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PubMedDate not supplied

Antithrombin III, plasminogen, plasmin, and alpha-2-antiplasmin in donor blood and plasma components.

The functional levels of antithrombin III, plasminogen, plasmin, and alpha-2-antiplasmin were evaluated in sequentially derived fresh frozen plasma, cryoprecipitate, and cryo-poor plasma aliquots from 20 registered blood donors. Antithrombin III is the major plasma inhibitor of the serine proteases of the procoagulant system. Plasminogen, the proenzymatic form of plasmin, is the primary endogenous profibrinolytic moiety; alpha-2-antiplasmin is the principal intermediate acting inhibitor of plasmin. As congenital or acquired deficiencies of antithrombin III and/or plasminogen predispose to thrombosis, and as these agents may be consumed in acute thrombosis, the goal of this investigation was to discern those plasma components which potentially might maximize both antithrombotic and fibrinolytic activities if used therapeutically. Using enzyme specific synthetic substrate methods, it was determined that no spontaneous plasmin activity was evident through phlebotomy or component processing and storage. Analysis of variance showed antithrombin III to be significantly decreased in cryoprecipitate as compared to the other components (p less than 0.0001). Furthermore, the level of antithrombin III or plasminogen in cryo-poor plasma and fresh frozen plasma was not statistically different. Also, the alpha-2-antiplasmin level was not statistically different among the specimen groups. Since fresh frozen plasma and cryo-poor plasma contain comparable total quantities of antithrombin III and plasminogen and as most of the activity of factors I, V, VIII, and XIII is diverted into cryoprecipitate, it is suggested that cryo-poor plasma may be preferable to fresh frozen plasma for the treatment of thrombosis associated with or complicated by antithrombin III and/or plasminogen deficiency.

Antithrombin III↗
PubMed1984

Acquired deficiency and urinary excretion of antithrombin III in nephrotic syndrome.

The published data concerning changes of antithrombin III (ATIII) in nephrotic syndrome (NS) are contradictory. While increased ATIII activity has been reported by some investigators, decreased concentration has been shown by others and normal values by yet another group of authors. We determined plasma and urine concentrations of ATIII in a group of 20 patients with NS using an immunologic assay. In addition, plasma ATIII activity was determined. The results were compared with those obtained in a group of normal volunteers. Plasma concentration and activity of ATIII were both greatly reduced in the patients with NS. In addition, substantial quantities of ATIII were recovered in the urine of all tested patients. The present study, therefore, substantiates the low plasma concentrations of ATIII and its urinary losses in NS. In addition, a parallel reduction in plasma ATIII activity is demonstrated providing functional evidence of acquired ATIII deficiency in this condition.

Adolescent↗
PubMed1996

[Role of the hemostasis laboratory in the etiologic approach to deep vein thrombosis].

Thrombophilia is characterized by an inherited or acquired defect in the blood coagulation pathway leading to an increased risk for thrombosis. The etiological approach following confirmed venous thrombotic events should rule out medical or chirurgical risk factors. Thrombophilia should be sought by laboratory tests. The recent discovery of a blood coagulation defect: inherited resistance to activated protein C which is found to 20% of patients with former thrombotic events has changed current laboratory approach. Deficiencies of one of the anticoagulant proteins (antithrombin III, protein C, protein S) are found in 10% of the patients, similar to the frequency of antiphospholipid antibodies. These tests may be difficult to interpret immediately after the thrombotic event because of various factors such as inflammatory states or anticoagulant treatments. Therefore this abnormal tests should be confirmed on a later sample analysis far from the event. The discovery of an inherited blood coagulation pathway defect may affect the duration of treatment, prophylaxis in situations with circumstantial risk factors and requires familial analysis. Inherited resistance to activated protein C may be associated with another inherited defect leading to an increased risk for thrombosis.

Antithrombin III Deficiency↗
PubMed1994

Three novel missense mutations in the antithrombin III (AT3) gene causing recurrent venous thrombosis.

