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Results for “Factor XI Deficiency”

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At least 343 records · Page 19Linked to original sources
PubMed2000

Age estimate of the N370S mutation causing Gaucher disease in Ashkenazi Jews and European populations: A reappraisal of haplotype data.

The N370S mutation at the GBA locus on human chromosome 1q21, which causes Gaucher disease (GD), has a high frequency in the Ashkenazim and is the second-most-widespread GD mutation in the European non-Jewish population. A common ancient origin for the N370S mutation in the Ashkenazi Jewish and Spanish populations has been proposed on the basis of both a similar haplotype for associated markers and an age estimate that suggests that this mutation appeared several thousand years ago. However, a reappraisal of haplotype data, using the Risch formula properly along with a Luria-Delbrück setting of the genetic clock, allows identification of the likely origin of the N370S mutation in Ashkenazi Jews between the 11th and 13th centuries. This result is consistent with the estimated ages of other mutations that are frequent among Ashkenazim, with the exception of type II (Glu117Stop) factor XI deficiency, which is deemed to be >3000 years old, predating the separation of the Ashkenazi and Iraqi Jews. The present finding supports the hypothesis of a more recent origin for the N370S mutation and is consistent with both a founder chromosome transfer from Ashkenazim who assimilated in some European populations and a non-Jewish origin of the European N370S-bearing chromosomes.

Alleles↗
PubMed1997

Stereotactic core breast biopsy of a minimal carcinoma complicated by a large hematoma: a management dilemma.

Stereotactic core biopsy of a 4-5-mm, suspicious mammographic lesion was complicated by substantial hematoma formation in a patient with subsequently diagnosed factor XI deficiency. As a result, the small infiltrating ductal carcinoma could no longer be identified at mammography to allow accurate needle localization for lumpectomy. Sufficient resorption of the hematoma at 3 months permitted successful needle localization and lumpectomy. In these cases, expectant management may obviate extensive surgery.

Biopsy↗
PubMed1998

Fetal bilateral subdural haemorrhages. Prenatal diagnosis and spontaneous resolution by time of delivery.

We report a patient diagnosed prenatally on routine fetal ultrasound, at 30 weeks' gestation, with subdural haemorrhage. The mother had suffered a mild abdominal trauma and had Factor XI deficiency; however, both were felt to be aetiologically insignificant. Prenatal follow-up showed a complete resolution of the haematoma and no postnatal sequelae have been noted to date. The aetiologies and outcomes in the few previously reported cases are reviewed and compared with our case.

Adult↗
PubMed2002

[Menorrhagia and inherited disorders of coagulation].

Menorrhagia, a common complaint among women, may be a manifestation of an underlying inherited disorder of coagulation. In this review, the most frequent hereditary bleeding disorders associated with menorrhagia are briefly analyzed. Particularly, the epidemiological, clinical and diagnostic characteristics of von Willebrand disease, factor VIII, factor IX and factor XI deficiencies are examined. The influence of external factors (age, phase of menstrual cycle and hormonal therapy) on coagulation factor levels is also analyzed. Finally, the main therapeutic options (such as hormonal therapy, tranexamic acid and desmopressin), for the treatment of menorrhagia in women with hereditary bleeding disorders are reviewed. Since inherited bleeding disorders are frequently associated with menorrhagia, the conclusion is drawn that an underlying congenital bleeding disorder should be ruled out in any woman with menorrhagia.

Blood Coagulation Disorders, Inherited↗
PubMedDate not supplied

Prolonged bleeding times with factor IX and XI deficiency von Willebrand's syndromes.

