Antithrombin III deficiency is an autosomal dominant disorder, which is manifested by recurrent venous thromboembolisms, such as: deep vein thrombosis and/or pulmonary embolism, but arterial embolisms are very rare. We report a case of a patient with hereditary antithrombin III deficiency, manifested by myocardial infarction and deep vein thrombosis.
Antithrombin III Deficiency* ; Antithrombin III* ; Embolism ; Humans ; Myocardial Infarction* ; Pulmonary Embolism ; Thromboembolism ; Venous Thrombosis*

Appropriate anticoagulation is essential for safe cardiopulmonary bypass (CPB). Two patients with infective endocarditis were scheduled for valve replacement. After an intravenous heparin injection for the CPB, the increases in the activated clotting time (ACT) in both patients were less than expected. Subsequent additional heparin administration failed to maintain a sufficient ACT for the CPB, and antithrombin III (AT III) tests during the CPB revealed low activities in both patients. Heparin resistance, due to consumption of circulating AT III as a result of infective endocarditis or prior heparinization, was postulated. While fresh frozen plasma (FFP) could not be timely administered in the first patient, ACT was successfully prolonged after the administration of FFP in the second. It is strongly suggested that adequate management of heparin resistance should be prepared for patients with infective endocarditis who require CPB.
Antithrombin III ; Antithrombin III Deficiency ; Cardiopulmonary Bypass* ; Endocarditis* ; Heparin* ; Humans ; Plasma

Appropriate anticoagulation is essential for safe cardiopulmonary bypass (CPB). Two patients with infective endocarditis were scheduled for valve replacement. After an intravenous heparin injection for the CPB, the increases in the activated clotting time (ACT) in both patients were less than expected. Subsequent additional heparin administration failed to maintain a sufficient ACT for the CPB, and antithrombin III (AT III) tests during the CPB revealed low activities in both patients. Heparin resistance, due to consumption of circulating AT III as a result of infective endocarditis or prior heparinization, was postulated. While fresh frozen plasma (FFP) could not be timely administered in the first patient, ACT was successfully prolonged after the administration of FFP in the second. It is strongly suggested that adequate management of heparin resistance should be prepared for patients with infective endocarditis who require CPB.
Antithrombin III ; Antithrombin III Deficiency ; Cardiopulmonary Bypass* ; Endocarditis* ; Heparin* ; Humans ; Plasma

OBJECTIVETo identify the antithrombin (AT) phenotype and gene mutation of a kindred with hereditary antithrombin deficiency.

METHODSPlasma AT activity and AT antigen level of the propositus and his kindred members were determined with chromogenic substrate method and immunoassay, respectively. All the seven exons and intron-exon boundaries of antithrombin gene were analyzed by PCR and direct sequencing of amplified PCR products from the propositus.

RESULTSThe propositus AT antigen level was normal but his AT activity was only 65% of normal value suggesting that he had type II AT deficiency. A heterozygous G13830A mutation in exon 6 resulting in Arg393His missense mutation in his AT polypeptide was identified in the propositus. The same phenotype and gene mutation were found in other 3 kindred members.

CONCLUSIONThe type II AT deficiency found in this kindred is caused by heterozygous G13830A mutation in AT gene.

Adult ; Antithrombin III ; genetics ; metabolism ; Antithrombin III Deficiency ; genetics ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree

OBJECTIVETo identify the clinical phenotype and gene mutation in two kindreds with type I inherited antithrombin (AT) deficiency.

METHODSThe coagulation and anticoagulation testing and thrombophilia screening were used for phenotypic diagnosis and immunonephelometry and chromogenic assay for plasma level of AT antigen (AT:Ag) and AT activity (AT:A), respectively. All of the seven exons and intron-exon boundaries and untranslation regions of AT gene were amplified by PCR, and the PCR products analysis was by direct sequencing. The corresponding gene sites of the two family members and healthy individuals were detected according to the gene mutation sites.

RESULTSThe plasma levels of AT:Ag of proband 1 and proband 2 were 126 mg/L and 117 mg/L, and AT:A was 49% and 48%, respectively. Heterozygotic deletion of 3239-3240delCT in proband 1 and nonsense mutation 3206A-->T (K70Stop) in proband 2 were rchaacterized in exon 2 of AT gene. And some of their family members were also detected with the heterozygotic gene mutation.

CONCLUSIONType I inherited antithrombin deficiency of the two probands were caused by AT gene mutation 3239-3240delCT and 3206A-->T (K70Stop).

