII) genes have different allele frequencies in the Inuit when compared with Caucasian populations. We have extended this study and evaluated whether or not this was also true for the genetic polymorphisms of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), angiotensin-converting enzyme (ACE) and angiotensinogen in a group of 133 Greenland Inuit, aged 30-34 y. In addition, we compared the plasma levels of these factors and those of C-reactive protein (CRP) and D-Dimer in Inuit and in Danes, comparable for age and gender. Frequencies (f) were assessed of the alleles that are known as the potential high risk alleles in Caucasians.In the Inuit, the f(insertion allele) of the t-PA intron8ins311 polymorphism was 0.37 (CI 0.32-0.43), the f(4G allele) of the PAI-1 promoter polymorphism was 0.88 (CI 0.83-0.91), the f(deletion allele) of the ACE intron16ins287 polymorphism was 0.40 (CI 0.33-0.47) and the f(M-allele) of the angiotensinogen M/T353 polymorphism was 0.30 (CI 0.25-0.38). As for fibrinogen and FVII polymorphisms, these frequencies are all significantly different from what is reported for Caucasian populations. In the Inuit, plasma levels of fibrinogen and D-Dimer were higher than in the Danes, the PAI-1 levels were lower and FVII, t-PA and CRP levels were comparable. The observed allele frequencies of the polymorphisms of t-PA, fibrinogen, FVII, ACE, angiotensinogen and the plasma levels of PAI-1 and D-Dimer were in accordance with the low CVD risk in the Inuit, considering the observed associations between these measures and CVD risk in Caucasian populations, but for other measures this was not the case (allele frequencies of the PAI-1 polymorphism, and plasma levels of fibrinogen, FVII and t-PA).In conclusion there are clear differences in genetic background and plasma levels of risk factors in Greenland Inuit compared with Caucasian populations, and these differences were sometimes, but not always, in accordance with the observed low cardiovascular disease risk of the Inuit population.

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Circulating Plasminogen Activator Inhibitor-1 (PAI-1) Is Reduced By In Vivo Thrombin Generation and Subsequent Formation of Activated Protein C (APC)

Blood ◽

10.1182/blood-2019-124731 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2389-2389

Author(s):

Sara Reda ◽

Franziska Isabelle Winterhagen ◽

Christina Berens ◽

Jens Müller ◽

Johannes Oldenburg ◽

...

Keyword(s):