This report describes three patients with a prolonged bleeding time and reduced platelet retention on glass beads, two of the three established criteria for conventional von Willebrand's disease (vWd). However, the third standard, the diminution of factor VIII, was replaced by a decrease of factor IX or XI in the first two instances, respectively, and combined factor VII and IX deficiency was present in the last patient. These associations suggest that the vW (bleeding time/platelet retention) factor is not necessarily homogeneous, may not be dependent on a single genetic determinant, and may be present in a molecular complex composed not only of factor VIII but of other blood clotting proteins as well. Although simulating classic vW, these homologues may more appropriately be called von Willebrand syndromes. Finally, unusual as they may be, their clinical recognition is important to insure that such patients receive not only factor VIII concentrates in treatment since these materials do not contain factors IX and XI and may not even be a suitable source of platelet retention factor under these modified circumstances.

Adolescent↗
PubMed1995

Feedback activation of factor XI by thrombin in plasma results in additional formation of thrombin that protects fibrin clots from fibrinolysis.

Recently, an alternative pathway for factor XI activation has been described in which factor XI is activated by thrombin. Patients with a factor XI deficiency bleed mostly from tissues with high local fibrinolytic activity. Therefore, the role of thrombin-mediated factor XI activation in both fibrin formation and fibrinolysis was studied in a plasma system. Clotting was induced by the addition of tissue factor or thrombin to recalcified plasma in the presence or absence of tissue-type plasminogen activator, after which clot formation and lysis were measured using turbidimetry. Thrombin-mediated activation of factor XI was found to take place in plasma under physiologic conditions in the absence of a dextran sulfate-like cofactor. At high tissue factor concentrations, no effect of factor XI was seen on the rate of fibrin formation. Decreasing amounts of tissue factor resulted in a gradually increasing contribution of factor XI to the rate of fibrin formation. In addition, thrombin-mediated factor XI activation resulted in an inhibition of tissue-type plasminogen activator-induced lysis of the clot. This inhibition occurred even at tissue factor concentrations at which no effect of factor XI was observed on fibrin formation. Trace amounts of activated factor XI (1.25 pmol/L, representing 0.01% activation) were capable of completely inhibiting fibrinolysis in our system. The inhibitory effect was found to be mediated by thrombin that is additionally generated in a factor XI-dependent manner via the intrinsic pathway and is capable of protecting the clot against lysis. We also observed that formation of additional thrombin continued after the clot had been formed. We conclude that thrombin-mediated factor XI activation can take place in plasma. The presence of factor XI during coagulation results in the formation of additional thrombin within the clot capable of protecting this clot from fibrinolytic attack. The large amounts of thrombin that are formed by the intrinsic pathway via factor XI may play an important role in the procoagulant and thrombogenic state of clots and may therefore have important clinical and therapeutic implications.

Blood Coagulation↗
PubMed1976

Coexistence of factor XI (plasma thromboplastin antecedent) deficiency and Gaucher's disease.

The findings of Factor XI (plasma thromboplastin antecedent) deficiency in a patient with Gaucher's disease was investigated. A family study, which included measurements of leukocyte glucocerebrosidase activity and Factor XI levels, revealed that the two genetic disorders segregated independently. One of 12 additional unrelated patients with Gaucher's disease showed a diminished Factor XI level and two of seven unrelated Factor XI-deficient patients showed decreased glucocerebrosidase activity. It is possible that the common occurrence of both genetic disorders results from a high gene frequency of both defects in Ashkenazic Jews.

Adult↗
PubMed1990

Determination of the minimal concentrations of contact activation factors in deficient substrate plasmas required to assess accurately factor XII, factor XI, factor IX, and high molecular weight kininogen.

Using combined deficient plasmas prepared by passage of a deficient plasma over an anti-factor XI-monoclonal antibody column, we have determined the threshold concentrations of each coagulation factor of contact phase in factor-deficient substrate plasmas required to determine accurately the functional activities of factor XII, factor XI, factor IX and high molecular weight kininogen (HMWK). In order to reliably quantitate factor XI and factor IX activity levels, at least 20% factor XII and 20% factor XI, respectively, were required in the deficient substrate plasmas. In the assessment of factor XII activity, approximately 40% factor XI was required in the factor XII-deficient substrate plasma. On the other hand, only 11-12% factor XI or HMWK was required in the deficient substrate plasmas in the assessment of these two clotting factors. Our data emphasize that deficiencies of other clotting factors may reduce the apparent activity of the clotting factor in question if their concentration is rate-limiting in the clotting assay.

