Biomedical subjects

Wayne L Chandler

Publications and source records attributed to Wayne L Chandler.

At least 19 recordsLinked to original sources

PubMed2006

Comparing the prothrombin time INR versus the APTT to evaluate the coagulopathy of acute trauma.

INTRODUCTION: In trauma patients, PT/INR or aPTT cutoffs of > or =1.5x normal are often used as triggers for the transfusion of plasma. MATERIAL AND METHODS: To evaluate the ability of the PT/INR or aPTT to predict low coagulation factor levels, these tests were compared to coagulation factor levels in samples with artificially prepared single and multiple factor deficiencies, 9 heparin-contaminated samples, 10 lupus inhibitor-containing samples, 21 samples with elevated factor VIII levels, and 35 samples from acute trauma patients. RESULTS AND CONCLUSIONS: The PT/INR and aPTT showed comparable sensitivity for single or multiple factor deficiencies in artificially deficient plasmas, but the PT/INR was more sensitive than the aPTT to low coagulation factor levels in actual trauma patients (sensitivity 84% versus 50%). The aPTT can show false positives with lupus anticoagulants and heparin contamination and false negatives in samples with elevated factor VIII. Thus, in the acute trauma setting, the PT/INR cutoff is a more reliable indicator of reduced coagulation factor levels.

Acute Disease↗

PubMed2006

External peer review quality assurance testing in von Willebrand disease: the recent experience of the United States College of American Pathologists proficiency testing program.

The U.S. College of American Pathologists (CAP) has conducted a focused study of the proficiency testing for von Willebrand disease (vWD) analysis from 2003 to 2005. This report summarizes the findings regarding the accuracy and precision of the various assays at different analyte levels, as well as the influence of the reference material used to construct the assay standard curve. The results show that testing of von Willebrand factor (vWF):antigen (vWF:Ag) and ristocetin cofactor activity (vWF:RCo) is reasonably accurate, with all-method mean values falling within 3.2 and 5.6%, respectively, of the International Society on Thrombosis and Haemostasis Secondary Coagulation Standard (lot 2) assigned values. vWF:Ag measurements are reasonably precise (all-method coefficients of variation [CVs] = 10.7 to 15.1%), even at lower levels of vWF. The highest precision was observed for immunoturbidometric assays (CVs, 6.3 to 9.7%). vWF:RCo measurements are less precise (all-method CVs, 23.3 to 30.9%). The reference materials used in the standard curves for immunoturbidometric vWF:Ag assays appear to have accurately assigned vWF values for the majority of commercial suppliers.

Antigens↗

PubMed2006

Antithrombin reduces monocyte and neutrophil CD11b up regulation in addition to blocking platelet activation during extracorporeal circulation.

BACKGROUND: Patients undergoing cardiac surgery requiring cardiopulmonary bypass develop a systemic inflammatory reaction. Antithrombin III (AT) has anticoagulant effects but also shows evidence of anti-inflammatory activity. The aim of this study was to examine whether exogenous AT could reduce white blood cell activation (CD11b up regulation or elastase release), in addition to inhibiting platelet (PLT) activation and fibrin generation, during simulated cardiopulmonary bypass (sCPB), undertaken in the absence of endothelium. STUDY DESIGN AND METHODS: sCPB was carried out with minimally heparinized (2 U/mL) human blood for 90 minutes in controls and with supplementation by low-dose (1 U/mL) and high-dose (5 U/mL) AT. RESULTS: High-dose AT blunted thrombin generation during sCPB (prothrombin fragment 1.2); both doses significantly inhibited thrombin activity (fibrinopeptide A). Complement activation (C3a and C5b-9) was unaffected by AT. High-dose AT inhibited PLT activation (P-selectin expression and P-selectin-dependent monocyte-PLT conjugate formation). AT supplementation at the higher dose significantly abrogated monocyte and neutrophil CD11b up regulation and neutrophil elastase release. CONCLUSION: In addition to anticoagulant and anti-PLT effects, pharmacologic AT doses significantly blunted monocyte and neutrophil CD11b up regulation and neutrophil elastase release during sCPB, independent of endothelial effects. These data provide evidence for the direct anti-inflammatory activity of AT that has clinical relevance for CPB complications.

Antithrombin III↗

PubMed2006

Effect of fondaparinux on coagulation assays: results of College of American Pathologists proficiency testing.

