fibrinopeptide-a and Disseminated-Intravascular-Coagulation

Topics: Biomarkers; Blood Coagulation Tests; Cerebral Infarction; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Fibrinopeptide B; Humans; Immunoenzyme Techniques; Myocardial Infarction; Peptide Fragments; Pulmonary Embolism; Radioimmunoassay; Thrombophilia; Venous Thrombosis

DIC is an acquired disorder in which intravascular coagulation may lead to microvascular fibrin formation and a hemorrhagic diathesis. If DIC is acute and severe, fibrin formation may lead to microvascular thrombosis, and consumption of coagulation factors and platelets may result in a hemorrhagic diathesis. Secondary to or simultaneously with coagulation, the fibrinolytic system may be activated, accentuating the bleeding tendency. All the systems involved in DIC, such as coagulation, fibrinolysis, kallikrein-kinin, complement, and possibly other systems are regulated. Coagulation is the central event of DIC. The different coagulation factor derivatives may be generated that can be determined and used as markers for the degree of DIC and for effective control of therapy. Some of the procoagulant and anticoagulant factors are converted in the course of coagulation to their active forms and activation peptides. The active factor is subsequently neutralized by forming a complex with an inhibitor. Hemostatic molecular markers, D-dimer of cross-linked fibrin degradation products (D-dimer), thrombin-antithrombin III complex (TAT), and plasmin-alpha 2-plasmin inhibitor complex (PIC) have all been used for the diagnosis of DIC.

Topics: alpha-2-Antiplasmin; Antifibrinolytic Agents; Antithrombin III; Biomarkers; Diagnosis, Differential; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinopeptide A; Humans; Leukemia, Promyelocytic, Acute; Peptide Hydrolases

The mutual relationships between malignant tumours and mechanisms of blood coagulation are presented in a brief survey. In this connection, the mechanisms of a tumour cell entering the circulation through the vessel well and its leaving into the tissues are discussed, the theory of microtrauma being used for explaining these processes. Subsequently, the alterations to be found in the count and function of thrombocytes after contact with a malignant cell and the impact on this cell by blood platelets are represented. As a third factor the activation of blood coagulation which is exercised by substances with a procoagulatory effect produced by the malignant tissue and the frequently observed thrombosis in the course of neoplastic diseases are dealt with in connection with blood level changes of some coagulation factors. In a fourth section the significance of fibrinolysis, its activation and inhibition as well as the production of fibrinolytic activators by neoplasms are discussed.

Topics: Animals; Blood Coagulation Factors; Blood Platelets; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Fibrinopeptide A; Fibrinopeptide B; Humans; Neoplasms; Neoplastic Cells, Circulating; Plasminogen Activators; Platelet Aggregation; Thromboembolism

Topics: Chemical Phenomena; Chemistry; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysin; Fibrinopeptide A; Fibrinopeptide B; Humans; Kidney Diseases; Kinetics; Methods; Pulmonary Embolism; Solubility; Thrombin; Thrombophlebitis

A variety of mechanisms may cause intravascular coagulation. Fibrinolysis is nearly always secondary to the initial clotting. In the acute form, ICF is characterized by depletion of platelets and several coagulation factors together with active fibrinolysis. There is a decrease in Factors V and VIII because they are sensitive to coagulation. The stable coagulation factors may be decreased as well because after activation they are removed from the circulation by the liver and reticuloendothelial system. Severe bleeding is the usual accompaniment of the acute syndrome, which may also occur in cancer and infection of all types. The acute syndrome may also occur in prolonged, extensive operations, after transfusion of incompatible blood, heat stroke, acute injury, certain snake bites, and with the administration of certain drugs. The chronic syndrome of intravascular coagulation is much more common and is associated with many diseases, including collagen diseases or immune diseases and malignancy. Many patients with chronic intravascular coagulation have normal or even increased levels of coagulation factors, and these patients have no unusual bleeding. The diagnosis depends on the demonstration of circulating complex of "soluble" fibrin revealed by the ethanol gel and protamine sulfate gelation tests. The secondary fibrinolysis results in elevation of FSP. Many laboratories are investigating the use of other procedures in the diagnosis of intravascular coagulation, including fibrinopeptides A and B, the VIII:C VIIIR:AG ratio, antithrombin III, PF 4, beta-thromboglobulin, D dimer, urinary FSP, and fibrinogen chromatography.

Topics: Animals; Antigens; Antithrombin III; Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Dogs; Factor VIII; Fibrinogen; Fibrinolysis; Fibrinopeptide A; Fibrinopeptide B; Humans; von Willebrand Factor

Topics: Animals; Antigen-Antibody Complex; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Chromatography, Gel; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinopeptide A; Fibrinopeptide B; Humans; Partial Thromboplastin Time; Peptide Hydrolases; Platelet Count; Prothrombin Time; Rabbits; Shwartzman Phenomenon; Thrombin; Thromboplastin

1. The lack of a general agreement on the definition of PE makes the interpretation of laboratory findings in different series of these patients difficult. 2. Thrombocytopenia is the most common hemostatic abnormality in patients with PE and is caused by platelet consumption. 3. There is little concrete evidence that thrombin mediates the thrombocytopenia in most of these patients. 4. Immune mechanisms or severe vasospasm with resultant endothelial damage may contribute to the thrombocytopenia in some patients.

Topics: Anemia, Hemolytic; Disseminated Intravascular Coagulation; Eclampsia; Epoprostenol; Factor VIII; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Humans; Hypertension; Platelet Count; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Thrombin; Thrombocytopenia; Thromboxane A2

Topics: Adult; Disseminated Intravascular Coagulation; Epitopes; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysin; Fibrinopeptide A; Fibrinopeptide B; Humans; Molecular Weight; Peptide Hydrolases; Pregnancy; Radioimmunoassay; Solubility; Thrombin

Fibrinogen plays a pivotal role in both the humoral and cellular mechanisms involved in hemostasis. In performing its hemostatic function, fibrinogen in turn is acted on by several independent enzyme systems that either modify its structure or cleave specific fragments of the molecule into the surrounding milieu. Measurements of enzymatically modified fibrinogen or its proteolysis products represent a means whereby the action of these specific enzymes can be quantitated both in vitro and in vivo. Advances in such techniques as protein purification, affinity chromatography, peptide synthesis, and radioimmunoassay technology permit the translation of recently acquired primary structural data on this important protein into sensitive and specific assays for its circulating derivatives. These assay systems are important tools for probing mechanisms of hemostasis and thrombosis.

Topics: Ancrod; Blood Coagulation Tests; Chemical Phenomena; Chemistry, Physical; Chromatography, Gel; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Fibrinolysin; Fibrinopeptide A; Fibrinopeptide B; Humans; Kinetics; Leukocytes; Peptide Hydrolases; Pulmonary Embolism; Thrombin; Thrombophlebitis

Topics: Disseminated Intravascular Coagulation; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Humans; Lupus Erythematosus, Systemic; Pulmonary Embolism; Radioimmunoassay; Thrombin; Thrombophlebitis

The investigations, concerning detection of the hemostasis system activation, were done in 26 patients, suffering various critical morbid states (an acute pancreatitis). The contents of products of the enzymes lysis of coagulation system and fibrinolytic system constitute one of the most precise indices. Fibrinopeptid A (FpA) is considered one of the most secure indices, confirming intravascular thrombin formation, and D-dimer--of a fibrin formation. In the patients examined a trustworthy increase of a D-dimer and FpA contents was registered, witnessing the hemostasis system activation in an acute pancreatitis as well as an excessive formation and lysis of fibrin. D-dimer and FpA contents in a plasma constitutes an important diagnostic index, its determination secures the possibility of early diagnosis and control of a hemostasis system disorders.

