Variations of factor XII level during pregnancy in a woman with Hageman factor deficiency.
Explore the source record for details and available documents.
Adult↗
SEARCH · Search PubMed
Results for “Factor XII Deficiency”
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.
Prolonged activated partial thromboplastin time and deficiency of high molecular weight kininogen in brown Norway rat mutant (Katholiek strain).
Activated partial thromboplastin time (APTT) was examined in Brown Norway (B/N) Katholiek rat, which was previously reported as high molecular weight kininogen deficient. APTT of B/N Katholiek was prolonged to 35 sec in comparison with B/N Kitasato and SD rat, showing APTT of 22-24 sec. The mixture of B/N Katholiek plasma and B/N Kitasato plasma (1:1) showed normal APTT value. B/N Katholiek plasma corrected the abnormally prolonged human coagulation factor deficient plasmas, such as XI, XII and prekallikrein deficient plasmas, while it did not correct the APTT of HMW kininogen deficient, Fitzgerald plasma. Intravenous injection of bromelain, which was previously reported to produce prolonged hypotension through the activation of factor XII to release bradykinin, induced slight effect in Katholiek rat, while in Kitasato rat it showed prolonged hypotension in similar degree as SD rat. Contents of coagulation factors in B/N Katholiek thus measured as well as the values of prekallikrein and HMW kininogen previously reported were summarized and suggested that B/N Katholiek rat could be similar deficiency as Fitzgerald trait.
Animals↗
Abnormalities in the contact activation through factor XII in Fujiwara trait: a deficiency in both high and low molecular weight kininogens with low level of prekallikrein.
Fujiwara trait, the first case of kininogen deficiency in Japan previously reported which did not show any clinical symptom except the prolonged activated partial thromboplastin time was further examined. The activated partial thromboplastin time of the patient was corrected by addition of normal, Factor XII deficient or Fletcher plasma, but not corrected by Fitzgerald or Williams plasma. It was also corrected by addition of highly purified bovine or human high molecular weight (HMW) kininogen, but not by low molecular weight (LMW) kininogen. When total kininogen was measured as the amount of bradykinin released by trypsin, only a trace amount was detected in Fujiwara as well as Williams plasma. No immunoreactive protein against anti-human-HMW-kininogen nor anti-human-LMW-kininogen was found in Fujiwara plasma. Acetone-kaolin-activated plasma kallikrein was not generated by Fujiwara plasma. Substitution with normal plasma in various ratios showed the generation of various plasma kallikrein activities. Calculations with these activities of mixed plasma gave the prekallikrein content of Fujiwara trait plasma about 30% of the normal level. These results suggest that Fujiwara trait is very similar to Williams trait in that both plasmas were deficient in HMW and LMW kininogens with reduced content of prekallikrein.
Factor XII↗
Assessment of Actin FS and Actin FSL sensitivity to specific clotting factor deficiencies.
We present a two centre study designed to assess the sensitivity of Actin FS and Actin FSL to deficiencies of factor VIII, IX, XI or XII. The study was undertaken at two centres to avoid bias due to the investigations being undertaken on one analyser. Samples from patients with a factor VIII (n = 36, F VIII = < 1.0-50 iu/dl), factor IX (n = 22, F IX = 2-48 iu/dl), factor XI (n = 23, F XI = 5-50 u/dl) or a factor XII (n = 18, F XII = 1-50 u/dl) deficient state were studied. Activated partial thromboplastin times (APTT) were determined using two batches of Actin FS and of Actin FSL; comparison of APTT results between centres was facilitated by the conversion of clotting times to ratios (test divided by geometric mean normal clotting time). APTT ratios were considered to be elevated if greater than two standard deviations above the mean normal. The factor deficient status of each sample was verified by assaying all samples for factors VIII, IX, XI and XII. Clotting factor assays were performed on a Sysmex CA-1000 fitted with research software, which permitted the auto-dilution and testing of three serial dilution of both a reference preparation and each patient's sample. Assay results were calculated using parallel-line Bioassay principles. This procedure allowed for variation in clotting times due to the effect of temporal drift of any of the reagents within the assay system. Actin FS and Actin FSL demonstrate acceptable sensitivity to factor VIII deficiency, however, both reagents failed to detect a large proportion of factor XI (17.4% and 30.4% of samples, respectively) and factor XII (66.7% and 72.2%, respectively) deficiencies. The detection rate with Actin FSL for factor IX deficiency was also poor (36.4% not detected). As factor IX and XI deficiencies are both associated with haemorrhagic disorders, the inability of these reagents to detect such abnormalities gave cause for concern.