The polymerase chain reaction and direct sequencing were used to determine the nature of the mutations in the antithrombin III (AT3) gene in seven unrelated patients with familial antithrombin III (ATIII) deficiency and recurrent venous thrombosis. Three novel mutations were found, two associated with a type I deficiency state (Pro80-->Thr and His120-->Tyr) manifesting reduced synthesis of ATIII. The other novel lesion (Met251-->Ile) was associated with a dysfunctional ATIII protein (type II ATIII deficiency) and is predicted to interfere either with a heparin-induced conformational change in the ATIII molecule or with docking to thrombin. A novel polymorphism (Tyr158-->Cys) was also found to occur in several individuals of Scandinavian origin.

Amino Acid Sequence↗
PubMedDate not supplied

A survey of inherited thrombotic syndromes in Italy. ad hoc Study Group.

A collaborative survey was conducted among Italian thrombosis centers to gather information about the number and clinical features of patients with inherited thrombotic syndromes. The survey, based on 74 unrelated kindreds, revealed that antithrombin III, protein C and protein S defects are the most frequent genetic disorders. Venous thromboembolism was more frequent than arterial thrombosis, which was seen in only a minority of cases, most frequently with dysfibrinogenemia. About half of the patients developed venous thrombosis with a similar incidence in antithrombin III, protein S and protein C defects. About half of the symptomatic patients had recurrences and 40% developed thrombosis after a triggering factor, most frequently after surgery, during the puerperium, pregnancy, oral contraceptive intake or bed rest. Deep venous thrombosis prevailed and superficial thrombophlebitis was rare in antithrombin III-deficient patients, whereas deep venous thrombosis was present in about half and superficial thrombophlebitis in about one third of the cases with protein S and protein C defects. The probability to be free of thrombosis decreases with increasing age and at 35 years can be estimated to be 47% both for men and women. There is, however, a group of patients who are still free of thrombosis despite their older ages.

Adolescent↗
PubMed2002

Recombinant human transgenic antithrombin in cardiac surgery: a dose-finding study.

BACKGROUND: Acquired antithrombin III (AT) deficiency may render heparin less effective during cardiac surgery and cardiopulmonary bypass (CPB). The authors examined the pharmacodynamics and optimal dose of recombinant human AT (rh-AT) needed to maintain normal AT activity during CPB, optimize the anticoagulant response to heparin, and attenuate excessive activation of the hemostatic system in patients undergoing coronary artery bypass grafting. METHODS: Thirty-six patients scheduled to undergo elective primary coronary artery bypass grafting and who had received heparin for 12 h or more before surgery were enrolled in the study. Ten cohorts of three patients each received rh-AT in doses of 10, 25, 50, 75, 100, 125, 175, or 200 U/kg, a cohort of six patients received 150 U/kg of rh-AT, and a control group of six patients received placebo. RESULTS: Antithrombin III activity exceeded 600 U/dl before CPB at the highest dose (200 U/kg). Doses of 75 U/kg rh-AT normalized AT activity to 100 U/dl during CPB. Activated clotting times during CPB were significantly (P < 0.0001) greater in patients who received rh-AT (844 +/- 191 s) compared with placebo patients (531 +/- 180 s). Significant (P = 0.001) inverse relations were observed between rh-AT dose and both fibrin monomer (r = -0.51) and D-dimer (r = -0.51) concentrations. No appreciable adverse events were observed with any rh-AT doses used in the study. CONCLUSIONS: Supplementation of native AT with transgenically produced protein (rh-AT) in cardiac surgical patients was well tolerated and resulted in higher activated clotting times during CPB and decreased levels of fibrin monomer and D-dimer.

Aged↗
PubMed1987

Clinical use of antithrombin III concentrates.

The biochemical and biological properties of antithrombin III (AT III) and the clinical consequences of a deficiency of this inhibitor are described. Therapy with concentrates of purified AT III has been carried out for about 10 years and the present experience is reviewed. In a relatively small number of patients with congenital AT III deficiency it is necessary, under certain condition to substitute AT III. A considerably more frequent use of AT III concentrates has been made in acquired AT III deficiency, especially in shock and diffuse intravascular coagulation (DIC). This therapy was shown to be promising since the duration of DIC could be considerably shortened and the frequency of fatal events could be significantly diminished. No undesirable side effects of substitution with virus-sterilized AT III concentrates have been hitherto observed.