Topics: Blood Coagulation; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Humans; Pancreatitis, Acute Necrotizing; Thrombin

Despite advances in left ventricular assist device (LVAD) design that permit support without anticoagulation, LVAD recipients often suffer profound bleeding complications. This bleeding diathesis may be attributable to pre-operative right-ventricular failure with concomitant hepatic dysfunction. The purpose of this study was to characterize coagulation abnormalities in LVAD recipients and determine the impact of pre-operative vitamin K administration on the incidence of postoperative bleeding.. Hemostatic and liver function profiles were obtained in 66 recipients of the Heartmate LVAD; 39 of these patients received perioperative vitamin K.. During LVAD support, hepatic synthetic function improved as evidenced by increases in clotting factors II, V, VII, XI. There was ongoing fibrinolysis with elevation of fibrinopeptide A and D-dimers and diminution of fibrinogen; however, plasminogen levels did not decline suggesting that systemic disseminated intravascular coagulation (DIC) did not occur. Bleeding requiring re-exploration more than 48 hours postimplantation occurred in 9 of 66 patients (13.6%). Prior to implantation, patients that bled had decreased levels of factor II (52.2 +/- 27.1% vs 69.7 +/- 26.6%; p = 0.048) and prolonged prothrombin times (16.5 +/- 2.4 seconds vs 13.8 +/- 3.1 seconds; p = 0.005) compared to patients that did not bleed. Seven of 27 patients (25.9%) not treated with vitamin K bled, while only 2 of 39 (5.1%) patients treated with vitamin K required re-exploration for bleeding (p = 0.026).. We conclude that: (1) Liver synthetic function improves during LVAD support resulting in increased levels of circulating coagulation factors; (2) ongoing fibrinolysis occurs but likely only represents remodeling of fibrin on the LVAD surface; (3) perioperative vitamin K reduces nonsurgical bleeding in LVAD recipients.

Topics: Disseminated Intravascular Coagulation; Factor V; Factor VII; Factor XI; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Fibrinopeptide A; Heart-Assist Devices; Hemostasis; Humans; Incidence; Liver; Liver Failure; Male; Middle Aged; Plasminogen; Postoperative Hemorrhage; Premedication; Prothrombin; Prothrombin Time; Reoperation; Ventricular Dysfunction, Right; Ventricular Function, Left; Vitamin K

Fibrinopeptide A and thrombin-antithrombin III complex were used respectively as markers for in vivo thrombin formation and beta-thromboglobulin as a marker for platelet activation. In cases of acute renal failure (ARF) a heightened plasma concentration in the hemostasis activation markers may occur, because of a renal elimination disturbance, without a previous activation of the hemostasis. In order to check the validity of fibrinopeptide A, thrombin-antithrombin III complex and beta-thromboglobulin as markers for the hemostasis activation in cases of ARF we examined 32 patients prior to renal replacement therapy. A significant rise in fibrinopeptide A (x +/- SD: 34 +/- 22 ng/mL, ref < 3.0), thrombin-antithrombin III complex (19 +/- 15 ng/mL, ref 1.0-4.0) and beta-thromboglobulin (149 +/- 58 U/mL, ref 10-40) was found. None of the parameters examined showed a correlation to the serum creatinine. A correlation was observed respectively between fibrinopeptide A (r = 0.34, p < .05), beta-thromboglobulin (r = 0.39, p < .05) and the beta-thromboglobulin/creatinine coefficient (0.50 +/- 0.30, r = 0.72, p < .001) on the one side and the thrombin-antithrombin III complex on the other. A greater rise in the concentration of all parameters in patients with disseminated intravascular coagulation (DIC) was established, in contrast to patients without DIC (fibrinopeptide A: 44 +/- 31 vs. 32 +/- 20 ng/mL, beta-thromboglobulin: 169 +/- 57 vs. 144 +/- 60 U/mL, thrombin-antithrombin III complex 40 +/- 21 vs. 14 +/- 7 ng/mL, p < .05). Fibrinopeptide A and beta-thromboglobulin/creatinine coefficient in combination with the thrombin-antithrombin III complex can be employed as markers for the activation of hemostasis in cases of ARF there is no direct relationship between restricted kidney function in ARF and the plasma concentration of these markers, which behave similarly in spite of their varying elimination patterns.

Topics: Acute Kidney Injury; Antithrombin III; beta-Thromboglobulin; Case-Control Studies; Creatinine; Disseminated Intravascular Coagulation; Female; Fibrinopeptide A; Hemofiltration; Hemostasis; Humans; Kidney; Male; Middle Aged; Peptide Hydrolases; Renal Dialysis

To determine the role of plasma tissue factor on disseminated intravascular coagulation (DIC) in trauma and septic patients, and also to investigate the relationships between tissue factor and various thrombin markers, we made a prospective cohort study. Forty trauma patients and 20 patients with sepsis were classified into subgroups according to the complication of DIC. Plasma tissue factor antigen concentration (tissue factor), prothrombin fragment F1+2 (PF1+2), thrombin antithrombin complex (TAT), fibrinopeptide A (FPA), and D-dimer were measured on the day of admission (day 0), and on days 1, 2, 3, and 4 after admission. The levels of plasma tissue factor in the DIC group were more elevated than those of the non-DIC group in both the trauma and the septic patients. In patients with sepsis, tissue factor levels on days 0 through 4 in the non-DIC group showed markedly higher values than those in the control patients (135 +/- 8 pg/ml). Significant correlations between tissue factor and PF1+2, TAT, FPA, and D-dimer were observed in the DIC patients, however, no such correlations were found in the non-DIC patients. These results suggest that elevated plasma tissue factor in patients with trauma and sepsis gives rise to thrombin generation, followed by intravascular coagulation.

Topics: Adult; Aged; Aged, 80 and over; Antithrombin III; APACHE; Biomarkers; Disseminated Intravascular Coagulation; Endothelium, Vascular; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Humans; Male; Middle Aged; Monocytes; Peptide Fragments; Peptide Hydrolases; Prospective Studies; Prothrombin; Sepsis; Thrombin; Thromboplastin; Wounds and Injuries

Disseminated intravascular coagulation (DIC) may lead to severe thrombotic or hemorrhagic complications. The present work was undertaken to study the effect of interleukin 6 (IL-6) on variations of key coagulation and fibrinolytic parameters in plasma in a baboon model of experimental DIC induced by injection of factor Xa and phospholipids at dosages leading to partial (48%) or complete fibrinogen depletion. Transient increases of D-dimer, fibrinopeptide A, thrombin-antithrombin and the activated partial thromboplastin time were observed. Each parameter had a particular (time and Xa/phospholipid dose dependent) pattern of changes. The principal effect of IL-6 was a more rapid restoration of fibrinogen concentrations and of overall coagulation tests. Injection of factor Xa/phospholipids led also to a rapid increase of tissue-type plasminogen activator (t-PA) the extent of which was dependent on Xa/phospholipid dose. Pretreatment with IL-6 induced a threefold increase of basal t-PA and a corresponding increase of the t-PA response. Plasminogen activator inhibitor type 1 (PAI-1) concentrations did not change after low dose Xa/phospholipids, but increased eightfold after high dose Xa/phospholipids, IL-6 pretreatment induced within 8 h a twentyfold increase of PAI-1 but no further increase was observed after injection of factor Xa/phospholipids. Thus, in vivo thrombin generation leads to dynamic modifications of the coagulation and fibrinolytic systems. The principal effect of IL-6 is a more rapid normalization of overall coagulation tests, due to normalization of fibrinogen, and an increased t-PA release response which is partially counteracted by increased PAI-1 concentrations.

