fibrinopeptide-a and Thrombophlebitis

Topics: Animals; Antithrombin III; Biological Availability; Biotransformation; Blood Coagulation Tests; Chemical Phenomena; Chemistry; Disease Models, Animal; Drug Evaluation; Drug Stability; Factor X; Factor Xa; Fibrinolysis; Fibrinopeptide A; Hemorrhage; Heparin; Humans; Kinetics; Prothrombin; Pulmonary Embolism; Structure-Activity Relationship; Thrombophlebitis

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

There are many reports in the literature of blood test abnormalities occurring in patients with venous or arterial thrombosis. Most of these have not used acceptable criteria for establishing an association between thrombosis and blood tests and, therefore, their interpretation is questionable. Recently, sensitive and specific assays have been developed for the detection of products of intravascular thrombin formation, of plasmin digests of fibrin or fibrinogen and of platelet specific proteins that are released into the plasma when platelets react with stimuli. Blood abnormalities have been sought that can either predict or detect venous thrombosis. Many of the predictive tests evaluated are nonspecific acute phase reactant responses to inflammation; of these, only reduced fibrinolytic activity has been consistently reported to be associated with postoperative venous thrombosis. Hereditary antithrombin III deficiency has been consistently shown to predispose patients to venous thrombosis. Abnormalities of the plasminogen and fibrinogen molecule have also been described in patients with familial or recurrent venous thrombosis but these are rare and the association could be coincidental. Two blood tests, the fibrinopeptide A assay and the assay for fibrin/fibrinogen fragment E are highly sensitive to acute venous thromboembolism in symptomatic patients but both are nonspecific. Elevated levels of beta thromboglobulin and platelet factor 4 have been reported in patients with arterial thromboembolism but the sensitivity and specificity of these findings is presently unknown.

Topics: Antithrombin III; Arteries; Blood Coagulation Tests; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Fibrinopeptide A; Humans; Inflammation; Platelet Adhesiveness; Platelet Aggregation; Risk; Thrombin; Thromboembolism; Thrombophlebitis; Thrombosis; Wounds and Injuries

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

Plasma levels of betathromboglobulin (BTG), fibrinopeptide A (FPA) and B beta 15-42 fragment, indices of platelet release, thrombin generation and plasmin activity respectively, were measured in 32 high risk patients during a double blind study of a single dose of the anabolic steroid stanozolol (50 mg IM) in the prevention of DVT after major gastro-intestinal surgery. The prevalence of malignancy and the incidence of DVT (125I fibrinogen scan) were similar in the two treatment groups. On the first postoperative day, BTG, FPA and B beta 15-42 levels were increased in most patients. Plasma BTG levels were significantly increased on the first post-operative day in patients who developed a DVT (n = 14) compared to those patients who did not (n = 18). A significant increase in FPA levels was found in the DVT group, 7 days after surgery. On the morning before surgery, plasma B beta 15-42 levels were significantly increased in patients who developed a DVT. In patients undergoing surgery for early malignancy (n = 17), we observed a pre-operative increase in FPA levels when compared to patients without malignancy. At post-operative day 7, B beta 15-42 levels were significantly increased in patients who received stanozolol (n = 15), when compared to the placebo group, suggesting that intramuscular stanozolol increases fibrinolysis in vivo.

Topics: Beta-Globulins; beta-Thromboglobulin; Clinical Trials as Topic; Double-Blind Method; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Humans; Peptide Fragments; Postoperative Complications; Stanozolol; Thrombophlebitis

Topics: Aged; Blood Platelets; Clinical Trials as Topic; Colonic Diseases; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Hemostasis; Heparin; Humans; Male; Middle Aged; Postoperative Complications; Thrombophlebitis

