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Results for “Antithrombin III Deficiency”

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At least 19 recordsLinked to original sources
PubMed1990

Premature arterial disease associated with familial antithrombin III deficiency.

Antithrombin III (ATIII) deficiency is one of the few known abnormalities of the coagulation system known to predispose to venous thromboembolism but its relation to arterial disease is not established. We describe two related patients with this disorder, both of whom suffered arterial thrombotic events, at an early age. Both patients had other potential risk factors, though these would normally be considered unlikely to lead to such catastrophic events at such an age. Thrombosis due to ATIII deficiency is potentially preventable, and this diagnosis should be sought more frequently in patients with arterial thromboembolism, particularly if occurring at a young age. In addition, in patients with known ATIII deficiency, other risk factors for arterial disease should be eliminated, if possible. In particular, these patients should be counselled against smoking.

Adult↗
PubMed1976

Hereditary antithrombin III deficiency. Effect of antithrombin III deficiency on platelet function.

Antithrombin III (AT III) is the main physiologic inhibitor of thrombin, and activated factors X and IX as well. Normal levels of AT III appear to be necessary to maintain blood fluidity and to prevent thrombosis. Four families with AT III deficiency and recurrent venous thromboembolism have been reported on. We present an additional family with AT III deficiency and a high incidence of thromboembolism. AT III levels were determined by both a functional and an immunologic assay. Results of platelet function tests, not previously reported in persons with AT III deficiency, were found to be normal. Following gel filtration, the platelets were very sensitive to thrombin. Thrombin-induced platelet aggregation appears to be dependent on a balance between the amount of thrombin and AT III present.

Adolescent↗
PubMed1992

[Acquired antithrombin III deficiency].

Acquired antithrombin III (AT III) deficiency is based on either decreased activity or synthesis, increased loss or increased consumption. The activity of AT III is decreased in metabolic acidosis, hyperlipoproteinemias and by lipid peroxides. Chronic liver diseases especially liver cirrhosis are associated with very low levels of AT III due to insufficient hepatic synthesis, reduced transcapillary flux ratios, diffuse intravascular coagulation and loss in the ascites. Gastrointestinal loss of AT III may occur in patients with active inflammatory bowel diseases. AT III deficiency is observed in nephrotic syndrome when urinary loss of protein exceeds 5 g/d. During hemodialysis we have not found low AT III levels. Disseminated intravascular coagulation is characterized by activation of the coagulation system and increased consumption of AT III. AT III complexes with activated coagulation factors are subsequently cleared by the reticuloendothelial system.

Antithrombin III↗
PubMed1992

The pregnant antithrombin III deficient patient: management without antithrombin III concentrate.

Pregnant patients with antithrombin III (AT III) deficiency have an unacceptably high risk of venous thromboembolism (VTE). Antithrombotic therapy is therefore recommended. The reported clinical experience of such prophylaxis is limited. Some authors have recommended the use of AT III concentrate in addition to heparin in the management of these patients. We report successful management with heparin alone during pregnancy and the postpartum period in two patients with AT III deficiency. Both patients had experienced VTE during a prior pregnancy; one also experienced VTE during the reported pregnancy. Both patients were therefore at particularly high risk of further VTE. Based on the good results in these two patients, and a review of previously reported cases, we propose that heparin alone, in a dose to maintain the APTT in a therapeutic range, provides adequate prophylaxis and treatment for VTE during pregnancy and delivery in many AT III deficient subjects.

Adult↗
PubMed1991

[Clinical and genetic aspects of antithrombin III deficiency and abnormal antithrombin III].

Antithrombin III (AT III) has been confirmed to play an important role as a serine protease inhibitor in the mechanism of blood coagulation, and its deficiency or abnormality is found to cause thromboembolic disorders by reducing the anticoagulant activity. In this paper AT III gene of patient with congenital AT III deficiency, which was suggested to have qualitative abnormality by isoelectric focusing, was investigated. Analysis of the genomic structure by Southern blot hybridization with a cDNA probe (pAT6) revealed no detectable changes indicating any deletions, rearrangements and translocations. Therefore, we focused to analyze the sequence of exon 6 of AT III gene by polymerase chain reaction (PCR) methods followed by direct sequencing analysis. Nucleotide sequencing of exon 6 of AT III gene showed a G to T transitional mutation resulting in the conversion of arginine-406 to methionine coexisted with normal allele which encodes arginine. The mutation is located near the reactive center of AT III molecule, which region has been proved to be highly conserved during the evolution of serine protease inhibitor (serpin) family. From these results, it is concluded that the new type of mutation at amino acid site 407, which is similar to AT III Utah, is important for maintaining the structural and biological function of this inhibitor.