Topics: Animals; Antithrombin III; Blood Coagulation; Disease Models, Animal; Disseminated Intravascular Coagulation; Factor Xa; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Fibrinopeptide A; Interleukin-6; Papio; Partial Thromboplastin Time; Peptide Hydrolases; Phospholipids; Plasminogen Activator Inhibitor 1; Recombinant Proteins; Thrombin; Time Factors; Tissue Plasminogen Activator

Pooled plasma from 40 patients with severe disseminated intravascular coagulation (DIC) secondary to septic conditions was subjected to gel permeation chromatography on Sephacryl S-500 HR after sample pretreatment with KSCN for dissociation of non-covalent fibrin complexes. Fibrin antigen in eluates was detected by an array of ELISA tests, using two monoclonal antibodies against fibrin degradation product D-dimer, a monoclonal antibody against an epitope generated by plasmin cleavage of the D-domain, and an antibody against the neo-N-terminus of the alpha-chain of fibrin exposed by cleavage of fibrinopeptide A. Tag antibodies were a polyclonal antibody against the fibrinogen/ fibrin D-domain, a POD-conjugated version of the monoclonal antibody against fibrin alpha-chain neo-N-terminus, and a polyclonal antibody against fibrinopeptide A. Most fibrin-related material present in the pooled DIC plasma was of higher molecular mass than fibrinogen. Fibrin polymers were reactive with antibodies against D-dimer, plasmin cleaved D-domain, and fibrin alpha-chain neo-N-terminus. Part of the polymers reacted with antibodies against fibrinopeptide A, indicating presence of fibrinogen or desA-fibrin monomer within the covalently linked complex. In conclusion, the primary analytes detected by monoclonal antibodies for D-dimer, plasmin-specific epitopes of fibrin degradation products, as well as sites exposed by fibrinopeptide cleavage in plasma from patients with disseminated intravascular coagulation are high molecular weight factor XIIIa-crosslinked fibrin complexes, containing plasmin-cleaved D-domains, intact fibrin monomer units, and fibrinogen or desA-fibrin monomer.

Topics: Antibodies, Monoclonal; Disseminated Intravascular Coagulation; Enzyme-Linked Immunosorbent Assay; Epitopes; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinopeptide A; Humans; Molecular Weight; Transglutaminases

Carcinoma of the prostate has historically been associated with the bleeding diathesis which accompanies disseminated intravascular coagulation. We have performed a prospective study into the prevalence of coagulopathy in patients with untreated prostate cancer using matched patients with benign prostatic hypertrophy (BPH) as controls. Haemostatic activation was assessed by measuring fibrinopeptide A (FpA) by an ELISA and D-dimer by a latex agglutination assay. FpA and D-dimer levels were correlated with serum prostate specific antigen (PSA) and bone scan status. Of the cancer patients, 40% had elevated FpA, levels being higher in those with bone scan positive disease (P < 0.05). D-dimer was detectable in 24% of those with prostate cancer but in none with BPH. Neither FpA nor D-dimer were related to serum PSA but D-dimer appeared to be a predictor of bone scan status with a positive predictive value of 91%. It is concluded that changes compatible with subclinical DIC are common in patients presenting with prostate cancer and that measurement of FpA and D-dimer may have roles as tumour markers in this disease.

Topics: Antifibrinolytic Agents; Biomarkers, Tumor; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Humans; Male; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms

To test the hypothesis that disseminated intravascular coagulation contributes to hemostatic failure in liver cirrhosis, fibrinopeptide A and fibrin(ogen) degradation fragment E were measured in 69 patients with stable liver cirrhosis and compared with fibrinopeptide A and fibrin(ogen) degradation fragment E in 32 healthy subjects, 33 patients with thromboembolism, and 10 patients with hypofibrinogenemic disseminated intravascular coagulation. Mean fibrinopeptide A in cirrhosis was slightly increased compared with healthy subjects (2.4 vs. 1.8 ng/ml, p < 0.005), but fourfold lower than in thromboembolism (mean fibrinopeptide A 9.7 ng/ml; p < 0.0001), and tenfold lower than in disseminated intravascular coagulation (mean FPA 24.3 ng/ml; p < 0.0001). Single fibrinopeptide A levels in cirrhosis were within the normal range in 75% of the patients, marginally increased in 9%, and definitely increased in 16%. A definite increase in both fibrinopeptide A and fibrin(ogen) degradation fragment E, which characterized the groups of patients with thromboembolism and disseminated intravascular coagulation, was found in 10% of the cirrhotic patients. Among 17 patients with cirrhosis and hypofibrinogenemia, mean fibrinopeptide A (2.7 ng/ml) was tenfold lower compared with mean fibrinopeptide A in patients with hypofibrinogenemic disseminated intravascular coagulation (p < 0.0001), whereas the frequency of increased single fibrinopeptide A levels (29%) was not significantly different compared with the 52 cirrhotic patients without hypofibrinogenemia (single levels elevated in 23% of the cases). Moreover, the frequency of hypofibrinogenemia, thrombocytopenia, or abnormal clotting times was not significantly different in cirrhotic patients with normal fibrinopeptide A level when compared with cirrhotic patients with increased fibrinopeptide A. These findings do not support an important contribution of disseminated intravascular coagulation to coagulopathy of liver cirrhosis.

Topics: Adult; Aged; Blood Coagulation Disorders; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Humans; Liver Cirrhosis; Male; Middle Aged; Reference Values; Thromboembolism

To determine the effects of disseminated intravascular coagulation (DIC) and head injury on posttrauma coagulation and fibrinolysis.. Case-control study.. General ICU (tertiary care center) in a city hospital serving a population of 150 million people.. Forty trauma victims: 15 with DIC; 25 without DIC.. Measurement of six types of coagulation and fibrinolytic molecular markers (fibrinopeptide A, fibrinopeptide B beta 15-42, plasmin antiplasmin complex, D-dimer, tissue plasminogen activator antigen concentration, tissue plasminogen activator activity) immediately after trauma, 3 days later, and 6 days later. Anticoagulant treatment with gabexate mesilate at 1.45 +/- 0.06 mg/kg/hr.. Fibrinopeptide A, fibrinopeptide B beta 15-42, plasmin antiplasmin complex, and D-dimer showed high values immediately after trauma and exceeded normal activity for the first 6 days. When trauma was complicated with DIC, the molecular markers showed significantly higher values than those for non-DIC patients on all days. In the head-injured patients, such effect was not noted. Tissue plasminogen activator antigen concentration and tissue plasminogen activator activity were within a normal physiologic range of variation. By contrast, tissue plasminogen activator antigen concentration increased significantly after trauma in patients with DIC. When anticoagulant treatment was found effective, it caused a reduction in fibrinopeptide A.. a) Fibrinolytic shut-down and its reactivation cannot be confirmed after trauma. b) Head injury does not lead to an increase in posttrauma coagulation or fibrinolytic activity. c) DIC enhances posttrauma coagulation and fibrinolytic activity and plasminogen activator inhibitor activity can be inferred in DIC patients. d) Increase in tissue plasminogen activator antigen concentration without tissue plasminogen activator activation may be a prognostic factor indicative of DIC and its chances of improvement, and fibrinopeptide A as an assessment criterion for the effectiveness of anticoagulant treatment.