Venous thrombosis is a relatively usual but serious complication of permanent transvenous pacing. However, the pathogenesis has not been defined. To clarify underlying abnormalities in the coagulation-fibrinolysis system in patients with permanent transvenous pacemakers, we measured serum levels of fibrinopeptide A (FPA), thrombin-antithrombin III complexes (TATs), plasmin-alpha 2 plasmin inhibitor complexes (PICs), D-dimer (D-D), beta-thromboglobulin (beta-TG), and platelet factor 4 (PF4) in 53 patients with permanent transvenous pacemakers and 10 control subjects. The patients were divided into two groups, as follows, according to the presence of mural thrombus documented along the pacing lead(s) by digital subtraction angiography and transesophageal echocardiography: Group Th (-), patients without venous route thrombus; and Group Th (+), patients with venous route thrombus. FPA and TAT levels increased significantly even in Group Th (-), and further increased in Group Th (+) compared with control subjects (FPA: 7.5 +/- 4.9, 15.3 +/- 8.8 vs 3.0 +/- 1.4 ng/mL, respectively, P < 0.05; TAT: 2.9 +/- 1.3, 4.8 +/- 2.3 vs 1.7 +/- 0.6 ng/mL, respectively, P < 0.05). There were no differences in levels of D-D, PIG, beta-TG, and PF4 among control subjects, Group Th (-), and Group Th (+). These findings suggest that the hypercoagulable state appears in patients with permanent transvenous pacemakers, even without apparent venous thrombosis. The patients with permanent transvenous pacemakers are thought to be in the prethrombotic state even if they have no venous route thrombosis.

Topics: Adult; Aged; Aged, 80 and over; alpha-2-Antiplasmin; Angiography, Digital Subtraction; Antifibrinolytic Agents; Antithrombin III; beta-Thromboglobulin; Blood Coagulation; Cardiac Pacing, Artificial; Echocardiography, Transesophageal; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Fibrinopeptide A; Heart Diseases; Humans; Male; Middle Aged; Pacemaker, Artificial; Peptide Hydrolases; Platelet Factor 4; Serine Proteinase Inhibitors; Thrombophlebitis; Thrombosis

Evidence of activation of coagulation was sought in serial plasma samples from 25 ABMT candidates with malignant lymphoma admitted for bone marrow harvesting: 10 females and 15 males, median age 41 years (range 27-58 years). Nineteen patients had non-Hodgkin's lymphoma (NHL) and six had Hodgkin's disease. Of those with NHL, 14 had high-grade and five low- grade disease. The plasma levels of markers of activation (prothrombin fragment 1 + 2, thrombin-antithrombin complexes, fibrinopeptide A and fibrinmonomers) increased significantly (P < 0.001) in association with harvesting. Except for fibrinopeptide A, the indicators of activation were still significantly elevated 24 h after marrow aspiration. Beta-thromboglobulin, a marker of the platelet release reaction, also increased significantly (P < 0.01). Four out of nine patients in whom a long-term central venous catheter was inserted just after marrow aspiration, developed catheter-related deep vein thrombosis, verified venographically, shortly after harvesting. These results suggest that patient with malignant lymphoma undergoing marrow harvesting develop a hypercoagulable state, and that insertion of a central intravenous catheter immediately after marrow harvesting should be avoided to prevent the development of symptomatic deep vein thrombosis.

Topics: Adult; Anticoagulants; Antithrombin III; beta-Thromboglobulin; Biomarkers; Blood Coagulation; Bone Marrow Transplantation; Catheterization, Central Venous; Circadian Rhythm; Female; Fibrin; Fibrinolysis; Fibrinopeptide A; Heparin; Hodgkin Disease; Humans; Ilium; Lymphoma; Lymphoma, Non-Hodgkin; Male; Middle Aged; Peptide Fragments; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Platelet Count; Premedication; Prothrombin; Sternum; Subclavian Vein; Thrombophlebitis; Transplantation, Autologous; Wounds and Injuries

Deep vein thrombosis may begin during surgery with the tourniquet inflated. Arterial levels of fibrinopeptide A, thrombin-antithrombin complexes, D-dimer, tissue plasminogen activator (t-PA) activity, and t-PA antigen were measured before surgery, during surgery with the tourniquet inflated, and following deflation of the tourniquet in 12 patients undergoing total knee arthroplasty. Minimal increases in fibrinopeptide A, thrombin-antithrombin complexes, and D-dimer were noted during surgery with the tourniquet inflated, but significant increases occurred immediately following deflation of the tourniquet. In 10 patients, intravenous heparin administration significantly suppressed the rise in fibrinopeptide A, but did not significantly alter the increases in either thrombin-antithrombin complexes, D-dimer, t-PA antigen, or t-PA activity. This study provides further evidence that deep vein thrombosis begins during surgery.