Antithrombin III↗
PubMed1992

Measurement of markers of activated coagulation in antithrombin III deficient subjects.

Functional antithrombin III levels were measured by factor Xa inhibition in 63 members of a large family with type 2 antithrombin III deficiency and individuals were classified as antithrombin III deficient or non-deficient according to the results. F1 + 2 and TAT complexes were measured using an ELISA and FPA levels were measured by radioimmunoassay. Thirty subjects (48%) were classified as antithrombin III deficient and 33 (52%) as antithrombin III non-deficient. The mean level of F1 + 2 was significantly higher in the deficient adults (0.87 +/- 0.26) compared to both the non-deficient adults (0.70 +/- 0.21) (p = 0.03) and the deficient adults receiving warfarin (0.16 +/- 0.01) (p less than 0.001). The differences in the mean values of TAT complexes and FPA between deficient and non-deficient individuals were not statistically significant. These findings suggest that untreated antithrombin III deficient subjects generate more thrombin than their non-deficient family members and that warfarin inhibits this thrombin formation. In this cross-sectional study, it is not possible to correlate the levels of the surrogate makers with future clinical outcome.

Adolescent↗
PubMed1991

Effective prophylaxis of thrombosis by antithrombin III concentrate in a pregnant woman with congenital antithrombin III deficiency: relations between plasma antithrombin III activity and the plasma levels of hemostatic molecular markers.

The value of antithrombin III (AT III) concentrate and a standard criterion for its use were examined in a pregnant woman with congenital AT III deficiency by continuous monitoring of plasma AT III activity and the plasma levels of hemostatic molecular markers. The rates of improvement of various markers after AT III administration (frequency of improvement/frequency of administration) were as follows: fibrinopeptide A (FPA) 82%, D-dimer 70%, fibrinopeptide B beta 15-42 73%, beta-thromboglobulin 60%, and platelet factor 4 50%. There was no significant correlation between the plasma AT III activity and all plasma FPA values, but FPA values of over 3.9 ng/ml showed a significant negative correlation with AT III activity: AT III activity (%) = -6.59 x FPA (ng/ml) + 125, r = -0.851, p less than 0.02. We therefore recommend continuous monitoring of the plasma FPA level and administration of AT III concentrate when the FPA level is elevated. According to the regression line shown above, plasma AT III activity should be raised to 100% to keep the FPA level below 6.0 ng/ml with 95% confidence limit.

Adult↗
PubMed1992

Prophylactic antithrombin III administration during pregnancy immediately reduces the thrombin hyperactivity of congenital antithrombin III deficiency by forming thrombin-antithrombin III complexes.

We examined the changes of haemostatic molecular markers after antithrombin III (AT III) administration in a 22-year-old woman with congenital AT III deficiency in the third trimester of pregnancy who did not have thrombosis. Various markers including fibrinopeptide A (FPA), thrombin-antithrombin III complex (TAT), prothrombin fragment F1 + 2 (F1 + 2), plasmin-alpha 2antiplasmin, D-dimer, beta-thromboglobulin, and platelet factor 4 were measured before and just after 3,000 U of AT III concentrate, which was given three times per week from the 34 week of pregnancy until delivery. Just after AT III administration, F1 + 2 and FPA levels decreased on most occasions, while TAT sometimes increased. Plasma FPA levels were markedly decreased on all 8 occasions when the plasma FPA levels was above 2.0 ng/ml before AT III administration. Plasma FPA levels were always greater than or equal to 6.4 ng/ml before AT III administration on the 4 occasions when TAT increased to above 115%. The changes of plasma F1 + 2 levels were significantly correlated with the AT III level. These results suggest that prophylactic AT III administration in the third trimester immediately inactivates intravascular thrombin to form TAT and reduce the plasma FPA level. Thus, the transient TAT elevation following AT III administration may not only be due to extraction of thrombin from the fibrin clots of thrombi but also to intravascular thrombin which is not attached to thrombi. FPA is the best molecular marker for thrombin hyperactivity and it should be monitored in AT III-deficient pregnant women in the third trimester.