Board Of Directors ◽

Plasma Levels ◽

Research Funding ◽

The Other ◽

Healthy Controls ◽

Advisory Committees ◽

Pai 1 ◽

D Dimer ◽

Thrombin Formation

Background: APC has been suggested to contribute to a hyperfibrinolytic state in various acquired coagulation disorders, including coagulopathies induced by trauma and sepsis. However, in vivo evidence for the proposed underlying mechanism of proteolytic degradation of PAI-1 by APC remains inconclusive. Recently, we have shown increased APC generation in response to in vivo thrombin formation in carriers of the factor V Leiden mutation (FVL). In this approach of stimulated hemostasis activity pattern evaluation (SHAPE), in vivo thrombin formation was triggered by low-dose administration of recombinant activated factor VII (rFVIIa). Aim of the present study was to investigate the resulting effects on the fibrinolytic system. Methods: The study population consisted of 30 FVL carriers (thereof 13 with a history of venous thromboembolism) and 15 healthy controls. Blood samples were collected immediately before and during a period of 8 hours following injection of 15 µg/kg rFVIIa. Plasma levels of APC were quantified using an oligonucleotide-based enzyme capture assay (OECA). Other monitored parameters included plasma levels of prothrombin activation fragment 1+2 (F1+2), tissue-type plasminogen (t-PA), PAI-1, plasminogen, α2-antiplasmin, plasmin-α2-antiplasmin complexes (PAP), soluble fibrin monomers, d-dimer, and thrombin-activatable fibrinolysis inhibitor (TAFI). Results: At baseline, FVL carriers showed higher median levels of APC in comparison to the controls (1.39 vs. 0.86 pmol/L, P=.001), higher PAI-1 levels (30.1 vs. 15.3 ng/mL, P=.002) and lower plasminogen levels (94.8 vs. 110.4%, P=6·10-4). The other baseline parameters did not differ significantly. In both cohorts a comparable increase of F1+2 was observed after administration of rFVIIa, whereas APC increased more (P=.004) in FVL carriers (by 6.40 pmol/L) than in healthy controls (by 2.14 pmol/L), Concurrently, median PAI-1 levels decreased more (P=.007) in FVL carriers (by 19.8 pmol/L) than in healthy controls (by 8.0 pmol/L) (Figure 1). TAFI levels decreased temporarily, from 104.8 to 94.4% (P=.007) in FVL carriers and from 105.0 to 92.1% (P=2·10-4) in healthy controls. PAP levels increased from 164 to 209 ng/mL (P<10-4) in FVL carriers and from 154 to 189 ng/mL (P=.023) in the control group. The extent of these changes did not differ between the two cohorts. D-dimer level increased only in FVL carriers, from 0.34 to 0.41 mg/L (P=.008). t-PA and the other parameters did not show significant changes after rFVIIa administration. Conclusion: Increased APC formation rates in FVL carriers were associated with a greater decline of PAI-1 levels in the absence of interfering changes in t-PA levels. These data provide further in vivo evidence that APC down-regulates PAI-1. Overall, the SHAPE approach utilized here does not induce a significant profibrinolytic response, even in patients with thrombophilia. Disclosures Reda: Grifols: Honoraria; Shire: Honoraria. Winterhagen:SOBI: Honoraria. Berens:Pfizer: Honoraria; Shire: Honoraria; Biotest: Honoraria; CSL Behring: Honoraria; Novo Nordisk: Honoraria; Baxter: Honoraria. Müller:NovoNordisk: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Siemens: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Oldenburg:CSL Behring: Consultancy, Research Funding, Speakers Bureau; NovoNordisk: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Research Funding, Speakers Bureau; Swedish Orphan Biovitrum: Consultancy, Speakers Bureau; Grifols: Consultancy, Speakers Bureau; Takeda (Shire): Consultancy, Research Funding, Speakers Bureau; Chugai: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Biotest: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau. Rühl:CSL Behring: Honoraria; Bayer: Honoraria; Shire: Honoraria; SOBI: Honoraria; Sanofi Genzyme: Honoraria; Grifols: Honoraria.

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Extensive Characterization of the Hemostatic Derangement Occurring in COVID-19 Patients Admitted to the Bergamo Hospital

Blood ◽

10.1182/blood-2020-136724 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 36-36

Author(s):

Patricia Gomez-Rosas ◽

Marina Marchetti ◽

Eleonora Sanga ◽

Sara Gamba ◽

Cristina Verzeroli ◽

...

Keyword(s):