Actins↗
Factor XII-induced fibrinolysis. Diminished proactivator activity and drastic reduction of activator activity in Fletcher factor-deficient plasma gamma globulin.
Fibrinolytic studies in gamma G fractions of three Fletcher factor-deficient plasmas (functionally deficient in prekallikrein) revealed weak or no factor XII-independent activator activity. Two of the three Fletcher trait patients showed no plasminogen activator activity in clot lysis, fibrin plate, and amidolytic assays. The third patient showed no activator activity as determined by clot lysis and amidolytic assays but gave 10% of the activator activity detected in normal undiluted gamma G fraction in absence of HFf when determined by fibrin plate assay. Normal plasma gamma G fractions showed detectable and significant plasminogen activator activity. These fractions did not contain kallikrein or activated factor XI activities, thus indicating that the activator activity could not be attributed to the presence in these fractions or trace of these activated factors. Furthermore, factor XI-deficient plasma gamma G fraction, which was shown to contain no activated prekallikrein, showed normal plasminogen activator activity. Finally, specific antibodies to prekallikrein were shown not to quench the activity of plasminogen activator present in normal plasma gamma fraction. A double genetic deficiency to explain the absence in Fletcher factor-deficient plasma gamma G fractions of both prekallikrein proactivator and activator activities is not likely. Thus plasma prekallikrein, besides being a known plasminogen proactivator, appears to be required for the expression of a plasminogen activator activity.
Electrophoresis, Polyacrylamide Gel↗
Alzheimer's beta-amyloid peptides can activate the early components of complement classical pathway in a C1q-independent manner.
beta-Amyloid (beta-A) accumulates in the brain of patients with Alzheimer's disease (AD) and is presumably involved in the pathogenesis of this disease, on account of its neurotoxicity and complement-activating ability. Although assembly of beta-A in particular aggregates seems to be crucial, soluble non-fibrillar beta-A may also be involved. Non-fibrillar beta-A does not bind C1q, so we investigated alternative mechanisms of beta-A-dependent complement activation in vitro. On incubation with normal human plasma, non-fibrillar beta-A 1-42, and truncated peptide 1-28, induced dose-dependent activation of C1s and C4, sparing C3, as assessed by densitometric analysis of immunostained membrane after SDS-PAGE and Western blotting. The mechanism of C4 activation was not dependent on C1q, because non-fibrillar beta-A can still activate C1s and C4 in plasma genetically deficient in C1q (C1qd). In Factor XII-deficient plasma (F.XIId) the amount of cleaved C4 was about 5-10% less that in C1qd and in normal EDTA plasma; the reconstitution of F.XIId plasma with physiologic concentrations of F.XII resulted in an increased (8-15%) beta-A-dependent cleavage of C4. Thus our results indicate that the C1q-independent activation of C1 and C4 can be partially mediated by the activation products of contact system. Since the activation of contact system and of C4 leads to generation of several humoral inflammatory peptides, non-fibrillar beta-A might play a role in initiating the early inflammatory reactions leading to a multistep cascade contributing to neuronal and clinical dysfunction of AD brain.
Alzheimer Disease↗
The contact system.
