Fibrinolyse- und Thrombophilieparameter unter systemischer Prostaglandin E1-Therapie bei peripherer arterieller Verschlusskrankheit

VASA ◽  
2003 ◽  
Vol 32 (3) ◽  
pp. 145-148 ◽  
Author(s):  
Kuss ◽  
Heidrich ◽  
Koettgen
Keyword(s):  
Coagulation Factor ◽  
Plasminogen Activator Inhibitor ◽  
Bleeding Risk ◽  
Arterial Disease ◽  
Prostaglandin E ◽  
Factor Xii ◽  
Significant Difference ◽  
Peripheral Arterial ◽  
Fibrinolytic Capacity

Background: The study was designed to evaluate if there is any evidence of a hyperfibrinolytic bleeding-risk under systemic treatment with prostaglandin E1 (PGE1) of patients with peripheral arterial disease (PAD). Patients and methods: The in vivo effect of PGE1 on the fibrinolytic and hemostatic process was tested on 15 patients before and after treatment with Alprostadil for 21 days using D-dimers (DD), fibrinogen, prothrombin time (PT), partial thromboplastin time (PTT), antithrombin (AT), ProC-Global®, plasminogen, plasminogen activator inhibitor activity (PAI), alpha2-antiplasmin, coagulation factor XII, basal and activated fibrinolytic capacity (fib. cap.). Results: There was no significant difference in DD, fibrinogen, PT, PTT, AT, ProC-Global®, plasminogen, PAI, alpha2-antiplasmin, coagulation factor XII, basal and activated fibrinolytic capacity observed after the treatment. Conclusion: Summarizing this study there is no hyperfibrinolytic bleeding-risk after the systemic therapy with Alprostadil to be expected.

Platelet Activation Markers in Patients with Peripheral Arterial Disease

1997 ◽  
Vol 78 (06) ◽  
pp. 1434-1437 ◽  
Author(s):  
Paolo Gresele ◽  
Mariella Catalano ◽  
Carlo Giammarresi ◽  
Raul Volpato ◽  
Rosanna Termini ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Platelet Function ◽  
Arterial Disease ◽  
Platelet Function Test ◽  
Activation Markers ◽  
Significant Difference ◽  
Peripheral Arterial

SummaryPeripheral vascular disease (PVD) is an indicator of diffuse atherosclerosis and is associated with a greatly increased incidence of coronary heart and cerebrovascular disease. Although several studies have assessed whether in vivo platelet activation takes place in patients with PVD, no data are available comparing different platelet function tests in this patient population.We have compared prospectively four tests for the measurement of in vivo platelet activation (plasma βTG, plasma PF4, intraplatelet (βTG and urinary excretion of 11-dehydro-TXB2) and one in vitro platelet function test (ADP-induced platelet aggregation) in 63 well-characterized patients with intermittent claudication and in 18 age- and sex- matched healthy volunteers.No statistically significant difference was found between patients and controls for plasma βTG (20.0 ± 11.8 vs. 18.8 ± 9.0 ng/ml, respectively), plasma PF4 (5.2 ± 2.9 vs. 6.3 ± 3.5 ng/ml), βTG/PF4 ratio (4.0 ± 2.9 vs. 3.6 ± 1.8), intraplatelet pTG (4503 ± 1482 vs. 4059 ± 1065 ng/ml), and threshold aggregatory concentration of ADP (1.7 ± 0.72 vs. 1.45 ± 0.56 μM).Urinary 11-dehydro-TXB2 was instead significantly higher in the PVD group (55.4 ± 27.5 vs. 26.7 ± 7.0 ng/h, p <0.001).Our study shows that urinary 11-dehydro-TXB2 is a more sensitive index of in vivo platelet activation than the measurement of either platelet specific proteins or of in vitro platelet aggregation in patients with PVD.