Adult↗
PubMed1987

[Prevention of thromboembolism during pregnancy in 3 sisters with congenital antithrombin III deficiency and decreased inducible fibrinolysis].

Antithrombin III (AT III) deficiency is associated with a high risk of venous thromboembolism, particularly in pregnancy. As prophylactic treatment it has been recommended that plasma levels of AT III be normalized by use of AT III concentrates, in addition to heparin. - We report on the prophylactic treatment of three sisters (age 21, 25, and 32 years) with congenital AT III deficiency (38-53%, normal 80-120%) and reduced inducible fibrinolytic activity (1.2, 5.8, 1.2%, normal greater than 8.5%), who had already had severe thromboembolism. During pregnancy prophylactic measures were taken individually, depending on the plasma level of beta thromboglobulin (BTG) determined every 2-3 weeks. In two patients prophylaxis with s.c. heparin (2 X 7500 IU/d) was started at the time of the first increase of BTG (around 10th week of gestation), leading to normalization of BTG. When BTG was again elevated, the dose of heparin was increased stepwise to 2 x 15,000 IU/d; in this way functional AT III levels remained in the range of 28-50%. Thus, these two patients received only heparin throughout pregnancy. However, in the third patient BTG levels could not be normalized by heparin alone (60-130 ng/ml, normal less than 43 ng/ml). Injections of AT III concentrate (1000 IU) led to reduction of BTG within 2 hours (60----42,220----61 ng/ml). Therefore, AT III was given from the 25th week of gestation in increasing amounts up to 5000 IU/week (funct. AT III in plasma 51-72%) in addition to heparin (2 x 12,500 IU/d), resulting in BTG levels of 33-51 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2026

Facial Dysmorphism and Severe Vascular Phenotype in TRNT1 Deficiency with Concomitant Antithrombin III Deficiency.

TRNT1 deficiency (SIFD syndrome) is a rare inborn error of immunity characterized by sideroblastic anemia, immunodeficiency, periodic fevers, and developmental delay. We report two Romanian patients with genetically confirmed TRNT1 deficiency presenting with characteristic hematologic and immunologic abnormalities and a distinctive facial dysmorphism. One patient additionally developed severe gastrointestinal ischemia and intracranial hemorrhage in the setting of concomitant hereditary antithrombin III deficiency. These observations expand the phenotypic spectrum associated with TRNT1 deficiency and highlight the marked clinical variability of this disorder. The contribution of TRNT1-associated inflammation to the vascular phenotype remains speculative and cannot be distinguished from the effects of the concomitant thrombophilic condition.

Humans↗
PubMed1990

[Management with antithrombin III concentrate in a pregnant woman with hereditary antithrombin III deficiency].

Pregnant women with hereditary antithrombin III (AT-III) deficiency are frequently associated with thromboembolic disorders. We have treated a pregnant woman with hereditary AT-III deficiency, who had suffered from thromboembolic disorders at her past three gestations, with AT-III concentrate. Dosage of AT-III concentrate to maintain plasma AT-III activity over 80% was 3,500 units per week during second and third trimesters, but more frequent administration was necessary around delivery. In recent reports, pregnant women with hereditary AT-III deficiency had been treated with heparin or warfarin except for during abortion and delivery, in which time AT-III concentrate was widely utilized. But the use of heparin or warfarin during gestation is occasionally harmful, AT-III concentrate should be chosen for management in pregnancy in women with hereditary AT-III deficiency.

Adult↗
PubMed1990

Evaluation of the safety, recovery, half-life, and clinical efficacy of antithrombin III (human) in patients with hereditary antithrombin III deficiency. Cooperative Study Group.

Antithrombin III (Human) (AT III) was administered to 18 patients with documented hereditary AT III deficiency. In eight patients with no ongoing clinical symptoms of thrombosis, the percent increase per unit AT III infused per kilogram of body weight ranged from 1.56% to 2.74%, and the half-life from 43.3 to 77.0 hours. No significant difference was noted between patients receiving and those not receiving coumarin therapy. In clinically ill patients, the in vivo recovery was significantly lower and ranged from 0.64% to 1.90% increase per unit AT III infused/kg. Efficacy of AT III was evaluated in 13 patients for the prevention or treatment of thrombosis. AT III was efficacious as assessed by the absence of thrombotic complications after surgery and/or parturition, and the nonextension and nonrecurrence of thrombosis in patients exhibiting an acute thrombotic episode. No side effects were noted. Follow-up studies indicated no hepatitis B seroconversion and no alanine aminotransferase elevations in patients who were not transfused with other blood products.

