fibrinopeptide-b and Pulmonary-Embolism

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

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

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

To determine the diagnostic and prognostic value of fibrinopeptides in patients with clinically suspected pulmonary embolism (PE), we made a pilot study in the Emergency Department with a general ICU. 32 patients with clinically suspected pulmonary embolism were the participants and 16 cases were diagnosed as PE-positive. After the diagnosis of PE, thrombolytic therapy with urokinase was administered, followed by heparin therapy. Plasma fibrinopeptide A (FPA) and fibrinopeptide B beta 15-42 (FPB beta 15-42) were measured before treatment and at 1, 2 and 6 days after treatment. In the PE-positive patients, the levels of both fibrinopeptides measured prior to the treatment were above the normal values, and were significantly higher than those of PE-negative patients. When the cutoff points of FPA and, FPB beta 15-42 were set at 15 ng/ml, 15 ng/ml respectively, both markers had a high sensitivity, a highly negative predictive value and a moderate specificity. Six of the PE-positive patients died. The FPB beta 15-42 levels were significantly lower in the survivors than those in the patients who died at 2 days (p = 0.0092) and 6 days (p = 0.0011). We can conclude that: 1) the fibrinopeptide measured in this study are useful for screening for PE; and 2) FPB beta 15-42 may possibly be useful as a method for predicting the clinical outcome of PE.

Topics: Biomarkers; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Fibrinopeptide B; Humans; Peptide Fragments; Pilot Projects; Predictive Value of Tests; Prognosis; Prospective Studies; Pulmonary Embolism; Reference Values

To explore the effect(s) of growth hormone signaling on thrombosis, we studied signal transduction and transcription factor 5 (STAT5)-deficient mice and found markedly reduced survival in an in vivo thrombosis model. These findings were not explained by a compensatory increase in growth hormone secretion. There was a modest increase in the activity of several procoagulant factors, but there was no difference in the rate or magnitude of thrombin generation in STAT5-deficient mice relative to control. However, thrombin-triggered clot times were markedly shorter, and fibrin polymerization occurred more rapidly in plasma from STAT5-deficient mice. Fibrinogen depletion and mixing studies indicated that the effect on fibrin polymerization was not due to intrinsic changes in fibrinogen, but resulted from changes in the concentration of a circulating plasma inhibitor. While thrombin-triggered clot times were significantly shorter in STAT5-deficient animals, reptilase-triggered clot times were unchanged. Accordingly, while the rate of thrombin-catalyzed release of fibrinopeptide A was similar, the release of fibrinopeptide B was accelerated in STAT5-deficient plasma versus control. Taken together, these studies demonstrated that the loss of STAT5 resulted in a decrease in the concentration of a plasma inhibitor affecting thrombin-triggered cleavage of fibrinopeptide B. This ultimately resulted in accelerated fibrin polymerization and greater thrombosis susceptibility in STAT5-deficient animals.

Topics: Animals; Blood Coagulation; Disease Models, Animal; Factor XIII; Fibrin; Fibrinopeptide B; Immunoblotting; Mice; Mice, Inbred C57BL; Mice, Knockout; Pulmonary Embolism; Signal Transduction; STAT5 Transcription Factor; Thrombin Time; Thrombosis

The role of active thrombosis in the pathophysiology of pulmonary embolism is unclear. We tested the hypothesis that venous thrombi significantly increase their thrombotic activity once they embolize into the high-flow circulation of the pulmonary arteries. Thrombotic activity was measured using an immunoassay that measures both fibrinopeptide B (FPB) as well as its most abundant metabolite des-arginine FPB. Thrombi were formed in the femoral veins of adult dogs. In one group, the thrombi were embolized without anticoagulation. In the second group, heparin (300 U/kg bolus, then 90 U x kg(-1) x h(-1) infusion) was administered before embolization to prevent subsequent thrombotic activity. Plasma FPB concentrations were significantly suppressed in the heparinized group relative to the nonheparinized group for 1 h postembolization (P = 0.038). We conclude that pulmonary embolization itself causes preexisting venous thrombi to greatly intensify their thrombotic activity and that embolization-associated thrombus propagation can be prevented by heparin.

Topics: Ancrod; Animals; Anticoagulants; Dogs; Fibrinogen; Fibrinopeptide B; Heparin; Humans; Male; Pulmonary Embolism; Thromboembolism; Thrombosis

Many patients with pulmonary thromboembolism remain undiagnosed, possibly because of the difficulty clinicians have in determining which patients merit work-up with accurate (but expensive) imaging techniques.. We present the first prospective clinical study of pulmonary embolism (PE) and deep venous thrombosis (DVT) detection using the FPBtot assay, which measures fibrinopeptide B and its first derivative, des-arginine fibrinopeptide B.. Twenty three patients with signs or symptoms of PE or DVT were enrolled in the study prior to the performance of definitive testing. Using a novel immunoassay, FPBtot levels were measured in urine and plasma samples from patients as well as from healthy controls. Urine and plasma FPBtot levels were compared to the diagnostic results, as blindly adjudicated by one of the investigators. Patients were excluded if they withdrew (n =1), had inconclusive diagnostic testing (n = 7), or did not give samples (n = 2 for urine, n = 3 for plasma).. The mean FPBtot concentration in the urine of the 'DVT/PE positive' group was 78.4 +/- 35.2 ng/ml and 2.7 +/- 1.9 ng/ml in the 'DVT/PE negative' group (p = 0.03). The urine FPB(tot) concentrations in the 'DVT/PE negative' group were not significantly different from those in the healthy control group (2.2 +/- 0.4 ng/ml, p = 0.40). The area under the ROC curve for urine FPB(tot) concentrations was 97.3 +/- 3.8%, suggesting a high degree of diagnostic accuracy. Plasma FPB(tot) concentrations were not significantly different between groups.. Urine FPBtot levels may help detect patients with PE and DVT.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Fibrinopeptide B; Humans; Male; Middle Aged; Osmolar Concentration; Prospective Studies; Pulmonary Embolism; Venous Thrombosis