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

Blood ◽  
1990 ◽  
Vol 75 (1) ◽  
pp. 33-39 ◽  
Author(s):  
D Menache ◽  
JP O'Malley ◽  
JB Schorr ◽  
B Wagner ◽  
C Williams ◽  
...  
Keyword(s):  
Half Life ◽  
Antithrombin Iii ◽  
Clinical Symptoms ◽  
Cooperative Study Group ◽  
Significant Difference ◽  
At Iii ◽  
Thrombotic Complications ◽  
Antithrombin Iii Deficiency

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.

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

Blood ◽  
1990 ◽  
Vol 75 (1) ◽  
pp. 33-39 ◽  
Author(s):  
D Menache ◽  
JP O'Malley ◽  
JB Schorr ◽  
B Wagner ◽  
C Williams ◽  
...  
Keyword(s):  
Half Life ◽  
Antithrombin Iii ◽  
Clinical Symptoms ◽  
Cooperative Study Group ◽  
Significant Difference ◽  
At Iii ◽  
Thrombotic Complications ◽  
Antithrombin Iii Deficiency

Abstract 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.

scholarly journals In Vitro Characterization of Rabbit Thrombin, Antithrombin III, and Thrombin-Antithrombin III Complex, and Determination of Their Survival Times in Vivo

1977 ◽  
Author(s):  
Christine N. Vogel ◽  
Kingdon S. Henry ◽  
Roger L. Lundblad
Keyword(s):  
Gel Electrophoresis ◽  
Half Life ◽  
Antithrombin Iii ◽  
Specific Activity ◽  
Sodium Dodecyl ◽  
In Vivo Studies ◽  
Survival Times ◽  
At Iii

Our intention is to study the interaction of rabbit thrombin with antithrombin III (AT-III) in vitro and in vivo. After activation of crude prothrombin with tissue thromboplastin and CaCl2, thrombin was purified and showed two species of thrombin with molecular weights of 36,000 and 39,000 daltons as determined by sodium dodecyl sulfate discontinuous gel electrophoresis. Rabbit AT-III was purified using a heparin agarose column and had a molecular weight of 55,000 daltons. The inhibition of thrombin by AT-III was followed by fibrinogen clotting assays and an AT-III-thrombin complex was observed on gel electrophoresis. For the in vivo studies both thrombin and AT-III were radiolabelled with Na125i using the solid state lactoperoxidase method and retained 99% of the pre-iodinated specific activity. Radiolabelled thrombin and a radiolabelled AT-III-thrombin complex were injected into different rabbits. The rate of removal of both was very similar with a half-life of approximately 9 hours. When radiolabelled AT-III was injected, the half-life was approximately 60 hours. Since the disappearance rate of thrombin more closely approximates that of the preformed AT-III-thrombin complex and is clearly shorter than the turnover rate of AT-III, the possibility is raised that thrombin combines in vivo with a native inhibitor such as AT-III and may in fact be removed from the circulation as a complex rather than as a native molecule.

scholarly journals Familial Thrombosis Due to Antithrombin III Deficiency

Blood ◽  
1974 ◽  
Vol 43 (2) ◽  
pp. 219-231 ◽  
Author(s):  
Ewa Marciniak ◽  
Claude H. Farley ◽  
Philip A. DeSimone
Keyword(s):  
Antithrombin Iii ◽  
Clinical Symptoms ◽  
Oral Anticoagulants ◽  
Laboratory Diagnosis ◽  
Blood Component ◽  
History Of ◽  
Antithrombin Iii Deficiency ◽  
Recurrent Venous Thrombosis

Abstract A large kindred from eastern Kentucky, with extensive history of recurrent venous thrombosis and pulmonary embolism, was studied. Low antithrombin III titers, ranging from 26% to 49% of normal values, were found in plasma of nine members in three consecutive generations; another five members, four of whom were not available for study, are suspected of having the biochemical defect. There was a good correlation between clinical symptoms and antithrombin III deficiency, although three of the younger members with the defect still remained free of thrombosis. In serum of the affected subjects antithrombin III was almost completely utilized, which indicates that stoichiometric binding to coagulation enzymes dominates under biological conditions. Antithrombin and antifactor Xa activities residing in the macroglobulin region of plasma and serum remained unchanged. The responsiveness to heparin in vitro and in vivo confirmed the evidence that antithrombin III is the sole blood component through which heparin exerts its anticoagulant effect. In five affected members therapy with oral anticoagulants increased very significantly the level of antithrombin III in plasma and contributed to a remarkable increase of residual antithrombin III in serum. This objective improvement after warfarin therapy may create significant difficulties in the laboratory diagnosis of antithrombin III deficiency.