CONTEXT: Fondaparinux, a factor Xa inhibitor, is approved for thromboprophylaxis after orthopedic surgery and for treatment of venous thromboembolism. It may also be efficacious, safe, and cost-effective for other patients; thus, more widespread use of fondaparinux is likely. The effect of fondaparinux on coagulation testing needs to be thoroughly examined. OBJECTIVE: To report the effects of fondaparinux on coagulation tests (prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, factor VIII, thrombin time, anti-factor Xa) across diverse methodologies. DESIGN: Samples with different concentrations of fondaparinux (0, 0.4, 0.8, and 2.0 microg/mL) were sent to laboratories participating in the College of American Pathologists Comprehensive Coagulation proficiency survey (N = 898). Laboratory-specific methods were used to assay coagulation parameters. RESULTS: Prophylactic or therapeutic fondaparinux prolonged the prothrombin time by approximately 1 second and the activated partial thromboplastin time by 4 to 5 seconds, and reduced factor VIII from 119% to 107% and 102%, respectively. Supratherapeutic fondaparinux reduced factor VIII to 85%. The activated partial thromboplastin time was prolonged in 19%, 29%, and 52% of laboratories with prophylactic, therapeutic, and supratherapeutic fondaparinux levels, respectively. Fibrinogen, antithrombin, and thrombin time assays did not show clinically significant changes. When measuring fondaparinux concentration using an anti-factor Xa assay, the most accurate results were obtained when fondaparinux was used as the calibrator. CONCLUSIONS: Fondaparinux, even in prophylactic doses, slightly prolongs the prothrombin time and activated partial thromboplastin time and can interfere with factor VIII assays, but it has no clinically relevant effect on fibrinogen, antithrombin, or thrombin time. A fondaparinux standard curve should be used for reporting fondaparinux levels using an anti-factor Xa assay.

Anticoagulants↗

PubMed2005

Strategies to reduce hemostatic activation during cardiopulmonary bypass.

INTRODUCTION: We evaluated whether a modified protocol for cardiopulmonary bypass (CPB) could reduced the systemic hemostatic activation associated with this procedure. MATERIALS AND METHODS: The in vivo rates of thrombin, fibrin, plasmin and D-dimer generation were determined in each subject during CPB using measured levels of hemostatic factors combined with a computer model of the cardiovascular and hemostatic systems. A standard CPB group using uncoated circuits, standard heparin levels and direct shed blood reinfusion (n=9) was compared to a modified CPB group using heparin-coated circuits, shed blood collection, washing and reinfusion post-operatively, lower heparin levels and epsilon-amino-caproic acid (n=10). RESULTS AND CONCLUSIONS: Standard CPB increased average thrombin generation 9-fold, decreased fibrin generation 2-fold, increased plasmin generation 11-fold and increased fibrin degradation and D-dimer generation 19-fold. During CPB in the modified group thrombin generation was not increased beyond surgical levels, lower heparin concentrations allowed each thrombin to make more fibrin prior to inhibition, while fibrin degradation was suppressed by epsilon-amino-caproic acid. At baseline for every 100 fibrins formed only 1-2 were degraded to D-dimer. During standard CPB for every 100 fibrins generated on average 34 fibrins were degraded with some subjects showing a net fibrin loss. In contrast, in the modified CPB group for every 100 fibrins formed only 4 fibrins were degraded (p<0.0001 vs. standard group). Kinetic modeling of hemostasis in individual patients showed that a modified CPB protocol could reduce excessive thrombin generation during CPB and suppress fibrin degradation moving hemostatic regulation back towards normal.

Aged↗

PubMed2005

The kinetics of plasmin inhibition by aprotinin in vivo.

