scholarly journals The Effects of Long-Term Graft Preservation on Intraoperative Hemostatic Changes in Liver Transplantation

HPB Surgery ◽  
1994 ◽  
Vol 7 (4) ◽  
pp. 265-280 ◽  
Author(s):  
C. Minke Bakker ◽  
Jan D. Blankensteijn ◽  
Peter Schlejen ◽  
Robert J. Porte ◽  
Maria J. Gomes ◽  
...  

We compared hemostatic changes during OLT and HLT after various periods of graft storage, to investigate whether the host liver in HLT protects the recipient from hemostatic deterioration induced by severe graft storage damage. In particular, the mechanism of fibrinolytic deterioration was investigated. The effect of prostaglandin E1 (PGE1) on these parameters was also studied.Material and Methods: 69 pigs underwent either OLT (N = 32) or HLT (N = 37) with a graft stored for 2 hr (N = 31), 24 hr (N = 16), 48 hr (N = 7), or 72 hr (N = 15). PGE1 was given intravenously to both donor and recipient animals and was added to the preservation and flushing solutions. Fibrinolysis (euglobulin clot lysis time, t-PA activity and α2-antiplasmin) and coagulation parameters (activated partial thromboplasmin time, prothrombin time, fibrinogen and platelet count) were measured at several intervals during transplantation.Statistics: Univariate non-parametric tests were used for analysis of coagulation and fibrinolysis parameters. For the three main variables- i.e., the type of transplantation, the use of PGE1, and the preservation time, multiple regression analysis was performed.Results: Fibrinolytic activity increased during the anhepatic period of OLT. Graft reperfusion was followed by a rise in t-PA in both OLT and HLT. In HLT, t-PA quickly returned to normal, whereas a continuous increase was found in OLT. The coagulation parameters, in turn, remained unchanged during the anhepatic period and deteriorated in OLT compared to HLT. The duration of graft storage was directly related to the severity of the hemostatic changes, although this effect was more apparent in OLT than in HLT.Conclusions: Changes in hemostasis are more pronounced in OLT than in HLT. This suggests that the host liver protects the recipient from the effects of graft storage damage, even after long preservation times. Early postreperfusion fibrinolytic activity was presumably due to t-PA release from the graft both in OLT and HLT. The further rise t-PA in OLT might be caused by the release of cytokines from the graft, that subsequently evoke endothelial t-PA release. In HLT, t-PA and cytokines may be cleared by the native liver. No positive or negative effect of PGE1 on coagulation or fibrinolysis parameters was noticed.

1987 ◽  
Author(s):  
I Keber ◽  
K Potisk ◽  
D Keber ◽  
M Stegnar ◽  
N Vene

To determine the origin of tissue plasminogen activator (t-PA) release during physical activity, we studied the separate and combined effects of venous occlusion and acute physical activity on t-PA release in arm and leg. In 15 healthy volunteers 20 min venous occlusions of arm and leg were performed simultaneously before physical activity ( maximal stress testing on treadmill)(occlusion I), immediately after physical activity and 45 min later (occlusion II). Blood samples were drawn from unoccluded arm before occlusion and after physical activity, and from occluded arm and leg after occlusion. Fibrinolytic activity was measured by euglobulin clot lysis time (ECLT) and t-PA activity assay. The amount of released t-PA during different stimuli (fibrinolytic potential) was calculated as the difference between post- and prestimulation fibrinolytic activity. Before physical activity there was a great increase in fibrinolytic activity due to t-PA in the occluded arm but no increase in the occluded leg. Physical activity itself caused a similar increase of systemic fibrinolytic activity as arm occlusion locally. After physical activity arm occlusion evoked equally good response than before it. Fibrinolytic activity during leg occlusion behaved differently: there was an increase in t-PA activity in the occluded leg which persisted one hour after physical activity, when systemic fibrinolytic activity already fell to initial level.These results demonstrated that walking and running triggered t-PA release from the leg vessels. Since leg occlusion was not a stimulus for t-PA release, it served only as a method to demonstrate the effect of physical activity.