Topics: Adult; Antifibrinolytic Agents; Antigen-Antibody Complex; Antigens; Antithrombin III; Biomarkers; Blood Coagulation Disorders; Case-Control Studies; Craniocerebral Trauma; Disseminated Intravascular Coagulation; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinolysis; Fibrinopeptide A; Fibrinopeptide B; Glasgow Coma Scale; Hospitals, General; Humans; Injury Severity Score; Japan; Male; Middle Aged; Multiple Trauma; Partial Thromboplastin Time; Platelet Count; Predictive Value of Tests; Prothrombin Time; Tissue Plasminogen Activator

We studied blood coagulation and fibrinolysis in 18 DIC patients with multiple organ failure. Blood was collected three times (1st, 3rd, 6th hospital days) from an indwelling arterial line, and FPA, FPB beta 15-42, alpha 2PI-P1-C, D-dimer, t-PA; Ag, and t-PA activity were measured. 1) Continuous FOY infusion (1.40 +/- 0.07 mg/kg/H) resulted in a statistically significant fall of FPA levels, which however, was still above normal. The FPA levels of the patients whose DIC score was not improved or who had massive hematomas were statistically higher than the patients whose DIC score was improved or without hematomas. 2) FPB beta 15-42, alpha 2PI-Pl-C, and D-dimer remained at consistently high levels following onset of the DIC. A significant positive correlations were seen between these indices; between the FPA and FPB beta 15-42, alpha 2PI-Pl-C. 3) The levels of alpha 2PI-Pl-C were found to be higher in the patients with hematomas than those without hematomas. 4) T-PA; Ag level remained at consistently high during all hospital day. On the other hand, t-PA activity level did not change significantly. There was dissociation between the t-PA; Ag and the t-PA activity. 5) The patients whose DIC score were not improved on the 6th hospital day had higher levels of t-PA; Ag than the patients whose DIC score were improved, but there were no differences in the number of the ischemic organs between these patients. In conclusion, regardless of the continuous FOY infusion some patients revealed the continuous production of thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; alpha-2-Antiplasmin; Antifibrinolytic Agents; Biomarkers; Disseminated Intravascular Coagulation; Female; Fibrinolysin; Fibrinopeptide A; Fibrinopeptide B; Humans; Male; Middle Aged; Multiple Organ Failure; Prognosis; Tissue Plasminogen Activator

Hematological and coagulating parameters were examined in 53 patients in an attempt to find possible evidence of disseminated intravascular coagulation after intravascular injection of 5% ethanolamine oleate to sclerose esophageal varices. FDP-E in the peripheral blood measured by latex photometric immunoassay significantly increased from 111.2 +/- 112.9 to 234.2 +/- 178.3 ng/ml and 370.4 +/- 189.5 ng/ml one hour after the first and second sessions of sclerotherapy, respectively (p less than 0.01). The other parameters showed no significant change, except on the first day after sclerotherapy. The increase of FDP-E was closely related to fibrinopeptide A (r = 0.689, p less than 0.01) and fibrinogen (r = 0.585, p less than 0.05), before the sclerotherapy. As repeated intravariceal sclerotherapy over short time intervals can lead to a deterioration of the coagulating system, especially in patients with abnormal preoperative coagulopathy, latex photometric immunoassay for FDP-E is a rapid and useful method of monitoring alterations in the coagulating system.

Topics: Adult; Aged; Blood Coagulation; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Esophageal and Gastric Varices; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Fibrinopeptide B; Humans; Male; Middle Aged; Oleic Acids; Sclerosing Solutions

We have evaluated the quantitative relationship between lipopolysaccharide (LPS, endotoxin), fibrinopeptide A (FPA), antithrombin (AT), protein C (PC) and extrinsic pathway inhibitor (EPI) in plasma from 39 consecutively admitted patients with systemic meningococcal disease (SMD). The most severely ill patients with fulminant meningococcal septicemia (n = 13, 6 dead) had significantly (p less than 0.01) higher plasma levels of LPS and FPA and lower levels of PC and AT on admission as compared with the less severe clinical presentations (n = 26, 1 dead). The levels of EPI on admission were significantly (p less than 0.05) higher in nonsurvivors vs survivors with fulminant septicemia. As the disease progressed, the levels of LPS, FPA, AT and PC declined, while the levels of EPI increased. Three of six nonsurviving septicemic patients had levels of EPI greater than 200% within 16 hours of admission vs two of 30 survivors (p = 0.02). The results suggest that increasing levels of LPS in SMD elicit increasing consumption coagulopathy, contributing to the organ pathophysiology. The kinetics of EPI, inhibiting the thromboplastin-FVIIa-FXa complex, differs markedly from the kinetics of AT and PC i.e. increases as opposed to decreases.

Topics: Antithrombin III; Disseminated Intravascular Coagulation; Endotoxins; Factor VII; Fibrinogen; Fibrinopeptide A; Humans; Lipopolysaccharides; Lipoproteins; Meningitis, Meningococcal; Meningococcal Infections; Multiple Organ Failure; Neisseria meningitidis; Protein C; Sepsis; Thromboplastin

Topics: Amino Acid Sequence; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Humans; Immunoassay; Molecular Sequence Data; Peptide Fragments; Reference Values; Thrombosis

Fibrinopeptide A (FPA) was systematically investigated in 74 patients with acute leukaemia at different stages of the disease (50 with non-lymphocytic leukaemia, ANLL; 24 with lymphocytic leukaemia, ALL). At diagnosis, 75% of the cases had high FPA levels (86% in ANLL and 54% in ALL) with significantly higher levels in ANLL than in ALL (13.4 vs 4.4 ng/ml; p less than 0.001). Patients with DIC (20 cases in ANLL and 1 case in ALL) had significantly higher levels (p less than 0.001). FPA levels were neither correlated with fibrinogen or FDP levels nor with blast cell count. During chemotherapy, median FPA did not show significant changes whereas, at the end of therapy, a return toward normality was generally observed both in ALL and ANLL apart from the group of patients with acute promyelocytic leukaemia. Among the 24 patients who entered post-remission follow-up (13 ANLL and 11 ALL), 10 cases out of the 11 relapsing (6/6 with ANLL and 4/5 with ALL) had increased FPA 1 to 2 months before the ascertainment of the relapse. However, 16% and 9% of the samples obtained on different occasions, respectively from ANLL and ALL cases in maintained first remission, showed FPA above the normal limit. This study demonstrates that subclinical activation of blood coagulation, as indicated by high FPA level, is common both in lymphocytic and non-lymphocytic leukemia and suggests that this phenomenon is related to disease activity.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Child; Cytarabine; Daunorubicin; Disseminated Intravascular Coagulation; Female; Fibrinogen; Fibrinopeptide A; Follow-Up Studies; Humans; Leukemia, Myeloid, Acute; Longitudinal Studies; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radioimmunoassay; Thioguanine; Time Factors

Topics: Acute Disease; Adolescent; Adult; Aged; Chromatography, High Pressure Liquid; Disseminated Intravascular Coagulation; Female; Fibrinogen; Fibrinopeptide A; Humans; Leukemia; Male; Middle Aged

Ascitic fluid reinfusion in severe cirrhosis has frequently been associated with intravascular coagulation (DIC). A low-grade DIC has been postulated to be present in liver cirrhosis. PT, APTT, fibrinogen, plasminogen, antiplasmin, fibrin degradation producers (FDP), euglobulin lysis time, tissue plasminogen activator, and fibrinopeptide A were investigated both in the plasma and ascitic fluid of cirrhotic patients before and after the concentration-reinfusion technique. Our results indicate that increased thrombin formation associated with hyperfibrinolysis is present in the plasma of cirrhotic patients. In ascitic fluid very high levels of thrombin and fibrinolysis activation were found. We conclude that (1) a DIC-like picture exists in ascites and (2) after ascites reinfusion procedures, ascitic fluid is the principal factor in the pathogenesis of DIC. During ascitic fluid reinfusion heparin treatment could be used successfully.