Antithrombin-III Deficiency Causing Deep Vein Thrombosis And Pulmonary Embolism In A Young Male

1981 ◽  
Author(s):  
K Genth ◽  
J Schaefer ◽  
J Frank ◽  
W Krämer ◽  
B Weinei ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Pulmonary Artery ◽  
Antithrombin Iii ◽  
Clinical Symptoms ◽  
Venous Pressure ◽  
Vein Thrombosis ◽  
At Iii ◽  
Antithrombin Iii Deficiency ◽  
Deep Vein

A 34 year old male was admitted to the hospital with typical clinical symptoms of acute pulmonary embolism caused by deep vein thrombosis in the upper leg detected by phlebography. Pulmonary embolism was verified by the lung-perfusion-scintigram. The patient developed an infarct pneumonia with hemoptoe. Episodic thromboembolic phenomena occurred due to antithrombin-III deficiency (AT-III). The method, using homogenic substrates exhibited low AT-III activity of 8.6 IU/ml(25°C) due to a familiar AT-III deficit. Fiberoptic pulmonary catheter was placed into the pulmonary artery to measure pulmonary artery pressure (PAP, PCP), right ventricular pressure (RVP) and to determine cardiac output (CO) using the dye dilution technique. Heart rate (HR), central venous pressure (CVP) and aortic pressure (AOP) were recorded continuously. Patient received immediately fibrinolytic therapy, initiated by an initial dose of streptokinase (SK)(250 000 IU/20 min.), followed by a maintenance dose (100 000 IU/h), lasting 3 days. M-mode echocardiography detected before SK a moderate enlarged right ventricle and a small left ventricle, indicating a low output. After SK these values were improved. In conclusion, this case demonstrated a serious thromboembolic disorder, related to AT-III deficit. SK-therapy improved the hemodynamic situation.

Familial antithrombin-III deficiency during cardiopulmonary bypass: a case report

Perfusion ◽  
2000 ◽  
Vol 15 (6) ◽  
pp. 553-556 ◽  
Author(s):  
H J Brinks ◽  
P W Weerwind ◽  
M WA Verkroost ◽  
I. Nováková ◽  
M HJ Brouwer
Keyword(s):  
Cardiopulmonary Bypass ◽  
Serine Proteases ◽  
Antithrombin Iii ◽  
Artery Bypass ◽  
Inhibitory Effect ◽  
At Iii ◽  
Antithrombin Iii Deficiency ◽  
Higher Doses ◽  
D Dimer

The serine protease inhibitor antithrombin-III (AT-III) is the principal in vivo inhibitor of blood coagulation, inactivating mainly thrombin, but also other serine proteases. Binding of AT-III to heparin dramatically increases its inhibitory effect. AT-III deficiency during cardiopulmonary bypass (CPB) can lead to insufficient anticoagulation which cannot be treated by higher doses of heparin. A 60-year-old male with familial AT-III deficiency was admitted to our hospital for coronary artery bypass surgery and aortic valve replacement. Four days before the operation, acenocoumarol was stopped and anti-Xanadroparincalcium (Fraxiparine) was started. AT-III activity at that time was 56%. Two hours before the operation, a single dose of 4500 IU AT-III concentrate was administered. Heparinization was performed with 400 IU/kg of porcine mucosal heparin, increasing the activated coagulation time (ACT) from a baseline of 115 to 549 s. AT-III activity at that time was above 100% and the plasma D-dimer concentration was 230 ng/l. ACTs during CPB remained above 999 s, whereas the AT-III activity dropped to 54% and the D-dimer increased up to 500 ng/l at the end of CPB. CPB was terminated uneventfully. Heparin was reversed with 3 mg/kg protamine chloride, decreasing the ACT to 155 s. In the intensive care unit (ICU), the patient received prophylactic Fraxiparine and 1500 IU AT-III, increasing the AT-III activity to 84%. Postoperatively, there was continued blood loss, which necessitated the administration of whole blood and eventually re-exploration. The case presented illustrates an uneventful treatment of a patient with a hereditary AT-III deficiency undergoing CPB. In spite of an uneventful treatment with AT-III pre-CPB, administration of prophylactic AT-III concentrate after surgery should be considered with caution, as this might increase the postoperative morbidity.