The Functional Promoter Polymorphism of the Coagulation Factor XII Gene is not Associated With Peripheral Arterial Disease

Angiology ◽  
2009 ◽  
Vol 61 (2) ◽  
pp. 211-215 ◽  
Author(s):  
Babak Yazdani-Biuki ◽  
Peter Krippl ◽  
Kerstin Brickmann ◽  
Florentine Fuerst ◽  
Uwe Langsenlehner ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Coagulation Factor ◽  
Arterial Disease ◽  
Promoter Polymorphism ◽  
Factor Xii ◽  
Peripheral Arterial

Association of Increased Fibrin Turnover and Defective Fibrinolytic Capacity with Leg Atherosclerosis

1994 ◽  
Vol 72 (02) ◽  
pp. 292-296 ◽  
Author(s):  
M Cortellaro ◽  
E Cofrancesco ◽  
C Boschetti ◽  
L Mussoni ◽  
M B Donati ◽  
...  
Keyword(s):  
Arterial Disease ◽  
Venous Stasis ◽  
Stepwise Discriminant Analysis ◽  
Predisposing Factor ◽  
Risk Of Death ◽  
Peripheral Arterial ◽  
Fibrinolytic Potential ◽  
Fibrinolytic Capacity ◽  
Control Study ◽  
D Dimer

SummaryPatients with peripheral arterial disease have a high risk of death from cardiovascular events. As defective fibrinolysis associated with leg atherosclerosis has been suggested as a predisposing factor, we sought a relation among decreased fibrinolysis, the presence of leg atherosclerosis and the incidence of thrombotic events in a case control study nested in the PLAT.Fifty-eight patients with coronary and/or cerebral atherothrombotic disease, free of leg atherosclerosis at Doppler examination, were compared with 50 atherosclerotic patients with leg involvement. High D-dimer (153.0 vs 81.3 ng/ml, p <0.001) and tPA antigen before venous stasis (14.4 vs 11.8 ng/ml, p <0.03), and low tPA antigen (6.7 vs 15.6 ng/ml, p <0.01) and fibrinolytic activity released after venous stasis (fibrinolytic capacity: 113.2 vs 281.4 mm2, p <0.001) were found in patients with leg atherosclerosis. D-dimer and fibrinolytic capacity, in addition to age, were selected by stepwise discriminant analysis as characterizing patients with leg atherosclerosis. Moreover, higher D-dimer and tPA inhibitor characterized patients with leg atherosclerosis who subsequently experienced thrombotic events.These findings constitute evidence of high fibrin turnover and impaired fibrinolytic potential in patients with leg atherosclerosis. Thus impaired fibrinolysis may contribute to the prothrombotic state in these patients.

Complex antithrombotic therapy and bleeding risk in patients with peripheral arterial disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Tseng ◽  
S Bhatt ◽  
M Girardo ◽  
D Liedl ◽  
P Wennberg ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Triple Therapy ◽  
Major Bleeding ◽  
Antithrombotic Therapy ◽  
Oral Anticoagulants ◽  
Bleeding Risk ◽  
Arterial Disease ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
Peripheral Arterial