1992 ◽  
Vol 68 (04) ◽  
pp. 442-447 ◽  
Author(s):  
S C L Gough ◽  
J Smyllie ◽  
T Sheldon ◽  
P J S Rice ◽  
P J Grant

SummaryRegional circulating plasma levels of fibrinolytic activity were assessed in 15 patients undergoing cardiac catheterisation. The euglobulin clot lysis time (ECLT) was longer in the abdominal aorta (AA) than the inferior vena cava (IVC), (median difference – 17.5 min, p = 0.008). This was associated with higher inhibition of plasminogen activator activity (PAI) in the AA than IVC, – 1.75 IU/ml, p = 0.002. In the venous circulation the ECLT was higher in the peripheral venous sample than in the IVC, –25.5 min, p = 0.003, with higher PAI peripherally than in the IVC, -1.9 IU/ml, p = 0.001. There were no differences in ECLT, PAI, PAI-l:Ag or t-PA:Ag throughout the arterial circulation. These results demonstrate higher fibrinolytic activity with lower inhibitor activity in the venous compared to the arterial circulation. Within the venous circulation fibrinolytic activity is lower peripherally with increased inhibitor activity.


1971 ◽  
Vol 26 (01) ◽  
pp. 083-087 ◽  
Author(s):  
B Lipiński ◽  
A Nowak ◽  
A Odrzywolska ◽  
J Dosiak

SummaryIt was found in the present work that the level of serum fibrinogen degradation products (FDP) determined by the immunoassay method correlated well with the staphylococcal clumping titer in serum (correlation coefficient r = 0.68). The content of FDP in serum of 30 healthy subjects and patients with various diseases did not correlate, however, neither with blood fibrinolytic activity estimated by the euglobulin clot lysis time, nor with fibrinogen content and plasma anticlotting activity. It is concluded, that FDP appear in circulation as a result of local proteolytic degradation of intravascularly deposited fibrin without generalized activation of fibrinolysis.


1998 ◽  
Vol 4 (2) ◽  
pp. 133-137
Author(s):  
Nobuo Nagai ◽  
Tetsumei Urano ◽  
Yumiko Takada ◽  
Akikazu Takada

From the point of local regulation, we investigated fibrinolytic activity both in local and systemic circulations, using a venous occlusion test as a stimulus of tissue plasmin ogen activator (t-PA) release in human volunteers. Blood samples were taken before, during, and after venous occlusion from the occluded arm as trapped blood and the unoccluded arm as blood of systemic circulation. In these samples, fibri nolytic activity by euglobulin-clot lysis time and related factors in t-PA and plasminogen activator inhibitor-1 (PAI-1) were measured. Venous occlusion increased fibrinolytic activity ac companied by an increase in t-PA without an increase in PAI-1 on the occluded arm. The fibrinolytic activity on the unoc cluded arm did not change. Five minutes after reperfusion, however, a transient increase in PAI-1 and no change of fibri nolytic activity were observed in the unoccluded arm. Transient increase of PAI-1 after reperfusion was also observed in the occluded arm. These results suggested that increased t-PA by venous occlusion was neutralized by released PAI-1 after reperfusion. Key Words: Tissue-plasminogen activator— Euglobulin-clot lysis time—Fibrinolysis.


1983 ◽  
Vol 50 (03) ◽  
pp. 664-668 ◽  
Author(s):  
W Theiss ◽  
F Asbeck ◽  
A Kriessmann ◽  
G Trübestein ◽  
K Knoch ◽  
...  

SummaryIn a prospective, randomized trial 33 patients with deep vein thrombosis were treated either with 2,200 or 1,100 IU/kg/h urokinase or with 100,000 IU/h streptokinase for at least 6 days. While streptokinase was given continuously, urokinase was administered intermittently (12 hr urokinase alternating with 12 hr heparin).Urokinase treatment resulted in a dose-dependent fibrinolytic state with shortening of the euglobulin clot lysis time, easily demonstrable amidolytic activity and moderate decrease of plasminogen. At the end of each urokinase-free interval the fibrinolytic activity had mostly faded, but was reproducibly elicited again by each new urokinase administration. Streptokinase immediately evoked the customary, intense fibrinolytic state, which progressively tapered off as plasminogen fell to 1% of its pretreatment concentration. In all treatment groups α-2-antiplasmin dropped to approximately 40% of its initial value during the first 12 hr with a further decrease to about 20% after 6 days, α-2-macroglo- bulin fell only moderately with either urokinase regimen, whereas it decreased progressively to 45% under streptokinase.While the fibrinolytic activity decreased under streptokinase over the 6-day infusion period, it appeared to increase with each successive urokinase infusion particularly with 1100 IU/kg/h. Thus the final euglobulin clot lysis times and the final fibrinogen concentrations were similar in all three treatment groups on the sixth day.