Immunologic Studies of Antithrombin III Heparin Cofactor in the Newborn

1978 ◽  
Vol 39 (03) ◽  
pp. 624-630 ◽  
Author(s):  
W E Hathaway ◽  
L L Neumann ◽  
C A Borden ◽  
L J Jacobson
Keyword(s):  
Gestational Age ◽  
Antithrombin Iii ◽  
Newborn Infants ◽  
Term Infant ◽  
Sick Newborn ◽  
At Iii ◽  
Thrombotic Complications ◽  
Low Levels ◽  
Collection Methods ◽  
Made In

SummarySerial quantitative immunoelectrophoretic (IE) measurements of antithrombin III heparin cofactor (AT III) were made in groups of well and sick newborn infants classified by gestational age. Collection methods (venous vs. capillary) did not influence the results; serum IE measurements were comparable to AT III activity by a clotting method. AT III is gestational age-dependent, increasing from 28.7% of normal adult values at 28-32 weeks to 50.9% at 37-40 weeks, and shows a gradual increase to term infant levels (57.4%) by 3-4 weeks of age. Infants with the respiratory distress syndrome (RDS) show lower levels of AT III in the 33-36 week group, 22% vs. 44% and in the 37-40 week group, 33.6% vs. 50.9%, than prematures without RDS. Infants of 28-32 week gestational age had only slight differences, RDS = 24%, non-RDS = 28.7%. The lowest levels of AT III were seen in patients with RDS complicated by disseminated intravascular coagulation and those with necrotizing enterocolitis. Crossed IE on representative infants displayed a consistent pattern which was identical to adult controls except for appropriate decreases in the amplitude of the peaks. The thrombotic complications seen in the sick preterm infant may be related to the low levels of AT III.

Congenital Antithrombin III Deficiency in 3 Families (7 Affected Members)

1979 ◽  
Author(s):  
J. Conard ◽  
M. Samama ◽  
M. H. Horellou ◽  
B. Cazenave ◽  
P. Griguer ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Antithrombin Iii ◽  
Oral Anticoagulants ◽  
Vena Cava ◽  
Oral Contraception ◽  
Vein Thrombosis ◽  
Heparin Treatment ◽  
At Iii ◽  
Antithrombin Iii Deficiency ◽  
Deep Vein

A congenital Antithrombin III (AT III) deficiency affecting 7 members of 3 families is reported.The first throrabo-embolic accidents were observed between the age of 22 and 35 : they were spontaneous or occured after delivery or oral contraception. in one patient, a deep vein thrombosis was observed during heparin treatment. in 2 cases, recurrent pulmonary embolic episodes required vena cava ligation. No thromboembolic accident was observed during oral anticoagulation.AT III was measured by an amidolytic method and by the Mancini method on plasma and serum ; the antithrombin activity was determined on serum by the von Kaulla method. in 7 patients, a decreased AT III was found by all the methods performed. The AT III level was around 50 % in patients treated or not by oral anticoagulants One patient was studied during heparin treatment and then under oral anticoagulants : AT III levels were lower under heparin.

Is Olfactory Epithelium Biopsy Useful for Confirming Alzheimer’s Disease?

2018 ◽  
Vol 128 (3) ◽  
pp. 184-192 ◽  
Author(s):  
Maria Dantas Costa Lima Godoy ◽  
Marco Aurélio Fornazieri ◽  
Richard L. Doty ◽  
Fábio de Rezende Pinna ◽  
José Marcelo Farfel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Olfactory Epithelium ◽  
Clinical Symptoms ◽  
Middle Turbinate ◽  
Superior Turbinate ◽  
Significant Difference ◽  
Amyloid Beta Proteins

Objectives: The clinical symptoms of Alzheimer’s disease (AD) are preceded by a long asymptomatic period associated with “silent” deposition of aberrant paired helical filament (PHF)-tau and amyloid-beta proteins in brain tissue. Similar depositions have been reported within the olfactory epithelium (OE), a tissue that can be biopsied in vivo. The degree to which such biopsies are useful in identifying AD is controversial. This postmortem study had 3 main goals: first, to quantify the relative densities of AD-related proteins in 3 regions of the olfactory neuroepithelium, namely, the nasal septum, middle turbinate, and superior turbinate; second, to establish whether such densities are correlated among these epithelial regions as well as with semi-quantitative ratings of general brain cortex pathology; and third, to evaluate correlations between the protein densities and measures of antemortem cognitive function. Methods: Postmortem blocks of olfactory mucosa were obtained from 12 AD cadavers and 24 controls and subjected to amyloid-beta and PHF-tau immunohistochemistry. Results: We observed marked heterogeneity in the presence of the biomarkers of tau and amyloid-beta among the targeted olfactory epithelial regions. No significant difference was observed between the cadavers with AD and the controls regarding the concentration of these proteins in any of these epithelial regions. Only one correlation significant was evident, namely, that between the tau protein densities of the middle and the upper turbinate ( r = .58, P = .002). Conclusion: AD-related biomarker heterogeneity, which has not been previously demonstrated, makes comparisons across studies difficult and throws into question the usefulness of OE amyloid-beta and PHF-tau biopsies in detecting AD.