Abstract Introduction Antiplatelet therapy is the cornerstone of treatment for many atherosclerotic vascular pathologies including peripheral arterial disease (PAD). Patients with PAD often have comorbid conditions that require complex antithrombotic therapy, i.e. combined antiplatelet and anticoagulation. Methods All adult patients undergoing ankle brachial index (ABI) measurements were included in the study. ABI values between 1.00 and 1.40 were considered normal, and values below 1.00 or above 1.40 were considered PAD. Demographic, comorbidity and outcome data were obtained using diagnostic codes from the electronic health record. Three medication classes were analyzed: aspirin, non-aspirin oral antiplatelets (e.g. P2Y12 inhibitors) and oral anticoagulants (warfarin and the direct oral anticoagulants). Medication use was determined for patients who had been on a medication for at least one year. Cox proportional hazard analysis for the time to first bleeding event was analyzed. Bleeding was defined as any bleeding requiring medical evaluation (including clinically-relevant non-major bleeding and major bleeding). Results In all, 40,144 patients were included in the analysis (mean age 66±15, 43% female). Patients with PAD were more likely to be on double therapy (one antiplatelet with anticoagulation) (28% vs 19%) and triple therapy (dual antiplatelet with anticoagulation) (10% vs 4%). Unadjusted hazard ratios for bleeding risk showed increased risk of bleeding for patients with PAD (1.18, 95% confidence interval [CI]: 1.08–1.29), though the association is no longer present after adjustment for antithrombotic therapy. Adjusting for age, sex and PAD class, compared to no antithrombotic therapy, there was increased risk of bleeding for monotherapy (1.91, 95% CI: 1.61–2.26), double therapy (3.40, 95% CI: 2.89–4.00) and triple therapy (5.00, 95% CI: 4.21–5.96). Among medications, aspirin and anticoagulant use was independently associated with the greatest increase in risk of bleeding. Conclusion Patients in PAD are at increased risk of bleeding secondary to antithrombotic therapy. Complex antithrombotic therapy with double or triple therapy confer additional bleeding risk, particularly regimens containing aspirin and oral anticoagulants. Funding Acknowledgement Type of funding source: None

Targeted deletion of murine coagulation factor XII gene-a model for contact phase activation in vivo

2004 ◽  
Vol 92 (09) ◽  
pp. 503-508 ◽  
Author(s):  
Hans-Ulrich Pauer ◽  
Thomas Renné ◽  
Bernhard Hemmerlein ◽  
Tobias Legler ◽  
Saskia Fritzlar ◽  
...  
Keyword(s):  
Fetal Loss ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Mendelian Inheritance ◽  
Biological Role ◽  
Factor Xii ◽  
Wild Type ◽  
Contact Phase ◽  
Health And Disease

SummaryTo analyze the biological role of factor XII (FXII, Hageman Factor) in vivo, we generated mice deficient for FXII using a gene targeting approach on two distinct genetic backgrounds, i.e. mixed C57Bl/6J X 129X1/SvJ and inbred 129X1/SvJ. Homozygous FXII knockout (FXII-/-) mice showed no FXII plasma activity and had a markedly prolonged activated partial thromboplastin time (aPTT). In contrast, coagulation factors XI, VIII, IX, X,VII,V, II and fibrinogen did not differ between FXII-/- mice and their wild-type littermates. Heterozygous matings segregated according to the Mendelian inheritance indicating that FXII deficiency does not increase fetal loss. Furthermore, matings of FXII-/- males and FXII-/females resulted in normal litter sizes demonstrating that total FXII deficiency in FXII-/females does not affect pregnancy outcome. Also, gross and histological anatomy of FXII-/mice was indistinguishable from that of their wild-type littermates on both genetic backgrounds. Thus it appears that deficiency of murine FXII does not cause thrombophilia or impaired fibrinolysis in vivo. These results indicate that FXII deficiency does not affect hemostasis in vivo and we anticipate that the FXII-/mice will be helpful to elucidate the biological role(s) of FXII in health and disease.

scholarly journals Coagulation Factor XII protects neurons from apoptosis by triggering a crosstalk between HGFR/c-Met and EGFR/ErbB1 signaling pathways

2020 ◽  
Author(s):  
Eugénie Garnier ◽  
Damien Levard ◽  
Carine Ali ◽  
Yannick Hommet ◽  
Tiziana Crepaldi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Egf Receptor ◽  
Neuronal Cell ◽  
Coagulation Factor ◽  
Receptor Activation ◽  
Target Cells ◽  
Cultured Neurons ◽  
Factor Xii ◽  
Protective Effects