OBJECTIVES: To review the literature for conditions, diseases, and disorders that affect activity of the contact factors, and further to review the literature for evidence that less than normal activity of any of the contact factors may be associated with thrombophilia. DATA SOURCES: MEDLINE search for English-language articles published from 1988 to 2001 and pertinent references contained therein, as well as search of references in recent relevant articles and reviews. STUDY SELECTION: Relevant clinical and laboratory information was extracted from selected articles. Meta-analysis was not feasible because of heterogeneity of reports. DATA EXTRACTION AND SYNTHESIS: Evidence for association of altered levels of the contact factors and thrombophilia was sought. A wide variety of disorders is associated with decreased activity of the contact factors; chief among these disorders are liver disease, hepatic immaturity of newborns, the antiphospholipid syndrome, and, for factor XII, being of Asian descent. These disorders are more common than homozygous deficiency. The few series and case reports of thrombophilic events in patients homozygous for deficiency of contact factors are not persuasive enough to support causality. The apparent association between levels consistent with heterozygosity (40%-60% of normal) of any of the contact factors (but especially factor XII) in persons with antiphospholipid antibodies appears to be due to falsely decreased in vitro activity levels of these factors, which are normal on antigenic testing. The apparent association with thrombosis is better explained by the antiphospholipid syndrome than by the modest reduction of the levels of contact factors. CONCLUSIONS: Presently, it is not recommended to measure activity of contact factors during routine evaluation of patients who have suffered venous or arterial thromboembolism or acute coronary syndromes.
Blood Coagulation↗
Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis.
Formation of fibrin is critical for limiting blood loss at a site of blood vessel injury (hemostasis), but may also contribute to vascular thrombosis. Hereditary deficiency of factor XII (FXII), the protease that triggers the intrinsic pathway of coagulation in vitro, is not associated with spontaneous or excessive injury-related bleeding, indicating FXII is not required for hemostasis. We demonstrate that deficiency or inhibition of FXII protects mice from ischemic brain injury. After transient middle cerebral artery occlusion, the volume of infarcted brain in FXII-deficient and FXII inhibitor-treated mice was substantially less than in wild-type controls, without an increase in infarct-associated hemorrhage. Targeting FXII reduced fibrin formation in ischemic vessels, and reconstitution of FXII-deficient mice with human FXII restored fibrin deposition. Mice deficient in the FXII substrate factor XI were similarly protected from vessel-occluding fibrin formation, suggesting that FXII contributes to pathologic clotting through the intrinsic pathway. These data demonstrate that some processes involved in pathologic thrombus formation are distinct from those required for normal hemostasis. As FXII appears to be instrumental in pathologic fibrin formation but dispensable for hemostasis, FXII inhibition may offer a selective and safe strategy for preventing stroke and other thromboembolic diseases.
Animals↗
Decreased blood coagulation activities in carbohydrate-deficient glycoprotein syndrome.
The carbohydrate-deficient glycoprotein (CDG) syndromes are a newly recognized group of inherited metabolic diseases. We report a Japanese brother and sister with a CDG syndrome. Both patients showed decreased activities of blood coagulation Factor XI and of the coagulation inhibitor protein C. In one of them there was also a somewhat decreased activity of Factor IX and of antithrombin III. Isoelectric focusing of antithrombin III revealed a decrease of negatively charged fractions and an increase of more cathodal bands. Furthermore, there was a discrepancy between activity and antigen level of Factor VIII and protein C. The patients had an incidental deficiency of factor XII. This is the first detailed report on blood coagulation systems in the CDG syndromes. These blood coagulation abnormalities may explain at least in part the thrombotic or haemorrhagic complications of the CDG syndromes.
Antithrombin III↗
[Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin III complex(TAT) and thrombophilia parameters in orally anticoagulated patients with inferior vena cava filters].
Prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin-III-complex (TAT) levels were compared in 31 orally anticoagulated patients with inferior vena caval filters and a control group of 31 orally anticoagulated patients without caval filters and the incidence of markers of thrombophilia (deficiency of antithrombin-III, protein C, protein S and factor XII, presence of lupus anticoagulants) was determined. 8 of 31 patients (26%) from the group of caval filter carriers showed markers of thrombophilia (3 protein S deficiencies, 1 protein C deficiency, 2 factor XII deficiencies and 2 patients with lupus anticoagulants). In all orally anticoagulated patients a significant interdependence (p < 0.05) between F1 + 2- and TAT-levels and intensity (INR) of the oral anticoagulation could be observed. Comparison of F1 + 2- and TAT-levels of caval filter carriers and controls revealed no significant difference which leads to the conclusion that inferior vena caval filters do not induce detectable systemic activation of prothrombin under adequate oral anticoagulation therapy.