Antithrombin III Deficiency ; genetics ; Heterozygote ; Humans ; Mutation ; Pedigree ; Phenotype

Hypercoagulability state is the result of the interplay of genetic predisposition and risk factors. Many key enzymes and reactions in coagulation and anti-coagulation system are involved. Hereditary antithrombin deficiency is one of the major risk factors of venous thromboembolic disease (VTE), whereas hyperhomocysteinemia may also play a role. This article reviews the recent researches on the contributions of these two factors to VTE.
Antithrombin III Deficiency ; complications ; Humans ; Hyperhomocysteinemia ; complications ; Venous Thrombosis ; etiology

Antithrombin is one of the main endogenous anticoagulants. Antithrombin deficiency may result from hereditary or acquired factors. Inherited antithrombin deficiency is an uncommon autosomal disorder associated with a tendency to venous thromboembolism. Stasis dermatitis occurs as a result of venous stasis caused by venous incompetence or deep vein thrombosis. Furthermore, lipodermatosclerosis that refers to the skin induration and hyperpigmentation of the legs, often occurs in patients who have venous insufficiency. We report a case of stasis dermatitis, complicated by lipodermatosclerosis on both legs of a patient with hereditary antithrombin III deficiency.
Anticoagulants ; Antithrombin III Deficiency* ; Antithrombin III* ; Dermatitis* ; Fibrin ; Humans ; Hyperpigmentation ; Leg ; Skin ; Venous Insufficiency ; Venous Thromboembolism ; Venous Thrombosis

OBJETIVE: To analyze the antithrombin III deficiency in patients with recurrent spontaneous abortion. MATERIALS AND METHOD: The blood samples were tested by chromogenic assay to evaluate the activity of antithrombin III. RESULTS: There was only one case of antithrombin III deficiency. This patient experienced one neonatal death after delivery and one FDIU (fetal death in utero). And also this patient showed a lupus anticoagulant and the prolongation of PTT. CONCLUSIONS: Women with recurrent miscarriage who have no obvious identified cause should consider hematologic screening. Antithrombin III deficiency could be a cause of recurrent spontaneous abortion. But the incidence is very rare in Korean patients.
Abortion, Habitual ; Abortion, Spontaneous* ; Antithrombin III Deficiency* ; Antithrombin III* ; Female ; Humans ; Incidence ; Lupus Coagulation Inhibitor ; Mass Screening ; Pregnancy

OBJECTIVETo study the molecular mechanisms of inherited antithrombin (AT) deficiency caused by AT L99 mutation.

METHODSWild type (WT), L99V, L99A, L99I and L99S AT were purified from drosophila expression system. The binding capacity of AT and the low molecular weight heparin sodium was analyzed by the heparin binding assay. Surface plasmon resonance (SPR) was used to detect the binding ability of AT to thrombin (FIIa) or AT to coagulation factor Xa (FXa). The activity of AT(AT∶A)was detected by chromogenic assay.

RESULTSThe purified WT and mutant AT were at the same size. No additional band was observed by coomassie blue staining and western blot assay. Compared to the WT AT, the binding abilities of the low molecular weight heparin sodium to the AT L99V, L99A, L99I and L99S were (44.8±3.6)%, (118.9±14.0)%, (15.2±8.8)%, and(23.0±8.2)%, respectively. The binding abilities of FIIa to AT L99V, L99A, L99I and L99S were 13%, 57%, 3%, and 29%, while the binding of FXa to AT L99V, L99A, L99I and L99S were 7%, 51%, 1%, and 25%. The AT∶A of WT, L99V, L99A, L99I and L99S AT were 146.5%, 21.4%, 120.9%, 10.8%, and 39.0%, respectively.

CONCLUSIONThe binding abilities of AT to heparin, FIIa and FXa were damaged by the L99 mutation, which resulted in decreased AT∶A and inherited AT deficiency.

Amino Acids ; genetics ; Animals ; Antithrombin III ; genetics ; Antithrombin III Deficiency ; genetics ; Antithrombins ; Drosophila ; Factor Xa ; genetics ; Genetic Vectors ; Humans ; Mutation

OBJECTIVE: To analyze the phenotype and genotype of a patient affected with inherited antithrombin deficiency. METHODS: All exons and exon-intron boundaries of the AT genes were subjected to PCR amplification and Sanger sequencing. The influence of variants on the disease was predicted using bioinformatic software (MutationTaster). RESULTS: The results of all coagulation tests were normal, though the antithrombin activity and antigen content of the proband and his father have decreased significantly (34%, 48% and 12.97 mg/dL, 15.60 mg/dL, respectively). His mother was normal. Genetic analysis revealed that the proband and his father both carried a heterozygous g.2736dupT variant of the AT gene. Bioinformatic analysis suggested that the variant may be pathogenic. CONCLUSION The proband and his father both had type I hereditary antithrombin deficiency caused by a g.2736dupT variant of the AT gene. The variant was unreported previously.
Antithrombin III/genetics* ; Antithrombin III Deficiency/genetics* ; DNA Mutational Analysis ; Genetic Testing ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree