Fibrin Degradation Products, Fibrin Monomer and Soluble Fibrin in Disseminated Intravascular Coagulation

SummaryWe previously reported a monoclonal antibody named IF-43 that specifically recognizes thrombin-modified fibrinogen (desAA- and desAABB- fibrin monomer) bound with fibrinogen or other D1 domain-containing plasmic fragments such as fragments X, Y, and D1, but not intact fibrinogen or cross-linked fibrin degradation products (XDP). Here, we tentatively named such complexes, soluble fibrin monomer (FM) -fibrinogen complex.By utilizing IF-43, we have developed a kit to measure soluble FM-fibrinogen complex and compared the profiles with those of two established molecular markers for thrombo-embolic disorders: i.e. the thrombin-antithrombin complex (TAT) and the D-dimer in plasma of patients who underwent surgery without any thrombo-embolic complications. The result indicated that soluble FM-fibrinogen complex is a distinct entity from the two established molecular markers. We have also attempted to observe their profiles in patients with the disseminated intravascular coagulation syndrome (DIC). Although the profiles of soluble FM-fibrinogen complex in individual patients appeared to vary from one patient to the other, the plasma level of soluble FM-fibrinogen complex was found to be increased at the initial phase of disseminated intravascular coagulation syndrome. Thus, the soluble FM-fibrinogen complex may serve as an independent molecular marker for the detection of thrombin generation and the diagnosis of thrombosis. The soluble FM-fibrinogen complex may also serve as a risk factor for thrombosis, because it may precipitate as insoluble complexes beyond its threshold in plasma, or when it is modified by thrombin.Part of this paper was originally presented at the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.

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Platelet Function in Experimentally Induced Pancreatitis in the Dog

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661521 ◽

1986 ◽

Vol 55 (02) ◽

pp. 197-200 ◽

Cited By ~ 6

Author(s):

R M Jacobs ◽

R J Murtaugh ◽

R H Fertel

Keyword(s):

Platelet Function ◽

Disseminated Intravascular Coagulation ◽

Degradation Products ◽

Plasma Concentrations ◽

Adenosine Diphosphate ◽

Intravascular Coagulation ◽

Fibrin Degradation Products ◽

Functional Defect ◽

And Function ◽

Experimentally Induced

SummaryEvidence suggests that changes in prostaglandins and disseminated intravascular coagulation accompany pancreatitis. Both may induce changes in platelet function. We wished to determine if experimentally induced pancreatitis in the dog was associated with altered platelet number and function, and whether there were concomitant changes in prostaglandins. Evidence for disseminated intravascular coagulation in the dogs with pancreatitis were red blood cell fragmentation, increased platelet turnover indicated by macro-platelets and the transient presence of fibrin degradation products in urine. There were no significant changes in platelet count. The platelets from dogs with pancreatitis showed a functional defect characterized by significantly decreased aggregation in response to adenosine diphosphate, arachidonic acid, and collagen. Release of adenosine triphosphate from platelets was reduced in collagen-stimulated aggregation. There were no changes in the plasma concentrations of thromboxane B2, 6-Keto-PGF1a, and PGE2. This defect may have been due to the generation of fibrin degradation products and platelet “exhaustion”.

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D-dimer kit with a High FDP/D-Dimer Ratio is Useful for Diagnosing Thrombotic Diseases

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/10760296211070584 ◽

2022 ◽

Vol 28 ◽

pp. 107602962110705

Author(s):

Nozomi Ikeda ◽

Hideo Wada ◽

Yuhuko Ichikawa ◽

Minoru Ezaki ◽

Motoko Tanaka ◽

...

Keyword(s):

Venous Thromboembolism ◽

Critically Ill ◽

Disseminated Intravascular Coagulation ◽

Critically Ill Patients ◽

Degradation Products ◽

Intravascular Coagulation ◽

Fibrin Degradation Products ◽

Peripheral Arterial ◽

Thrombotic Diseases ◽

D Dimer

Introduction Although D-dimer is a useful biomarker of thrombosis, there are many D-dimer kits, with high and low fibrinogen and fibrin degradation products (FDP)/ D-dimer ratios. Methods Plasma D-dimer levels were measured using three different kits in critically ill patients to examine the usefulness of such measurements for detecting the thrombotic diseases and determining the correlation with the FDP and FDP/D-dimer ratio. Results Although three D-dimer kits showed marked utility for diagnosing disseminated intravascular coagulation (DIC) and peripheral arterial and venous thromboembolism (PAVTE), the D-dimer levels determined using the three kits varied among diseases. Indeed, one D-dimer kit showed a high FDP/D-dimer ratio, and another kit showed a low FDP/D-dimer ratio. D-dimer kit with low FDP/D-dimer ratio tended to have high cut-off values and low specificity for diagnosing DIC and PAVTE. In D-dimer kit with high FDP/D-dimer ratio, FDP/D-dimer ratios in patients with thrombosis was significantly higher than that in patients without thrombosis. Conclusion All three D-dimer kits show utility for detecting thrombotic diseases. However, the D-dimer levels determined using the kits varied due to differences in the FDP/D-dimer ratio. In combination with the FDP level, a D-dimer kit with a high FDP/D-dimer ratio may be useful.

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The Resistance of Soluble Derivatives of Fibrinogen and the Sensitivity of Its Insoluble Forms to Fibrinolytic Degradation in Blood

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647727 ◽

1974 ◽

Vol 32 (02/03) ◽

pp. 582-591 ◽

Cited By ~ 1

Author(s):

Victor Gurewich ◽

Andrzej Nowak ◽

Izabella Lipinska ◽

Boguslaw Lipinski

Keyword(s):

Fibrinolytic Activity ◽

Degradation Products ◽

Venous Occlusion ◽

Protamine Sulfate ◽

Electrophoretic Method ◽

Soluble Fibrin ◽

Fibrin Degradation Products ◽

Fibrin Monomer ◽

Derivatives Of

SummaryThe effect of naturally induced fibrinolytic activity on fibrinogen and certain soluble and insoluble derivatives was studied. Experiments were performed on blood removed after venous occlusion of the arm and immediately after death. A previously described electrophoretic method was used by which the heterogeneity of fibrinogen can be demonstrated directly in intact plasma. It was shown that fibrinogen, soluble fibrin monomer (FM) complexes and fibrin degradation products are resistant to degradation by naturally-induced fibrinolytic activity. By contrast, rapid lysis of fibrin, protamine sulfate (PS) precipitated fibrinogen, and PS and ethanol induced gels of FM occurred. The observations are believed relevant to our understanding of the pathway of fibrinogen and FM catabolism and the interpretation of the origin of serum FDP.

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Effect of Vitamin E on Endotoxin-Induced Disseminated Intravascular Coagulation in Rats

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657264 ◽

1982 ◽

Vol 48 (02) ◽

pp. 235-237 ◽

Cited By ~ 14

Author(s):

T Yoshikawa ◽

Y Furukawa ◽

M Murakami ◽

K Watanabe ◽

M Kondo

Keyword(s):

Platelet Count ◽

Vitamin E ◽

Disseminated Intravascular Coagulation ◽

Fibrinogen Level ◽

Degradation Products ◽

Tocopheryl Acetate ◽

Preventive Effect ◽

Intravascular Coagulation ◽

Fibrin Degradation Products ◽

Fibrin Thrombi

SummaryExperimental disseminated intravascular coagulation (DIC) can be induced by 4 hr sustained infusion of endotoxin in a dose of 100 mg/kg in rats. The experimental model of DIC in rats was used to study the preventive effect of vitamin E, α-tocopheryl acetate, against DIC. Before the infusion of endotoxin, 0.01, 0.1, 1.0 or 10.0 mg/kg/day of α-tocopheryl acetate was injected intraperitoneally for 4 successive days. The preventive effect against DIC was noted in all the parameters, such as fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count, and the number of renal glomeruli with fibrin thrombi, in rats treated with 1.0 or 10.0 mg/kg of α-tocopheryl acetate. From these results, it was shown that vitamin E, α-tocopheryl acetate, inhibited endotoxin-induced experimental DIC in rats.

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Effects of Ticlopidine and Aspirin on Endotoxin-Induced Disseminated Intravascular Coagulation in Rats

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657359 ◽

1983 ◽

Vol 49 (03) ◽

pp. 190-192 ◽

Cited By ~ 13

Author(s):

T Yoshikawa ◽

M Murakami ◽

Y Furukawa ◽

S Takemura ◽

M Kondo

Keyword(s):

Platelet Count ◽

Continuous Infusion ◽

Disseminated Intravascular Coagulation ◽

Partial Thromboplastin Time ◽

Fibrinogen Level ◽

Degradation Products ◽

Preventive Effect ◽

Intravascular Coagulation ◽

Fibrin Degradation Products ◽

Fibrin Thrombi

SummaryThe effects of ticlopidine and aspirin on endotoxin-induced experimental disseminated intravascular coagulation (DIC) were studied in rats. Experimental DIC was induced by a 4 hr sustained infusion of endotoxin at a dose of 100 mg/kg. The rats were intraperitoneally injected with ticlopidine at 2.0, 20.0, 50.0, 100.0 or 200.0 mg/kg, or aspirin at 0.03, 0.3, 3.0 or 30.0 mg/kg, followed by the continuous infusion of 100 mg/kg/4 hr of endotoxin. A preventive effect against DIC was noted in all the parameters, such as fibrinogen and fibrin degradation products (FDP), fibrinogen level, prothrombin time, partial thromboplastin time (PTT), platelet count and the number of renal glomeruli with fibrin thrombi, in the rats treated with 20.0, 50.0, 100.0 or mg/kg of ticlopidine. Although a preventive effect was also noted in FDP, PTT, platelet count and the number of glomeruli with thrombi in rats treated with 0.03 or 0.3 mg/kg of aspirin, this agent was less effective than ticlopidine.