Disease Severity ◽

Median Time ◽

Plasma Levels ◽

Hypercoagulable State ◽

Icu Patients ◽

Fibrinolytic Proteins ◽

Pai 1 ◽

D Dimer

INTRODUCTION The occurrence of a hypercoagulable state in hospitalized COVID-19 patients is supported by studies conducted with routine coagulation tests, including plasma D-dimer and fibrinogen, and platelet count. AIM In this study we performed an extensive characterization of the hemostatic alterations by both global and specific assays in a cohort of 78 patients hospitalized for COVID-19. The aims were to: 1) clarify mechanisms underlying the coagulopathy, and 2) identify predictive factors of disease severity and thrombotic events (i.e. deep vein thrombosis [DVT], pulmonary embolism [PE] or arterial thromboembolism [ATE]). METHODS COVID-19 patients admitted to the Hospital Papa Giovanni XXIII in Bergamo, Italy, from March 23 to May 30, 2020, were enrolled prospectively, providing informed consent. As a global assay, thromboelastometry (ROTEM) was performed in whole blood by EXTEM, INTEM, and FIBTEM tests. Specific assays included plasma levels of intrinsic and extrinsic pathway coagulation factors, von Willebrand factor (vWF) antigen and activity, anticoagulant proteins (i.e. protein C [PC], free-protein S [PS], and antithrombin [AT]), fibrinolytic proteins (i.e. tissue plasminogen activator [t-PA], and inhibitor [PAI-1]), and hypercoagulation biomarkers (i.e. prothrombin fragment 1+2 [F1+2], and D-dimer). In addition, biomarkers of immunoinflammation (i.e. neutrophil extracellular traps [NETs], CRP and procalcitonin) were measured. Occurrence of thrombotic events and death were monitored during follow up. RESULTS 78 patients (56M/22F), median age 62.7 years (25-87), were analyzed. According to disease severity, 45 were ICU, and 33 non-ICU patients. Sixty-three of them were on thromboprophylaxis. Global hemostasis analysis by ROTEM showed a prothrombotic profile in patients compared to controls, with a significantly shorter clot formation time (CFT), and increased maximum clot firmness (MCF), which were significantly greater in the ICU vs non-ICU patients. The occurrence of an 'in vivo' hypercoagulable state was confirmed by increased plasma levels of F1+2 and D-dimer, with the highest values of D-dimer in the ICU subjects. Hypercoagulability, rather than factors' consumption, was also shown by the findings of significantly higher plasma procoagulant factors V, VIII, IX and fibrinogen in ICU compared to non-ICU patients (p<0.001). Endothelium activation was shown by extremely elevated vWF antigen and activity levels in all patients (highest values in ICU subjects). Moreover, the concentrations of fibrinolytic proteins, t-PA, and its inhibitor PAI-1, were elevated (p<0.01) in patients compared to normal controls, without difference between ICU and non-ICU subjects. Finally, the inflammatory parameters' analysis in the ICU group demonstrated significantly increased plasma levels of NETs, CRP, and procalcitonin, compared to non-ICU patients. Of note, NETs levels significantly (p<0.02) correlated with vWF, D-dimer and t-PA, while CRP and procalcitonin inversely correlated with anticoagulant PC. After a median time of 8.8 days, 19 (24%) patients experienced thrombosis (3 DVT, 8 PE, 8 ATE). Thirteen (17%) patients from total population died after a median time of 33 days of hospitalization. Baseline D-dimer and t-PA levels were significantly higher in patients developing VTE, while baseline FVIII, vWF and D-dimer levels were greater in subjects who died during follow-up. By Cox analysis, high D-dimer and younger age were significantly associated with mortality. CONCLUSIONS Our study provides for the first time an extensive overview of the hypercoagulable state induced by SARSCoV-2 infection, demonstrating alterations in all of the different hemostatic compartments analyzed. The viral infection-induced hemostatic abnormalities are exacerbated by the severity of the disease and strongly correlate with the proinflammatory status, demonstrating the link between coagulation and inflammation. This link is further supported by the clear correlation found between NETosis and markers of endothelial and blood clotting activation. Finally, these data add evidence to the role of D-dimer as a significant predictor of intra-hospital mortality. Disclosures No relevant conflicts of interest to declare.

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One Month Follow-up of Haemostatic Variables in Patients Undergoing Aortocoronary Bypass Surgery

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653780 ◽

1995 ◽

Vol 73 (03) ◽

pp. 356-361 ◽

Cited By ~ 23

Author(s):

L Mannucci ◽

P S Gerometta ◽

L Mussoni ◽

C Antona ◽

A Parolari ◽

...

Keyword(s):

Cardiopulmonary Bypass ◽

Bypass Surgery ◽

Fibrinolytic System ◽

Aortocoronary Bypass ◽

Protamine Sulphate ◽

Aortocoronary Bypass Surgery ◽

Intraoperative Period ◽

Pai 1 ◽

D Dimer

SummaryIt is already known that activation of the coagulation and fibrinolytic system occurs in patients undergoing cardiopulmonary bypass (CPB). We have thus studied twenty patients (10 treated with aprotinin during CPB and 10 untreated) both during the intraoperative period and during thirty days follow up. In untreated patients D-dimer levels increased 4-fold during CPB and the levels were above baseline for the whole follow up (p<0.0001). D-dimer levels were reduced in aprotinin treated patients in comparison to untreated patients (p = 0.0172); levels then gradually increased to the values of the untreated patients over the following 24 h later and remained higher during the thirty day follow up. The behavior of haemostatic variables in the 24 h after CPB did not vary between untreated and aprotinin treated patients. In particular, five minutes after protamine sulphate administration, levels of F1 + 2 and TAT rose significantly (p = 0.0054, p = 0.0022 respectively), whereas fibrinogen significantly decreased (p<0.0001) and PAI-1 antigen levels were reduced. Two days after CPB the concentrations of F1 + 2 and TAT lowered, whereas fibrinogen and PAI-1 antigen levels increased. On the 5th, 8th and 30th days after CPB, F1 + 2 and TAT levels remained higher than those reported at baseline in both groups of patients, whereas fibrinogen levels increased over basal levels in aprotinin treated patients only.Thus, in addition to the activation of the coagulation and fibrinolytic system occurring during the intraoperative period, in patients undergoing CPB, there are alterations of haemostatic variables up to thirty days from surgery.