Abstract Background Factor XII (FXII) is a serine protease that participates in the intrinsic coagulation pathway. Several studies have shown that plasmatic FXII exert a deleterious role in cerebral ischemia and traumatic brain injury by promoting thrombo-inflammation. Nevertheless, the direct impact of FXII on neuronal cell fate remains unknown.Methods We investigated whether FXII influenced neuronal death induced in vivo by stereotaxic injection of N-methyl-D-Aspartate (NMDA) and in vitro by serum deprivation of cultured neurons.Results We found that FXII reduced brain lesions induced in vivo and protected cultured neurons from apoptosis through a growth factor-like effect. This mechanism was triggered by direct interaction with epidermal growth factor (EGF) receptor, activation of this receptor and engagement of anti-apoptotic intracellular pathways. Interestingly, the “proteolytically” active and two-chain form of FXII, αFXIIa, exerted additional protective effects by converting the pro-form of hepatocyte growth factor (HGF) into its mature form, which in turn activated HGF receptor (HGFR/c-Met) pathway. Lastly, the use of non-proteolytic FXII (αFXIIa-PPACK) unveiled an alternative EGFR and HGFR co-activation pathway, through co-receptor transphosphorylation. Conclusion This study describes novel mechanisms of action of FXII and discloses neurons as target cells for the protective effects of single and double-chain forms of FXII.

Abstract 53: Ablation of Thrombin Signaling in Platelets but Not in Endothelial Cells Impairs Hemostasis in a Mouse Model of Spontaneous Gastrointestinal Bleeding

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Stephen J Wilson ◽  
Maria M Stevens ◽  
Shaun R Coughlin
Keyword(s):  
Myocardial Infarction ◽  
Endothelial Cells ◽  
Platelet Activation ◽  
Bleeding Risk ◽  
Arterial Disease ◽  
Gi Bleeding ◽  
Intestinal Polyposis ◽  
Wild Type ◽  
Spontaneous Bleeding ◽  
Peripheral Arterial

Human PAR1 is expressed in endothelial cells as well as in platelets where it facilitates the response to thrombin and platelet activation. Vorapaxar, a PAR1 antagonist, prevents myocardial infarction and stroke in patients with prior MI or peripheral arterial disease at a cost of increased bleeding risk. Par1 is also highly expressed in endothelial cells in mice, and Par1-deficiency is associated with bleeding in the mouse embryo at midgestation. Additionally, known actions of endothelial PAR1 activation suggest pro-hemostatic functions. This raises the question of whether inhibition of PAR1 function in endothelial cells (in addition to PAR1 inhibition in platelets) contributes to the bleeding risk associated with Vorapaxar treatment. Our previous work demonstrated that Par1 deficiency results in loss of thrombin signaling in mouse endothelial cells but not mouse platelets, while Par4 deficiency ablated thrombin-induced platelet activation in mice. Thus, mice allow us to separate loss of thrombin signaling in platelets from loss of thrombin signaling in endothelial cells. Accordingly, we used Apc min/+ mice, which develop intestinal polyposis and spontaneous GI bleeding, as a model to determine whether loss of thrombin signaling in platelets (Par4 KO) or endothelial and other cells (Par1 KO) exacerbates spontaneous bleeding. Hematocrit and other hematologic parameters were measured biweekly from 7 weeks through 15 weeks of age. Hematocrits in mice wild-type for Apc were stable over this period (41.48 ± 0.48 at 7 weeks; 40.48 ± 0.37 at 15 weeks, n=15). Hematocrits in Apc min/+ mice fell approximately linearly from 37.06 ± 0.82 at 7 weeks to 14.39 ± 1.12 at 15 weeks (n=15). Hematocrits in Par1-deficient Apc min/+ mice were indistinguishable from those in Apc min/+ without Par deficiency (14.39 ± 1.12 vs 14.47 ± 1.66 at 15 weeks; n=6-15). By contrast, Par4-deficient Apc min/+ mice were already severely anemic at 7 weeks compared to Apc min/+ mice (19 ± 2.0 vs 39 ± 3.6; p<0.01, n=4). Par-dependent differences in polyp count and size were not detected. Taken together, our results suggest that loss of thrombin signaling in platelets promotes spontaneous GI bleeding in the Apc min model while loss of thrombin signaling in endothelial cells is without effect in this system.

