scholarly journals Fibrin fragment D-dimer and fibrinogen B beta peptides in plasma as markers of clot lysis during thrombolytic therapy in acute myocardial infarction

Blood ◽  
1990 ◽  
Vol 76 (7) ◽  
pp. 1341-1348 ◽  
Author(s):  
CM Lawler ◽  
EG Bovill ◽  
DC Stump ◽  
DJ Collen ◽  
KG Mann ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Degradation Product ◽  
Degradation Products ◽  
Tissue Type ◽  
Clot Lysis ◽  
Fibrin Degradation Product ◽  
Fibrin Degradation Products ◽  
Group 2 ◽  
D Dimer ◽  
Group 1

Abstract The validity of markers in plasma of in vitro thrombolysis was investigated in 12 patients with extensive fibrinogen breakdown (greater than 80%, group 1) and in 12 patients with minimal breakdown (less than 20%, group 2). The patients were treated with 100 mg of recombinant tissue-type plasminogen activator (rt-PA) in the “Thrombolysis in Myocardial Infarction II” (TIMI II) trial. Cross- linked fibrin degradation product levels were measured with two variant enzyme-linked immunosorbent assays (ELISAs), both using a fibrin fragment D-dimer specific capture antibody. In one instance, a tag antibody was used that cross-reacts with fibrinogen (pan-specific tag ELISA); in the other, the tag antibody was specific for fibrin fragment D (fibrin-specific tag ELISA). Apparent concentrations of cross-linked fibrin degradation products at baseline were within normal limits with both assays in most patients. At 8 hours after rt-PA infusion, the measured cross-linked fibrin degradation products were increased about twofold to fourfold in group 2 with both assays. However, in group 1, levels were significantly higher with the pan-specific tag ELISA (5.8 +/- 4.2 micrograms/mL) compared with the fibrin-specific tag ELISA (1.5 +/- 1.3 micrograms/mL). This observation was most likely a result of detection of fibrinogen degradation products in the pan-specific ELISA. Apparent levels of fibrinopeptide B beta 1–42, a marker of fragment X formation, increased during thrombolysis from 4.2 +/- 2.8 pmol/mL to 2,000 +/- 230 pmol/mL in group 1 and from 4.1 +/- 2.1 pmol/mL to 300 +/- 43 pmol/mL in group 2, and were correlated significantly with the extent of fibrinogen breakdown (r = -0.8). Fibrinopeptide beta 15–42 levels increased from 4.3 +/- 3 pmol/mL to 70 +/- 19 pmol/mL in group 1, but did not increase in group 2. The apparent increase in group 1 could be explained by cross-reactivity of fibrinopeptide B beta 1–42 in the fibrinopeptide beta 15–42 assay. We conclude that cross-linked fibrin degradation product levels as measured with a pan-specific tag ELISA and fibrinopeptide beta 15–42 levels as measured with certain monoclonal antibody-based ELISA are influenced by the extent of fibrinogen degradation. Fibrinopeptide B beta 1–42 is a marker specific for fibrinogen breakdown. Cross-linked fibrin degradation product levels, measured with a fibrin-specific tag ELISA, appear to be markers specific for thrombolysis. Consequently, assays similar to the fibrin- specific tag ELISA may provide more accurate information when correlated with clinical endpoints.

scholarly journals Fibrin fragment D-dimer and fibrinogen B beta peptides in plasma as markers of clot lysis during thrombolytic therapy in acute myocardial infarction

Blood ◽  
1990 ◽  
Vol 76 (7) ◽  
pp. 1341-1348 ◽  
Author(s):  
CM Lawler ◽  
EG Bovill ◽  
DC Stump ◽  
DJ Collen ◽  
KG Mann ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Degradation Product ◽  
Degradation Products ◽  
Tissue Type ◽  
Clot Lysis ◽  
Fibrin Degradation Product ◽  
Fibrin Degradation Products ◽  
Group 2 ◽  
D Dimer ◽  
Group 1

