scholarly journals Decreased Thrombin Activity of Fibrin Clots Prepared in Cord Plasma Compared with Adult Plasma

1996 ◽  
Vol 39 (5) ◽  
pp. 826-830 ◽  
Author(s):  
Paresh Patel ◽  
Jeffrey Weitz ◽  
Lu Ann Brooker ◽  
Bosco Paes ◽  
Lesley Mitchell ◽  
...  
Keyword(s):  
Cord Plasma ◽  
Thrombin Activity ◽  
Adult Plasma ◽  
Fibrin Clots

Fibrin Clot Lysis by Thrombolytic Agents Is Impaired in Newborns due to a Low Plasminogen Concentration

1992 ◽  
Vol 68 (03) ◽  
pp. 325-330 ◽  
Author(s):  
M Andrew ◽  
L Brooker ◽  
M Leaker ◽  
B Paes ◽  
J Weitz
Keyword(s):  
Thrombolytic Agent ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Therapeutic Effectiveness ◽  
Thrombolytic Agents ◽  
Cord Plasma ◽  
Tissue Plasminogen ◽  
Adult Plasma ◽  
Low Levels ◽  
Fibrin Clots

SummaryAlthough thrombolytic drugs have been extensively used in adults, there is sparse information on their effectiveness in newborns whose fibrinolytic system differs significantly from adults. The purpose of this study was to determine if low plasma levels of plasminogen in cord plasma limited the therapeutic effectiveness of thrombolytic agents. Urokinase (UK), streptokinase (SK) and tissue plasminogen activator (TPA) were compared for their ability to lyse washed 125I-labelled adult or cord fibrin clots suspended in cord or adult plasma. 125I-labelled fibrin clots were prepared by recalcifying cord or adult plasma spiked with labelled fibrinogen and then placed into cord or adult plasma which contained either saline or differing amounts of a specific thrombolytic agent. After a 60 min incubation, the remaining 125I-fibrin in clots released 125I-fibrin fragments, and concentrations of fibrinogen, α2-antiplasmin, and plasminogen in the bathing plasma were measured and compared to starting values. Cord fibrin clots were more resistant than adult fibrin clots to all thrombolytic drugs tested (p <0.001). On average, the cord system retained 27% more 125I-fibrin in clots, and released 32% less 125I-fibrin fragments into plasma. Fibrinogenolysis was also decreased in cord plasmas compared to adult plasmas. The degree of fibrinolysis and fibrinogenolysis in cord plasma increased to adult values when plasminogen concentrations were increased in the bathing plasma. Thus, cord fibrin clots have an impaired response to thrombolytic agents secondary to low levels of plasminogen. We speculate that the clinical response of newborns to thrombolytic agents is also impaired and will not be enhanced by increasing doses of thrombolytic agents but may be enhanced by increasing the concentration of plasminogen.

The procoagulant effects of factor V Leiden may be balanced against decreased levels of factor V and do not reflect in vivo thrombin formation in newborns

2006 ◽  
Vol 95 (03) ◽  
pp. 434-440 ◽  
Author(s):  
Satu Hyytiäinen ◽  
Ulla Wartiovaara-Kautto ◽  
Veli-Matti Ulander ◽  
Risto Kaaja ◽  
Markku Heikinheimo ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Platelet Rich Plasma ◽  
Venous Blood ◽  
Factor V Leiden ◽  
Factor V ◽  
Cord Plasma ◽  
Adult Plasma ◽  
Thrombin Formation