Topics: Fibrinolysis; Fibrinopeptide A; Humans; Knee Joint; Knee Prosthesis; Osteoarthritis; Thrombophlebitis; Tissue Plasminogen Activator; Tourniquets

The effect of sera and IgG from 12 patients with systemic lupus erythematosus (SLE) on the endothelial cell (EC) procoagulant activity (PCA) was investigated in an in vitro thrombosis model. Six of the 12 SLE sera contained antiphospholipid antibodies (aPL). EC were stimulated for 8 h at 37 degrees C with or without 50 pM tumor necrosis factor (TNF) in culture medium containing 20% patient or control serum. Then the endothelial cell matrix (ECM) was isolated and subsequently exposed in a perfusion chamber to circulating normal whole blood, anticoagulated with low molecular weight heparin (LMWH). The PCA of the ECM was determined as the amount of generated fibrinopeptide A (FPA) in samples taken before and after perfusion. Furthermore, cross sections were made of the perfused matrix and analyzed for platelet adhesion and aggregate formation. All six aPL containing sera induced a small, but significant increase of ECM procoagulant activity. When added in combination with a low dose of TNF (50 pM), a synergistic enhancement of ECM procoagulant activity was found. The FPA generation was increased to 150-614% from the values obtained after stimulation with TNF and control serum. Also a shift towards the formation of larger platelet thrombi was observed. After stimulation with TNF and patient serum the surface of ECM covered with large aggregates (greater than 5 microns) was increased by 124-329% compared to the results obtained after stimulation with control serum and TNF. When patient sera were depleted from IgG the effects were strongly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antibodies; Cells, Cultured; Endothelium, Vascular; Female; Fibrinopeptide A; Humans; Immunoglobulin G; Male; Perfusion; Phospholipids; Thrombophlebitis; Tumor Necrosis Factor-alpha

Elevated levels of fibrin peptide A were found in venous occlusion only in the patients unconsuming C protein, which indicates that there is a relationship between the thrombin production processes during venous occlusion and the C protein system functioning, the anticoagulant function of the endothelium in particular. Moreover, this makes it possible to employ the standard venous occlusion test to make an integral assessment of endothelial function.

Topics: Adult; Blood Coagulation; Coronary Disease; Female; Fibrinopeptide A; Humans; Male; Middle Aged; Protein C; Thrombin; Thrombophlebitis; Thrombosis; Tissue Plasminogen Activator

Congenital dysfibrinogenemia was found in a patient with venous thrombosis. Blood clot lysis was prolonged and suggested an impairment of fibrinolysis. We investigated whether this was related to the fibrinogen abnormality. Fibrinopeptide release was normal but fibrin polymerization was defective in the patient. The stimulating effect of the patient's fibrin on t-PA mediated plasminogen activation was impaired. This could not be attributed to defective binding of plasminogen. However, the binding of t-PA to the patient's fibrin was about 16% less than to normal fibrin. A variant t-PA (G K1 K2 P), which contained only one of the two fibrin binding sites, i.e. the kringle-2 domain, was bound to the abnormal fibrin for only 50% of normal. We conclude that the prolongation of blood clot lysis and the impaired stimulation of t-PA mediated plasminogen activation are related to the defective binding of the kringle-2 domain of t-PA onto the fibrin moiety of the abnormal fibrinogen. The impairment of fibrinolysis might explain the occurrence of thrombosis in the patient.

Topics: Blood Coagulation Disorders; Fibrinogen; Fibrinogens, Abnormal; Fibrinopeptide A; Fibrinopeptide B; Humans; Male; Middle Aged; Pedigree; Plasminogen; Protein Binding; Thrombophlebitis; Tissue Plasminogen Activator; Whole Blood Coagulation Time

To investigate whether vasopressin (aVP) could have a role in the regulation of coagulation and fibrinolysis during hip surgery, venous blood samples were taken for assay of FVIII:C, FVIII R:Co, vWF:Ag, fibrinopeptide A (FPA), euglobulin clot lysis time (ECLT), high molecular weight fibrin breakdown products (XL-FDP) platelet aggregation in whole blood and aVP from seven patients undergoing elective hip surgery. Samples were taken at set points over the operative period. FVIII:C increased during the operation from a geometric mean of 0.7 iU/ml pre-operatively to 1.09 iU/ml (p less than 0.05) post-operatively. vWF:Ag and FVIII R:Co rose in a similar manner. PAA (10(6)/ECLT2) rose from 12 units pre-operatively to 167 units (p less than 0.001) at prosthesis cementing, and post-operatively fell to subnormal levels. FPA increased from 13 pmol/ml to 58 pmol/ml (p less than 0.05) at prosthesis cementing, and fell to 9 pmol/ml post-operatively. Plasma XL-FDP rose from 115 ng/ml pre-operatively to 456 ng/ml at skin closure (p less than 0.05). Plasma aVP rose from 0.5 pg/ml pre-operatively to 40 pg/ml (p less than 0.01) at division of the femoral neck. There were no changes in platelet aggregation using 1.5 microM ADP. The results demonstrate activation of coagulation and fibrinolysis during the operative procedure. The mechanisms involved in these changes are complex, but the results support the hypothesis that aVP has effects on factor VIII and fibrinolysis similar to those described for abdominal surgery.