The validity of markers in plasma of in vitro thrombolysis was investigated in 12 patients with extensive fibrinogen breakdown (greater than 80%, group 1) and in 12 patients with minimal breakdown (less than 20%, group 2). The patients were treated with 100 mg of recombinant tissue-type plasminogen activator (rt-PA) in the “Thrombolysis in Myocardial Infarction II” (TIMI II) trial. Cross- linked fibrin degradation product levels were measured with two variant enzyme-linked immunosorbent assays (ELISAs), both using a fibrin fragment D-dimer specific capture antibody. In one instance, a tag antibody was used that cross-reacts with fibrinogen (pan-specific tag ELISA); in the other, the tag antibody was specific for fibrin fragment D (fibrin-specific tag ELISA). Apparent concentrations of cross-linked fibrin degradation products at baseline were within normal limits with both assays in most patients. At 8 hours after rt-PA infusion, the measured cross-linked fibrin degradation products were increased about twofold to fourfold in group 2 with both assays. However, in group 1, levels were significantly higher with the pan-specific tag ELISA (5.8 +/- 4.2 micrograms/mL) compared with the fibrin-specific tag ELISA (1.5 +/- 1.3 micrograms/mL). This observation was most likely a result of detection of fibrinogen degradation products in the pan-specific ELISA. Apparent levels of fibrinopeptide B beta 1–42, a marker of fragment X formation, increased during thrombolysis from 4.2 +/- 2.8 pmol/mL to 2,000 +/- 230 pmol/mL in group 1 and from 4.1 +/- 2.1 pmol/mL to 300 +/- 43 pmol/mL in group 2, and were correlated significantly with the extent of fibrinogen breakdown (r = -0.8). Fibrinopeptide beta 15–42 levels increased from 4.3 +/- 3 pmol/mL to 70 +/- 19 pmol/mL in group 1, but did not increase in group 2. The apparent increase in group 1 could be explained by cross-reactivity of fibrinopeptide B beta 1–42 in the fibrinopeptide beta 15–42 assay. We conclude that cross-linked fibrin degradation product levels as measured with a pan-specific tag ELISA and fibrinopeptide beta 15–42 levels as measured with certain monoclonal antibody-based ELISA are influenced by the extent of fibrinogen degradation. Fibrinopeptide B beta 1–42 is a marker specific for fibrinogen breakdown. Cross-linked fibrin degradation product levels, measured with a fibrin-specific tag ELISA, appear to be markers specific for thrombolysis. Consequently, assays similar to the fibrin- specific tag ELISA may provide more accurate information when correlated with clinical endpoints.

PLASMA LEVELS OF FRAGMENT D-DIMER OF CROSSLINKED FIBRIN DURING THROMBOLYTIC THERAPY WITH RECOMBINANT TISSUE-TYPE PLASMINOGEN ACTIVATOR

1987 ◽  
Author(s):  
P Declerck ◽  
P Mombaerts ◽  
P Holvoet ◽  
D Collen
Keyword(s):  
Thrombolytic Therapy ◽  
Plasma Levels ◽  
Degradation Products ◽  
Fibrin Clot ◽  
Tissue Type ◽  
Fibrin Degradation Products ◽  
Type Plasminogen Activator ◽  
Rate Of Increase ◽  
Significant Difference ◽  
D Dimer

Plasma levels of crosslinked fibrin degradation products (XLDP) were measured before and at the end of the administration of rt-PA (40 to 100 mg over 1.5 to 8 hours) in healthy volunteers (n=5) and patients with deep venous thrombosis (DVT) (n=8), pulmonary embolism (PE) (n=16)and myocardial infarction(MI)(n=10). Determinations were performed using our newly developed ELISA, specific for crosslinked fibrin derivatives, based on two monoclonal antibodies (15C5 and 8D3H2) raised against purified human fragment D-dimer. All plasma samples were collected on citrate and trasylol. Results are expressed as mean and range of D-dimer equivalents (μg/ml).Baseline levels in patients with MI are only slightly elevated. The increased levels inDVT and PE are in agreement with previous studies. After infusion of rt-PA a small increase of XLDP is seen even innormal subjects. A very marked increasof XLDP is detected in patients with PE and DVT but not in patients with MI. This may reflect differences in the amounts of fibrin clot dissolved in these patient groups.No significant correlation was found between the increase of XLDP and success of therapy, although a significant difference in D-dimer levels was formed between the two groups with PE: successful (n=ll): 116 (range 61-192) vs. unsuccessful (n=5): 68 (36-155).Thus, XLDP are already elevated under baseline conditions in patients with DVT and PE and increase very markedly during thrombolytic therapy. The absolute levels after thrombolytic therapy do not strictly correlate with success of therapy. It could be useful to measure D-dimer levels during early stages of therapy, because the rate of increase of XLDP levels might correlate with the efficacy of thrombolytic treatment.

scholarly journals The cofactor role of protein S in the acceleration of whole blood clot lysis by activated protein C in vitro

Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 1189-1192 ◽  
Author(s):  
NJ de Fouw ◽  
F Haverkate ◽  
RM Bertina ◽  
J Koopman ◽  
A van Wijngaarden ◽  
...  
Keyword(s):  
Whole Blood ◽  
Protein C ◽  
Degradation Products ◽  
Blood Clot ◽  
Activated Protein C ◽  
Protein S ◽  
Tissue Type ◽  
Clot Lysis ◽  
Fibrin Degradation Products

Abstract The effect of purified human activated protein C (APC) and protein S on fibrinolysis was studied by using an in vitro blood clot lysis technique. Blood clots were formed from citrated blood (supplemented with 125I-fibrinogen) by adding thrombin and Ca2+-ions; lysis of the clots was achieved by adding tissue-type plasminogen activator. The release of labeled fibrin degradation products from the clots into the supernatant was followed in time. We clearly demonstrated that APC accelerates whole blood clot lysis in vitro. The effect of APC was completely quenched by antiprotein C IgG, pretreatment of APC with diisopropylfluorophosphate, and preincubation of the blood with antiprotein S IgG. This demonstrates that both the active site of APC and the presence of the cofactor, protein S, are essential for the expression of the profibrinolytic properties. At present, the substrate of APC involved in the regulation of fibrinolysis is not yet known. Analysis of the radiolabeled fibrin degradation products demonstrated that APC had no effect on the fibrin cross-linking capacity of factor XIII.

Fibrinogen Fragments X, Y, D and E Increase Levels of Plasma Fibrinogen and Liver mRNAs Coding for Fibrinogen Polypeptides in Rats

1985 ◽  
Vol 53 (02) ◽  
pp. 212-215 ◽  
Author(s):  
H M G Princen ◽  
H J Moshage ◽  
J J Emeis ◽  
H J W de Haard ◽  
W Nieuwenhuizen ◽  
...  
Keyword(s):  
Regulatory Mechanism ◽  
Degradation Products ◽  
Mrna Level ◽  
Plasma Fibrinogen ◽  
Fibrin Degradation Product ◽  
Fibrinogen Degradation Products ◽  
Fibrin Degradation Products ◽  
First Time ◽  
D Dimer

SummaryPreviously, we demonstrated that in vivo regulation of liver fibrinogen synthesis occurs via the fibrinogen mRNA level. However, the molecular regulatory mechanism of fibrinogen synthesis is still not well understood. Fibrinogen or fibrin degradation products might play an important role in regulating fibrinogen synthesis. In our present study, we have injected rats intraperitoneally with purified homologous fragments and measured the liver content of mRNA specific coding for fibrinogen. Increased levels of fibrinogen mRNA and elevated plasma fibrinogen concentrations were observed in rats after administration of fibrinogen degradation products X, Y, DEGTA Dcate or E. Fragment E or E’ has a less stimulatory effect than X, Y or Dcate, whereas cross-linked fibrin degradation product D dimer does not increase fibrinogen synthesis. This article reports for the first time a stimulatory effect of the high molecular weight fibrinogen degradation products on fibrinogen synthesis.

DISSOCIATION BETWEEN DDE LEVEL AND RECANALIZATION IN PATIENTS UNDERGOING THROMBOLYTIC THERAPY FOR MYOCARDIAL INFARCTION. A POSSIBLE EXPLANATION

1987 ◽  
Author(s):  
Mc Mirshahi ◽  
J Soria ◽  
C Soria ◽  
Ma Xi ◽  
M Mirshahi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Monoclonal Antibody ◽  
Thrombolytic Therapy ◽  
Degradation Products ◽  
Careful Analysis ◽  
Tissue Type ◽  
Fibrin Degradation Products ◽  
Type Plasminogen Activator ◽  
Sds Page ◽  
Almost All

The aim of this work was to determine whether plasma fibrin degradation products (FbDP) level may be used as a marker of recanalization in patients undergoing thrombolytic therapy for myocardial infarction. Samples were collected in patients treated by a 90 minutes infusion of 60 mg recombinant tissue type plasminogen activator (rtpA). Plasma FbDP (DDE complexes) were specifically and reliably determined by Elisa using a personal monoclonal antibody. Additional identification of FbDP and fibrinogen derived fragment D was performed by SDS PAGE followed by their detection using an anti D neo monoclonal antibody.Fragment D was only evidenced up to the end of rtpA infusion. Concerning FbDP levels : prior to treatment, each patient presented FbDP levels within the normal range. After rtpA infusion, FbDP were increased in almost all cases, but our results clearly demonstrated that this increase was not correlated with coronary recanalization : on one hand, FbDP (D dimer and YD complex) were increased at the end of rtpA infusion in patients for whom the treatment was efficient as proved by angiography but also in five of seven patients who did not reperfuse. On the other hand, in most cases even in patients presenting a good recanalization at the end of rtpA infusion, a further increase in FbDP was noted even 6 hours after the end of the infusion.It is therefore suggested that FbDP came either from a degradation of fibrin from different sources that coronary thrombus or coagulation in coranary artery was going on. A careful analysis of a possible activation of coagulation during thrombolytic therapy is under investigation.In this way in patients under thrombolytic therapy, we propose to investigate the balance between coagulation and fibrinolysis by determining at the same time the level of plasma fibrinopeptide A and DDE complexes.