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DETECTION OF SOLUBLE FIBRIN MONOMER COMPLEXES - COMPARISON OF A HAEMAGGLUTINATION ASSAY WITH THE ETHANOL GELATION TEST

10.1055/s-0038-1644886 ◽

1987 ◽

Author(s):

G Oehler ◽

H Klaus ◽

E Spanuth ◽

K E Stötzer

Keyword(s):

Degradation Products ◽

Positive Test ◽

Test Results ◽

Soluble Fibrin ◽

Fibrin Degradation Products ◽

Fibrin Monomer ◽

At Iii ◽

Positive Results ◽

Fibrin Monomers ◽

Gelation Test

Hypercoagulability and disseminated intravascularcoagulation (DIC) are characterized by the presenceof circulating fibrin monomer complexes in plasma.In342 patients with possible DIC fibrin monomers, fibrinogen, reptilase time, antithrombin III and othercoagulation parameters were determined at frequent intervals.Testing of soluble fibrin monomer complexeswas performed using a sensitive and reliable haemagglut- ination assay, with red cells sensitized by fibrin monomers (FM-Test) and the ethanol gelation test(EGT). Method comparison regarding the influence offibrinogen levels and fibrin degradation products shows that high fibrinogen levels lead to false positive results with EGT. The same effect is observed forfibrin degradation products and EGT whereas no influence of fibrinogen level and fibrin degradation products on the FM-Test occurs.It could be shown that with normal fibrinogen concentrations (200-400 mg/dl) the positive test results by FMT and EGT are comparable, whereas with fibrinogen concentrations below 200 mg/dl the number of positive results obtained with the EGT amounted to half the number given by FMT. In the case of fibrinogen concentrations above 400 mg/dl, positive results obtained with EGT were 3.3 times higher than FMT. Nearlyidentical results were obtained by comparing the influence of degradation products. In case of high degradation product concentrations, EGT gives 4.5 timesmore positive results than FMT.Further we compared the number of positive test results obtained by the FMT with the level of AT III because it is wellknown that the AT IIIHevel decreases caused by proteolytic activity generated in DIC.In this study it could be shown that fibrin monomer increases in parallel with the decrease of AT III. Thiseffect does not occur with fibrin degradation products.

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A Pathological Clarification of Sepsis-Associated Disseminated Intravascular Coagulation Based on Comprehensive Coagulation and Fibrinolysis Function

Thrombosis and Haemostasis ◽

10.1055/s-0040-1713890 ◽

2020 ◽

Vol 120 (09) ◽

pp. 1257-1269 ◽

Cited By ~ 1

Author(s):

Tomoko Onishi ◽

Keiji Nogami ◽

Takashi Ishihara ◽

Satoki Inoue ◽

Masahiko Kawaguchi ◽

...

Keyword(s):

Disseminated Intravascular Coagulation ◽

Degradation Products ◽

Waveform Analysis ◽

Peak Ratio ◽

Intravascular Coagulation ◽

Fibrin Degradation Products ◽

Functional Dynamics ◽

Underlying Diseases ◽

Plasmin Inhibitor ◽

Coagulation And Fibrinolysis

Abstract Background The functional dynamics of coagulation and fibrinolysis in patients with disseminated intravascular coagulation (DIC) vary due to the pathology and severity of various underlying diseases. Conventional measurements of hemostasis such as thrombin–antithrombin complex, plasmin-α2-plasmin-inhibitor complex, and fibrinogen-fibrin degradation products may not always reflect critical pathophysiologic mechanisms in DIC. This article aims to clarify the pathology of sepsis-associated DIC using assessment of comprehensive coagulation and fibrinolysis. Methods Plasma samples were obtained from 57 patients with sepsis-associated DIC at the time of initial diagnosis. Hemostasis parameters were quantified by clot-fibrinolysis waveform analysis (CFWA) and thrombin/plasmin generation assays (T/P-GA). The results were expressed as ratios relative to normal plasma. Results CFWA demonstrated that the maximum coagulation velocity (|min1|) ratio modestly increased to median 1.40 (min − max: 0.10 − 2.60) but the maximum fibrinolytic velocity (|FL-min1|) ratio decreased to 0.61 (0 − 1.19). T/P-GA indicated that the peak thrombin (Th-Peak) ratio moderately decreased to 0.71 (0.22 − 1.20), whereas the peak plasmin (Plm-Peak) ratio substantially decreased to 0.35 (0.02 − 1.43). Statistical comparisons identified a correlation between |min1| and Th-Peak ratios (ρ = 0.55, p < 0.001), together with a strong correlation between |FL-min1| and Plm-Peak ratios (ρ = 0.71, p < 0.001), suggesting that CFWA reflected the balance between thrombin and plasmin generation. With |min1| and |FL-min1| ratios, DIC was classified as follows: coagulation-predominant, coagulation/fibrinolysis-balanced, fibrinolysis-predominant, and consumption-impaired coagulation. The majority of patients in our cohort (80.7%) were coagulation-predominant. Conclusion A pathological clarification of sepsis-associated DIC based on the assessment of coagulation and fibrinolysis dynamics may be useful for the hemostatic monitoring and management of optimal treatment in these individuals.