Antithrombin III↗
PubMedDate not supplied

Simultaneous double-culprit in-stent thrombosis. Who is the guilty prisoner behind bars: drug-eluting stent, bare-metal stent, or indication for treatment?

BACKGROUND: The intrinsic thrombogeneity of stents was the historic limitation to their usage during the early phases of stenting. The risk of stent thrombosis has been minimized by the widespread use of platelet antiaggregation. Nowadays, the risk of subacute stent thrombosis is around 1%. Thrombotic risk depends on several factors, such as type of stent, complexity of lesion, and clinical picture. CASE REPORT: We present a case of recurrent acute in-stent thrombosis in a patient with mild antithrombin III (AT) deficiency despite the combined administration of clopidogrel and aspirin. CONCLUSION: In our patient, several factors, such as diabetes, AT deficiency, and the use of a paclitaxel-eluting stent, have contributed to the development of recurrent acute stent thrombosis. Although we were not able to identify the culprit factor, we should keep in mind that the deployment of a drug-eluting stent could be unsafe if it is not supported by a clear clinically oriented pathway that considers the overall condition of the patient since, in some cases, neither coronary lesions nor coronary stents are responsible for the negative outcome of patient therapy, which may be caused instead by incomplete or inadequate patient assessment.

Antithrombin III Deficiency↗
PubMed2004

Significance of antithrombin III, protein C and protein S in acute mesenteric ischemia patients.

It is well established that a condition of hypercoagulation due to deficiencies of antithrombin III, protein C and protein S may result in thrombo-embolism. To evaluate the possibility of hypercoagulation in acute mesenteric ischemia (AMI); clinical features, ECG changes, drug history, the length of intestine remaining after the resection and mortality of 15 consecutive patients were recorded and plasma levels of antithrombin III, Protein C and protein S were measured. Antihypertensive, antidiabetic and digitalis were the main drugs used by the patients. Atrial fibrillation was the main ECG finding (60%). AMI was attributed to thrombo-embolic phenomena because of atrial fibrillation in these patients. Levels of antithrombin III and protein S were lower in patients without atrial fibrillation compared to those with the condition (mean values 16.18 vs. 18.04 and 87.33 vs. 94.22 respectively) but the difference was not statistically significant. Levels of Protein C were lower and the length of intestine remaining after resection was shorter in patients without, compared to those with, atrial fibrillation (mean values 77.00 vs. 88.66, and 52.5 cm vs. 86.11 cm respectively). The difference was statistically significant (p < 0.05). Postoperative mortality rate was 33.3% (5 patients) and the length of intestine remaining after resection was the main determining factor in the prognosis of the patients. We conclude that a condition of hypercoagulation due to a deficiency of protein C has a significant role in the pathogenesis of AMI especially in patients without atrial fibrillation.

Acute Disease↗
PubMed1994

Liver transplantation for Budd-Chiari syndrome--palliation or cure?

This report documents two cases of Budd-Chiari syndrome (BCS) with essential thrombocytosis and antithrombin (AT) III deficiency as underlying etiological factors. Orthotopic liver transplantation was successfully performed in both patients but with different therapeutic intention. In the patient with essential thrombocytosis, hepatic transplantation only relieved the symptoms of the predisposing thrombogenic condition; it did not cure the underlying disorder. Prophylactic long-term anticoagulation, as well as adjuvant therapy for the causative disease, remained necessary. On the other hand, in the patient with AT III deficiency, liver transplantation was curative, resulting in complete reconstitution of serum AT III activity with resolution of the hypercoagulable state postoperatively. Thus, depending on the underlying etiology, liver transplantation for BCS can be considered as palliative, necessitating long-term adjuvant therapy, or as curative, with correction of a metabolic defect.

Adult↗
PubMed1991

[Homozygous (or double heterozygous) antithrombin III defect: AT-III, Budapest 4].

A quantitative-qualitative AT-III deficiency was found in a young woman with severe thromboembolic episodes. Only AT-III molecules with a low heparin affinity were detected in her plasma and these pathological AT-III molecules could not increase the rate of the thrombin-inactivation at all. The pathological AT-III molecules were present in the blood of her father and one of her sisters, but only in a 50% quantity, the other half of the AT-III molecules proved to be functionally normal. The mother of the proposita had deceased earlier, thus she could not be investigated. However, the authors suggest a heterozygous state for her as well, because this assumption can explain the homozygous (or double heterozygous) state of the proposita. In accordance with the convention, this abnormality was designated as AT-III Budapest 4, and the exact biochemical and genetic background of the disorders can be clarified only by further investigations.