Administration, Oral↗
The influence of serum on random migration and chemotaxis of polymorphonuclear leucocytes: methodological evaluation using sera from infection-prone patients and normals.
The effects on normal polymorphonuclear leucocytes (PMN) of chemotactic and chemokinetic factors in sera from normal subjects and infection-prone patients were examined by means of the leading-front technique, using a modified Boyden chamber. The analysis scheme used made it possible to differentiate between chemotactic and chemokinetic factors and demonstrated that different factors account for the major chemotactic and chemokinetic activities of serum. The major chemotactic activity of unactivated serum was heat-labile, and the chemotactic activity of factor XII-deficient sera was normal, suggesting the major chemotactic activity to be distinct from C5a and factor XII-dependent pathways. The existence of both heat-stable and heat-labile chemokinetic factors was shown. The possibility that the reduced chemokinetic effect of several patient sera was caused by abnormal levels of the serum proteins alpha 1-antitrypsin, alpha 2-macroglobulin and albumin was excluded.
Adolescent↗
[Increased risk of thrombosis in FXII deficiency?].
Explore the source record for details and available documents.
Factor XII Deficiency↗
Severe prekallikrein (Fletcher factor) deficiency due to a compound heterozygosis (383Trp stop codon and Cys529Tyr).
We investigated a family with prekallikrein deficiency, using both standard coagulation tests and molecular biology techniques. The propositus was found to be a compound heterozygote for a Trp383 stop codon and a Cys529Tyr point mutation. The former mutation was located in exon 11, the latter in exon 14. The propositus inherited the first defect from his father and the second from his mother. Both parents had slightly low prekallikrein levels, but the combination of the two genetic defects produced a phenotype characterized by an extremely low prekallikrein activity and antigen. The propositus' plasma showed a progressive reduction in APTT when incubated for a long time. Conversely, plasma deficient in factor XII, factor XI or high molecular weight kininogen (HMWK) failed to show shortening of the APTT. No circulating anticoagulant was found because the patient's APTT was fully corrected by pooled nor-mal and factor XII-, factor XI- or HMWK deficient plasma. No associated abnormality was apparent in the propositus or his parents. As expected, no tendency for bleeding was noted even after tonsillectomy.
Adolescent↗
Activation of human blood coagulation factor XI independent of factor XII. Factor XI is activated by thrombin and factor XIa in the presence of negatively charged surfaces.
Human blood coagulation factor XI was activated by either autoactivation or thrombin. These reactions occurred only in the presence of negatively charged materials, such as dextran sulfate (approximately Mr 500,000), sulfatide, and heparin. During the activation, factor XI was cleaved at a single Arg-Ile bond by thrombin or factor XIa to produce an amino-terminal 50-kDa heavy chain and a carboxyl-terminal 35-kDa light chain. This activation pattern is identical to that produced by factor XIIa. The addition of a small amount of thrombin and sulfatide to factor XII-deficient plasma produced shorter clotting times than when these agents were added to factor XI/factor XII combined-deficient plasma. These results suggest that the activation of factor XI by thrombin and possibly the autoactivation of factor XI proceed in plasma to lead fibrin clot formation. These reactions may have a role on an appropriate negatively charged surface in normal hemostasis.
Anions↗
Evaluation of bedside prothrombin time and activated partial thromboplastin time measurement by coagulation analyzer CoaguCheck Plus in various clinical settings.
In the present study CoaguCheck Plus (CCP), a coagulation test system using whole blood, was evaluated with respect to its comparability with widely distributed conventional routine coagulation assays. A correlation of r = 0.997 (p < 0.0001) was found between INR of CCP-prothrombin time (CCP-PT) and Thrombotest (KC-1 analyzer) in patients on oral anticoagulant therapy. A correlation of r = 0.899 (p < 0.001) between CCP-aPTT and Actin ES aPTT (STA analyzer) was found in heparinized patients. Impaired hepatic hepatic coagulation factor synthesis in liver cirrhosis patients was detected by CCP-PT with a sensitivity of 0.75 and by Normotest (STA analyzer) with a sensitivity of 0.92. Those patients with normal CCP-PT values and liver disease had, only mild reductions (> 30% of normals) in coagulation factors II, V, VII or X. CCP-aPTT was also performed in patients with a deficiency in the so called endogenous coagulation factors VIII, IX, XI and XII. CCP-aPTT showed a sensitivity similar to that of Actin FS aPTT in the detection even of mild deficiencies in factors VIII, IX and XII; factor XI deficiency was however detected only in patients with severe (< 12% of normals) disease; lupus anticoagulants were detected with a high sensitivity.
