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PubMed1991

Zinc ions promote the binding of factor XII/factor XIIA to acidic phospholipids but have no effect on the binding of high-Mr kininogen.

Binding of high-Mr kininogen and factor XII/factor XIIa to phospholipids coated on to polystyrene microtiter plates was investigated by ELISA. Both high-Mr kininogen and factor XII/factor XIIa bound specifically to the phospholipid surface. Binding was observed to negatively charged phospholipids only. The binding of high-Mr kininogen was not affected by the presence of zinc ions. At a surface concentration of 20% phosphatidylinositol phosphate in phosphatidylcholine a dissociation constant (kD) of 10 nM for the binding of high-Mr kininogen was calculated. The amount of bound purified alpha-factor XIIa could be increased 4-5-fold in the presence of zinc ions. The lowest zinc ion concentration giving maximal binding was 0.1 mM. The binding of alpha-factor XIIa was inhibited by high-Mr kininogen. Independent of the presence of zinc ions or high-Mr kininogen, a kD of 7.9 nM was calculated for alpha-factor XIIa binding. The binding of prekallikrein was dependent upon the presence and the concentration of high-Mr kininogen. In plasma containing aprotinin, the binding of high-Mr kininogen was apparently inhibited in the presence of zinc ions, which was a prerequisite for the binding of factor XII. This apparently inhibitory effect of zinc ions on the binding of high-Mr kininogen was probably due to the increased binding of factor XII, which displaced high-Mr kininogen.

Binding Sites↗
PubMed2002

Inhibition of contact activation by a kininogen peptide (HKH20) derived from domain 5.

Contact activation can be initiated by interaction of Factor XII, prekallikrein (PK) and high molecular weight kininogen (HK) with inorganic negatively charged biologic macromolecules, or upon cell surfaces, or interaction with membrane protein derivatives such as aggregated beta amyloid. The latter two examples are zinc-dependent. The interaction with cells is dependent on peptides derived from HK domains 3 and 5 termed LDC27 and HKH20, respectively. We have tested the ability of each of these peptides to inhibit HK-dependent contact activation. HKH20 inhibited activation of prekallikrein when a mixture containing HK, prekallikrein and Factor XII was incubated with dextran sulfate, gC1qR, amyloid beta or endothelial cells. Comparable quantities of LDC27 had no effect. The binding of biotinylated HK or biotinylated Factor XII was inhibited in a dose response fashion by increasing concentrations of HKH20 while LDC27, again had no effect. The N-terminal region of HKH20 (amino acids 475-485) is of particular importance for binding and histidine 485 prominently enhances the reaction as assessed employing overlapping and deleted peptides. Since there is a role for HK heavy chain in binding to endothelial cells and LDC27 can be employed as an affinity ligand to isolate the binding proteins, we increased the LDC27 concentration from 10-fold to 250-fold to determine whether it is functional. Inhibition of endothelial cell-dependent prekallikrein activation required 100-fold greater concentration of LDC27 when compared to HKH20 to achieve significant inhibition. We conclude that the interactions of the light chain of HK via HKH20 is of particular importance for activation of the bradykinin forming cascade in zinc-dependent or independent reactions and is true for all "surface" initiators tested thus far.

Amino Acid Sequence↗
PubMed1978

Reaction of blood with artificial surfaces of hemodialyzers. Studies of human blood with platelet defects or coagulation factor deficiencies.

Heparinized human blood was exposed to the dialysis membranes of commercially available pediatric size hemodialyzers in an in vitro flow circuit. Bloods from normal subjects and from patients with various blood coagulation and platelet function deficiencies were tested in this model system. In most cases, there was a heavy linear deposit of leukocytes on the dialysis membrane overlying support structures. In other areas, the cellular deposit was less uniform and consisted of single platelets, platelet aggregates, leukocytes, and occasional fibrocellular microthrombi. The number of adherent platelets was smaller in tests with blood from patients with congenital afibrinogenemia, factor XII deficiency, severe von Willebrand's disease, and thrombasthenia then in tests with blood from normal subjects or hemophilic patients. Hence, fibrinogen, factor XII, the von Willebrand factor, and a normal platelet plasma membrane appear necessary for adhesion of platelets to dialysis membranes.

Afibrinogenemia↗
PubMed1989

Apolipoprotein B-100 of plasma low density lipoproteins undergoes proteolysis by contact activation factors when plasma is treated with dextran sulfate-500-MgCl2.