Topics: Aged; Ascites; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinopeptide A; Humans; Liver Cirrhosis; Male; Middle Aged; Partial Thromboplastin Time; Plasminogen; Prothrombin Time; Reference Values; Tissue Plasminogen Activator

Topics: Adult; Aged; Blood Coagulation; Disseminated Intravascular Coagulation; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Fibrinopeptide A; Fibrinopeptide B; Gabexate; Guanidines; Humans; Male; Middle Aged; Peptide Fragments

Purified fibrinogen as well as normal plasma, or plasma from patients with DIC or undergoing streptokinase(SK)-therapy was subjected to 1D- and 2D SDS-electrophoresis under reducing conditions. The pattern was revealed either by Coomassie-staining or immunostaining after Western-blotting and then compared. The use of polyclonal antibodies to fibrinogen as well as two monoclonal anti-bodies reacting with FPA and C-terminal part of the A alpha-chain confirmed immunologically the previously reported molecular weight heterogeneity of the A alpha-chain of the fibrinogen molecule as being a constituent of normal plasma, and lead to the following conclusions: 1. The MW-heterogeneity is observed in the fibrinogen pool of normal plasma as well as in DIC-plasma, SK-plasma and in purified fibrinogen, being the least noticeable in normal plasma and most advanced in SK-plasma. Patterns obtained using immunostaining with monoclonal anti-FPA confirm that the MW-heterogeneity of fibrinogen is mainly due to C-terminal degradation of the A alpha-chain. 2. Numerous A alpha-chain remnants (at least 9), with intact N-terminal ends, are found to be present in normal plasma, with a MW range from 66,200 to 36,000 Da, demonstrating that each of the "classical" HMW, LMW, LMW' subgroups consist of fibrinogen molecules which are very heterogeneous. 3. Two populations of A alpha-chains in purified fibrinogen and in fibrinogen in plasma react with the C-terminal specific Mab G-8. This is in contrast to the findings in plasma from streptokinase-treated patients, where several bands of lower molecular weights than the gamma-chain can be seen, suggesting the presence of free, circulating A-alpha chains split in the N-terminal half of the chain beyond the last inter-chain disulphide bond. 4. 2D electrophoresis disclosed substantial deviations in the patterns obtained with DIC-plasma, SK-plasma and with fibrinogen purified by beta-alanine-precipitation from that observed with normal plasma. The present technique allows selective characterization of fibrinogen independently of the other proteins present in plasma and offers extreme sensitivity.

Topics: Blotting, Western; Disseminated Intravascular Coagulation; Electrophoresis, Polyacrylamide Gel; Fibrinogen; Fibrinopeptide A; Humans; Immunochemistry; Molecular Weight; Peptide Fragments; Streptokinase

Topics: Disseminated Intravascular Coagulation; Fibrinopeptide A; Humans; Liver Cirrhosis

We have developed a two-step enzyme immunoassay (EIA) that allows the quantitation of degradation products derived from fibrinogen (FbgDP) and that does not detect degradation products derived from cross-linked (XDP) or noncrosslinked fibrin (fdp). The EIA is based on two monoclonal antibodies (FDP-14 and Y-18), developed in our institute. FDP-14 is used as catching antibody. It complexes exclusively with degradation products, irrespective whether these are derived from fibrinogen or from fibrin. It does not complex with intact fibrinogen or fibrin. Y-18 is reactive with fibrinogen and fibrinopeptide A-comprising fibrinogen fragments. It is used, conjugated with horse-radish peroxidase, as tagging antibody. The FbgDP-EIA is highly specific, accurate and sensitive. The coefficient of variation is between 3 and 8%; the lower detection limit is less than 0.025 micrograms/ml. The assay has been applied to plasma from patients with suspected disseminated intravascular coagulation (DIC), to plasma from patients undergoing streptokinase (SK) therapy for acute myocardial infarction and to plasma from newborn babies. DIC patients had no or very low levels of FbgDP, but high levels of other degradation products, SK-treated patients showed high levels of degradation products two hours after termination of the SK infusion. A considerable fraction of these degradation products was shown to be FbgDP. Plasma from newborn babies contained elevated levels of FbgDP associated with prolonged prothrombin times.

Topics: Antibodies, Monoclonal; Disseminated Intravascular Coagulation; Dose-Response Relationship, Drug; Epitopes; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Humans; Immunoenzyme Techniques; Reference Values; Streptokinase

Topics: Aged; Antithrombins; Arginine; Disseminated Intravascular Coagulation; Drug Therapy, Combination; Female; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Pipecolic Acids; Platelet Aggregation Inhibitors; Renal Dialysis; Sulfonamides; Thrombocytopenia; Thrombosis

Increased fibrinopeptide A (FPA) levels have been reported in various non-thrombotic disorders, including cancer, acute myocardial infarction, liver cirrhosis and collagen vascular diseases. To investigate the significance of these findings, the present study combined the radioimmunoassay of FPA with that of fibrinogen/fibrin degradation fragment E (FgE) in the aforementioned disorders and compared the results with those observed in healthy subjects as well as in patients with thromboembolism and overt disseminated intravascular coagulation (DIC). Mean FPA and FgE in malignancy were 6.3 and 305 ng/ml, in myocardial infarction 5.6 and 98 ng/ml, in liver cirrhosis 2.7 and 132 ng/ml and in collagen vascular diseases 5.6 and 142 ng/ml. All these values were significantly higher than in healthy controls (mean FPA 1.6 ng/ml, mean FgE 49 ng/ml) but significantly lower than in thromboembolism (mean FPA 10.7 ng/ml, mean FgE 639 ng/ml). and DIC (mean FPA 22.0 ng/ml, mean FgE 1041 ng/ml). The overall correlation between FPA and FgE was highly significant. However, different disorders showed peculiar patterns in FPA, FgE and fibrinogen levels. In malignancy, a definite increase of FPA, FgE and plasma fibrinogen levels was observed. This finding probably indicates a compensated state of (intra- or extravascular) fibrin formation and lysis. Acute myocardial infarction was characterized by a high FPA to FgE ratio, which is interpreted to reflect acute thrombin generation and fibrin formation. FPA in cirrhosis was only marginally elevated with most single values within the normal range, indicating that intravascular coagulation was infrequent and unimportant in quantitative terms.

Topics: Collagen Diseases; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Humans; Liver Cirrhosis; Myocardial Infarction; Neoplasms; Thromboembolism

Fibrinopeptide levels were measured in 20 women during transcervical chorionic villus sampling (CVS). Fibrinopeptide A, a sensitive indicator of fibrinogen cleavage by thrombin, significantly increased in five subjects, whereas there was no change in B beta peptide, an indicator of fibrinolysis. The data suggest that modest fibrin formation, uncompensated by fibrinolysis, may be induced in some women by CVS.

Topics: Adult; Biopsy; Chorionic Villi; Disseminated Intravascular Coagulation; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Humans; Maternal-Fetal Exchange; Peptide Fragments; Pregnancy; Prenatal Diagnosis; Risk Factors

Concentrations of plasma fibrinopeptide A (FPA) were measured by radioimmunoassay in 50 patients with venous thromboembolism or disseminated intravascular coagulation or both. A consistent discrepancy was observed in values obtained with two anti-FPA antisera. Analysis of extracts from plasma of these patients by high-performance liquid chromatography (HPLC) revealed the presence of a phosphorylated and an unphosphorylated form of the A peptide. Differences in concentrations of FPA measured with the two antisera could be accounted for by their different reactivity with phosphorylated FPA (FPA-P). The differences were abolished by treatment with alkaline phosphatase. A good correlation was observed between the FPA-P content of free A-peptide material and of fibrinogen in plasma as determined by HPLC (r = .88, P less than .001, n = 11). In patients with elevated FPA levels, the mean FPA-P content of fibrinogen was significantly higher (P less than .002, n = 13) than in patients with normal FPA levels (n = 8) and in healthy controls (n = 14). Phosphorus in fibrinogen did not correlate with fibrinogen degradation products or fibrinogen levels and became normal on adequate anticoagulation. Therefore, blood-clotting activation may lead to a high phosphate content of fibrinogen and of free FPA in plasma.