scholarly journals In vivo roles of factor XII

Blood ◽  
2012 ◽  
Vol 120 (22) ◽  
pp. 4296-4303 ◽  
Author(s):  
Thomas Renné ◽  
Alvin H. Schmaier ◽  
Katrin F. Nickel ◽  
Margareta Blombäck ◽  
Coen Maas
Keyword(s):  
Thrombus Formation ◽  
Coagulation Factor ◽  
Special Focus ◽  
Factor Xii ◽  
Excessive Bleeding ◽  
Charged Surfaces ◽  
Factor Xiia ◽  
Knockout Model

Abstract Coagulation factor XII (FXII, Hageman factor, EC = 3.4.21.38) is the zymogen of the serine protease, factor XIIa (FXIIa). FXII is converted to FXIIa through autoactivation induced by “contact” to charged surfaces. FXIIa is of crucial importance for fibrin formation in vitro, but deficiency in the protease is not associated with excessive bleeding. For decades, FXII was considered to have no function for coagulation in vivo. Our laboratory developed the first murine knockout model of FXII. Consistent with their human counterparts, FXII−/− mice have a normal hemostatic capacity. However, thrombus formation in FXII−/− mice is largely defective, and the animals are protected from experimental cerebral ischemia and pulmonary embolism. This murine model has created new interest in FXII because it raises the possibility for safe anticoagulation, which targets thrombosis without influence on hemostasis. We recently have identified platelet polyphosphate (an inorganic polymer) and mast cell heparin as in vivo FXII activators with implications on the initiation of thrombosis and edema during hypersensitivity reactions. Independent of its protease activity, FXII exerts mitogenic activity with implications for angiogenesis. The goal of this review is to summarize the in vivo functions of FXII, with special focus to its functions in thrombosis and vascular biology.

scholarly journals Quick Evaluation of Lower Leg Ischemia in Patients with Peripheral Arterial Disease by Time Maximum Intensity Projection CT Angiography: A Pilot Study

2020 ◽  
Author(s):  
Daming Zhang ◽  
Xueyan Zhou ◽  
Haiping Zhang ◽  
Xiaobing Fan ◽  
Zehong Lin ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Subjective Evaluation ◽  
Maximum Intensity Projection ◽  
Objective Evaluation ◽  
Arterial Disease ◽  
Lower Leg ◽  
Maximum Intensity ◽  
Ct Attenuation ◽  
Significant Difference ◽  
Peripheral Arterial

Abstract Background: The purpose of this study is to evaluate the new method of time maximum intensity projection (t-MIP) which was postprocessed from dynamic computed tomographic angiography (dyn-CTA) in diagnosing peripheral arterial disease (PAD). Methods: A population of 34 patients with known PAD was examined with a combined CTA protocol consisting of an s-CTA of the lower extremity and a dyn-CTA scan of the calves. For each lower leg, t-MIP images consisting of the MIP0 (sagittal MIP), and MIP+θ (45degree lateral MIP), MIP-θ (-45degree lateral MIP) were automatically generated from dyn-CTA. An objective evaluation of vascular CT attenuation of the best enhancement phase of dyn-CTA and t-MIP was measured; subjective evaluation of vessel stenosis and occlusion with a score was assigned for t-MIP and s-CTA. A comparison between the CT attenuation of t-MIP and dyn-CTA was made, so was the runoff score of t-MIP and s-CTA.Results: The CT attenuation of t-MIP CTA of three vascular segments from 68 lower extremities was higher than that of the best enhancement phase of dyn-CTA and s-CTA, with statistical significant difference at posterior tibial artery and fibular artery (all p＜0.05) . There were strong correlations (r ≥0.75, p < 0.05) of runoff scores between t-MIP and s-CTA. Conclusions: There is potential clinical application of t-MIP for assisting with the diagnosis of lower leg vascular stenosis in dyn-CTA with reliable diagnostic accuracy and convenient immediacy.

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