1977 ◽  
Author(s):  
R. Zimmermann ◽  
A. Hoffrichter ◽  
E. Walter ◽  
P.D. Lang ◽  
W. Ehlers ◽  
...  

In addition to their effect on lipids Clofibrate and related drugs can influence platelet function and fibrinolytic activity. Interaction of these drugs with coumarin anticoagulants may induce hemorrhagic complications. Therefore the effect of a new hypolipemic agent (bezafibrate) on blood coagulation and components of the fibrinolytic encyme system was investigated.15 patients on long term treatment with phenprocoumon received bezafibrate (450 or 600 mg daily) for 4 weeks. Evaluation of platelet function demonstrated a reduced platelet aggregation induced by collagen (p < 0.05) and prolongation of bleeding time (p< 0.05), dependent on the given dose. Plasma fibrinogen was reduced moderately. Examination of the fibrinolytic activity yealded a shortened euglobulin clot lysis time (p < 0.05) but no changing of inhibitors. Serum level of phenprocoumon and bezafibrate were determined to obtain data about the mechanism of drug interaction. After reduction of the phenprocoumon dose by 20.6 or 28.7% the serum phenprocoumon levels decreased by 9-3 and 30.6%, respectively.Hypo-prothrombinemia was maintained (p< 0.05). The results support the hypothesis, that hypolipemic drugs such as bezafibrate augment the anticoagulant response to phenprocoumon by increasing the affinity of the receptor site for coumarin and not by effecting the rate of metabolism.


1964 ◽  
Vol 42 (1) ◽  
pp. 153-156 ◽  
Author(s):  
J. G. Ashwin ◽  
W. R. Coughlin

The plasma fibrinolytic activity in rats was measured by the euglobulin clot lysis time technique after injection of reserpine, serotonin, epsilon-aminocaproic acid, and UML-491. Fibrinolytic activity was increased by reserpine and serotonin, the extent depending on the dosage and route of administration. With serotonin, clot lysis time returned to normal after 6–12 hours. With reserpine, this occurred after 4 days. The antifibrinoiysin E-ACA was able to reduce fibrinolytic activity for more than 24 hours, whether given alone or with reserpine or serotonin. The antiserotonin UML-491 had a paradoxical fibrinolytic enhancing action that lasted for several hours alone, or given with serotonin it increased the fibrinolytic effect of serotonin.


1988 ◽  
Vol 59 (03) ◽  
pp. 495-499 ◽  
Author(s):  
V Grimaudo ◽  
J Hauert ◽  
F Bachmahh ◽  
E K O Kruithof

AbstractTo elucidate which component(s) of thei fibrinolytic system is (are) responsible for the diurnal variation of fibrinolytic activity we have studied several parameters of this system in 8 healthy male volunteers during a period of. 24 h. Blood was collected at 8 a. m., 10 a. m., 12 a. m., 4 p.m., 8 p.m. and 8 a. m. next morning. The following tests were performed: euglobulin clot lysis time (ECLT), fibrinolytic activity of euglobulins on fibrin plates in the presence and absence of blocking antibodies to tissue-type plasminogen activator (t-PA) and/or urokinase (u-PA), overall plasminogen activator inhibitor (PAI) activity, antigen levels of t-PA, u-PA and PAI-I and zymography of the euglobulin fraction after SDS-PAGE. From 8-10 a. m. to 4-8 p. m., total fibrinolytic activity increased by 1l3% (p <0.01) or 71%h (p <0.01) when measured by ECIX or by fibrin plate assay, respectively. The immunoquenching experiments showed that this increase was entirely due to t-PA related activity whereas u-PA activity and t-PA/u-PA independent activity remained constant during the day. Average antigen levels of u-PA and t-PA in the afternoon were 6% and 25% lower than those measured in the morning. During this period, overall PAI activity and PAI-1 antigen decreased by 3l% (p <0.01) and 52% (p <0.01) respectively. Electrophoretic-zymographic analysis of_ the euglobulins revealed that throughout the day the majority of t-PA was present in the form of the 110 kDa t-PA/PAI-I complex. The intensity of this cornplex was lowest in the afternoon. Free t-PA was almost undetectable in morning samples, but constituted a significant proportion of total t-PA in the afternoon. The diurnal increase of fibrinolytic activity, therefore, is not due to an augmentation of antigen levels of t-PA and/or u-PA but to a decline of those of PAI-1.


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