Hemodialysis with Defibrotide: Effects on Coagulation Parameters

1992 ◽  
Vol 15 (10) ◽  
pp. 590-594 ◽  
Author(s):  
E. Filimberti ◽  
S. Cinotti ◽  
M. Salvadori ◽  
M. Amato ◽  
G. Longo ◽  
...  

In a crossover study conducted with eight uremic patients maintained on hemodialysis, the Authors compared the effects of heparin (100 IU/kg at the start of dialysis) and defibrotide (400 mg at the start, repeated at 2 hours of ongoing dialysis) on the parameters of blood coagulation (VIII:C, AT III, TAT, PC antigen and activity, PS, and FPA), each being assessed before dialysis and at 2, 3 and 4 hours of the ongoing procedure. Heparin-assisted dialysis resulted in a significant rise of VIII:C and AT III; with defibrotide, instead, there was evidence of thrombin activation (increased FPA and TAT). PC levels were raised with both dialysis modalities; however, PC activity and PS levels were increased only in defibrotide-assisted dialysis. There were no adverse reactions or evidence of fibrin formation. These results confirm the antithrombotic activity of defibrotide in the course of dialysis and indicate that this action is independent of thrombin neutralization.

1984 ◽  
Vol 51 (02) ◽  
pp. 232-235 ◽  
Author(s):  
D C Triantaphyllopoulos

SummaryTwenty-one rabbits were infused with 20μg/kg/hr of E. coli endotoxin for 6 hr. Eight of the animals were preinjected immediately before the infusion of endotoxin, with a bolus dose of human AT III calculated to increase the antithrombin content of the plasma by about 4 units/ml. All eight animals which were preinjected with AT III survived, while 5 of the 13 control rabbits infused with endotoxin alone died. The changes in coagulation parameters from the baseline values, between the 8 control rabbits which survived and the 8 animals which were preinjected with AT III were compared. The concentration of the preinjected human AT III declined significantly faster (P: <0.01) than that of the native rabbit AT III. AT III prevented the decline of F.XII throughout the infusion of the endotoxin. However, the decline in F.V, fibrinogen, prothrombin and platelets was not affected (P: >0.5) by the injection of AT III.


1990 ◽  
Vol 63 (03) ◽  
pp. 430-434 ◽  
Author(s):  
Peter Bärtsch ◽  
André Haeberli ◽  
P Werner Straub

SummaryPhysical exercise causes shortening of activated partial thromboplastin time (aPTT) and euglobulin clot lysis time. To investigate whether this activation of coagulation and fibrinolysis leads to in vivo thrombin or plasmin action after long distance running, 19 well trained male runners (36-65 years) were examined 5 to 53 min after termination of a 100 km race and 5 days later after at least 1 day without physical exercise. Compared to the control examination aPTT was decreased (30.2 ± 2.8 vs 35.3 ± 3.0 sec) and the following parameters were increased after the race: betathromboglobulin (40 ± 16 vs 23 ± 7 ng/ml), thrombin-antithrombin III (TAT) complexes (5.5 ± 3.4 vs 2.3 ± 0.7 pg/1), the fibrin(ogen) degradation products fragment E (57 ± 15 vs 35 ± 7 ng/ml) and B(3 15-42 (8.5 ± 2.5 vs 6.5 ± 2.5 ng/ml) (all p values <0.001). Platelet count, platelet factor 4, fibrinoepetide A (FPA) and haematocrit did not change significantly. Increased TAT complexes and unchanged FPA suggest that the generated thrombin was fully inactivated by antithrombin III (AT III) and did therefore not give rise to fibrin formation. The small increase of fibrin(ogen) degradation products indicates a minor in vivo activity of the fibrinolytic system. This investigation demonstrates the importance of AT III in the regulation of haemostasis in activated blood coagulation.