Adult↗
PubMed1991

Mortality in hereditary antithrombin-III deficiency--1830 to 1989.

To determine whether antithrombin-III (AT-III) deficiency leads to an excess mortality, we studied 171 individuals from ten families with a proven hereditary deficiency. 73 were classified as certainly deficient either by direct measurement of AT-III concentration or by mendelian inheritance patterns. 98 individuals had a high probability (0.5) of deficiency. The 64 deaths recorded did not exceed those expected for the general population adjusted for age, sex, and calendar period. We suggest that a policy of prophylactic anticoagulation for patients with AT-III deficiency cannot be recommended.

Adolescent↗
PubMed1992

[Prophylaxis of thrombosis in a pregnant woman with congenital antithrombin III deficiency: changes in hemostatic molecular markers before the onset of thrombosis].

A pregnant woman with congenital antithrombin III (AT III) deficiency was given AT III concentrate and warfarin at the first and after 36th week of gestation periods and at the other gestation period, respectively. The patient developed thrombosis in the left leg, but fibrinopeptide A (FPA) and thrombin-AT III complex (TAT) had already shown high values one week before, suggesting the possibility of their being forecast markers of thrombosis. The administration of AT III concentrate caused an improvement in thrombosis. Therefore, in case of high FPA and TAT values as determined one or two times a week, the administration of AT III concentrate was thought necessary. In case of warfarin, however, non-administration during the 6th-9th weeks of gestation for the purpose of avoiding teratogenicity and frequent blood coagulation tests taking heed of overdosage for the purpose of avoiding fetal central nervous system abnormalities were suggested necessary. Delivery was uneventful, both mother and child being doing very well; umbilical blood AT III activity was 18%. It is generally difficult for us to form the diagnosis as AT III deficiency only from AT III activity at neonatal stage, but in the present study, we analyzed the restriction fragment length polymorphism of the AT III gene using umbilical blood, and succeeded in diagnosing the neonatal child as AT III deficiency.

Adult↗
PubMed1979

Central retinal vein occlusion in a patient with familial antithrombin III deficiency: case report.

A 60-year old man with familial antithrombin III deficiency, a primary cause of hypercoagulation, developed central retinal vein occlusion. Familial antithrombin III deficiency is inherited as an autosomal dominant condition. It is characterized by recurrent episodes of thromboembolism. The occurrence of central retinal vein occlusion in a person with familial deficiency of antithrombin III suggests the possibility of a casual relationship.

Animals↗
PubMed1977

Familial thrombosis due to antithrombin III deficiency in a Greek family.

A Greek family with hereditary antithrombin III (AT III) deficiency associated with venous thrombosis is reported. 5 members of the family were affected. In these patients, AT III and heparin cofactor activities were decreased. Immunoreactive AT III showed a positive correlation to both AT III and heparin cofactor activities. alpha2-Macroglobulin and alpha1-antitrypsin were normal. The pattern of inheritance of the defect is autosomal dominant.

Adult↗
PubMed1989

Molecular genetics of inherited antithrombin III deficiencies.

The cloning of antithrombin III (ATIII) complementary deoxyribonucleic acids and the determination of the ATIII gene structure have permitted a systematic evaluation of the molecular basis for inherited ATIII deficiencies. Sixteen kindreds with the most common form of the deficiency, in which plasma ATIII antigen levels and activity are proportionately reduced, were studied. Two polymorphic deoxyribonucleic acid markers were used to resolve parental ATIII alleles and to trace their inheritance patterns. In 15 of 16 cases, the structure of the affected ATIII allele was indistinguishable from normal, suggesting that relatively small mutations, resulting in gene inactivation, are responsible for the lower ATIII levels in these affected families. In the remaining kindred, complete deletion of one ATIII allele was seen. Also investigated was the molecular basis for a qualitative form of ATIII deficiency in a French-Canadian family with normal levels of immunoreactive protein but only half the expected levels of serine protease inhibitor activity. Using polymorphic markers, the abnormal allele was identified, cloned, and partially sequenced from the propositus. A single G----A transition was seen in the first base of codon 382, resulting in an alanine----threonine substitution in the defective protein. This mutation, together with others in this vicinity, defines a minimal length for a fully functional thrombin-binding domain.

Antithrombin III↗