INTRODUCTION: The purpose of this study was to estimate, in patients undergoing cardiopulmonary bypass (CPB), the in vivo rates of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) secretion, plasmin generation, fibrin degradation, and plasmin inhibition by aprotinin versus antiplasmin. MATERIALS AND METHODS: Estimates of in vivo rates were based on measured levels of tPA, PAI-1, antiplasmin, plasmin-antiplasmin complex (PAP), total aprotinin, plasmin-aprotinin complex and D-dimer, combined with a computer model of each patient's vascular system that continuously accounted for secretion, clearance, hemodilution, blood loss and transfusion. Plasmin regulation was studied in nine control patients undergoing CPB without aprotinin versus six patients treated with aprotinin. RESULTS: In controls, plasmin-antiplasmin levels rose from a baseline of 3.0+/-0.9 to a peak of 8.1+/-2.7 nmol/L after CPB due to an average 44-fold rise in the plasmin generation rate. This rise in plasmin generation during CPB lead to increased fibrin degradation causing D-dimer levels to increase from a baseline of 1.2+/-0.6 to a peak of 9.7+/-4.4 nmol/L due to an average 74-fold rise in the D-dimer generation rate. During CPB in the aprotinin group, plasmin-antiplasmin levels dropped, plasmin-aprotinin complex levels rose, while D-dimer levels remained unchanged from baseline. Compared to controls, the aprotinin group showed similar rates of plasmin generation during CPB, but an 11-fold faster plasmin inhibition rate and a 10-fold lower D-dimer generation rate. CONCLUSIONS: The rise in plasmin generation and fibrin degradation that occurs during standard CPB is suppressed by the addition of aprotinin, which returns the patient to near baseline fibrin degradation rates during CPB.

Adult↗

PubMed2005

Effects of hemodilution, blood loss, and consumption on hemostatic factor levels during cardiopulmonary bypass.

OBJECTIVES: The purpose of this study was to determine quantitatively the effects of consumption, hemodilution, and blood loss on coagulation and fibrinolytic factor levels during cardiopulmonary bypass. DESIGN: A combination of measured levels of prothrombin, antithrombin, fibrinogen, plasminogen, and antiplasmin along with their activation markers F1.2, thrombin-antithrombin complex, fibrinopeptide A, plasmin-antiplasmin complex, and D-dimer were used with a computer model of each patient's vascular and hemostatic systems to estimate the cardiopulmonary bypass-associated loss of each factor because of hemodilution, blood loss, and consumption. SETTING: University hospital. PARTICIPANTS: Nine patients undergoing coronary artery bypass graft surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At baseline, it was estimated that on average 2%, 3%, and 25%, respectively, of the baseline liver secretion of plasminogen, prothrombin,and fibrinogen were consumed by activation of these proteins. During cardiopulmonary bypass, thrombin and plasmin generation were increased, whereas fibrin generation was decreased because of heparin. Compared with baseline, hemodilution during cardiopulmonary bypass resulted in an average 35% +/- 7% decrease in the concentration of coagulation and fibrinolytic proteins, whereas blood loss was responsible for an average 6% +/- 5% decrease in these proteins. Blood loss varied substantially among patients, resulting in <1% to 14% decreases in hemostatic protein levels. On average, consumption because of activation resulted in less than a 1% drop in the concentration of coagulation and fibrinolytic factors during cardiopulmonary bypass. CONCLUSIONS: Hemodilution is the primary cause of the drop in coagulation and fibrinolytic proteins during routine cardiopulmonary bypass, followed by blood loss, whereas consumption accounts for less than a 1% drop in most patients.

Aged↗

PubMed2005

Ventricular cerebrospinal fluid hypocretin-1 inversely correlates with glucose levels in cerebrospinal fluid and serum from patients with neurological injuries.

INTRODUCTION: Hypocretin-1 is a hypothalamic neuropeptide that may help regulate arousal and feeding behavior and is quantifiable in cerebrospinal fluid (CSF). In this retrospective pilot study, hypocretin-1 levels obtained from ventricular CSF of neurologically injured patients were correlated with clinical and laboratory results to test whether arousal or metabolic factors might be related to the level of hypocretin-1. METHODS: CSF samples from a heterogeneous group of neurosurgical patients with externally draining intraventricular catheters were assayed in a standard manner for hypocretin-1 and other routine laboratories. Associations were sought between hypocretin-1 and clinical data such as body mass index (BMI), temperature, and Glasgow Coma Scale (GCS) score and between hypocretin-1 and laboratory data such as serum and CSF glucose, protein, and cell counts. RESULTS: Lower levels of ventricular CSF hypocretin-1 were correlated with higher levels of serum (p = 0.020) and ventricular CSF glucose (p = 0.001). Clinical findings such as BMI, temperature, and GCS failed to correlate with hypocretin-1. CONCLUSIONS: In a group of neurologically injured patients, hypocretin-1 and glucose levels are inversely correlated. More studies are needed to investigate these associations, particularly in a homogenous patient sample.

Adult↗

PubMed2004

Lack of depression effect on platelet activation in patients with heart failure.

P-selectin is a marker of platelet activation. Previous studies have reported elevated P-selectin in patients with congestive heart failure (CHF) and depression as separate disorders. We examined if comorbid depression had an effect on platelet activation in CHF patients. Soluble (s)P-selectin was measured in 108 CHF patients; 24 with comorbid depression. There were no significant differences in age, cardiac parameters or (s)P-selectin levels between CHF-only patients and patients with comorbid depression. Our data show no group differences in P-selectin values, which suggests that comorbid depression has no additive effect on platelet activation in CHF patient.

Comorbidity↗

PubMed2004

The relation between cavitation and platelet aggregation during exposure to high-intensity focused ultrasound.

Our previous study showed that high-intensity focused ultrasound (HIFU) is capable of producing "primary acoustic hemostasis" in the form of ultrasound (US)-induced platelet activation, aggregation and adhesion to a collagen-coated surface. In the current study, 1.1 MHz continuous-wave HIFU was used to investigate the role of cavitation as a mechanism for platelet aggregation in samples of platelet-rich plasma. A 5 MHz passive cavitation detector was used to monitor cavitation activity and laser aggregometry was used to measure platelet aggregation. Using spatial average intensities from 0 to 3350 W/cm2, the effects of HIFU-induced cavitation on platelet aggregation were investigated by enhancing cavitation activity through use of US contrast agents and by limiting cavitation activity through use of an overpressure system. Our results show that increased cavitation activity lowers the intensity threshold to produce platelet aggregation and decreased cavitation activity in the overpressure system raises the intensity threshold for platelet aggregation.

Albumins↗

PubMed2004

The effect of submaximal exercise on fibrinolysis.

We studied the relationship between sustained submaximal exercise, increased tissue plasminogen activator (t-PA) levels and decreased hepatic clearance of t-PA. Six healthy male volunteers exercised for 35 min while receiving constant rate infusions of either saline or two different doses of recombinant t-PA for 90 min (40 min before, 35 min during and 15 min after exercise). Liver blood flow was estimated simultaneously by constant rate indocyanine green infusion. Since t-PA is cleared rapidly by the liver in direct proportion to liver blood flow, it was expected that a significant decrease in liver blood flow during sustained submaximal exercise would be associated with a proportional increase in plasma t-PA. During submaximal exercise with a saline (placebo) infusion, steady-state t-PA antigen increased from a resting baseline of 6.3 +/- 3.1 to 15.1 +/- 5.1 ng/ml; with a 20 microg/min t-PA infusion, t-PA antigen increased from 33 +/- 12 to 84 +/- 25 ng/ml during exercise; and with a 40 microg/min t-PA infusion, t-PA antigen increased from 77 +/- 38 to 166 +/- 42 ng/ml during exercise. During submaximal exercise, liver blood flow fell on average 71, 68 and 70%, respectively, during the three procedures, while calculated t-PA clearance decreased on average 59, 59 and 53%. t-PA concentration versus time curves, displayed in proportional units, were similar. The comparable relative increases in endogenous and exogenous t-PA with simultaneous proportional decreases in liver blood flow suggests that diminished hepatic t-PA clearance is the major cause of increased t-PA concentration and blood fibrinolytic activity enhancement during sustained submaximal exercise.

Adult↗

PubMed2004

Plasmin generation and D-dimer formation during cardiopulmonary bypass.

The purpose of this study was to estimate the in vivo rates of plasmin and D-dimer generation for comparison with the rate of fibrin formation during cardiopulmonary bypass (CPB), a procedure known to induce a hyperfibrinolytic state. Plasmin and D-dimer generation rates were based on measured levels of antiplasmin, plasmin-antiplasmin complex and D-dimer obtained before, during and after CPB from nine males, combined with a computer model of each patient's vascular system that continuously accounted for secretion, clearance, hemodilution, blood loss and transfusion. At baseline the average plasmin and D-dimer generation rates were 0.27 +/- 0.07 and 0.18 +/- 0.07 pmol/s, respectively. Within 5 min of CPB initiation, plasmin generation increased over 100-fold to 36 +/- 40 pmol/s while D-dimer generation increased 200-fold to 37 +/- 39 pmol/s. For the remainder of the CPB, average plasmin and D-dimer generation remained 20-fold to 30-fold above baseline levels. During CPB, the rate of D-dimer generation was similar to the rate of total fibrin formation, indicating that, in the absence of fibrinolytic inhibitors, CPB induces plasmin-mediated removal of fibrin from the vascular system at a rate similar to the rate of fibrin formation.