SummaryThrombin regulation in newborns remains incompletely understood.We studied tissue factor-initiated thrombin formation in cord plasma in vitro, and the effects of Factor VLeiden (FVL) heterozygosity on thrombin regulation both in vitro and in vivo in newborns. Pregnant women with known thrombophilia (n=27) were enrolled in the study. Cord blood and venous blood at the age of 14 days were collected from 11 FVL heterozygous newborns (FVL-positive) and from 16 FVL-negative newborns. Prothrombin fragment F1+2 and coagulation factors were measured. Tissue factor-initiated thrombin formation was studied in cord platelet-poor plasma (PPP) of FVL-negative and -positive newborns, and in both PPP and platelet-rich plasma (PRP) of healthy controls. The endogenous thrombin potential (ETP) in cord PPP or PRP was ∼60% of that in adult plasma, while thrombin formation started ∼55% and ∼40% earlier in cord PPP and PRP, respectively. Further, in FVL-positive newborns thrombin formation started significantly earlier than in FVL-negative newborns. Exogenous activated protein C (APC) decreased ETP significantly more in cord than in adult PRP. In FVL-negative cord plasma 5nM APC decreased ETP by 17.4±3.5% (mean±SEM) compared with only 3.5±3.8% in FVL-positive cord plasma (p=0.01). FVL-positive newborns showed similar levels of F1+2 but significantly decreased levels of factor V compared with FVL negative newborns both in cord plasma (FV 0.82±0.07 U/ml vs. 0.98±0.05 U/ml, p=0.03) and at the age of two weeks (FV 1.15±0.04 U/ml vs. 1.32±0.05 U/ml, p=0.03). In conclusion, newborn plasma showed more rapid thrombin formation and enhanced sensitivity to APC compared with adult plasma. FVL conveyed APC resistance and a procoagulant effect in newborn plasma. Lack of elevated F1+2 levels in FVL-positive infants, however, suggested the existence of balancing mechanisms; one could be the observed lower level of factor V in FVL heterozygous newborns.

scholarly journals Higher Concentrations of Heparin and Hirudin Are Required to Inhibit Thrombin Generation in Tissue Factor–Activated Cord Plasma Than in Adult Plasma

2005 ◽  
Vol 57 (5 Part 1) ◽  
pp. 685-689 ◽  
Author(s):  
Katrin Baier ◽  
Gerhard Cvirn ◽  
Peter Fritsch ◽  
Martin Köstenberger ◽  
Siegfried Gallistl ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Thrombin Generation ◽  
Cord Plasma ◽  
Adult Plasma

Decreased Concentrations of Heparinoids Are Required to Inhibit Thrombin Generation in Plasma from Newborns and Children Compared to Plasma from Adults due to Reduced Thrombin Potential

2002 ◽  
Vol 87 (04) ◽  
pp. 606-613 ◽  
Author(s):  
Leslie Berry ◽  
Paul Monagle ◽  
Maureen Andrew ◽  
Anthony Chan
Keyword(s):  
Low Molecular Weight Heparin ◽  
Thrombin Generation ◽  
The Other ◽  
Low Molecular Weight ◽  
Chromogenic Substrate ◽  
Contact Activation ◽  
Cord Plasma ◽  
Α2 Macroglobulin ◽  
Adult Plasma ◽  
Similar Peak

SummaryThrombin generation is decreased and delayed in plasma from newborns and children compared to adults. We hypothesized that lower doses of heparinoid anticoagulants are required to give similar thrombin generation in newborn (umbilical cord) and child plasmas compared to that of adults. Thrombin generation was performed in either the absence or presence of unfractionated heparin (UFH), low molecular weight heparin (LMWH) or a covalent antithrombin-heparin complex (ATH). After contact activation and recalcification of each plasma, thrombin activity was measured by periodic sub-sampling into chromogenic substrate. UFH inhibited thrombin generation to a greater extent compared to LMWH in all plasmas. Cord plasma was more sensitive to inhibition and displayed a greater difference in the effectiveness of UFH compared to LMWH than other plasmas. Lower concentrations of UFH and LMWH were required to inhibit thrombin generation in cord and child plasmas compared to adult plasma. In comparison, ATH strongly inhibited thrombin generation in all 3 plasmas. Similar peak thrombin concentrations were observed at lower ATH concentrations (0.1 U/mL) compared to either UFH (0.25 U/mL) or LMWH (0.25 U/mL). As with UFH and LMWH, cord plasma was more sensitive to inhibition by ATH than the other plasmas and lower ATH concentrations inhibited thrombin generation in cord and child plasmas compared to adult plasma. Decreased thrombin generation with heparinoids in cord and child plasmas compared to adult plasma coincided with decreased rates of prothrombin consumption and increased proportion of thrombin- α2-macroglobulin inhibitor complexes. In summary, lower doses of UFH, LMWH or ATH result in similar peak thrombin generation in newborn and child plasmas compared to adult plasma. Cord plasma was the most sensitive to inhibition, with ATH being more effective than UFH or LMWH.