Human plasma low density lipoproteins (LDL) isolated by ultracentrifugation showed a single band corresponding to apolipoprotein B-100 (apoB-100) by SDS-gradient gel electrophoresis (GGE). In turn, apoB-100 of LDL precipitated from plasma by dextran sulfate-500 (DS)-MgCl2 exhibited several bands indicative of a degradative process. The degradation was more extensive at 0 degrees C than at either 23 degrees C or 37 degrees C, and appeared to be related to a protease activity that cleaved both the synthetic peptide, Z-Phe-Arg-7-amido-4-methylcoumarin (Z-Phe-Arg-AMC) and apoB-100. Proteolysis was proportional to the DS added to the plasma, was prevented by the kallikrein inhibitor, D-Phe-L-Phe-L-Arg-CHCl2, and was significantly decreased in plasma specimens of patients with either factor XII or prekalikrein deficiency. LDL pre-purified by ultracentrifugation and then precipitated by DS in the absence of plasma exhibited no proteolysis. However, proteolysis was observed when LDL interacted with kallikrein. The two main apolipoproteins of HDL3, apoA-I and apoA-II, were not affected by this proteolytic process. We interpret the results to indicate that the negatively charged surface provided by DS accelerates in plasma the autoactivation of factor XII and the activation of prekallikrein, resulting in an increase of the effective concentration of kallikrein and possibly other proteases and proteolysis of LDL-apoB-100. The higher degree of the DS-induced proteolysis of apoB-100 at 0 degrees C than at 23 degrees C is likely the consequence of enhanced autoactivation of factor XII and a decreased efficiency of plasma inhibitors, such as C1-inhibitor. We speculate that the proteolysis of apoB-100 induced by DS is not limited to this polyanion, but may also be the property of other negatively charged agents, particularly at cold temperatures.

Apolipoprotein B-100↗
PubMed1983

Modulation of disseminated intravascular coagulation (DIC) by steroidal and non-steroidal anti-inflammatory drugs.

Activation of the coagulation systems by endotoxin and release of vasoactive agents are both essential for the production of microthrombosis. Glucocorticoids prevent activation of factor XII by endotoxin in vivo and decrease production of tissue factor by macrophages. NSAID do not interfere with factor XII activation and increase the severity and risks of microthrombosis by inhibiting synthesis and release of protective prostaglandins. On the other hand, prolonged administration of glucocorticoids results in the reduction of the immune defence and fibrinolysis, increases the alpha-adrenergic response to endotoxin and sensitizes to endotoxin-induced intravascular coagulation like NSAID.

Animals↗
PubMed2000

Coagulation system and platelets are fully activated in uncomplicated sepsis.

OBJECTIVE: To test the hypothesis that the coagulation system and platelets are activated in sepsis, the uncomplicated and usually earliest stage of the septic process, and to compare the findings detected in sepsis with those found in severe sepsis and septic shock. DESIGN: Prospective study comparing patients with sepsis, severe sepsis, and septic shock, and healthy volunteers. SETTING: General intensive care unit in a tertiary university hospital. PATIENTS: Seventy-four consecutive septic patients (45 with sepsis, 15 with severe sepsis, and 14 with septic shock). Fourteen healthy volunteers served as control subjects. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: After blood sampling, molecular activation markers of coagulation (prothrombin fragments 1 and 2, fibrinopeptide A, thrombin-antithrombin complexes, and monomers of fibrin) and of platelets (beta-thromboglobulin and platelet factor 4), several coagulation factors, global tests of coagulation (prothrombin time and activated partial thromboplastin time), and platelet count (PTL) were measured. In sepsis, prothrombin fragments 1 and 2, fibrinopeptide A, thrombin-antithrombin complexes, and monomers of fibrin were increased to 2.52+/-0.21 nmol/L, 20.88+/-2.52 ng/mL, 33.8+/-2.9 microg/L, and 69% positive, respectively, compared with control subjects (0.86+/-063 nmol/L, 1.14+/-0.15 ng/mL, 16.07+/-1.01 microg/L, and 0%, respectively). Beta-Thromboglobulin and the beta-thromboglobulin-to-platelet factor 4 ratio were also increased to 107.87+/-11.87 IU/mL and 8.86+/-1.06, compared with controls (18.36 +/-2.99 IU/mL and 2.67+/-0.52, respectively). With the exception of a decrease in factor XII and an increase in fibrinogen, coagulation factors, global coagulation tests, and PTL were not changed in sepsis. In severe sepsis and mainly in septic shock, coagulation factors were markedly decreased, global coagulation tests were prolonged, and PTL was reduced. All changes were independent of the causative infectious pathogen. CONCLUSION: Coagulation system and platelets are strongly activated in sepsis. In this stage, only factor XII is decreased. In contrast, in severe sepsis and mainly in septic shock, most of the coagulation factors are depleted, PTL is decreased, and global coagulation tests are prolonged, indicating exhaustion of hemostasis. Finally, Gram-positive, Gram-negative, and other microorganisms produce identical impairment of coagulation.