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Aktivierungs- und Umsatzmarker der Hämostase im Verlauf der akuten tiefen Beinyenenthrombose

Hämostaseologie ◽

10.1055/s-0038-1655292 ◽

1995 ◽

Vol 15 (02) ◽

pp. 87-91 ◽

Cited By ~ 4

Author(s):

Ch. Burstein ◽

S. Bitter ◽

M. Kundt ◽

M. Freund ◽

O. Anders

Keyword(s):

Thrombolytische Therapie ◽

Pai 1 ◽

D Dimer

ZusammenfassungIn einer prospektiven Untersuchung wurde das Verhalten von Thrombin-Antithrombin-lll-(TAT-)Komplex, D-Dimer, Plasminogenaktivator-lnhibitor-1 (PAI-1) und weiteren Parametern der Hämostase bei 50 Patienten mit spontaner tiefer Beinvenenthrombose bei Stellung der Diagnose während der initialen Behandlung und bei der ambulanten Kontrolle untersucht: 37 Patienten erhielten eine thrombolytische Therapie, davon 31 Patienten mit Streptokinase in ultrahoher Dosierung (UHSK) und sechs Patienten mit Urokinase; 13 Patienten wurden mit einer Heparininfusion behandelt.Im Vergleich zu den Patienten mit einer Heparintherapie führte die thrombolytische Therapie zu einem Anstieg von TAT (p <0,05), D-Dimer (p <0,01) und von PAI-1 (p <0,05). Bei vier Patienten trat eine Rethrombose nach Thrombolyse auf. Nach fibrinolytischer Therapie wurde eine Aktivierung der Gerinnung und eine erhöhte Aktivität von PAI-1 nachgewiesen, die für die Entstehung einer Rethrombose von Bedeutung sein können.

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Influence of insulin-induced hypoglycemia on the hemostatic and fibrinolytic system in patients with hypothalamicpituitary disorders

Hämostaseologie ◽

10.1055/s-0038-1655335 ◽

1998 ◽

Vol 18 (02) ◽

pp. 74-79

Author(s):

K.-H. Zurborn ◽

H. D. Bruhn ◽

H. Mönig

Keyword(s):

Factor Viii ◽

Plasminogen Activator ◽

Tolerance Test ◽

Insulin Tolerance Test ◽

Fibrinolytic System ◽

Tissue Type ◽

Insulin Tolerance ◽

Factor Viii Antigen ◽

Pai 1 ◽

D Dimer

SummaryIn order to study the acute and prolonged effects of hypoglycemia on the hemostatic and fibrinolytic system we measured prothrombin fragment (F1+2), thrombin-antithrombin III complex (TAT), platelet factor 4 (PF4), β-thromboglobulin (âTG), factor VIII antigen (F VIII antigen), D-dimer, tissue-type plasminogen activator (t-PA) antigen, and plasminogen activator inhibitor (PAI-1) in 22 patients during insulin tolerance test. F1+2 and TAT increased significantly 15 and 90 minutes after administration of insulin, as did PF4 and âTG. At 4 and 24 hours, these parameters were not different from baseline. Factor VIII antigen was not significantly altered. D-dimer concentration did not change. However, the D-dimer/TAT ratio significantly decreased at 15 and 90 minutes but increased markedly above baseline at 4 and 24 hours. t-PA antigen was also found to be elevated at 15 and 90 minutes but had returned to baseline at 4 and 24 hours. PAI-1 concentration did not change. We conclude from these data that both coagulation and fibrinolysis are activated in the short-term response to acute insulin-induced hypoglycemia, followed by a prolonged activation of fibrinolysis. Our study may explain why patients undergoing insulin tolerance test, despite marked clotting and platelet activation, almost never develop thromboembolic complications.

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