Topics: Arginine Vasopressin; Blood Coagulation; Factor VIII; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Fibrinopeptide A; Hip Prosthesis; Humans; Thrombophlebitis; von Willebrand Factor

In 22 patients with suspected pulmonary embolism and 19 patients with suspected deep vein thrombosis, thrombin-antithrombin III complex (TAT) as an indicator of thrombin activation was measured using a newly developed ELISA. For comparison fibrinopeptide A (FPA), as a marker of an activated coagulation, as well as platelet factor 4 (PF4), and beta-thromboglobulin (beta-TG), as markers of platelet activation, were determined. In all patients in whom pulmonary embolism was confirmed by perfusion lung scan and in 15 of 16 patients in whom deep vein thrombosis was confirmed by phlebography, TAT exceeded the upper limit of normal (3.0 ng/ml). FPA was increased in 71% of the pulmonary embolism patients, PF4 in 53%, and beta-TG in 59%. The data for the patients with deep vein thrombosis were comparable. PF4 and beta-TG were increased in more than 25% of the normal controls, FPA in 17%, and TAT in 9%. TAT is very sensitive in detecting an activation of the coagulation system in patients with suspected thromboembolic events. The test, however, is not specific for thromboembolism; it only indicates an activation of the coagulation system. Acute pulmonary embolism or deep vein thrombosis would appear to be unlikely if TAT is normal. The measurement of TAT is easier and less susceptible to disturbances than that of FPA, PF4, and beta-TG.

Topics: Antithrombin III; beta-Thromboglobulin; Female; Fibrinogen; Fibrinopeptide A; Humans; Male; Middle Aged; Platelet Factor 4; Pulmonary Embolism; Thrombin; Thrombophlebitis

We describe the coagulopathy of a 65-year-old woman with a thrombotic disorder associated with dysfibrinogenemia and lupus anticoagulant (LA). The patient's prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), and batroxobin time were prolonged and could not be corrected by mixing with equal volumes of normal plasma. Fibrinogen quantitation showed approximately twice as much immunoreactive as thrombin-clottable protein. The batroxobin and thrombin clotting times of the patient's isolated fibrinogen were prolonged and could not be corrected by mixture with normal fibrinogen. Turbidimetrically assessed fibrin monomer aggregation in response to thrombin, ancrod, or batroxobin and fibrin monomer reaggregation experiments disclosed clearly delayed onset and a lower maximum opacity. In other turbidimetric and clotting-time experiments, the patient's fibrinogen displayed a dose-dependent inhibition of the reaggregation of normal fibrin. Fibrinopeptide A and B release rates and sialic acid content were normal. Assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of reduced samples, the subunit structure of the patient's fibrinogen and its fully cross-linked fibrin was normal. The presence of LA was established by two techniques, the blood thromboplastin inhibition test and the platelet neutralization procedure (PNP). A positive PNP could not be produced by mixing afibrinogenemic plasma with the patient's purified fibrinogen. The patient's inactivated serum and her isolated IgG prolonged the PT and PTT of normal plasma but showed no inhibitory effect on the clotting of purified normal fibrinogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Humans; Immunoglobulin G; Lupus Coagulation Inhibitor; Partial Thromboplastin Time; Platelet Aggregation; Prothrombin Time; Thrombophlebitis

Human fibrinogen is phosphorylated in vivo to an equal extent at two positions, one at Ser 3 located on fibrinopeptide A, the other at Ser 345 of the A alpha-chain. As has been shown previously, the degree of phosphorylation of the circulating fibrinogen pool can be determined in vitro from the ratio between the HPLC peaks formed by phosphorylated and non-phosphorylated fibrinopeptide A which has been cleaved from plasma fibrinogen by thrombin or reptilase. Plasma samples were obtained from patients with venous thrombosis undergoing fibrinolytic therapy with urokinase (n = 8). The degree of phosphorylation increased from about 35% before treatment to values between 50% and 70% within 48 hours. It remained at these high levels as long as urokinase was administered and declined slowly thereafter. This behaviour of the degree of phosphorylation of fibrinogen is explained by a model which assumes that fibrinogen is secreted in the phosphorylated form and then dephosphorylated in the circulation by an up to now unidentified phosphatase by first order kinetics. When this system is in steady state, the degree of phosphorylation is about 25% under normal conditions. If the elimination rate of fibrinogen is greatly enhanced by fibrinogenolysis the system will approach a new steady state with a higher degree of phosphorylation, the magnitude of which will depend on the new ratio of dephosphorylation and elimination.