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Disseminated Intravascular Coagulation Syndrome as a Complication in Acute Spontaneous Canine Babesiosis

Macedonian Veterinary Review ◽

10.2478/macvetrev-2020-0027 ◽

2020 ◽

Vol 43 (2) ◽

pp. 141-149

Author(s):

Oksana A. Dubova ◽

Diana V. Feshchenko ◽

Tetiana I. Bakhur ◽

Oksana A. Zghozinska ◽

Anatoliy A. Antipov ◽

...

Keyword(s):

Blood Pressure ◽

Blood Volume ◽

Disseminated Intravascular Coagulation ◽

Degradation Product ◽

Fibrin Degradation Product ◽

Canine Babesiosis ◽

Circulating Blood Volume ◽

Soluble Fibrin ◽

Intravascular Coagulation ◽

Fibrin Monomer

AbstractThe polyetiological syndrome of disseminated intravascular coagulation (DIC) is characterized by changes in patients’ hemostasis. The aim of the current research was to elucidate the main factors for the development of DIC syndrome during canine babesiosis, and to assess their correlation level. Dogs included in this study were of various breeds and sex, weighing 10-40 kg and aged 2-7 years. They were separated in two groups (n=50) according to their diagnosis to babesiosis. Oscillometry (blood pressure, pulse rate), vascular-platelet hemostasis, coagulogram, hematological, biochemical (fibrinogen, fibrin degradation product, soluble fibrin-monomer complex) and hemodynamic (circulating blood volume) assessment methods were used. The group of dogs positive on Babesia spp., had clear manifestation of DIC with 5-7% of the erythrocyte population being affected. DIC was manifested by a significant increase in soluble fibrin-monomer complex and fibrin degradation product (p<0.001), hypofibrinogenemia (p<0.001), thrombocytopenia (p<0.001), and an increase in indicators of spontaneous aggregation ability of platelets and red blood cells (p<0.001). Significant hemodynamic disorders were observed: a decrease in circulating blood volume, circulating erythrocytes volume (p<0.05), specific circulating blood volume and hematocrit value (p<0.001). The average blood pressure was reduced (p<0.001), and the Allgöwer’s shock index was increased 2 times (p<0.05). A shock of II degree (medium, subcompensated) was confirmed. Therefore, it can be concluded that acute spontaneous dogs’ babesiosis can be characterized by the occurrence of DIC in a consumption coagulopathy form, and shock of II degree. This condition renders the patients for emergency admission.

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DISSEMINATED INTRAVASCULAR COAGULATION IN THE NEWBORN

PEDIATRICS ◽

10.1542/peds.43.2.233 ◽

1969 ◽

Vol 43 (2) ◽

pp. 233-240

Author(s):

William E. Hathaway ◽

Marilyn M. Mull ◽

Giselle S. Pechet

Keyword(s):

Respiratory Distress ◽

Disseminated Intravascular Coagulation ◽

Degradation Products ◽

Newborn Infants ◽

Screening Tests ◽

Clotting Factor ◽

Intravascular Coagulation ◽

Fibrin Degradation Products ◽

Sick Newborn ◽

Idiopathic Respiratory Distress Syndrome

Eleven of 19 sick newborn infants were shown to have either laboratory and/or pathologic evidence of disseminated intravascular coagulation (DIC) during an observation period of 8 months. Three of the affected infants had severe viral diseases (rubella, cytomegalic inclusion virus, and herpes simplex). Seven of the infants had severe idiopathic respiratory distress syndrome (IRDS), and one infant (the product of a severely toxemic mother) had transient respiratory distress. The remainder of the sick infants had mild IRDS without evidence of DIC. Diagnosis of DIC in the newborn is best made by reliance upon specific clotting factor assays (platelets, fibrinogen, and factors V and VIII) rather than nonspecific screening tests or presence of fibrin degradation products. DIC may be a more common complication of severely ill newborn infants than is generally realized.

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