Topics: Adult; Aged; Chromatography, High Pressure Liquid; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Phlebitis; Phosphates

Coagulation parameters were initially monitored in 8 patients receiving whole body hyperthermia (WBH). Patients were heated by the warm water blanket technique to 41.8 degrees C (Tmax), maintained at this temperature for 2 hours, then allowed to cool. A fall in platelets was apparent by the time Tmax was achieved and continued during the 18 hours after WBH. Levels of beta-thromboglobulin (BTG) and platelet factor 4 rose by 56% and 191% by the end of treatment but returned to baseline 18 hours later. Fibrinogen, plasminogen and alpha 2-antiplasmin levels declined and FDP and fibrinopeptide A (FPA) levels increased during WBH. Factor XII and Factor VIII:C fell moderately during WBH while Factors VIII R:Ag, VIII:RC and V did not change or showed a late rise. Factor VII levels fell in 7 of 8 patients, reaching levels of 30% of normal in four. To better define the sequence of these coagulations perturbations, earlier and more frequent timepoints were studied in an additional 3 patients. This revealed that decreases in fibrinogen and plasminogen and increases in FPA and BTG occur very early (by the time the patient reaches 39 degrees C). On the other hand, a decrease in Factor VII activity was not apparent until patients had reached Tmax. WBH is therefore associated with a consumption coagulopathy. Possible mechanisms are discussed and extrapolations to the situation seen in heat stroke are suggested.

Topics: Adult; Aged; Blood Coagulation; Blood Coagulation Factors; Disseminated Intravascular Coagulation; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Fibrinopeptide A; Humans; Hyperthermia, Induced; Male; Middle Aged; Neoplasms; Platelet Count

Topics: Acute Disease; Aged; Blood Coagulation; Brain Injuries; Cerebral Hemorrhage; Disseminated Intravascular Coagulation; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Fibrinopeptide A; Fibrinopeptide B; Humans; Hypertension; Male; Middle Aged; Peptide Fragments

Subnormal concentrations of alpha 2 Antiplasmin (alpha 2 AP) in liver cirrhosis may be due to an impaired hepatic synthesis and/or to a fibrinolysis activation in disseminated intravascular coagulation (DIC). In order to clarify this problem, in 26 cirrhotic patients (15 compensated and 11 decompensated) alpha 2 AP plasma activity and plasma Fibrinopeptide A (FPA) were measured. Serum albumin, p-Cholinesterase (p-CHE), Fibrinogen and Fibrinogen Degradation Products (FDP) were also carried out. Our data show that alpha 2 AP and FPA were equally abnormal in compensated and decompensated cirrhosis. The significant negative correlation obtained between alpha 2 AP and FPA as well as the lack of correlation between alpha 2 AP and albumin, alpha 2 AP and p-CHE in both groups suggests that, in our patients, alpha 2 AP decrease may be due to a fibrinolysis activation induced by a DIC which appears chronic since Fibrinogen and FDP were normal. These findings are in agreement with the results obtained in the four subgroups a posteriori selected on the basis of FPA levels: alpha 2 AP in subgroups with high FPA was significantly different from controls while it did not differ in subgroups with normal FPA.

Topics: Adult; alpha-2-Antiplasmin; Cholinesterases; Disseminated Intravascular Coagulation; Female; Fibrinolysis; Fibrinopeptide A; Humans; Liver Cirrhosis; Male; Middle Aged; Serum Albumin

Urinary fibrinopeptide A immunoreactivity was determined by radioimmunoassay using two anti-fibrinopeptide A sera with a different specificity in patients with venous thromboembolism, disseminated intravascular coagulation and rheumatoid arthritis. Elevated levels were frequently observed with both sera, and intravenous administration of heparin in patients with a thromboembolic disorder resulted in a decline of urinary fibrinopeptide A (FPA) concentrations to normal or nearly normal values. For both sera significant correlations with plasma levels were found although one of the sera reacted significantly better with the material in urine samples from these patients than the other (p less than 0.0001, n = 73). Analysis of urinary fibrinopeptide A immunoreactivity by high performance liquid chromatography (HPLC) provided evidence that A peptide material present in this body fluid was heterogeneous. In view of the characteristics of the antisera used in this study, data suggest that urinary FPA immunoreactivity consists to a large extent of carboxyterminally degraded FPA. Excretion of circulating FPA immunoreactive material through the kidneys apparently involves dephosphorylation and carboxyterminal breakdown of the A peptide. Since both synthetic and native phosphorylated or unphosphorylated fibrinopeptide A appeared to be stable in urine in vitro, an active role of the kidney in degrading the A peptide is likely.

Topics: Arthritis, Rheumatoid; Chromatography, High Pressure Liquid; Disseminated Intravascular Coagulation; Fibrinogen; Fibrinopeptide A; Humans; Kidney; Phosphorylation; Thrombophlebitis

Topics: alpha-2-Antiplasmin; Blood Coagulation Factors; Disseminated Intravascular Coagulation; Factor XIII; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Fibrinopeptide A; Fibrinopeptide B; Humans; Immunoelectrophoresis

Fibrinopeptide A (FpA), fibrin monomers, fibrinogen, fibrin degradation products (FDP) aand platelets have been studied during pregnancy, parturition and during toxemia and compared with normal non-pregnant controls in order to evaluate thrombin activity under these conditions. We found a significant rise in fibrinopeptide A levels in late pregnancy and even more so during parturition with a maximum immediately after placental expulsion. We also found elevated FpA levels in toxemic patients, but no significant differences from normal pregnancies. Fibrin monomers were more often elevated during delivery and toxemia during normal pregnancy. One case report concerning a patient with deficient thrombin activation and heavy postpartum bleeding is added. Our studies indicate an increased thrombin activity and fibrinogen turnover in both normal and toxemic pregnancies. During normal childbirth, coagulation activity seemed to reach a maximum immediately after placental separation.

Topics: Adult; Blood Coagulation; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Humans; Labor, Obstetric; Platelet Count; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Complications, Hematologic; Thrombin

Plasma levels of fibrinopeptide A (FPA) in 30 untreated patients with acute non-lymphocytic leukemia (ANLL) were significantly higher than in 30 healthy controls (p less than 0.001). Patients without laboratory signs of disseminated intravascular coagulation (DIC) had levels of FPA higher than controls (p less than 0.02) but markedly lower than patients with DIC (p less than 0.001). Five patients with M3 leukemia had a higher mean FPA level (p less than 0.02) and a lower peripheral blast cell count (p less than 0.05) than patients with other cytological subtypes of ANLL. When patients with M3 were excluded, a significant correlation was observed between the peripheral blast cell counts and the FPA levels (r = 0.66, p less than 0.001). FPA levels were similar with body temperature either above or below 38 degrees C. After intravenous bolus of heparin FPA dropped to normal levels in 14 out of 17 patients who had high baseline values. These findings indicate that intravascular thrombin formation, which probably result from the expression of procoagulant activities of blast cells, is the main cause of high FPA in the majority of patients with acute non-lymphocytic leukemia.

Topics: Acute Disease; Adolescent; Adult; Aged; Disseminated Intravascular Coagulation; Female; Fibrinogen; Fibrinopeptide A; Heparin; Humans; Leukemia; Male; Middle Aged

In a search for new variables, for the diagnosis of disseminated intravascular coagulation (DIC) and for guidelines of therapy in such conditions, 22 severely ill patients were studied. The diagnosis of DIC was based on determinations of platelet counts, prothrombin complex (Normotest), antithrombin (AT), fibrinogen degradation products and fibrinogen. Nine patients were diagnosed as having DIC, eight patients were referred to a suspected DIC group and five to a group of no DIC. The laboratory findings were found to agree with the clinical status. In addition several new parameters were investigated: factor XII, prekallikrein, Simplastin A--another prothrombin complex factor method, factor X, plasminogen (PLG), antiplasmin (AP) and kallikrein inhibitors (KI). Platelet counts, prothrombin complex and antithrombin were mostly pathological in DIC-patients. Of the alternative tests prothrombin complex, fibrinopeptide A and the kallikrein inhibitor as well as the two tests for fibrinolysis (PLG and AP) were significantly altered in DIC-patients. The inhibitor capacity (AT, APV and KI) was lower in patients who died than in survivors and decreased still further in those of the non-survivors who had DIC. Thus the inhibitors can be used as predictors of outcome and hopefully for guiding therapy. To establish the diagnosis of DIC we suggest measurement of platelet count, prothrombin complex, plasminogen as well as of the inhibitors.