α2-MACROGLOBULIN IS A MORE IMPORTANT INHIBITOR OF THROMBIN IN INFANT PLASMA THAN IN ADULT PLASMA

1987 ◽  
Author(s):  
F Fernandez ◽  
B Schmidt ◽  
M Andrew ◽  
F A Ofosu
Keyword(s):  
Antithrombin Iii ◽  
The Other ◽  
Heparin Cofactor Ii ◽  
Cord Plasma ◽  
Α2 Macroglobulin ◽  
Sds Page ◽  
Adult Plasma ◽  
Presence And Absence

The concentrations of the three major inhibitors of thrombin (IIa) differ significantly in adult and infant plasma. The extent to which these differences contribute to the rates and profiles of IIa inhibition in infant and adult plasma is unknown. We determined this by adding 2 NIH U/mL of I-human α-IIa to anequal volume of defibrinated plasma for 30s at 37°C. After SDS�PAGE and autoradiography, free Ila and complexes of IIa with antithrombin III (IIa-ATIII), heparin cofactor II (IIa-HCII) and α2-macroglobulin (αa-α2M) were quantitated in 3 types of pooled plasmas: cord; 6 month old infant and adult. Thrombin was inhibited more slowly incord plasma than in adult plasma (p‹0.001). in addition, while ATIII was the major inhibitor of Ila in adult plasma, ouM was equally as important as ATI 11 in cord and infant plasmas (p‹0.001). When cord plasma was supplemented with purified ATIII, the extents and profile of Ila inhibition by cord and adult plasmas were indistinguishable. The addition of heparin (0.2U/mL) accelerated the inhibition of Ila by all 3 plasmas, with ATIII the predominant inhibitor. Thus, 83% of the inactive Ila was bound to ATIII in adult plasma, 77% in each of cord and 6 month old infant plasmas. However, significantly more Ila was inactivated by adult plasma than the other two plasmas. These results suggest that cord plasmas are intrinsically less able to inactivate Ila than adult plasma. While the overall ability of the plasma of 6 month old infants to inactive Ila is comparable to adult plasma, the profile of inhibition of Ila in the former, both in the presence and absence of heparin, is more closely related to neonatal than adult plasma, likely reflecting high αM levels.

Radiolabeled r-Hirudin as a Measure of Thrombin Activity at, or within, the Rabbit Aorta Wall In Vitro and In Vivo

1994 ◽  
Vol 71 (04) ◽  
pp. 499-506 ◽  
Author(s):  
Mark W C Hatton ◽  
Bonnie Ross-Ouellet
Keyword(s):  
Rabbit Aorta ◽  
Balloon Injury ◽  
Recombinant Hirudin ◽  
Aorta Wall ◽  
Thrombin Activity ◽  
Before And After ◽  
The Matrix

SummaryThe behavior of 125I-labeled recombinant hirudin towards the uninjured and de-endothelialized rabbit aorta wall has been studied in vitro and in vivo to determine its usefulness as an indicator of thrombin activity associated with the aorta wall. Thrombin adsorbed to either sulfopropyl-Sephadex or heparin-Sepharose bound >95% of 125I-r-hirudin and the complex remained bound to the matrix. Binding of 125I-r-hirudin to the exposed aorta subendothelium (intima-media) in vitro was increased substantially if the tissue was pre-treated with thrombin; the quantity of l25I-r-hirudin bound to the de-endothelialized intima-media (i.e. balloon-injured in vitro) correlated positively with the quantity of bound 131I-thrombin (p <0.01). Aortas balloon-injured in vivo were measured for thrombin release from, and binding of 125I-r-hirudin to, the de-endothelialized intimal surface in vitro; 125I-r-hirudin binding correlated with the amount of active thrombin released (p <0.001). Uptake of 125I-r-hirudin by the aorta wall in vivo was proportional to the uptake of 131I-fibrinogen (as an indicator of thrombin activity) before and after balloon injury. After 30 min in the circulation, specific 125I-r-hirudin binding to the uninjured and de-endo- thelialized (at 1.5 h after injury) aorta wall was equivalent to 3.4 (± 2.5) and 25.6 (±18.1) fmol of thrombin/cm2 of intima-media, respectively. Possibly, only hirudin-accessible, glycosaminoglycan-bound thrombin is measured in this way.

In Vitro Studies on the Mechanism of the Antifibrino-lytic Action of E-Aminocaproic Acid (EACA)

1968 ◽  
Vol 19 (03/04) ◽  
pp. 584-592 ◽  
Author(s):  
Hanna Lukasiewicz ◽  
S Niewiarowski
Keyword(s):  
Aminocaproic Acid ◽  
Test Tube ◽  
In Vitro Studies ◽  
Lytic Action ◽  
Human Plasminogen ◽  
Experimental Findings ◽  
Fibrin Clots

Summary and Conclusion1. It has been found that EACA does not inhibit activation of human plasminogen into plasmin by SK and UK in a concentration of 5 × 10–2 M. The activation of bovine plasminogen by SK and UK is inhibited by this concentration of EACA but not by a lower one.2. EACA in concentrations of 1,5 × 10–1 – 10–4 M does not inhibit casein proteolysis by plasmin. The proteolysis of fibrinogen and fibrin measured by the release of TCA soluble tyrosine is inhibited by EACA in concentrations of 1,5 × 10–1 – 10–2 M.3. The lysis of non-stabilized clots by plasmin measured in a test tube was inhibited by an EACA concentration of 5 × 10–3 – 5 × 10–4 M. The lysis of stabilized clots by plasmin was inhibited by an EACA concentration of 10–5 M.4. On the basis of experimental findings and data given in literature the authors postulate that the mechanism of the antifibrinolytic effects of EACA consists mainly in a modification of plasmin action on fibrin. These effects are dependent on the structure of the fibrin clots.

Molecular Forms of Human Protein C: Comparison and Distribution in Human Adult Plasma

1989 ◽  
Vol 62 (03) ◽  
pp. 902-905 ◽  
Author(s):  
Brian S Greffe ◽  
Marilyn J Manco-Johnson ◽  
Richard A Marlar
Keyword(s):  
Heavy Chain ◽  
Protein C ◽  
Molecular Forms ◽  
Post Translational Modification ◽  
Single Chain ◽  
Beta Form ◽  
Sds Page ◽  
Dependent Protein ◽  
Adult Plasma ◽  
The Difference

SummaryProtein C (PC) is a vitamin K-dependent protein which functions as both an anticoagulant and profibrinolytic. It is synthesized as a single chain protein (SC-PC) and post-transla-tionally modified into a two chain form (2C-PC). Two chain PC consists of a light chain (LC) and a heavy chain (HC). The present study was undertaken to determine the composition of the molecular forms of PC in plasma. PC was immunoprecipitated, subjected to SDS-PAGE and Western blotting. The blots were scanned by densitometry to determine the distribution of the various forms. The percentage of SC-PC and 2C-PC was found to be 10% and 90% respectively. This is in agreement with previous work. SC-PC and the heavy chain of 2C-PC consisted of three molecular forms (“alpha”, “beta”, and “gamma”). The “alpha” form of HC is the standard 2C form with a MW of 40 Kd. The “beta” form of HC has also been described and has MW which is 4 Kd less than the “alpha” form. The “gamma” species of the SC and 2C-PC has not been previously described. However, its 3 Kd difference from the “beta” form could be due to modification of the “beta” species or to a separate modification of the alpha-HC. The LC of PC was shown to exist in two forms (termed form 1 and form 2). The difference between these two forms is unknown. The molecular forms of PC are most likely due to a post-translational modification (either loss of a carbohydrate or a peptide) rather than from plasma derived degradation.

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