Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FACTOR XII”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources
PubMedDate not supplied

Studies on the components of the contact phase system in patients with acute nonlymphoblastic leukemia.

The objective of the present study was to evaluate factors of the plasma kallikrein system in patients with acute nonlymphoblastic leukemia (ANLL), and compare the results to a normal control group. A prospective study was performed in the Tertiary Health Care Institution, Hemocentro, Campinas State University, Campinas, São Paulo, Brazil. Thirty-five patients, diagnosed as ANLL between 1988 and 1991, were considered for participation. Eleven patients were not eligible, according to the exclusion criteria: infection/septicemia, previous treatment or blood transfusion. The study was performed with 24 ANLL patients, average age 34 years (16-69 years), 14 men and 10 women. Nineteen healthy volunteers, workers from the Hematology Center, average age 32 years (21-59 years), 11 men and 8 women, were the control group. Plasmatic prekallikrein, C1-inhibitor, alpha 2-macroglobulin, activated partial thromboplastin time, prothrombin time, factor XII, factor XI, factor V and prealbumin were measured. Plasmatic prekallikrein (p = 0.02) and prealbumin (p = 0.03) were significantly decreased, and prothrombin time increased (p = 0.003) in the patient group when compared to the control. Significant correlation (r = 0.49, critical value = 0.43, p < 0.05) between prekallikrein and prealbumin, and between prothrombin time and factor V (r = 0.54, critical value = 0.44, p < 0.05) was demonstrated in the patient group. No correlation was found between parameters analysed and circulant blast count or leukemia subgroups. Statistical analysis was performed by the Wilcoxon test. Correlation between the parameters was also verified. These results suggest activation of the contact system or impaired liver synthesis in patients with ANLL, and could contribute to disease complications.

Adolescent↗
PubMed2001

Genetic screening of candidate genes for a prothrombotic interaction with type I protein C deficiency in a large kindred.

The incomplete penetrance of thrombosis in familial protein C deficiency suggests disease occurs when this deficit is combined with additional abnormalities in the hemostatic system. The pattern of inherited thrombophilia in the Vermont II kindred, which is affected by a clinically dominant type I protein C deficiency, provides strong evidence for a second unidentified gene that segregates independently of protein C deficiency and increases susceptibility to thrombosis. To test the second gene hypothesis, thirty-four candidate genes for proteins involved in hemostasis or inflammation were tested as the unknown defect, using highly polymorphic short tandem repeat (STR) markers in an informative subset (n = 31) of the kindred. The genes considered are; alpha-fibrinogen, beta-fibrinogen, gamma-fibrinogen, prothrombin, tissue factor, factor V, protein S, complement component 4 binding protein, factor XI, factor XII, factor XIIIa, factor XIIIb, histidine rich glycoprotein, high molecular weight kininogen, kallikrein, von Willebrands factor, platelet factor 4, thrombospondin, antithrombin III, alpha-1-antitrypsin, thrombomodulin, plasminogen, tissue plasminogen activator, urokinase plasminogen activator, plasminogen activator inhibitor-1, plasminogen activator inhibitor-2, protein C inhibitor, alpha-2-plasmin inhibitor, kallistatin, lipoprotein a, interleukin 6, interleukin 1, cystathionine-beta-synthase, and methylenetetrahydrofolate reductase. Mutations in many of these genes have been previously established as independent risk factors for thrombosis. However, linkage analysis provided no evidence to implicate any of the candidate genes as the second inherited factor that promotes thrombophilia in this kindred.

Blood Coagulation Factors↗
PubMed1992

Plasma prekallikrein, coagulation and fibrinolytic parameters in myeloma patients.

Plasmatic prekallikrein, factor XII, factor XI, C1-inactivator and alpha 2-macroglobulin were evaluated in myeloma patients. Results suggest no modification in the contact phase since there was no significant difference between patients and controls. Other parameters of blood coagulation and fibrinolysis (APTT, TT, fibrinogen, factor V, ELT and LAFP) gave findings consistent with those described in the literature.

Adult↗
PubMed1991

Effect of Eupatorium odoratum on blood coagulation.