Fibrin Metabolism in Patients with Acute Myocardial Infarction During and After Treatment with Tissue-Type Plasminogen Activator

1988 ◽  
Vol 60 (03) ◽  
pp. 428-433 ◽  
Author(s):  
Michael E Ring ◽  
Samuel M Butman ◽  
Denise C Bruck ◽  
William M Feinberg ◽  
James J Corrigan
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Molecular Markers ◽  
Plasminogen Activator ◽  
Degradation Products ◽  
Fibrinolytic Therapy ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Fibrin Degradation Products ◽  
Type Plasminogen Activator

SummaryIn order to define some of the determinants of successful thrombolysis and reocclusion during fibrinolytic therapy for acute myocardial infarction (AMI), specific molecular markers of fibrin metabolism were serially measured in 15 patients with AMI treated with tissue-type plasminogen activator (t-PA). Fibrin formation was assessed by measurement of fibrinopeptide A (FpA) and fibrinolysis by assay of B-P peptides 1—42 and 15—42 and crosslinked fibrin degradation products (XDP). At baseline, FpA levels were high while markers of fibrinolysis were near normal. Following a 90-minute infusion of t-PA (0.5—1.1 mg kg−1 hr−1), all markers of fibrinolysis increased. Levels of FpA remained elevated despite heparin at the initiation of cardiac catheterization. None of these markers discriminated between patients with successful reperfusion from those without. At 4 hours, B-β 15—42 peptide and XDP levels remained elevated suggesting persistence of fibrinolysis beyond the short circulatory half-life of t-PA. FpA levels at 4 hours were lower in patients who underwent acute coronary angioplasty compared to those who received additional low dose t-PA (12.3 ± 4.5 vs. 30.4 ± 5.5 ng/ ml, p <0.05). By 48 hours, markers of fibrinolysis had returned toward normal except in 2 patients with persistently elevated B-P 15—42 peptide levels who suffered reocclusion on days 5 and 6 (75 and 44 vs. 29 ± 3 nM, p <0.005). In conclusion, molecular markers of fibrin metabolism during fibrinolytic therapy may provide clinically relevant data.

scholarly journals The cofactor role of protein S in the acceleration of whole blood clot lysis by activated protein C in vitro

Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 1189-1192
Author(s):  
NJ de Fouw ◽  
F Haverkate ◽  
RM Bertina ◽  
J Koopman ◽  
A van Wijngaarden ◽  
...  
Keyword(s):  
Whole Blood ◽  
Protein C ◽  
Degradation Products ◽  
Blood Clot ◽  
Activated Protein C ◽  
Protein S ◽  
Tissue Type ◽  
Clot Lysis ◽  
Fibrin Degradation Products

The effect of purified human activated protein C (APC) and protein S on fibrinolysis was studied by using an in vitro blood clot lysis technique. Blood clots were formed from citrated blood (supplemented with 125I-fibrinogen) by adding thrombin and Ca2+-ions; lysis of the clots was achieved by adding tissue-type plasminogen activator. The release of labeled fibrin degradation products from the clots into the supernatant was followed in time. We clearly demonstrated that APC accelerates whole blood clot lysis in vitro. The effect of APC was completely quenched by antiprotein C IgG, pretreatment of APC with diisopropylfluorophosphate, and preincubation of the blood with antiprotein S IgG. This demonstrates that both the active site of APC and the presence of the cofactor, protein S, are essential for the expression of the profibrinolytic properties. At present, the substrate of APC involved in the regulation of fibrinolysis is not yet known. Analysis of the radiolabeled fibrin degradation products demonstrated that APC had no effect on the fibrin cross-linking capacity of factor XIII.