2007 ◽  
Vol 97 (03) ◽  
pp. 478-486 ◽  
Author(s):  
Sandra Larkin ◽  
Jef Emeis ◽  
Anthony Allison ◽  
Frans Kuypers

SummaryAnnexin V(AV), a protein with anticoagulant activity, exerts antithrombotic activity by binding to phosphatidylserine (PS), inhibiting activation of serine proteases important in blood coagulation. The potential use of this protein as an anticoagulant is limited as it rapidly passes from the blood into the kidneys due to its relatively small size (36 kDa). We used recombinant DNA technology to produce a homodimer of human AV (DAV, 73 kDa), which exceeds the renal filtration threshold, and has a 6.5-hour half-life in the rat circulation. Human red blood cells with externalized PS were used to show that DAV had a higher affinity for PS-exposing cells than AV. DAV labeling sensitively identifies PS-exposing cells, was found to be a potent inhibitor of the activity of the prothombinase complexes and inhibits the ability of secretory phospholipase A2 to hydrolyze phospholipids of PS-exposing cells, reducing the formation of mediators of blood coagulation and reperfusion injury. DAV exerts dose-dependent antithrombotic activity in ratveins. This combination of activities suggests that DAV is a valuable probe to measure PS exposure and may be efficacious as a novel drug in a wide range of clinical situations.


Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1420 ◽  
Author(s):  
Feiyan Wen ◽  
Tiezhu Chen ◽  
Hongxiang Yin ◽  
Juan Lin ◽  
Hao Zhang

The resource shortage of Rhizoma Paridis has never been effectively addressed, and the industry continues to search for alternative resources. The in vitro effects on thrombin of Paris saponins and in vivo hemostatic activity of Paris fargesii var. brevipetala (PF) were evaluated in this study. PF is considered to be an alternative source of Rhizoma Paridis (RP). The in vitro incubation experiment was designed to investigate the effects on thrombin activity of Paris saponin H (PS H) and saponin extract in PF. The bleeding time of mouse tail snipping was used to evaluate the in vivo hemostatic effects of Paris saponins. Also, in vivo changes in four blood coagulation parameters in rats after oral administration of different groups of Paris saponins were compared. The effects of Paris saponins on liver function and blood lipid parameters were examined in order to avoid drug-induced liver injury. Activity studies of thrombin after ultra-filtration centrifugation showed that Paris saponins were able to enhance thrombin activity. Ultra performance liquid chromatography mass spectrometry (UPLC-MS) analysis results of the substrates led us to speculate that there is a specific binding between Paris saponins and thrombin. PS H and Paris saponins in PF significantly shortened the bleeding time in mice. One pathway by which Paris saponins enhance in vivo blood coagulation is by increasing fibrinogen (FIB), among the four blood coagulation parameters in rats. At the same time, the effects on liver and blood lipid parameters were insignificant. P. fargesii var. brevipetala can be developed as an alternative medicinal source of Rhizoma Paridis.


2020 ◽  
Vol 12 ◽  
pp. 251584142090392
Author(s):  
Constantinos D. Georgakopoulos ◽  
Olga E. Makri ◽  
Athina Pallikari ◽  
Konstantinos Kagkelaris ◽  
Panagiotis Plotas ◽  
...  

Purpose: Treatment with intravitreal injections of anti-vascular endothelial growth factor agents has been associated with an increased risk of arterial thromboembolic events. The aim of the present pilot study was to assess the effect of a single intravitreal injection of aflibercept on coagulation. Methods: Treatment-naïve patients with age-related macular degeneration ( n = 47), who were scheduled to undergo treatment with intravitreal injections of aflibercept, were enrolled. None of the included patients received any anticoagulation therapy or had a history of a recent arterial thromboembolic event. Blood samples were collected before the first intravitreal injection, and at 7 and 30 days after aflibercept administration. We evaluated coagulation parameters, such as platelet count and plasma fibrinogen and D-dimer levels; functional clotting parameters, such as prothrombin time, international normalized ratio, and activated partial thromboplastin time; and anticoagulant parameters, such as the levels of Proteins S and C. Results: The levels of all of the evaluated biomarkers were within the normal range at baseline and at both the time points throughout the study. No statistically significant changes were observed in any of the measured parameters at 1 week and 1 month after aflibercept administration. Conclusion: A single intravitreal injection of aflibercept in treatment-naïve patients with exudative age-related macular degeneration has no statistically significant effect on blood coagulation parameters for up to 1 month after aflibercept administration. Our results also provide an explorative statistical data, and further studies are required to evaluate any significant clinical effects of aflibercept on blood coagulation parameters. ClinicalTrials.gov ID: NCT03509623.


1996 ◽  
Vol 35 (3) ◽  
pp. 331-333 ◽  
Author(s):  
Pieter Westerduin ◽  
Jan E. M. Basten ◽  
Marc A. Broekhoven ◽  
Vera de Kimpe ◽  
Will H. A. Kuijpers ◽  
...  

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