Topics: Adolescent; Adult; Aged; Antithrombins; Blood Coagulation Factors; Blood Coagulation Tests; Child; Critical Care; Disseminated Intravascular Coagulation; Factor X; Factor XII; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Fibrinopeptide A; Humans; Kallikreins; Middle Aged; Platelet Count; Prekallikrein; Prognosis

Six patients with disseminated intravascular coagulation (DIC) in association with acute promyelocytic leukemia (APL) were studied with sensitive radioimmunoassays that are able to quantitate the extent of thrombin generation within the human circulation. The levels of prothrombin activation fragment, F1 + 2, and thrombin-antithrombin complex (TAT) were obtained at clinical presentation and were then followed serially in several patients during induction chemotherapy. The antileukemic therapy often resulted in a rise in the plasma levels of these molecular species. Simultaneous measurements of fibrinopeptide A (FPA) were also obtained, and the concentrations of this polypeptide were correlated with the levels of F1 + 2 and TAT in patients who were not receiving heparin. Nine individuals with other morphological subtypes of acute nonlymphocytic leukemia (ANLL) were investigated and were usually found to have increased levels of F1 + 2, TAT, and FPA at clinical presentation. However, the magnitude of the elevations was considerably greater and the correlation between TAT and FPA levels was stronger in APL than in ANLL. These studies provide direct evidence that patients with APL, as well as ANLL, generate excessive amounts of thrombin within their vascular system. Furthermore, the data suggest that the concentrations of F1 + 2, compared with the levels of FPA, may be a more sensitive indicator of hemostatic system hyperactivity in individuals with DIC.

Topics: Adult; Cytarabine; Disseminated Intravascular Coagulation; Doxorubicin; Female; Fibrinopeptide A; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Prednisolone; Thrombin; Vincristine

Topics: Blood Platelets; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Fibrinolysin; Fibrinopeptide A; Fibrinopeptide B; Humans; Thrombin

Topics: Antibodies; Aspirin; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Cell Adhesion; Cell Communication; Cyclooxygenase Inhibitors; Disseminated Intravascular Coagulation; Epoprostenol; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Humans; Indomethacin; Monocytes; Neoplasm Transplantation; Neoplasms; Syndrome; Thrombocytopenia; Thrombocytosis; Thromboembolism; Thromboplastin

Topics: Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Factor XII; Factor XIII; Female; Fibrinogen; Fibrinopeptide A; Humans; Kallikreins; Kininogens; Kinins; Pregnancy; Pregnancy Complications, Hematologic; Prekallikrein

Topics: Disseminated Intravascular Coagulation; Electrophoresis, Polyacrylamide Gel; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Fibrinopeptide B; Hemorrhage; Humans; Models, Chemical; Molecular Weight; Thrombosis

The relationship between FPA level and fibrinogen turnover rate as well as fibrinolytic activity was studied in 18 patients with malignant diseases. It was found that the FPA levels were significantly elevated and were correlated with fibrinogen turnover rate (r = 0.74, p less than 0.001) and FDP (r = 0.58, p less than 0.02). The estimated FPA turnover rate was also correlated with fibrinogen turnover rate (r = 0.70, p less than 0.001). These results suggest that fibrinogen catabolism in patients with malignant disease is related to thrombin proteolysis. However, ratios of 1/2 FPA turnover rate to fibrinogen turnover rate suggest that intravascular thrombin proteolysis is not the major determinant of fibrinogen catabolism. It is suspected that extravascular thrombin proteolysis is responsible for the elevation of plasma FPA level which is correlated with acceleration of fibrinogen catabolism.

Topics: Adult; Aged; Disseminated Intravascular Coagulation; Female; Fibrinogen; Fibrinolysis; Fibrinopeptide A; Humans; Male; Middle Aged; Neoplasms; Thrombin

We performed coagulation studies in 16 patients with advanced neuroblastoma. Four of these patients had major hemorrhagic or thromboembolic complications. Abnormal coagulation screening tests were seen in all patients with active metastatic disease. We also measured plasma fibrinopeptide A, a sensitive measure of intravascular thrombin generation. Increased concentrations of fibrinopeptide A were found in each patient studied with active metastatic disease. Coagulopathy is a frequent finding in metastatic neuroblastoma and may cause severe morbidity. Laboratory studies suggesting either hyper- or hypocoagulability are frequent findings.

Topics: Blood Coagulation Factors; Child, Preschool; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Humans; Infant; Male; Neuroblastoma; Partial Thromboplastin Time; Prothrombin Time

Topics: Adult; Aged; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Female; Fibrinopeptide A; Humans; Liver Cirrhosis; Male; Middle Aged; Platelet Count; Thrombin; Thrombocytopenia

This study was made to know the significance of fibrinopeptide A(FPA) as an indicator for coagulative analysis in thrombotic diseases. In normal control subjects (n=21), values of FPA by the radioimmunoassay were 0.5 +/- 1.4 ng/ml (mean +/- SD). In animal models, using Lyoplastin (tissue thromboplastin, n=5) or Ancrod (n=5) to piglets, plasma FPA levels elevated rapidly as a reflection of fibrin formation, and these changes of FPA were found to be most rapid and sensitive among the indicators for coagulation and fibrinolysis. In patients with thrombosis (n=32), elevated FPA levels (14.7 +/- 13.8 ng/ml) and beta-thromboglobulin (beta-TG)(86.1 +/- 65.6 ng/ml) were found. FPA levels in these patients positively correlated to beta-TG (r=0.5539, P less than 0.05) and inversely to fibrinogen (fbg) (r= -0.3622, P less than 0.05). In patients with acute myelocytic leukemia (AML, n=112), acute promyelocytic leukemia (APL, n=18) and acute lymphocytic leukemia (ALL, n=15), mean FPA levels in patients with active signs and symptoms were significantly higher (AML: 13.5 ng/ml, APL: 20.8 ng/ml, ALL: 12.4 ng/ml) than those examined during remission states (AML: 7.7 ng/ml, P less than 0.02, APL: 3.9 ng/ml, P less than 0.01, ALL: 2.7 ng/ml, P less than 0.01). FPA levels in patients with APL inversely correlated to fbg (r= -0.6399, P less than 0.01). In patients with lung cancer (n=75), mean FPA level in advanced stage (17.7 ng/ml, n=67) were significantly higher than those examined in early stage 6.5 ng/ml, n=8, P less than 0.001). In patients with acute disseminated intravascular coagulation (n=12), prolonged prothrombin time and activated partial thromboplastin time, severely reduced fbg and platelets, and remarkably elevated fibrin degradation product were found. Elevated FPA and beta-TG levels were also found (FPA: 23.5 +/- 15.0 ng/ml, beta-TG: 100.0 +/- 63.0 ng/ml). In five patients with thrombotic diseases who were treated successfully with 12500 IU of heparin per 12 hours (subcutaneous injection), plasma FPA levels were reduced to near normal levels quicker than changes of other indicators. These clinical and experimental data suggested that FPA was an useful indicator for active coagulation process.