The purified compound, 4', 5, 6, 7-tetramethoxyflavone, is an active ingredient isolated from Eupatorium odoratum, a Thai indigenous plant that has long been used to stop bleeding. This compound was studied in vitro for the effect on blood clotting factor activities. It was found that the compound enhanced blood coagulation, the observed APTT being shorter than that observed in the control. The result suggested that the compound accelerated clotting time through the intrinsic pathway of the coagulation which may involve the reaction of factor XII, factor XI, factor IX or factor VIII.

Blood Coagulation↗
PubMed1976

Cold activation of complement i. presence of coagulation-related activator.

Determination of the complement titer in the serum and plasm of 120 patients with chronic liver diseases showed that in eight (7%) patients with cirrhosis of the liver, chronic active or chronic inactive hepatitis complement in the serum was less than half in the plasma. The dissociation of complement serum and plasma was due to cold activation of the classical pathway of complement in vitro since serum drawn from these patients at 37 degrees C lost hemolytic activity in 4 hours when transferred to a cold environment. Neither HB antigen nor cryoglobulin participated in this phenomenon. The activation of complement in the cold could be prevented by increasing the ionic strength, or by adding vitamin E or, to a lesser extent its vehicle HCO-60, while heparin, Trasylol, soybean trypsin inhibitor, or hirudin had no effect. Trans-AMCHA prevented activation in one case. It is speculated that a factor appearing as a result of blood clotting is able to activate the classical pathway of complement in the cold; it is probably not related to Hageman factor (factor XII), factor VII, thrombin, kallikrein.

Antithrombins↗
PubMed1981

Pseudo-factor-XI deficiency: effect of an inhibitor of factor XI adsorption to surface.

Recently we have described a normal plasma activity that modulates contact activation by inhibiting adsorption of factor XI to activating surfaces. Here we report the first identified case in which a patient has abnormal clotting tests due to an excess of a similar activity. The patient's plasma had a prolonged partial thromboplastin time and low apparent factor XI assay. His plasma prolonged the partial thromboplastin time of normal plasma and partially neutralized normal factor XI activity in vivo and in vitro. Analysis in dilute plasma revealed normal amounts of factor XI activity and antigen. Factor XI adsorption from plasma to activating surfaces was tested by adding a small amount of 125I-labeled purified factor XI to plasma, exposing the mixture to a glass tube or kaolin, and determining the amount of factor XI adsorbed to the surface. Whereas normal plasma and plasmas deficient in factor XII, factor XI, or Fletcher factor yielded about 4% adsorption to glass, factor XI adsorption from patient's plasma was less than 1%, indicating the presence of an adsorption inhibitor. This inhibitor did not affect factor XI activation or the activity of preformed factor XIa. It was not adsorbed by AI(OH)3 and was present in serum and the macroglobulin peak on gel filtration of the plasma through Sephadex G-200. The patient's history does not allow a definitive conclusion as to whether this inhibitor was associated with abnormal bleeding.

Adolescent↗
PubMed1993

Influence of C1-inhibitor on inflammation, edema and shock.

C1-Inhibitor (Berinert, C1 INH), a 104 kDa protein, inhibits complement components (C1 esterase) as well as enzymes of the contact phase of coagulation (Factor XII, Factor XI) and kallikrein, thus regulating kinin generation. C1 INH is used for the treatment of the hereditary angioneurotic edema. This paper will give a survey about the evidence in recent literature concerning the potential efficacy of the compound on other diseases associated with shock, capillary leakage and inflammation as well. In our own experiments we evaluated whether the compound could influence acute inflammatory reactions or the severe systemic inflammatory response syndrome (SIRS) as a consequence of an experimental septic shock. To prevent the sepsis-induced DIC we co-infused the thrombin inhibitors AT III or rec. hirudin in combination with C1 INH. Coinfusion of C1-inhibitor (50-200 U/kg x h) with either rec. hirudin or AT III significantly improved survival rate compared to thrombin inhibitor alone.

Angioedema↗
PubMed1998

Very low activated factor VII and reduced factor VII antigen in familial abetalipoproteinaemia.