Topics: Blood Circulation; Chromatography, High Pressure Liquid; Female; Fibrinogen; Fibrinolytic Agents; Fibrinopeptide A; Humans; Male; Phosphorylation; Protein Conformation; Thrombophlebitis; Urokinase-Type Plasminogen Activator

Topics: Blood Coagulation Disorders; Fibrinopeptide A; Heparin; Humans; Neoplasms; Thrombophlebitis

A previous study of neurosurgical patients demonstrated an imbalance between thrombin and plasmin action following surgery. The present study was designed to determine the effect of intermittent pneumatic calf compression on postoperative enzyme activity. Fibrinopeptide A (FPA) and B beta 1-42 levels, reflecting thrombin and plasmin action respectively, were measured daily in patients undergoing elective craniotomy. Two of 9 patients not receiving calf compression developed positive fibrinogen leg scans, while none of 5 patients receiving prophylaxis had positive scans. Calf compression was associated with a markedly altered pattern of changes in the fibrinopeptide values following surgery. Without compression, there was perturbation of the balance between thrombin and plasmin action on the day after surgery as reflected by an increase in the FPA/B beta 1-42 ratio. In contrast, in those receiving prophylaxis there was no change in this ratio on the first postoperative day. Calf compression both blunted the mean postoperative increase in the FPA level (1.8 nM vs 4.7 nM; p less than .05) and augmented the mean B beta 1-42 value (3.0 nM vs 0.2 nM; p less than .05) so that the mean increase in the FPA/B beta 1-42 ratio was only 0.1 with calf compression as compared to 2.2 without it (p less than .05). Systemic modulation of both the coagulation and fibrinolytic pathways thus occurred in association with calf compression.

Topics: Adult; Craniotomy; Fibrinolysin; Fibrinopeptide A; Fibrinopeptide B; Humans; Iodine Radioisotopes; Leg; Postoperative Period; Pressure; Radionuclide Imaging; Thrombin; Thrombophlebitis; Time Factors

A congenitally abnormal fibrinogen was isolated from blood of a young man with deep-vein thrombosis. Two other affected members of his family had three episodes of severe arterial thrombosis. The fibrinogen showed a delayed clotting by thrombin, but a normal clotting by Arvin, Reptilase, and prothrombin-staphylocoagulase complex. Analysis of the fibrinopeptides A and B by High Performance Liquid Chromatography did not reveal an abnormal peptide structure. The rate of release of A and B peptides by thrombin was strongly delayed, whereas the rate of release of fibrinopeptide A by Arvin appeared to be normal. The fibrin polymerization rate was normal. Interactions between the abnormal fibrinogen, platelets and the fibrinolytic system were also normal. Evidence is presented that the defective interaction between fibrinogen Milano II and thrombin is associated with a defective binding of thrombin to the fibrin moiety of the abnormal fibrinogen.

Topics: Adult; Blood Coagulation Disorders; Fibrin; Fibrinogen; Fibrinogens, Abnormal; Fibrinopeptide A; Fibrinopeptide B; Humans; Male; Pedigree; Platelet Aggregation; Thrombin; Thrombophlebitis; Thrombosis

Fibrinaemia following total hip replacement was evaluated in eighteen patients, grouped according to a negative and a positive fibrinogen uptake test (FUT), after having excluded two patients due to a false negative test, using phlebography as reference. The ethanol gelation test (EGT) was employed for detection of circulating soluble fibrin, and the conversion of fibrinogen to fibrin was evaluated by the level of fibrinopeptide A (FPA). Eight patients were cleared with respect to thrombosis, whereas ten had a positive FUT. All patients developed a positive EGT, irrespective of thrombosis, coinciding with the postoperative increase in fibrinogen. FPA increased to approximately twice its preoperative level in both groups of patients, but reached its maximum earlier in patients with thrombosis. However, this parameter had no discriminative value in this type of postoperative thrombosis, possibly due to massive thromboplastin release in both groups.

