Elevated plasma procoagulant and fibrinolytic markers in patients with chronic obstructive pulmonary disease.
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OBJECTIVE: There is clinical and pathological evidence of thrombosis in pulmonary vessels of patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to investigate the presence of hypercoagulability and determine the extent of this abnormality in COPD patients. PATIENTS AND METHODS: We measured plasma levels of thrombin antithrombin III complex (TAT), fibrinopeptide A (FPA), tissue plasminogen activator-plasminogen activator inhibitor (tPA-PAI): markers of coagulation-fibrinolysis-system, and also beta-thromboglobulin (beta-TG): a marker of platelet activation, in 40 COPD patients and in 20 control subjects. Measurements were also repeated 12 months after entry in all patients. RESULTS: TAT, FPA, tPA-PAI, and beta-TG concentrations were significantly higher in COPD than in control subjects. At 12 months follow-up, deltaA-aDO2 and delta%FEV1 were significantly higher in patients with high TAT or tPA-PAI levels than in patients with low levels and TAT, FPA and tPA-PAI levels remained elevated, although beta-TG levels decreased after domiciliary O2 therapy. CONCLUSION: Our results showed an enhanced prothrombotic process in COPD patients, which could potentially account for the increased thrombosis in pulmonary vessels in these patients. (+info)
Physician knowledge and practices in the evaluation of coagulopathies in stroke patients.
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BACKGROUND AND PURPOSE: Coagulopathies are a rare cause of ischemic stroke. Prior studies demonstrate that current physician test-ordering practices for the evaluation of these conditions in patients with ischemic stroke is not optimal. We sought to determine neurologists' views regarding their use of specialized coagulation testing to better understand the possible reasons for these practices. METHODS: A survey with multiple-choice and open-ended questions regarding knowledge of and approaches to the evaluation of coagulopathies was sent to a convenience sample of 79 neurologists (26 academic neurology faculty, 24 residents/fellows, and 29 community-based practitioners). RESULTS: Fifty-nine (75%) surveys were completed (response rates: faculty 73%, residents/fellows 88%, and community-based practice 66%). Specialized coagulation tests were reported to infrequently influence stroke patient management (<25% of the time or never for 95% of respondents). Factors reported to increase test-ordering included young patient age (76%), history of thrombosis (46%), history of miscarriages (36%), and having few traditional stroke risk factors (35%). Most (88%) indicated they would order specialized coagulation tests for a hypothetical young patient with no known stroke risk factors. In contrast, only 14% would obtain the tests for a patient having traditional stroke risk factors, and none would order the tests for a stroke patient with atrial fibrillation. CONCLUSIONS: Physician-reported practices for obtaining specialized coagulation tests differ from those found in observational studies in which more indiscriminate test ordering was observed. Closing knowledge gaps and improving application of physician's current knowledge to their test-ordering practices could help to optimize diagnostic testing for coagulopathies in patients with ischemic stroke. (+info)
Utility of whole blood hemostatometry using the clot signature analyzer for assessment of hemostasis in cardiac surgery.
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BACKGROUND: A hemostatic monitor capable of rapid, accurate detection of clinical coagulopathy within the operating room could improve management of bleeding after cardiopulmonary bypass (CPB). The Clot Signature Analyzer is a hemostatometer that measures global hemostasis in whole blood. The authors hypothesized that point-of-care hemostatometry could detect a clinical coagulopathic state in cardiac surgical patients. METHODS: Fifty-seven adult patients scheduled for a variety of elective cardiac surgical procedures were studied. Anesthesia, CPB, heparin anticoagulation, protamine reversal, and transfusion for post-CPB bleeding were all managed by standardized protocol. Clinical coagulopathy was defined by the need for platelet or fresh frozen plasma transfusion. The Clot Signature Analyzer collagen-induced thrombus formation (CITF) assay measured platelet-mediated hemostasis in vitro. The activated clotting time, platelet count, prothrombin time, activated partial thromboplastin time, and fibrinogen concentration were also measured. RESULTS: The postprotamine CITF was greater in patients who required hemostatic transfusion than in those who did not (17.6 +/- 8.0 min vs. 10.5 +/- 5.7 min, respectively; P < 0.01). Postprotamine CITF values were highly correlated with platelet and fresh frozen plasma transfusion (Spearman r = 0.50, P < 0.001 and r = 0.40, P < 0.005, respectively). Receiver operator characteristic curves showed a highly significant relation between the postprotamine CITF and intraoperative platelet and fresh frozen plasma transfusion (area under the curve, 0.78-0.81, P < 0.005) with 60-80% sensitivity, specificity, positive and negative predictive values at cutoffs of 12-14 min. Logistic regression demonstrated that the CITF was independently predictive of post-CPB hemostatic transfusion, but standard hemostatic assays were not. CONCLUSIONS: The Clot Signature Analyzer CITF detects a clinical coagulopathic state after CPB and is independently predictive of the need for hemostatic transfusion. Hemostatometry has potential utility for monitoring hemostasis in cardiac surgery. (+info)
Williams trait. Human kininogen deficiency with diminished levels of plasminogen proactivator and prekallikrein associated with abnormalities of the Hageman factor-dependent pathways.
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An asymptomatic woman (Ms. Williams) was found to have a severe abnormality in the surface-activated intrinsic coagulation, fibrinolytic, and kinin-generating pathways. Assays for known coagulation factors were nromal while Fletcher factor (pre-kallikrein) was 45%, insufficient to account for the observed markedly prolonged partial thromboplastin time. Plasminogen proactivator was present at 20% of normal levels and addition of highly purified plasminogen proactivator containing 10% plasminogen activator partially corrected the coagulation and fibrinolytic abnormalities but not the kinin-generating defect. This effect was due to its plasminogen activator content. In addition, Williams trait plasma failed to convert prekallilrein to lakkilrein or release kinin upon incubation with kaolin. Kininogen antigen was undetectable. When normal plasma was fractionated to identify the factor that corrects all the abnormalities in Williams trait plasma, the Williams factor was identified as a form of kininogen by its behavior on ion exchange chromatography, gel filtration, disc gel electrophoresis, and elution from an anti-low molecular weight kininogen immunoadsorbent. High molecular weight kininogen as well as a subfraction of low molecular weight kininogen, possessed this corrective activity while the bulk of low molecular weight kininogen functioned only as a kallikrein substrate. Kininogen therefore is a critical factor required for the functioning of Hageman factor-dependent coagulation and fibrinolysis and for the activation of prekallikrein. (+info)
A pathological inhibitor of fibrin cross-linking.
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Lewis et al. recently reported on a patient who died of hemorrhages attributable to an acquired inhibitor of fibrin-stabilizing factor. They indicated that the inhibitor was associated with the immune globulins. Using the postmortem serum in the isolated fibrin cross-linking system, we have now further localized the site of inhibition in the scheme of blood coagulation. The interference occurs at the transpeptidation step catalyzed by the thrombin-activated fibrin-stabilizing factor. The patient's serum also uniquely delayed the clotting time of Homarus plasma, a test for specific inhibitors of transpeptidation. Since the inhibitor was effective in two such widely different systems, it probably is not an antibody, but falls into the category of cross-linking inhibitors which we have previously described (4, 5, 10, 12-17). While the exact nature of the inhibitor remains unknown, we raise the question whether some unusual metabolic transformation of isonicotinic acid hydrazide (with which the patient was treated and which itself we found to be a potent inhibitor fibrin cross-linking), in combination with a macromolecule, might not have given rise to an inhibitory compound. (+info)
The effects of cardiopulmonary bypass with hollow fiber membrane oxygenator on blood clotting measured by thromboelastography.
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In cardiac surgical patients we investigated the effects of cardiopulmonary bypass (CPB) with a hollow fiber membrane oxygenator on blood clotting measured by thromboelastography (TEG). We found only a minimal change in the strength of blood clot described either by the TEG parameter MA (maximum amplitude) or by the shear modulus G calculated from MA. After CPB there was also a significant tendency towards hypercoagulation as defined by shortened parameters R, K and increased a-angle. After comparison with published data obtained in cardiac surgical patients using a bubble oxygenator we conclude that currently used extracorporeal technology exerts a less negative influence on blood clotting than had been conceived previously. (+info)
Structural and functional characterization of tissue factor pathway inhibitor following degradation by matrix metalloproteinase-8.
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Vascular injury results in the activation of coagulation and the release of proteolytic enzymes from neutrophils and connective- tissue cells. High concentrations of these inflammatory proteinases may destroy blood coagulation proteins, contributing to coagulation and bleeding disorders associated with severe inflammation. Matrix metalloproteinase-8 (MMP-8) is released from neutrophils at sites of inflammation and vascular disease. We have investigated the effect of MMP-8 degradation on the anticoagulant function of tissue factor pathway inhibitor (TFPI) as a potential pathological mechanism contributing to coagulation disorders. MMP-8 cleaves TFPI following Ser(174) within the connecting region between the second and third Kunitz domains ( k (cat)/ K (m) approximately 75 M(-1).s(-1)) as well as following Lys(20) within the NH(2)-terminal region. MMP-8 cleavage of TFPI decreases the anticoagulant activity of TFPI in factor Xa initiated clotting assays as well as the ability of TFPI to inhibit factor Xa in amidolytic assays. Yet, MMP-8 cleavage does not alter the ability of TFPI to inhibit trypsin. Since the inhibition of both factor Xa and trypsin is mediated by binding to the second Kunitz domain, these results suggest that regions of TFPI other than the second Kunitz domain may directly interact with factor Xa. (125)I-factor Xa ligand blots of TFPI fragments generated following MMP-8 degradation were used for probing binding interactions between factor Xa and regions of TFPI, other than the second Kunitz domain. In experiments performed under reducing conditions that disrupt the Kunitz domain structure, (125)I-factor Xa binds to the C-terminal fragment of MMP-8-degraded TFPI. This fragment contains portions of TFPI distal to Ser(174), which include the third Kunitz domain and the basic C-terminal region. An altered form of TFPI lacking the third Kunitz domain, but containing the C-terminal region, was used to demonstrate that the C-terminal region directly interacts with factor Xa. (+info)
Thermal effect of intravascular MR imaging using an MR imaging-guidewire: an in vivo laboratory and histopathological evaluation.
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BACKGROUND: Intravascular magnetic resonance (MR) imaging to guide interventional procedures is a rapidly growing field. A primary concern with these new techniques is their thermal safety. The purpose of this study was to evaluate, in vivo, the thermal effect of an MR imaging-guidewire (MRIG) for intravascular MR imaging (IVMRI). MATERIAL/METHODS: Two indications of potentially adverse local heating were investigated: blood coagulation disorders and pathologic changes in target vessels. Experiments were performed on ten rabbits with a 1.5 T MR scanner. Using a 0.64-mm MRIG as the RF receiver, we imaged the target aorta using a fast spin-echo pulse sequence with an average specific absorption rate (SAR) of 0.6 W/kg. The total MR imaging time was approximately 70 minutes. RESULTS: There were no abnormal value changes of the coagulation factors between pre- and post-IVMRI, no clinical manifestations of blood coagulation disorders, and, histopathologically, no thermal damage in target vessels. CONCLUSIONS: This study demonstrates, from a pathophysiological point of view, the potential safe use of the MR imaging-guidewire for intravascular MR imaging. Further study is required to precisely define the boundaries of these safe operating parameters. (+info)