Aged↗

PubMed2004

Reducing hemostatic activation during cardiopulmonary bypass: a combined approach.

UNLABELLED: Interventions such as heparin-coated circuits, epsilon-aminocaproic acid, and reduced shed blood reinfusion have shown mixed results when applied individually for limiting hemostatic activation during cardiopulmonary bypass (CPB). We compared coagulation and fibrinolytic activation during conventional CPB (control) (CTRL) using noncoated circuits, no antifibrinolytics, and open cardiotomy with a combined strategy (HAC) that used heparin-coated circuits, epsilon-aminocaproic acid, and closed cardiotomy. Blood samples were drawn before, during, and after CPB for primary coronary bypass grafting surgery from 9 CTRL patients and 10 HAC patients. Thrombin-antithrombin complex and fibrinopeptide A levels (markers of thrombin and fibrin generation) were reduced in the HAC versus CTRL group after 30 min of CPB (P < 0.05). Average tissue plasminogen activator (tPA) levels were significantly lower in the HAC group by 30 min on CPB (P < 0.05), resulting in preservation of plasminogen activator inhibitor (PAI)-1 during CPB (P < 0.05). D-Dimer, a measure of intravascular fibrin formation and removal, was reduced in the HAC group during and after CPB (P < 0.005). Overall, the combined strategy was associated with a reduction in CPB-induced increases in markers of thrombin generation, fibrin formation, tPA release, and fibrin degradation and better preservation of PAI-1. IMPLICATIONS: A combined approach during cardiopulmonary bypass (CPB) that uses heparin-coated circuits, epsilon-aminocaproic acid, and limited reinfusion of shed pericardial blood is associated with reduced activation of the coagulation and fibrinolytic systems that typically occurs during conventional CPB.

Aged↗

PubMed2004

Heritability of multivariate factors of the metabolic syndrome in nondiabetic Japanese americans.

A rapidly growing body of evidence demonstrates important associations between the metabolic syndrome, characterized by a cluster of risk factors or phenotypes that include dyslipidemia, central obesity, hypertension, and hyperinsulinemia, and both cardiovascular disease and type 2 diabetes. The purpose of the present study was to characterize the metabolic syndrome in a sample of 432 individuals from 68 Japanese-American families, using factor analysis of quantitative phenotypes, and to estimate the heritability of these independent factors. Using nine characteristic phenotypes that included LDL particle size and C-reactive protein (CRP), factor analysis identified three multivariate factors interpreted as lipids, body fat/insulin/glucose/CRP, and blood pressure, explaining 65% of the variance. Heritability analysis revealed significant genetic effects on all of the factors: lipids (h(2) = 0.52, P < 0.001), body fat/insulin/glucose/CRP (h(2) = 0.27, P = 0.016), and blood pressure (h(2) = 0.25, P = 0.026). This analysis shows that independent, multivariate factors of the metabolic syndrome are heritable, demonstrating genetic influences on the underlying pathophysiological mechanisms of the syndrome.

Asian People↗

PubMed2003

Cardiac ischemia during hemolytic uremic syndrome.

Increased thrombin generation and impaired fibrinolysis during Escherichia coli O157:H7-associated hemolytic uremic syndrome (HUS) plausibly diminish myocardial blood flow, but the frequency of cardiac ischemia during HUS is unknown. We identified a 9-year-old boy with HUS in whom myocardial diastolic dysfunction was demonstrated by echocardiography, who also had elevated serum troponin-I and creatine kinase MB mass. However, eight additional patients with HUS did not have elevated markers of cardiac injury. When present, elevated troponin-I should be considered to represent myocardial injury, and not attributed simply to renal insufficiency. It is possible that myocardial ischemia and secondary arrhythmias account for some sudden deaths that occur during acute HUS.

Biomarkers↗

PubMed2003

Effect of valproate on hemostatic function in patients with traumatic brain injury.

OBJECTIVES: To evaluate whether valproate (VPA) resulted in laboratory or clinical evidence of a change in bleeding-related measures associated with VPA therapy in patients sustaining a traumatic brain injury. METHODS: Fibrinogen, platelet count and clot elastic shear modulus using the Thrombelastograph (TEG) coagulation analyzer were measured at baseline, 4, 14, 30, and 180 days post-injury. Clinically significant events, defined as the trigger for requiring a transfusion, were identified and evaluated as to possible treatment effects. RESULTS: Compared to baseline, the platelet count in the VPA groups was decreased on day 4, increased by 100% on day 14, and returned to baseline levels by day 30. Fibrinogen was significantly increased by day 4 and returned to baseline by day 30. The platelet count was correlated with an increase in the maximum amplitude or width of the TEG tracing; a measure of strength of the clot, suggesting that valproate did not alter the clot strength contributed by platelets. None of the clinical events requiring transfusions appeared to be treatment related. CONCLUSIONS: No serious hemostatic adverse events occurred in the trauma patients receiving VPA or phenytoin that could be attributed to treatment.

Adult↗

PubMed2003

Secretion of tissue plasminogen activator and plasminogen activator inhibitor 1 during cardiopulmonary bypass.

INTRODUCTION: Cardiopulmonary bypass (CPB) is associated with elevated tissue plasminogen activator (t-PA) levels during CPB and increased plasminogen activator inhibitor 1 (PAI-1) levels post-operatively. The goal of this study was to estimate the rate of t-PA and PAI-1 secretion in vivo, before, during and after CPB. MATERIALS AND METHODS: Estimated rates of t-PA and PAI-1 secretion were based on measured levels of active and total t-PA, and active and total PAI-1, obtained before, during and after CPB from nine males, combined with a computer model of each patient's vascular system that continuously accounted for secretion, clearance, hemodilution, blood loss and transfusion. RESULTS AND CONCLUSIONS: At baseline, the average t-PA and PAI-1 secretion rates were 0.74+/-0.33 and 1.28+/-0.74 pmol/s, respectively. Within 5 min of CPB initiation, t-PA secretion increased six-fold to 4.41+/-2.58 pmol/s, while PAI-1 secretion was unchanged, resulting in a six-fold increase in active t-PA levels. t-PA secretion remained elevated throughout CPB and into the early post-operative period. Average PAI-1 secretion did not start to increase until the end of CPB. By 2 h after surgery, average PAI-1 secretion had increased 15-fold to 19.60+/-17.10 pmol/s, resulting in reduced levels of active t-PA even though t-PA secretion was still elevated. We conclude that CPB induces an immediate sustained increase in t-PA secretion followed by a delayed progressive increase in PAI-1 production. Variations in the level of active t-PA are a function of the relative rates of t-PA versus PAI-1 secretion at different times during and after surgery.

Blood Chemical Analysis↗

PubMed2003

Failure of peripheral arterial thrombolysis due to elevated plasminogen activator inhibitor type 1.

To reduce the risk of intracerebral hemorrhage during thrombolytic therapy, a lower dose of tissue plasminogen activator (t-PA) or urokinase is used for acute peripheral arterial thrombi versus coronary thrombi. We hypothesized that elevated plasminogen activator inhibitor-1 (PAI-1) activity could neutralize infused t-PA or urokinase, resulting in lysis failure. Active PAI-1, active t-PA and total t-PA antigen were measured in 20 patients receiving t-PA, and active PAI-1 was measured in four patients receiving urokinase for acute peripheral arterial thrombosis. The 18 patients that successfully lysed their thrombi all had low active PAI-1 levels (10 +/- 19 pmol/l) during infusion of thrombolytic therapy, while six patients that failed to lyse their thrombi had high active PAI-1 levels (1533 +/- 1384 pmol/l, P = 0.00007) during infusion. Active t-PA levels during t-PA infusion were higher in the group that lysed their thrombi (536 +/- 423 pmol/l versus 42 +/- 45 pmol/l, P = 0.04) even though total t-PA levels were lower (1240 +/- 493 pmol/l versus 1956 +/- 709 pmol/l, P = 0.03). In the patients that failed to lysed their thrombi, > 95% of infused t-PA was neutralized by PAI-1. We conclude that elevated PAI-1 during acute peripheral arterial thrombolysis is associated with an increased risk of lysis failure due to reduced levels of circulating active t-PA or urokinase.

Female↗