Topics: Adult; Animals; Blood Coagulation; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinopeptide A; Heparin; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lung Neoplasms; Male; Radioimmunoassay; Swine; Thrombosis

To provide more information on the pathways of fibrinogen catabolism in generalized cancer, the effect of heparin on fibrinopeptide A (fpA) and on 125I-fibrinogen kinetics was studied in 15 patients with disseminated neoplasia. Three patients had evidence of venous thrombosis and in 2 additional patients a low fibrinogen level together with increased amounts of FDP/fdp and a positive ethanol test indicated disseminated intravascular coagulation (DIC). The plasma levels of fpA were grossly elevated (4.6--20, mean 11.4 ng/ml, normal values 1.01 +/- 0.45 ng/ml) in patients with thrombosis or DIC, and normal to grossly elevated (0.4--10.4, mean 6.1 ng/ml) in the other patients. Intravenous heparin bolus lowered the fpA level in 11/11 patients, and continuous heparin treatment led to an impressive suppression or complete normalization of the plasma fpA in 5/6 patients. This finding is thought to reflect heparin suppression of thrombin activity on fibrinogen. In some cases, the fpA fall after heparin bolus was slow and/or incomplete, suggesting fpA generation at sites not easily accessible to heparin or insufficient heparin dosage. The 125I-fibrinogen kinetics were characterized by a significantly shorter half-life (t1/2: 2.5 days), increased catabolic rate constant (j: 0.44 days-1), and increased absolute turnover (68.9 mg fibrinogen/kg/day) as compared to 4 normal subjects (t1/2: 4.2 days; j: 0.26 days-1; turnover 21.7 mg fibrinogen/kg/day). As estimated from the fpA generation rates, intravascular thrombin action on fibrinogen contributed only in minor part to increase the turnover of 125I-fibrinogen. In particular, the turnover was greatly accelerated in heparin-treated patients despite impressive suppression or normalization of the fpA levels in 5/6 cases.

Topics: Adult; Aged; Disseminated Intravascular Coagulation; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Heparin; Humans; Iodine Radioisotopes; Kinetics; Male; Middle Aged; Neoplasm Metastasis; Neoplasms

Topics: Child; Child, Preschool; Disseminated Intravascular Coagulation; Female; Fibrinopeptide A; Hemolytic-Uremic Syndrome; Heparin; Humans; Infant; Male

An episode of defibrination with bleeding following high dose Edinburgh Factor IX (D.E.F.IX) replacement in a patient with haemophilia B undergoing knee joint replacement is reported. We have also monitored plasma fibrinopeptide A levels in patients with haemophilia B following ten standard doses of D.E.F.IX (15-20 u/kg) and have been unable to document any change. Activation of the coagulation system, as previously noted, appears to be related to the use of Factor IX concentrates in high doses.

Topics: Adult; Blood Coagulation; Disseminated Intravascular Coagulation; Dose-Response Relationship, Drug; Factor IX; Fibrinopeptide A; Hemophilia B; Humans; Male

Topics: Blood Coagulation Tests; Bradykinin; Disseminated Intravascular Coagulation; Fibrinogen; Fibrinopeptide A; Humans; Thromboembolism; Thrombophlebitis

The mechanism of isolated thrombocytopenia in septicemia is unknown, but compensated disseminated intravascular coagulation (DIC) has been suggested as a possible cause. To investigate this possibility, platelet counts and sensitive assays for in vivo thrombin and plasmin generation, including fibrinogen gel chromatography and fibrinopeptide A (FPA) assays, were obtained on 31 septicemic patients. Fifteen of 17 patients with gram-negative septicemia and 8 of 14 patients with gram-positive septicemia had thrombocytopenia. Platelet survival studied demonstrated a decreased platelet survival. In 11 of 12 patients with severe thrombocytopenia (platelet count less than 50,000mul), there was laboratory evidence of intravascular coagulation. In contrast, there was little evidence of intravascular coagulation in 8 of 11 patients with moderate thrombocytopenia (platelet counts 50,000 to less than 150,000/mul) or in 7 of 8 patients with normal platelet counts. This report indicates that while DIC accompanies thrombocytopenia in many patients with severe thrombocytopenia, there is frequently little evidence for intravascular coagulation in patients with moderate thrombocytopenia. It is apparent that factors other than intravascular thrombin must play a role in producing the thrombocytopenia of septicemia.

Topics: Adult; Aged; Blood Platelets; Cell Survival; Disseminated Intravascular Coagulation; Female; Fibrinogen; Fibrinolysin; Fibrinopeptide A; Humans; Male; Middle Aged; Platelet Count; Sepsis; Thrombin; Thrombocytopenia

Topics: Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinopeptide A; Humans; Pregnancy; Pregnancy Complications, Hematologic

FPA immunoreactivity was elevated in 14 out of 15 patients with disseminated neoplasia. Two of the patients showed signs of DIC, two had clinically evident thrombosis and one a positive 125I-fibrinogen uptake test suggesting thrombosis. Infusion of heparin produced a prompt fall in FPA levels. FPA immunoreactivity correlated well with the turnover of intravasal 125I-fibrinogen. The results confirm that the RIA of FPA provides a specific and quantitative index of the conversion of fibrinogen into fibrin and indirectly of the thrombin action in vivo.

Topics: Disseminated Intravascular Coagulation; Fibrinogen; Fibrinopeptide A; Heparin; Humans; Iodine Radioisotopes; Neoplasms; Radioimmunoassay; Thrombosis

Topics: Anemia, Sickle Cell; Disseminated Intravascular Coagulation; Female; Fibrinogen; Fibrinopeptide A; Humans; Kidney Failure, Chronic; Male; Malingering; Pain

Topics: Blood Coagulation Tests; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Fibrinopeptide A; Humans

Topics: Adult; Aged; Arteries; Batroxobin; Disseminated Intravascular Coagulation; Female; Fibrinogen; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Radioimmunoassay; Vascular Diseases

Topics: Animals; Anticoagulants; Disseminated Intravascular Coagulation; Dogs; Epitopes; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Heparin; Humans; Radioimmunoassay; Thrombin; Thromboembolism; Thrombosis

A radioimmunoassay for fibrinopeptide A (FPA) has been developed. This assay uses rabbit antibodies induced by injection of native FPA-human serum albumin conjugates and 125I introduced into tyrosine-FPA synthesized in out laboratory. Plasma FPA is separated from fibrinogen by TCA extraction. The assay is capable of detecting as little as 50 pg/ml of FPA. In 20 normal donors this assay revealed a mean concentration of 0.9 ng/ml (0.3 SD). In five patients with disseminated intravascular coagulation, FPA concentrations ranged from 13.0 to 346 ng/ml. Two groups of patients with systemic lupus erythematosus (SLE) whose disease had achieved complete remission were studied; one consisted of four patients with no history of lupus nephritis and another with a history of nephritis. Mean FPA concentrations of 1.5 ng/ml (range, 0.7-1.8 ng/ml) and 2.7 ng/ml (range, 1.1-5.6 ng/ml) were found in these two groups, respectively. Another group of nine patients with active SLE, but without evidence of lupus nephritis, had a mean FPA concentration of 4.5 ng/ml (range, 2.4-7.8 ng/ml). Finally, a group of seven patients with active SLE, including active nephritis, had a mean FPA concentration of 10.2 ng/ml (range, 5.3-17.0 ng/ml). A positive correlation was found between the concentration of plasma FPA and serum DNA-binding activity and an inverse correlation was found between plasma FPA and the concentration of serum C3. No correlation existed between plasma FPA and concentration of serum creatinine. Several possibilities for the origin of plasma FPA in patients with SLE were considered; at present it seems most likely that FPA arises through the action of thrombin on fibrinogen.

Topics: Adolescent; Adult; Antibodies; Child; Disseminated Intravascular Coagulation; DNA; Female; Fibrinogen; Fibrinopeptide A; Humans; Lupus Erythematosus, Systemic; Male

Topics: Blood Preservation; Blood Specimen Collection; Burns; Disseminated Intravascular Coagulation; Fibrinogen; Fibrinopeptide A; Freezing; Humans; Immune Sera; Neoplasms; Plasma; Radioimmunoassay; Streptokinase; Thrombin; Thrombophlebitis; Uremia; Venous Pressure; Wounds and Injuries