Topics: Aged; Aprotinin; Female; Fibrin; Fibrinogen; Fibrinopeptide A; Heparin; Hip Prosthesis; Humans; Male; Middle Aged; Postoperative Complications; Reference Values; Thrombophlebitis; Time Factors; Warfarin

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

Septic pelvic thrombophlebitis is an uncommon but potentially life-threatening complication of puerperal endometritis. The lack of specific physical findings necessitates a diagnosis based by exclusion on the patient's response to anticoagulation. Fibrinopeptide A (FPA) is the first peptide cleaved from fibrinogen during thrombin-mediated fibrin generation. Because of its short half-life, FPA accurately reflects the level of ongoing fibrin generation. In a preliminary study of 40 puerperal patients, FPA successfully differentiated puerperal fever secondary to endometritis or abscess from fever responsive to a heparin trial. The mean FPA level in patients presumed to have septic pelvic thrombophlebitis was 23.8 ng/ml as opposed to 7 ng/ml in patients with endometritis. No patient with septic pelvic thrombophlebitis as diagnosed by her response to a heparin trial had a level of FPA less than 14 ng/ml. There was no overlap of FPA levels between patients with endometritis or abscess and septic pelvic thrombophlebitis. The data suggest further prospective evaluation of FPA for the diagnosis of septic pelvic thrombophlebitis is warranted.

Topics: Anti-Bacterial Agents; Anticoagulants; Endometritis; Female; Fibrinogen; Fibrinopeptide A; Humans; Pelvis; Pregnancy; Puerperal Infection; Radioimmunoassay; Thrombophlebitis

The purpose of this study was to investigate the degree of platelet activation and thrombin generation in 40 patients with stable angina pectoris and in 20 patients with acute myocardial infarction (AMI) by determining the plasma beta thromboglobulin (BTG) and fibrinopeptide A (FPA) concentrations. In patients with angina pectoris increased platelet activation correlated with extensive coronary pathology; the activation, however, was not influenced by a previous myocardial infarction, use of oral anticoagulants, beta-blocking agents, or hyperlipidemia. The plasma beta thromboglobulin concentration predicted more accurately the extent of the coronary artery disease than the functional angina pectoris classification. Thrombin generation was within the normal range. In patients with acute myocardial infarction increased platelet activation and enhanced thrombin generation were found, which were not related to the infarct localization, infarct size, or the presence of complications. Consequently, in these patients determination of plasma beta thromboglobulin and fibrinopeptide A concentrations is useless for the diagnosis of venous thromboembolism.

Topics: Adult; Aged; Angina Pectoris; Beta-Globulins; beta-Thromboglobulin; Blood Platelets; Coronary Disease; Fibrinogen; Fibrinopeptide A; Humans; Middle Aged; Myocardial Infarction; Myocardium; Thrombin; Thrombophlebitis

Topics: Adult; Aged; beta-Thromboglobulin; Blood Platelets; Female; Fibrinopeptide A; Humans; Middle Aged; Platelet Factor 4; Sclerosing Solutions; Thrombophlebitis; Varicose Veins

The assay of fibrinopeptide A (FPA) has stimulated particular interest because of its high sensitivity and unique specificity for the action of thrombin. It has proved to be an extremely useful tool in research studies concerning the pathophysiology of thrombotic disease. Use of FPA in the diagnosis and treatment of deep venous thrombosis and pulmonary embolism is reviewed, and the potential usefulness of measuring FPA in the monitoring of the effectiveness of anticoagulant therapy is discussed.

Topics: Blood Preservation; Fibrinogen; Fibrinopeptide A; Humans; Pulmonary Embolism; Specimen Handling; Thrombophlebitis; Thrombosis

In a group of 111 consecutive patients (mean age 65 years) with suspected deep venous thrombosis (DVT) phlebography demonstrated DVT in 51. In all patients blood tests for fibrinopeptide A (FPA), fibrin degradation products (FDP) and beta-thromboglobulin (beta-Tg) were carried out. There was a significant difference in FPA concentration between the group of patients with a positive and a negative phlebography. However, there was a wide variation of individual values in both groups. The difference in FPA concentration between the groups was not related to differences in predisposing diseases, age or sex. FDP and beta-Tg did not differ between the groups and, again, a wide variation of individual values was found in both groups. In our hands, none of these three methods reflecting activities in the hemostasis seems to be useful to diagnose DVT in clinical routine work.