Abetalipoproteinaemia is a rare disorder of apolipoprotein B metabolism associated with extremely low plasma concentrations of triglyceride. To discover whether the general positive association between factor VII and triglyceride levels extends to this condition, 5 patients were compared with 18 controls. All patients had a triglyceride below 100 micromol/l. Plasma unesterified fatty acid concentration was normal. Although factor IX activity was only slightly reduced (mean 88% standard) and factor IX antigen was normal, mean activated factor VII in patients was strikingly reduced to 34% of that in controls, a level similar to that found in haemophilia B. The patients' mean factor VII activity and factor VII antigen were also significantly reduced to 54% and 63% of those in controls, respectively. Mean factor XI activity and tissue factor pathway inhibitor activity were reduced in patients to 70% and 75% of control values respectively, while factor XII, factor XI antigen, factor X, prothrombin and protein C were normal.

Abetalipoproteinemia↗
PubMed1997

Continuous venovenous haemofiltration using polyacrylonitrile filters does not activate contact system and intrinsic coagulation pathways.

OBJECTIVES: To investigate whether continuous venovenous haemofiltration using polyacrylonitrile filters causes activation of the contact system and intrinsic coagulation pathways and if this, and/or low plasma levels of endogenous anticoagulants, influences filter lifespan. DESIGN: Observational study. SETTING: University Teaching Hospital Intensive Care Unit. PATIENTS: Twelve critically ill patients with acute renal failure receiving continuous venovenous haemofiltration. INTERVENTIONS: Blood samples were taken before starting haemofiltration, at 15 min, 1 h, 3-4 h, 8-12 h, 24 h and at 24-h intervals thereafter until filter blockage occurred. Measurement was made of the contact and intrinsic coagulation system proteins factor XII, activated factor XII and prekallikrein and the protease inhibitors antithrombin III, heparin co-factor II, alpha 2-macroglobulin and C1-esterase inhibitor. Thrombin-antithrombin complex levels were measured to provide evidence of thrombin generation. RESULTS: (i) Factor XII, prekallikrein and contact system inhibitors were subnormal in 10/12 and activated factor XII raised in 11/12 patients at baseline, implying pre-existing contact pathway activation. (ii) No change occurred during haemofiltration in the intrinsic coagulation pathway factor or inhibitor levels. (iii) Clotting of the filter circuit within the first 24 h occurred in 5/12 and was associated with low baseline levels of antithrombin III and heparin co-factor II. Only in these patients did thrombin-antithrombin complex levels rise significantly. CONCLUSIONS: The contact system was not activated further by continuous venovenous haemofiltration using polyacrylonitrile filters in critically ill patients. Premature clotting of the haemofilter circuit was more common in patients with very low levels of antithrombin III and heparin co-factor II; although this was related to thrombin generation, the intrinsic coagulation pathway does not appear to be implicated.

Acrylic Resins↗
PubMed1999

Contact activation factors in plasma from women on estrogen replacement therapy after ovariohysterectomy.

The plasma levels of factor XII, prekallikrein, factor XI, and high molecular weight kininogen were studied in women with bilateral oophorectomy and hysterectomy who received hormone replacement therapy with a 2 mg daily dose of estradiol valerate. Also plasminogen activator activity was investigated. The observations made provide support for the assumption that the low doses of estrogen used in hormone replacement therapy do not significantly affect the levels of contact activation or fibrinolytic factors in plasma. Plasma obtained from young, healthy women was used as a standard reference material. Significantly higher levels of factor XII and prekallikrein were registered in functional tests in the ectomized women than in the reference material, an increase not observed in the immunological assays. These observations are discussed in light of recently published data from our laboratory on an increase in the measured level of factor XII obtained upon the removal of IgG before assay. Also a marked increase in urokinase activity was registered in the ectomized women. The high levels of factor XII, prekallikrein, and urokinase, as compared with the reference material, seemed to be age dependent, being also observed in a group of naturally postmenopausal women.

Adult↗
PubMed1985

Contact phase of coagulation in diabetes mellitus after aspirin administration.

The purpose of our study was to investigate the connection between platelets and the contact phase of coagulation. In 17 patients affected by diabetes mellitus we studied the behaviour of prekallikrein, factor XII and factor XI before and after aspirin administration. To evaluate the activity of aspirin we measured platelet production of thromboxane B2 using a radioimmunoassay. In our diabetic patients a hypercoagulable state was confirmed: PK, factor XII and XI levels were significantly higher as compared with normal controls. After aspirin administration a significant decrease of PK levels was found. After 7 days of aspirin administration and 7 days after stopping aspirin a modest but not significant improvement of factor XII and factor XI was observed. In conclusion, we believe that the contact phase of coagulation is another index of the hypercoagulable state in diabetes mellitus. In addition, the decrease of PK obtained by aspirin administration could support the possible connection between the contact phase of coagulation and platelets.