Blood Coagulation Disorders↗
PubMed1979

The role of endothelial cells and subendothelial components in the initiation of blood coagulation.

The effect of collagen on isolated platelets, platelet-rich plasma and whole blood has been studied. Collagen failed to generate factor XIa-like activity in mixtures of isolated platelets, collagen and Ca++. Moreover, collagen added to whole blood or platelet-rich plasma containing 125I-factor IX and Ca++, also failed to form cleaved (activated) factor IX. In preliminary studies, lysed endothelial cells were found to enhance the formation of factor Xa and thrombin and to induce cleavage of 125I-factor IX in normal plasma, factor XII and factor-XI-deficient plasma even in the presence of antibody to tissue factor.

Blood Coagulation↗
PubMed1998

Identification of mutations and polymorphisms in the factor XI genes of an African American family by dideoxyfingerprinting.

Congenital deficiency of factor XI is a rare condition associated with a mild to moderate bleeding diathesis that is most commonly found in persons of Jewish ancestry. The disorder has been reported sporadically in a number of other ethnic groups, but rarely in the black population. We report on the genetic analysis of the factor XI genes of two African American patients: a 9-year-old boy (the propositus) with mild factor XI deficiency and his mother. Both individuals have lifelong histories of excessive bleeding. Dideoxyfingerprinting, a technique combining components of single-strand conformational polymorphism analysis and dideoxy-chain termination sequencing, was used in the analysis. Both patients were found to be heterozygous for a mutation changing serine 248 to asparagine [corrected], whereas the propositus was heterozygous for an additional mutation on the paternal allele changing glutamine 226 to arginine. Both mutations reside in the third apple domain of the factor XI heavy chain, an area that has been shown to contain binding sites for factor IX, platelets, and glycosaminoglycans. Previously reported mutations in the factor XI gene seem to cause deficiency primarily by reducing protein expression. Because both alleles in the propositus contain amino acid substitutions, the significant amount of circulating factor XI in his plasma must be comprised entirely of abnormal molecules. Factor XI circulates as a homodimer, and the presence of mutations in both alleles of the factor XI gene suggests that his bleeding disorder is caused in part by the effect of the two abnormal gene products forming dimers in different combinations. Three neutral (not associated with amino acid changes) DNA polymorphisms were also identified in the two subjects: a C to T change at nucleotide 472 in exon 5, A to G at nucleotide 844 in exon 8, and T to C at nucleotide 1234 in exon 11. Analysis of a random sample of normal volunteers showed that these polymorphisms are relatively common, with allele frequencies of 7.4%, 19%, and 18%, respectively. This suggests that there is considerable genetic heterogeneity in the factor XI gene.

Adult↗
PubMed1986

Studies on a circulating anticoagulant inhibiting factor XI in a patient with congenital deficiency and carcinoma of the prostate.

An inhibitor of plasma thromboplastin antecedent (PTA, factor XI), measured in coagulant and radioimmunoassays, was detected in a 60-year-old man with carcinoma of the prostate who had no evidence of a bleeding tendency. Family studies indicated that the patient was either a homozygote or a heterozygote for hereditary factor XI deficiency. In contrast to earlier described patients with factor XI deficiency in whom inhibitors were detected, the patient was unaware of having been transfused with blood or blood products at any time before the discovery of the inhibitor. The inhibitor of factor XI in the patient's plasma appeared to be predominantly in the IgG4 fraction and to be directed at a locus on the factor XI molecule other than the active site; it did not block the amidolytic properties of activated factor XI (XIa). Rather, it appeared to block adsorption of factor XI to negatively charged surfaces. The inhibitor interfered with measurement of other components of the intrinsic pathway of thrombin formation, perhaps explaining the low titres of other coagulation factors of the intrinsic system reported in patients with strong inhibitors directed against factor XI.