Topics: Adult; Aged; Beta-Globulins; beta-Thromboglobulin; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Humans; Male; Middle Aged; Phlebography; Thrombophlebitis

Topics: Adolescent; Adult; Aged; beta-Thromboglobulin; Female; Fibrinopeptide A; Fibrinopeptide B; Humans; Leg; Lung; Male; Middle Aged; Platelet Factor 4; Postoperative Complications; Radionuclide Imaging; Thrombin; Thromboembolism; Thrombophlebitis; Thromboplastin

Topics: Aged; Antithrombins; Female; Fibrinopeptide A; Hemostasis; Heparin; Humans; Male; Middle Aged; Postoperative Complications; Risk; Thrombophlebitis; Urologic Diseases

Topics: Blood Coagulation; Bradykinin; Fibrinopeptide A; Fibrinopeptide B; Humans; Inflammation; Thrombophlebitis

Plasma concentrations of thrombin sensitive peptide fibrinopeptide A (FpA), plasmin sensitive fibrinogen fragment B beta 1-42 and the platelet release product beta-thromboglobulin (beta TG) have been measured in 36 patients before and after total hip replacement. Statistically significant elevations of all three activation products were observed in the days following operation. There were small differences in plasma concentrations of FpA, B beta 1-42 and beta TG in patients who did (n = 13) and did not (n = 23) develop post operative deep vein thrombosis, as assessed by ascending venography on post operative day 10, but these differences were not statistically significant. It is concluded that coagulation and fibrinolytic systems and also blood platelets are activated following total hip replacement operations. However, the formation of post operative deep vein thrombosis can not be effectively monitored by measurement of the activation products.

Topics: Adult; Aged; Beta-Globulins; beta-Thromboglobulin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Hip Prosthesis; Humans; Peptide Fragments; Preoperative Care; Thrombophlebitis

The purpose of this study was to assess the predictive values of the assays of fibrinopeptide A (FPA), beta-thromboglobulin (BTG) and their combination in patients suspected of having acute deep venous thrombosis (DVT) or pulmonary embolism (PE). In 80 controls the mean (+/- SD) plasma concentrations of FPA and BTG were 0.72 +/- 0.47 and 28.2 +/- 10.1 ng/ml, respectively. In 26 patients in whom DVT was confirmed by phlebography and Doppler ultrasound, clearly raised mean FPA (5.62 ng/ml) and BTG (70.6 ng/ml) concentrations were measured compared to those in 13 patients in whom this disorder was excluded (1.00 and 33.6 ng/ml, respectively). Also in 25 patients, in whom PE was established by perfusion lung scanning, clearly increased mean FPA (6.28 ng/ml) and BTG (82.4 ng/ml) concentrations were measured compared to those in 12 patients without this disease (1.03 and 32.5 ng/ml, respectively). Raised FPA and BTG concentrations were also found in 20 patients with inflammatory disorders and in 10 with various types of malignancy. The mean FPA and BTG concentrations did not differ between patients with renal failure or diabetes mellitus and patients without these diseases. From the predictive values of these assays and their combination it can be concluded that raised FPA and BTG concentrations are not specific for thrombosis. However, when normal FPA and BTG concentrations are present, acute DVT or PE can safely be excluded in symptomatic patients. In the group with confirmed DVT/PE, anticoagulant treatment (heparin and phenprocoumon) brought down the mean FPA concentration to levels within the normal range in less than 1 hour while the mean BTG concentration remained elevated throughout the 10-day study period.

Topics: Acute Disease; Adult; Aged; Beta-Globulins; beta-Thromboglobulin; Fibrinogen; Fibrinopeptide A; Heparin; Humans; Middle Aged; Pulmonary Embolism; Thrombophlebitis

Topics: Acute Disease; Adult; Aged; Beta-Globulins; beta-Thromboglobulin; Fibrinogen; Fibrinopeptide A; Follow-Up Studies; Humans; Middle Aged; Pulmonary Embolism; Thrombophlebitis; Time Factors