Aspirin↗
PubMed1983

Arterial and venous thrombosis and normal response to streptokinase treatment in a young patient with severe Hageman factor deficiency.

The case history of a patient with severe factor XII deficiency (factor XII activity and concentration below 1%) is described. The case reported gives further evidence that factor XII deficiency leads to a prolonged euglobulin lysis time. This might be a risk factor indicating a proneness to thromboembolic events. The young man suffered from arterial and venous thrombosis, and underwent lower extremity amputation without bleeding complications, as well as thrombolytic therapy to save the other leg. There was a normal response to streptokinase, heparin, and phenprocoumon treatment.

Adult↗
PubMed1975

A case of Hageman factor deficiency with myeloid leukaemia.

The co-existence of blastic transformation of chronic myeloid leukaemia and an isolated deficiency of coagulation factor XII (Hageman Factor), is reported. In the absence of any evidence of factor XII deficiency in the patient's siblings and children, it is uncertain if this represents an acquired factor XII deficiency due to myeloid leukaemia, or the coincidental occurrence of myeloid leukaemia with this autosomal recessive condition.

Blood Coagulation Disorders↗
PubMed1999

Zinc-dependent activation of the plasma kinin-forming cascade by aggregated beta amyloid protein.

Beta Amyloid proteins (Abeta) of 38, 40, and 42 amino acids long were assessed for their ability to activate the plasma kinin-forming cascade in vitro. Incubation with a mixture of Factor XII (Hageman Factor), prekallikrein, and high-molecular-weight kininogen (HK) led to conversion of prekallikrein to kallikrein that was dependent on zinc ion. No activation occurred if Factor XII was omitted. There was rapid generation of bradykinin equal to the molar HK input indicating complete cleavage. Incubation of aggregated Abeta with diluted human plasma also led to prekallikrein activation and HK cleavage. Activation of the cascade by Abeta (1-38) was dependent upon its preincubation time in buffer, suggesting that aggregation of Abeta is required, and studies with Abeta (1-40) revealed time-dependent aggregation by microscopy and augmented zinc-dependent binding of both Factor XII and HK to aggregated Abeta. These data demonstrate that aggregated Abeta can bind and activate proenzymes of the plasma kinin-forming cascade in a zinc-dependent reaction to release bradykinin and is of sufficient potency to do so at physiologic concentrations of each protein and in the presence of naturally occurring protease inhibitors.

Amyloid beta-Peptides↗
PubMedDate not supplied

Assembly of the human plasma kinin-forming cascade along the surface of vascular endothelial cells.

The generation of bradykinin by contact activation requires autoactivation of factor XII (Hageman factor) upon initiating surfaces, conversion of prekallikrein to kallikrein, and digestion of high-molecular-weight (HMW) kininogen. Endothelial cells have a high-affinity receptor that binds either HMW kininogen or factor XII in a zinc-dependent interaction, and activation of factor XII can occur along this surface to initiate kinin formation. Tissue injury, exposure of proteoglycans, or release of mast cell heparin will markedly accelerate these reactions. The bradykinin released binds to endothelial cell B-2 receptors along the inner surface of blood vessels which results in dilatation and increased vascular permeability.

Bradykinin↗
PubMed1975

Partial purification and characterization of contact activation cofactor.