Adolescent↗
PubMed2002

Human coagulation factor XII-related "new pressor protein": role of PACAP in its cardiovascular and sympathoadrenal effects.

OBJECTIVE: To investigate the role of pituitary adenylate cyclase-activating polypeptide (PACAP)-38 and -27 as possible mediators of the actions of "new pressor protein" (NPP), which is related to coagulation factor XIIa, on blood pressure (systolic and diastolic blood pressure) and heart rate, and on the release of adrenal medullary catecholamines. METHODS: Adult male Wistar bioassay rats (n=8 to 18 per group) were anesthetized with inactin (100 mg/kg intraperitoneally), ganglion-blocked with pentolinium (19.2 mg/kg subcutaneously) and treated with captopril (2.5 mg/kg intravenously). Human NPP was injected at 20 L plasma equivalent per approximately 300 g of rat intravenously, and both PACAPs were injected at 10 g/kg intravenously. The systolic and diastolic blood pressure and heart rate responses to all of these agonists were determined using a MacLab/8 system. Arterial plasma adrenaline and noradrenaline were determined by high performance liquid chromatography with fluorimetric detection. Responses to NPP, the PACAPs and a specific PACAP antagonist were compared to assess the PACAPs as potential mediators of the cardiovascular effects of NPP. RESULTS: PACAP-38 mimicked the effects of NPP on systolic and diastolic blood pressure and heart rate more closely than did PACAP-27. Generally, NPP raised diastolic blood pressure and heart rate, and especially plasma adrenaline and noradrenaline, more impressively in degree and duration than that achieved by the PACAPs. The antagonism of PACAP receptors (PAC-1) significantly reduced the cardiovascular effects of NPP by 30% to 50%. CONCLUSIONS: PACAP-38, especially, may qualify as a potential mediator of the cardiovascular and sympathoadrenal effects of NPP but incomplete inhibition of NPP activity by PAC-1 receptor antagonism and the observed differences all suggest that PACAP is not the only peptide involved. Such peptidic mediation of the effects of NPP may explain the potentiation of NPP by captopril and why NPP remains effective after cholinergic blockade. These data suggest that PACAP is involved in a novel axis between NPP, cardiac function and blood pressure that resists angiotensin-converting enzyme inhibition. Any endogenous production of NPP could raise clinically relevant issues pertaining to therapy with ACE inhibitors.

Analysis of Variance↗
PubMed1994

The prevalence of moderate and severe FXII (Hageman factor) deficiency among the normal population: evaluation of the incidence of FXII deficiency among 300 healthy blood donors.

Factor XII (FXII) deficiency has been reported to be a risk factor for the development of arterial and venous thromboembolism. However, no data are available on the prevalence of FXII deficiency within the normal population. Measuring APTT and FXII activity, seven FXII deficiencies could be detected among 300 healthy blood donors. This corresponds to an incidence of FXII deficiency of 2.3%. On the basis of these data the prevalence of severe and mild FXII deficiency in the normal population can be estimated to be 1.5-3.0%. Assessment of FXII antigen levels revealed, that all seven FXII deficient individuals had FXII antigen levels matching the activity. One presented a severe FXII deficiency (1/300, 0.3%) without detectable FXII activity and an APTT prolongation of more than 120 s. The remaining six FXII deficiencies (6/300, 2.0%) were moderate variations with FXII activities ranging from 20-45% and less prolonged APTTs. Among the 300 healthy donors 16 (5.3%) subjects with prolonged APTTs were identified. Causes for APTT-prolongation were FXII deficiency (7/16), lupus anticoagulant (6/16), mild FVIII deficiency (1/16) and hepatic disorder (1/16). In the remaining sample (1/16) the cause for the prolongation of the APTT remained unexplained. Although 8.7% (26/300) of the donors had a positive family-history of thromboembolism (TE-FHx), none of the FXII deficient subjects were among those with positive TE-FHx.