Factor XI↗
PubMed1993

Activation of factor XI in plasma is dependent on factor XII.

The activation of factor XI initiates the intrinsic coagulation pathway. Until recently it was believed that the main activator of factor XI is factor XIIa in conjunction with the cofactor high molecular weight kininogen on a negatively charged surface. Two recent reports have presented evidence that in a purified system factor XI is activatable by thrombin together with the soluble polyanion dextran sulfate. To assess the physiological relevance of these findings we studied the activation of factor XI in normal and factor XII-deficient plasma. We used either kaolin/cephalin or dextran sulfate as a surface for the intrinsic coagulation pathway, tissue factor to generate thrombin via the extrinsic pathway, or the addition of alpha-thrombin directly. 125I-factor XI, added to factor XI-deficient plasma at physiologic concentrations (35 nmol/L), is rapidly cleaved on incubation with kaolin. The kinetics appear to be exponential with half the maximum cleavage at 5 minutes. Similar kinetics of factor XI cleavage are seen when 40 nmol/L factor XIIa (equal to 10% of factor XII activation) is added to factor XII-deficient plasma if an activating surface is provided. Tissue factor (1:500) added to plasma did not induce cleavage of factor XI during a 90-minute incubation, although fibrin formation within 30 seconds indicated that thrombin was generated via the extrinsic pathway. Adding 1 mumol/L alpha-thrombin (equivalent to 50% prothrombin activation) directly to factor XII deficient or normal plasma (with or without kaolin/cephalin/Ca2+ or dextran sulfate) led to instantaneous fibrinogen cleavage, but again no cleavage of factor XI was observable. We conclude that in plasma surroundings factor XI is not activated by thrombin, and that proposals of thrombin initiation of the intrinsic coagulation cascade are not supportable.

Autoradiography↗
PubMed2003

Platelet functional defects in women with unexplained menorrhagia.

Menorrhagia is a common clinical problem and is unexplained in more than 50% of women. Although studies suggest that von Willebrand's Disease (VWD) is found in a substantial number of women with unexplained menorrhagia, the prevalence of platelet defects in women with menorrhagia is unknown. To determine the prevalence of platelet and other hemostatic defects, we evaluated women ages 17-55 diagnosed with unexplained menorrhagia. Seventy-four women (52 white, 16 black, six other) were studied. Bleeding time was prolonged in 23 women (31.5%). Maximal percent platelet aggregation was decreased with one or more agonists in 35 (47.3%) women. The most commonly found platelet function defects were reduced aggregation responses to ristocetin in 22 women and to epinephrine in 16 women. Sixteen of 22 women with reduced ristocetin aggregation had von Willebrand ristocetin cofactor (VWF:RCo) and von Willebrand factor antigen (VWF:Ag) > 60%. Platelet ATP release was decreased with one or more agonists in 43 (58.1%) women. Of the black women studied, 11/16 (69%) had abnormal platelet aggregation studies compared with 20/52 white women (39%) (P = 0.06). Black women with menorrhagia had a higher prevalence of decreased platelet aggregation in response to ristocetin and epinephrine than did white women (P = 0.0075, P = 0.02). Ten women (13.5%) had VWF:RCo and/or VWF:Ag < 60%. Using race and blood group specific ranges, 5 (6.8%) women had decreased VWF:RCo, VWF:Ag and/or collagen binding (VWF:CB). Mild factor XI deficiency was found in two women and one woman with mild factor V deficiency and one hemophilia A carrier were identified. We conclude that the prevalence of platelet function defects and other inherited bleeding disorders is substantial in a multiracial US population of women with unexplained menorrhagia.

Adolescent↗
PubMed1993

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↗