The purpose of this study was to assess the usefulness of plasma fibrinopeptide A and beta-thromboglobulin concentrations for the diagnosis of acute venous thromboembolism in patients with a major bacterial infection. In 80 controls the mean plasma fibrinopeptide A concentration was 0.72 +/- 0.47 (ng/ml +/- SD) and the mean plasma beta-thromboglobulin concentration 28.2 +/- 10.1 (ng/ml +/- SD). On admission the mean fibrinopeptide A concentration was significantly raised (5.42 ng/ml) in these patients and 17 of them had a raised fibrinopeptide A concentration. However, the mean beta-thromboglobulin concentration was not significantly different from that of the healthy individuals (35.4 ng/ml) and only three patients had an increased beta-thromboglobulin concentration. Our data show that patients with major bacterial infections tend to have increased fibrinopeptide A and normal beta-thromboglobulin concentrations. Consequently, the measuring of plasma fibrinopeptide A concentration is useless for the diagnosis of acute venous thromboembolism in these patients. However, the determination of plasma beta-thromboglobulin concentration can still be used for this purpose, since a normal beta-thromboglobulin concentration excludes the presence of acute venous thrombosis.

Topics: Adult; Aged; Bacterial Infections; Beta-Globulins; beta-Thromboglobulin; Diagnosis, Differential; Fibrinogen; Fibrinopeptide A; Humans; Middle Aged; Thrombophlebitis

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

Fibrinopeptide A (FPA), which is considered to be a quantitative indicator for the thrombin activity in vivo, was measured in 136 patients treated with phenprocoumon in order to obtain information on the effectiveness of the inhibition of the coagulation system. The results show a decrease of the FPA concentration in relation to the efficacy of the anticoagulant therapy as measured by the thrombotest coagulation method (p less than 0.01). However, elevated FPA was observed even under an effective oral anticoagulation. These data indicate that an increased thrombin activity cannot be completely prevented by oral anticoagulants in every patient. Combined measurement of FPA and the thrombotest coagulation methods might be used to detect patients with an elevated risk of recurrent thromboembolism despite treatment with phenprocoumon.

Topics: 4-Hydroxycoumarins; Administration, Oral; Anticoagulants; Blood Coagulation; Fibrinogen; Fibrinopeptide A; Humans; Myocardial Infarction; Partial Thromboplastin Time; Phenprocoumon; Thrombin; Thrombophlebitis

Fibrinopeptide A (FPA) levels were measured in a group of 130 controls and patients with various types of primary hyperlipidemia to investigate whether an increased steady state level of thrombin activity is present in hyperlipidemic patients. In a subset of 56 subjects, levels of clotting factors II, VII, and X were measured as well. FPA levels in hyperlipidemic patients were not significantly different from those of control subjects. Furthermore, on multiple regression analysis, no significant relationships were found between FPA levels and the concentrations of serum cholesterol or triglyceride, or log triglyceride levels. Statistically significant relationships were found between all three clotting factor levels and triglyceride concentration. The correlation coefficients for these relationships, however, were low, so that the correlations are of questionable pathophysiological significance. A weak relationship also was found between the plasma levels of cholesterol and of factor II. Thus, although small increases in various clotting factors may be found in patients with hyperlipidemia, plasma FPA levels are normal. These data indicate that hyperlipidemia is not associated with a steady state of increased thrombin activity in vivo in humans.

Topics: Cholesterol; Factor VII; Factor X; Fibrinogen; Fibrinopeptide A; Humans; Hyperlipidemias; Prothrombin; Thrombophlebitis; Triglycerides

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

Topics: Fibrinogen; Fibrinopeptide A; Humans; Pulmonary Embolism; Thrombophlebitis; Thrombosis

The formation of fibrin clots or circulating soluble fibrin is accompanied by the appearance of fibrinopeptides. Measurement of the fibrinopeptide concentration in plasma can provide important information on the rate of conversion of fibrinogen to fibrin by thrombin. This rate varies under different physiologic and pathologic conditions. Fibrinopeptide A is a better molecular marker of the conversion than fibrinopeptide B since it is the first peptide to be cleaved by thrombin. A radioimmunoassay technique has been developed for the quantitative determination of human fibrinopeptide A. The procedure detects human fibrinopeptide A at a concentration of approximately 0.05 ng/ml. The variation of fibrinopeptide A content in normal persons may reflect its rapid formation and catabolism. A significantly increased concentration of this peptide was found in a patient during defibrination therapy with a purified enzyme from the venom of Agkistrodon rhodostoma and in patients suffering from retinal vascular occlusions.

Topics: Amino Acid Sequence; Batroxobin; Fibrinogen; Fibrinopeptide A; Humans; Immune Sera; Protein Binding; Radioimmunoassay; Retinal Diseases; Retinal Vessels; Thrombophlebitis; Thrombosis; Tyrosine