Adult↗
PubMedDate not supplied

[Effect of immobilized noradrenaline on the contact phase of blood coagulation].

Specificity of interaction between factors of contact phase of blood coagulation and noradrenaline was studied. Human blood plasma lost the capacity to contact activation after chromatography on a column with noradrenaline-Sepharose. High specificity in binding of factors of contact phase with ligand-noradrenaline, "utilization" of factor XII during interaction with the ligand, the high specific activity of factor XII bound to noradrenaline-Sepharose were observed.

Blood Coagulation↗
PubMed2001

[Antiphospholipid antibodies in asymptomatic pediatric patients].

BACKGROUND: Findings of prolonged activated partial thromboplastin time (APTT) and lupus anticoagulant are rare in asymptomatic children and are often preceded by certain types of surgery. Clinical behaviour is usually favorable. PATIENTS AND METHODS: We assessed the biological and clinical features of antiphospholipid antibodies found in 13 children diagnosed between January 1996 and September 2000 (mean age at diagnosis: 5 years). The patients were prospectively followed-up for a median of 16 months (range: 15-60). The diagnosis of lupus anticoagulant was based on the guidelines of the International Society of Thrombosis and Hematosis and included coagulation-based assays as well as enzyme-linked immunosorbent assay for anticardiolipin and anti-beta 2 glycoprotein I. RESULTS: In all patients lupus anticoagulant was detected after investigation of prolonged APTT prior to surgery (adenoidectomy in eight patients, orchidopexy in one and eye surgery in one). The antibody was associated with infectious mononucleosis in one patient and was detected during routine laboratory investigations in two. All antibodies were primary and 53.6% of events were transient. In all patients lupus anticoagulant IgG and anti-beta 2 glycoprotein I were negative. Slightly reduced factor XII:C plasma concentrations (mean: 38.2 UI/dl) were found in 30.7% of the patients. No clinical manifestations of antiphospholipid symptoms were associated with the diagnosis of antiphospholipid antibodies and none of the patients experienced bleeding after surgery. CONCLUSIONS: Primary antiphospholipid antibodies were infrequent in asymptomatic pediatric patients and were typically associated with certain types of surgery (adenoidectomy, tonsillectomy) or viral infections. They were usually transient and clinically irrelevant. These antibodies may be associated with slightly reduced plasma concentrations of factor XII and consequently a differential diagnosis with a mild factor XII deficiency should be considered.

Adenoidectomy↗
PubMed1996

Hemostatic abnormalities and the severity of illness in patients at the onset of clinically defined sepsis. Possible indication of the degree of endothelial cell activation?

OBJECTIVE: To find out whether changes within the hemostatic system are related to the severity of illness and organ failure in patients at the onset of clinically defined sepsis and to find some indications for the contribution of endothelial cell activation or perturbation to the patient's status. The following measurements were undertaken: Acute Physiology and Chronic Health Evaluation (APACHE) II score, multiple organ failure (MOF) score, plasma levels of thrombin-antithrombin III complexes (TAT), antithrombin III (AT III), protein C antigen, factor XII, and plasminogen activator inhibitor type 1 antigen (PAI-1), neopterin, and interleukin 6 (IL-6). DESIGN: A prospective case series study. SETTING: Intensive care unit (ICU) of the Department of Internal Medicine, Justus Liebig University, Giessen, Germany. PATIENTS: 28 consecutive patients (11 females, 17 males; mean age 58 years) with clinically defined sepsis. Eleven patients were admitted from the surgical ICU (9 after elective surgery, 2 after trauma surgery). The operations were done 1-26 days (mean 14 days) prior to the onset of sepsis. MAIN RESULTS: At the onset of sepsis we found elevated plasma levels of TAT, PAI-1, neopterin, and IL-6, and lowered plasma levels of AT III, factor XII, and protein Cantigen. Neopterin, PAI-1, IL-6, and factor XII showed a statistically significant correlation with the APACHE II score. The MOF score is significantly correlated with IL-6 and neopterin. The extent of hemostatic abnormalities was related to increasing levels of IL-6. CONCLUSIONS: Clinical evidence of a septic process is most likely to be preceded by activation of the hemostatic system, the vascular endothelium, and the monocyte/macrophage system. IL-6 may have a regulatory function for hemostasis in inflammation. Laboratory monitoring could be helpful in deciding whether to start early intensive therapy in patients at risk for sepsis.