Adult↗
PubMed1999

[Segmental short bowel stenosis after a superior mesenteric vein thrombosis. Report of a case].

We report a 24 years old female with a Superior Mesenteric and Portal Vein Thrombosis due to an Antithrombin III factor deficiency, associated to oral contraceptive use and smoking. She presented with severe abdominal pain and the diagnosis was reached after surgery with a CT scan. The patient was treated with intravenous heparin and oral anticoagulation, with a good clinical and Doppler endo-sonographic response. One month after the onset, she developed an intestinal occlusion caused by two concentric jejunal stenoses, measuring 2 and 0.7 cm in length and demonstrated with a barium jejunogram. A 35 cm intestinal resection was done and the patient recovered uneventfully. The pathological study showed granulation tissue on both stenotic zones with an ulcer near to the distal stricture, that reached the internal muscularis propria, with subserosal fibrosis. The development of segmental stenosis is a rare complication superior mesenteric vein thrombosis, that must be bore in mind.

Adult↗
PubMed1988

Management of pregnancy in women with antithrombin III congenital defect: report of four cases.

Four pregnant women with antithrombin III congenital deficiency underwent thrombosis prophylaxis including oral anticoagulants administered from the 16-18th week to the 36-37th week of pregnancy, subcutaneous heparin before the 16-18th week and after the 36-37th week, and a single infusion of AT III concentrate in the peripartum period in order to obtain a minimal level of 0.8 U/ml of AT III functional activity. The level of circulating AT III after the concentrate infusion needs to be evaluated by functional methods, because of a consistent amount in the concentrates of inactive AT III immunoreactive material. No thrombotic or haemorrhagic complication occurred after starting prophylaxis in any woman either in any newborn.

Administration, Oral↗
PubMed1990

Familial variant of antithrombin III (AT III Bligny, 47Arg to His) associated with protein C deficiency.

The association of a variant of antithrombin III (AT III Bligny) and protein C deficiency is described in a 36-year-old patient having suffered from severe thrombotic episodes. His mother has protein C deficiency and showed a single episode of thrombophlebitis following surgery. His father, sister and daughter have the variant AT III and are asymptomatic. The abnormal AT III was characterized in plasma by the discrepancy between a normal progressive activity and a reduced heparin cofactor activity. This variant AT III was purified, separated from the normal protein by heparin-Sepharose chromatography and was eluted with increased NaCl concentrations. At pH 7.4, the variant AT III eluted at lower (0.3 to 0.5 M) NaCl concentrations than normal (1 to 1.5 M) AT III, thus demonstrating a decreased affinity for heparin. At pH 6.0, however, the abnormal molecule bound more avidly to heparin-Sepharose and was eluted like normal AT III at pH 7.4. Similarly, the heparin enhancement of intrinsic fluorescence of the variant AT III, markedly reduced at pH 7.4, was normalized at pH 6.0. The abnormal AT III showed a normal antiprotease activity, a normal molecular weight by SDS-PAGE, but displayed only a partial immunological identity with the normal protein. Analysis of amplified genomic DNA from this patient by dot-blot demonstrates a heterozygous substitution of arginine by histidine at position 47.

Adult↗
PubMed1992

Anti-thrombin III deficiency in Nigerian children with sickle cell disease. Possible role in the cerebral syndrome.

A prospective study of Nigerian children with sickle cell disease was undertaken to determine serum levels of antithrombin III (AT-III) and compare these with normal controls. Mean serum AT-III was significantly lower in patients than in controls (14.51 +/- 4.84 mg/dl and 17.75 +/- 5.92 mg/dl) respectively. Seven of the 49 sickle cell patients had AT-III levels below 50% of normal values. Mean platelet counts were significantly higher in sicklers than in normal controls. AT-III deficiency may predispose to thrombotic complications in children with sickle cell disease.

Acute Disease↗