FIBRIN DEGRADATION PRODUCTS (FbDP) IN HEALTHY VOLUNTEERS AFTER INFUSION OF RECOMBINANT TISSUE-TYPE PLASMINOGEN ACTIVATOR(rt-PA)

1987 ◽  
Author(s):  
E Seifried ◽  
D C Rijken ◽  
B Hoeqee ◽  
P TansiAiell ◽  
C Kluft ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Degradation Products ◽  
Systemic Effect ◽  
Tissue Type ◽  
Group Iii ◽  
Coronary Thrombolysis ◽  
Fibrin Degradation Products ◽  
Group I ◽  
Type Plasminogen Activator ◽  
D Dimer

During thrombolytic therapy of myocardial infarction (MI) with urokinase or streptokinase (SK), levels of fibrin(ogen) degradation products in serum are often dramatically elevated as a result of a combination of systemic fibrinogenolysis and local thrombolysis. Others have measured increased levels of D-dimer in serum of MI patients after SK therapy and postulated that thrombolysis could be monitored during SK therapy by measuring D-dimer levels. In the present study rt-PA was infused into healthy volunteers to analyse if elevated FbDP levels in MI patients really reflect coronary thrombolysis or could be due to a systemic effect. Over a period of 60 min., three groups (n = 6 each) were given i.v. 0.23 mg rt-PA/'kg (group I), 0.50 mg rt-PA/kg (group II) and a placebo infusion (group III), respectively. Two blood samples were taken from an anticubital vein in the arm contralateral to the site of infusion (one on citrate/ aprotinin, the other on citrate alone) at different time points. Using a new enzyme immunoassay (EIA), based on monoclonals and development by us, we measured FbDP in plasma (not serum). Before infusion all volunteers had FbDP levels ≪ 0.5µg/ml. Upon infusion FbDP levels in groups I and II increased to average values of 1.0 ± 0.4/µg/ml and 0.8 ± 0.2/µg/ml, respectively, for the samples taken in citrate/aprotinin. The values in citrate alone did not differ significantly, and were 1.1 ± 0.5/µg/ml and 0.8 ± 0.3/µg/ml for groups I and II, respectively. FbDP levels in group III remained ≪ 0.5/µg/ml. The results show that FbDP levels increase upon rt-PA infusion, even in healthy volunteers. This suggests lysis of systemic fibrin. We conclude that lysis of systemic fibrin limits the value of FbDP levels as a measure for coronary thrombolysis.

Usefulness of Dialysate Fibrin Degradation Products and Lactic Dehydrogenase Isoenzyme Patterns in Assessing the Clinical Course of Peritonitis

1994 ◽  
Vol 14 (3) ◽  
pp. 231-235 ◽  
Author(s):  
Kazuyuki Suzuki ◽  
Makoto Ishizaki ◽  
Osamu Hotta ◽  
Ikuo Horigome ◽  
Katsuhiko Sudo ◽  
...  
Keyword(s):  
Clinical Course ◽  
Degradation Products ◽  
Lactic Dehydrogenase ◽  
Fibrin Degradation Products ◽  
Ldh Isoenzyme ◽  
Group 3 ◽  
Group 2 ◽  
Isoenzyme Patterns ◽  
Lactic Dehydrogenase Isoenzyme ◽  
Group 1

Objective To establish the usefulness of fibrin degradation products (FDP) and lactic dehydrogenase isoenzyme patterns (LDH isoenzyme) in assessing the clinical course of peritonitis. Design A retrospective study of patients with peritonitis who were divided into three groups according to their clinical course. Setting Single dialysis unit of a general hospital. Interventions Patients were treated by intraperitoneal and oral antibiotics. Patients Twenty-six patients with 34 episodes of peritonitis were studied. Group 1 consisted of 21 patients with 26 recoveries from peritonitis; Group 2 consisted of 5 patients with 5 relapsing episodes of peritonitis, and Group 3 consisted of 3 patients with 3 persistent episodes of peritonitis. Main Outcome Measures Concentrations of WBCs, FDP, LDH isoenzyme and microbiological culture of the dialysate were determined. Results In most of Group 1, WBCs, FDP, and LDH isoenzyme returned to normal within 2 weeks. In 4 patients of Group 1, who had complications (diverticulitis, cholecystitis, cystitis, and tunnel infection), WBCs, FDP, and LDH isoenzyme returned to normal gradually within 3 weeks. In Group 2, WBCs returned to normal, but FDP remained relatively high and LDH isoenzyme did not normalize. In Group 3, WBCs, FDP and LDH isoenzyme did not normalize. Conclusions Failure of normalization of FDP and LDH isoenzyme suggests an incomplete recovery from peritonitis. FDP and LDH isoenzyme are useful in assessing the course of peritonitis.

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