Adult↗
PubMed1976

Assay of factors of the kinin system in plasma from patients with specific exogenous allergies.

Factors of significance for the release of kinin were estimated in plasma from patients with specific, exogenous allergies and in that from healthy individuals. There was no evidence that the rapid initial kinin release in plasma from allergic patients caused by submaximum concentrations of hog pancreas kalikrein or by acetone-activated human plasma (2) was due to an increased level of prekallikrein activator (activated factor XII), to prekallikrein itself or to a factor possibly positioned between active factor XII and prekallikrein. In addition, the rapid halt in kinin release observed for the patient plasma could not be ascribed to an increased level of alpha2-macroglobulin, CI-inactivator or alpha1-antitrypsin. It is suggested that the differences in kinin release registered between the patient plasma and the normal plasma might reflect differences in the relative amounts of kininogen fractions present.

Acetone↗
PubMed1992

Analysis of intraarticular fibrinolytic pathways in patients with inflammatory and noninflammatory joint diseases.

OBJECTIVE: Intraarticular activation of the fibrinolytic system has been suspected to occur in patients with arthritis. We undertook the present study to investigate the relation of this activation to clinical symptoms, and the molecular pathways involved. METHODS: We quantitatively assessed levels of plasmin-alpha 2-antiplasmin (PAP) complexes in synovial fluid (SF) from 25 patients with rheumatoid arthritis (RA), 7 with seronegative spondylarthropathy (SSA), and 10 with osteoarthritis (OA), and conducted an analysis to determine the plasminogen-activating pathway via which these complexes were generated. In addition, we studied the relationship of intraarticular fibrinolysis to clinical and biochemical parameters. RESULTS: All patients studied had increased SF levels of PAP complexes. Levels in patients with RA and SSA were slightly higher than those in patients with OA. These complexes were probably formed by activation of urokinase-type plasminogen activator (u-PA), and not tissue-type plasminogen activator (t-PA), since SF levels of both u-PA antigen and u-PA-plasminogen activator inhibitor (PAI) complexes were increased in 27 of the 42 patients. Conversely, SF levels of t-PA were below normal in all but 1 patient. In some patients, activation of factor XII presumably also contributed to plasminogen activation in SF, since levels of factor XIIa-C1 inhibitor in SF were increased in 8 of the 42 patients and correlated, as did u-PA-PAI levels, with levels of PAP complexes. Several of the parameters of fibrinolysis in SF, particularly u-PA antigen and u-PA-PAI-1 complexes, were found to correlate with clinical and biochemical parameters. CONCLUSION: Our results suggest that plasminogen is frequently activated in the joints of patients with inflammatory or noninflammatory arthropathy and that this activation mainly occurs via a u-PA-, and in some cases also via a factor XII-, dependent pathway. The possible relation of this activation process to stimulation of synovial cells by cytokines is discussed.

Adult↗
PubMed2004

Activation of the contact system and inflammation after thrombolytic therapy in patients with acute myocardial infarction.

Thrombolytic therapy activates the contact system, and factor XII activation may activate the coagulation cascade and inflammation. It is not known whether an early inflammatory response is induced by thrombolytic therapy in patients with acute myocardial infarction (AMI). We prospectively measured the plasma levels of activated factor XII, cleaved kininogen, prothrombin fragment 1 + 2 (as indexes of the contact phase and coagulation activation), and interleukin-6 and C-reactive protein (CRP) (as indexes of inflammation) in 39 patients hospitalized for AMI within 12 hours of symptom onset: 26 receiving thrombolytic therapy and 13 heparin alone. Blood samples were collected at baseline and after 90 minutes and 24 hours. Patients undergoing thrombolysis had a significant early increase in activated factor XII (from 2.2 ng/ml at baseline to 4.7 ng/ml after 90 minutes; p = 0.0001), cleaved kininogen (from 26% to 37%; p = 0.001), and fragment 1 + 2 (from 1.4 to 2.1 nmol/L; p = 0.0001), whereas the 24-hour levels were similar to baseline levels. The levels of interleukin-6 significantly increased during the first 90 minutes (from 3.9 to 6.3 microg/ml; p = 0.001), and were even higher after 24 hours (11.9 ng/ml, p = 0.0001). CRP levels increased only after 24 hours (p = 0.0001). There were no changes in these parameters in patients receiving heparin alone, except for a 24-hour increase in interleukin-6 and CRP levels. Thus, in patients with AMI receiving thrombolytic therapy, early activation of inflammation parallels the activation of the contact system and the coagulation cascade, which might contribute to microvascular obstruction and reperfusion injury.