Blood Coagulation Tests↗
Purified plasma factor XIIa aggregates human neutrophils and causes degranulation.
Plasma kallikrein has been shown to aggregate human neutrophils and release human neutrophil elastase. However, neutrophils resuspended in factor XII-deficient plasma released only 30% of the elastase compared with normal plasma. Isolated human neutrophils were aggregated in a concentration-dependent fashion by 0.06 to 0.6 U/mL factor XIIa (0.022 to 0.22 mumol/L). Factor XIIa (0.1 to 1.0 U/mL) also induced neutrophil degranulation as evidenced by a concentration-dependent release of the specific granule protein, lactoferrin, and azurophilic granule protease, elastase. The release of neutrophil elastase was biphasic, reaching 40% of maximum at 15 seconds with maximal release by 90 minutes. The active site of factor XIIa was required, since the synthetic inhibitor, D-Pro-Phe-Arg-CH2Cl, which reacts with an essential histidine, and the natural plasma inhibitor, Cl-inhibitor, which interacts with the critical serine, both inhibit by more than 90% the release of elastase. The heavy chain is also required, since factor XII fragments failed to aggregate neutrophils or stimulate degranulation. Factor XIIa (0.6 U/mL) can completely correct the defect in elastase release evident in factor XII-deficient plasma. These studies demonstrate that factor XIIa, at concentrations potentially obtainable in plasma in disease states, can activate neutrophils, and thus may participate in the inflammatory response.
Cell Aggregation↗
Myocardial infarction and arterial thrombosis in severe (homozygous) FXII deficiency: no apparent causative relation.
Twenty-one patients (12 female and 9 male) with severe (homozygous) factor XII (FXII) deficiency and 58 (32 female and 26 male) with heterozygous FXII deficiency were observed for an average 16.2 years. No patient with homozygous FXII deficiency experienced myocardial infarction or any other arterial thrombosis. The same was true for heterozygotes. The cases of FXII deficiency and arterial thrombosis reported in the literature were evaluated. In every instance, associated risk factors were present that could justify the arterial thrombosis. Dyslipidemia, hypertension, smoking, and diabetes mellitus were the most frequent findings. The examination of the few papers that dealt with the prevalence of arterial thrombosis in patients with severe FXII deficiency showed that only 1 patient of 61 experienced myocardial infarction. In conclusion, it seems that the role of FXII deficiency in the pathogenesis of arterial thrombosis is minor.
Adolescent↗
Identifying hypocoagulable states with a modified global assay of overall haemostasis potential in plasma.
To test the sensitivity of the global assay of overall haemostasis potential (OHP) in detecting hypocoagulation, the OHP was assayed in plasma containing exogenous thrombin (0.04 IU/ml), tissue-plasminogen activator (330 ng/ml), Ca and a platelet reagent. Commercial plasmas with factor II, V, VIII, IX, X, XI, XII or VII deficiency were mixed with normal plasma in different proportions to imitate different severities. Samples from patients with haemophilia and factor XII deficiency were also examined. No clot was found in the absence of factor II/factor X, indicating that the tiny dose of thrombin worked solely as a trigger for the intrinsic pathway activation. Changed levels of the investigated coagulants, apart from factor XII, influenced the outcome. OHPs were decreased in patients with haemophilia but were unchanged or even increased in those with factor XII deficiency. This modified OHP method may therefore be useful for estimating the bleeding tendency in haemophilic patients and to find suitable doses and intervals for prophylactic treatment. It may also be of use in investigations of the effect of antifibrinolytic drugs as well as for identifying a thrombotic tendency in patients with factor XII deficiency. For detection of other coagulation factor deficiencies, our investigations with the commercial plasmas suggest that the OHP assay is also valuable, especially when the intrinsic pathway of the coagulation cascade is impaired.
Blood Coagulation↗