The contact phase of intrinsic clotting involves Factor XI, Factor XII, Fletcher factor, and a fourth activity that we call contact activation cofactor (CAC). All four of these activities are reduced or absent in Dicalite-adsorbed plasma. A modified activated partial thromboplastin time assay for CAC has been defined by using a substrate of Dicalite-adsorbed plasma combined with partially purified sources of Factors XI and XII, and Fletcher factor. The following properties of CAC in plasma have been determined by using the assay: it is stable up to 60 min at 56 degrees C; gradually loses activity at 80 degrees C; is stable between pH 6 and 9; is precipitated by ammonium sulfate between 40% and 50% saturation; is slightly adsorbed by A1(OH)3; and is eluted from DEAE-cellulose after the major protein peaks. A purification procedure has been devised that separates CAC from other known clotting factors. Isolated CAC was less stable than CAC in plasma, but in the presence of dilute human serum albumin it retained full activity for 80 min at 56 degrees C. On gel filtration CAC had an apparent mol wt of 220,000 daltons. These properties are consistent with those described for Fitzgerald factor, which further supports the conclusion that CAC and Fitzgerald factor represent the same activity. Isolated CAC promoted the generation of activated Factor XI (XIa) in a mixture containing purified Factor XI, Factor XII, and kaolin. The amount of Factor XIa generated was proportional to the amount of added CAC. No time-consuming reaction between Factor XI or Factor XII and CAC could be demonstrated.

Blood Coagulation Factors↗
PubMed1987

Clotting changes in borderline hypertension.

Coagulation factors evaluated in a group of patients with borderline hypertension. The following tests were carried out: prothrombin time (PT) and partial thromboplastin time (PTT), Factor VIII coagulant activity, Factor VIII antigen and Factor VIII ristocetin cofactor, Factor XII and Factor XI activities. These tests were selected for their relationship to the contact coagulative activation near the vascular wall. Comparing the results with those of normal controls, Factor VIII coagulant activity, Factor XII and PTT levels were significantly higher. Other tests were all within normal limits in both groups. High Factor VIII and Factor XII levels associated with PTT shortening suggest that an increased synthesis and/or release of these coagulation factors was present in our patients. Activated coagulation seems to be present in borderline hypertension before the appearance of clinical signs of vascular lesions.

Adult↗
PubMed2005

Formation of bradykinin: a major contributor to the innate inflammatory response.

The plasma kinin-forming cascade can be activated by contact with negatively charged macromolecules leading to binding and autoactivation of factor XII, activation of prekallikrein to kallikrein by factor XIIa, and cleavage of high molecular weight kininogen (HK) by kallikrein to release the vasoactive peptide bradykinin. Once kallikrein formation begins, there is rapid cleavage of unactivated factor XII to factor XIIa, and this positive feedback is favored kinetically over factor XII autoactivation. Examples of surface initiators that can function in this fashion are endotoxin, sulfated mucopolysaccharides, and aggregated Abeta protein. Physiological activation appears to occur along the surface of endothelial cells both by the aforementioned contact-initiated reactions as well as bypass pathways that are independent of factor XII. Factor XII binds primarily to cell surface u-PAR (urokinase plasminogen activator receptor); HK binds to gC1qR via its light chain (domain 5) and to cytokeratin 1 by its heavy chain (domain 3) and, to a lesser degree, by its light chain. Prekallikrein circulates bound to HK (as does coagulation factor XI), and prekallikrein is thereby brought to the surface as HK binds. All cell-binding reactions are dependent on zinc ion. Endothelial cells (HUVECs) have bimolecular complexes of u-PAR-cytokeratin 1 and gC1qR-cytokeratin 1 at the cell surface plus free gC1qR, which is present in substantial molar excess. Factor XII appears to interact primarily with the u-PAR-cytokeratin 1 complex, whereas HK binds primarily to the gC1qR-cytokeratin 1 complex and to free gC1qR. Release of endothelial cell heat shock protein 90 (Hsp90) or the enzyme prolylcarboxypeptidase leads to activation of the bradykinin-forming cascade by activating the prekallikrein-HK complex. In contrast to factor XIIa, neither will activate prekallikrein in the absence of HK, both reactions require zinc ion, and the stoichiometry suggests interaction of one molecule of Hsp90 (for example) with one molecule of prekallikrein-HK complex. The presence of factor XII, however, leads to a marked augmentation in reaction rate via the kallikrein feedback as well as to a change to classic enzyme-substrate kinetics. The circumstances in which activation is initiated by factor XII autoactivation or by these factor XII bypasses are yet to be defined. The pathologic conditions in which bradykinin generation appears important include hereditary and acquired C1 inhibitor deficiency, cough and angioedema due to ACE inhibitors, endotoxin shock, with contributions to conditions as diverse as Alzheimer's disease, stroke, control of blood pressure, and allergic diseases.

Amino Acid Sequence↗