C-Reactive Protein↗
PubMedDate not supplied

Activation of the plasma kallikrein/kinin system on endothelial cells.

For more than two decades, it has been known that activation of the plasma kallikrein/kinin system only occurs when it is exposed to artificial, negatively charged surfaces. The existence of physiological, negatively charged surfaces has, however, never been demonstrated in vivo. In this report, we describe current knowledge about how the proteins of the plasma kallikrein/kinin system interact with and become activated on cell membranes. In this model, activation of the plasma kallikrein/kinin system on endothelial cells is not initiated by factor XII autoactivation, as seen on artificial surfaces. On endothelial cells, plasma prekallikrein is activated by a membrane-associated cysteine protease. This activation is dependent on the presence of high molecular weight kininogen and an optimal zinc (Zn2+) concentration. Although the initiation of activation of plasma prekallikrein is independent of factor XII, kallikrein-mediated factor XIIa generation, in turn, accelerates the activation of the system. Further kallikrein formed on endothelial cell membranes is capable of cleaving its receptor and native substrate, high molecular weight kininogen, liberating bradykinin and terminating activation. In addition, the kallikrein formed on the surface of endothelial cells results in kinetically favorable activation of prourokinase and, subsequently, plasminogen. Activation of the plasma kallikrein/kinin system on endothelial cells proceeds by a physiological mechanism to initiate cellular fibrinolysis independent of plasmin, fibrin, and tissue-type plasminogen activator.

Endothelium, Vascular↗
PubMed1983

Hydrogels by irradiation of a synthetic heparinoid polyelectrolyte.

Gamma irradiation of aqueous solutions of a synthetic heparinoid polyelectrolyte results in the formation of hydrogels, varying in water content and mechanical strength. The equilibrium water content and the mechanical strength of the hydrogels are dependent on the initial polyelectrolyte concentration, the molecular weight of the polyelectrolyte, the percentage of double bonds in the polyelectrolyte and the radiation dose. The polyelectrolyte hydrogels do not deplete Antithrombin III from blood and there is no activation of factor XII according to an in vitro kallikrein generation test. However, in a very sensitive test for factor XII activation (contact promoted shortening of the thrombotest) a slight activation of this factor was observed.

Biocompatible Materials↗
PubMed1999

Factor XIIa is a kinetically favorable plasminogen activator.

Initiation of the plasma contact system has been shown to play a significant role in the fibrinolysis, activating both pro-urokinase and plasminogen. The aim of the present study was to further evaluate the functional role of the factor XIIa catalyzed activation of plasminogen. Activation of plasminogen by factor XIIa followed the Michaelis-Menten rate equation. In a continuous assay system the Km was 0.27 microM; the kcat 0.078 min(-1) and the kcat/Km 0.31x10(6) M(-1) x min(-1). In an end-point assay system the Km was 0.58 microM; the kcat 0.096 min(-1) and the kcat/Km 0.16x10(6) M(-1) x min(-1). The discrepancy between the kcat in the two assays is not significant. Theoretically the higher Km in the end-point assay system may be due to the presence or generation of an unidentified competitive inhibitor in this assay system. Comparing the catalytic constants of factor XIIa with those of urokinase activation of plasminogen, the specificity constant, kcat/Km, of factor XIIa activation of plasminogen was 20-fold lower. However, taking the low physiological concentration of urokinase into account, the efficiency of activated factor XII is equivalent to that of urokinase. When monitoring factor XIIa activation of plasminogen in a clot lysis assay, the clot lysis time was 2- to 4-fold as long as that accommodated by urokinase at factor XIIa concentrations equivalent with 5-20% of the zymogen concentration in plasma. The factor XIIa mediated clot lysis was prevented completely by the presence of a polyclonal antibody to factor XII.

Animals↗