scholarly journals Minimally Invasive Lumbar Spinal Decompression in Elderly Patients with Magnetic Resonance Imaging Morphological Analysis

2018 ◽  
Vol 12 (2) ◽  
pp. 285-293 ◽  
Author(s):  
Seungman Ha ◽  
Youngho Hong ◽  
Seungcheol Lee
Keyword(s):  
Minimally Invasive ◽  
Elderly Patients ◽  
Clinical Outcomes ◽  
Spinal Stenosis ◽  
Clinical Symptoms ◽  
Morphological Features ◽  
Radiological Parameters ◽  
Significant Difference ◽  
Lumbar Spinal

<sec><title>Study Design</title><p>Case-control study.</p></sec><sec><title>Purpose</title><p>In this study, we aimed to investigate clinical outcomes and morphological features in elderly patients with lumbar spinal stenosis (LSS) who were treated by minimally invasive surgery (MIS) unilateral laminectomy for bilateral decompression (ULBD) using a tubular retractor.</p></sec><sec><title>Overview of Literature</title><p>Numerous methods using imaging have been attempted to describe the severity of spinal stenosis. But the relationship between clinical symptoms and radiological features remains debatable.</p></sec><sec><title>Objective</title><p>In this study, we aimed to investigate clinical outcomes and morphological features in elderly patients with LSS who were treated by MIS-ULBD.</p></sec><sec><title>Methods</title><p>We methodically assessed 85 consecutive patients aged &gt;65 years who were treated for LSS. The patients were retrospectively analyzed in two age groups: 66–75 years (group 1) and &gt;75 years (group 2). Clinical outcomes were assessed using the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and the modified MacNab criteria. Outcome parameters were compared between the groups at the 1-year follow-up. Core radiologic parameters for central and lateral stenosis were analyzed and clinical findings of the groups were compared.</p></sec><sec><title>Results</title><p>At the 1-year follow-up, patients in both groups 1 and 2 demonstrated significant improvement in their VAS and ODI scores. All clinical outcomes, except postoperative ODI, were not significantly difference between the groups. In addition, no significant difference was noted in the preoperative radiological parameters between the groups. There was no statistically significant correlation between radiological parameters and clinical symptoms or their outcomes. Moreover, no differences were noted in perioperative adverse events and in the need for repeat surgery at follow-ups between the groups.</p></sec><sec><title>Conclusions</title><p>MIS-ULBD by tubular approach is a safe and effective treatment option for elderly patients with LSS. Clinical outcomes in patients with LSS and aged &gt;75 years were comparable with those in patients with LSS and aged 66–75 years. Moreover, we did not find any correlation between radiological parameters and clinical outcomes in either of the two patient groups.</p></sec>

scholarly journals Hereditary Antithrombin III Deficiency. Evidence of Increased Thrombin Formation in the Early Stage of Hemostasis

1977 ◽  
Author(s):  
F. Josso ◽  
M. H. Aurousseau ◽  
A. M. Fischer ◽  
M. D. Dautzenberg ◽  
S. Beguin
Keyword(s):  
Antithrombin Iii ◽  
Early Stage ◽  
Young Male ◽  
Massive Pulmonary Embolism ◽  
New Family ◽  
Mild Deficiency ◽  
Antithrombin Iii Deficiency ◽  
Thrombin Formation

High incidence of thromboembolism in observed in families with antithrombin III deficiency, despite the rather moderate defect (25 to 50 per cent) observed in the affected subjects, considered as heterozygous for the disease. The mechanism by which such a mild deficiency may promote thrombosis still remains unknown.A new family with antirhrombin III deficiency is reported, including three affected generations. Three young male adults of a same sibship died from massive pulmonary embolism aged from 22 to 28 years. In four living members of the family, three of which had antecedents of thrombophlebitis, antithrombin III level was close to 50 per cent by all assay methods used. Electro-phoretic and immunochemical studies failed to demonstrate any qualitative defect of the antithrombin III molecule.In these patients the only abnormalities of hemostasis lied in the early stage of the hemostatic pathway. In vitro, thrombin formation occured very rapidly after initiation of coagulation, as demonstrated by the kinetics of thrombin generation and factors V and VIII activation. In vivo, factors V and VIII were activated during bleeding much more rapidly than in controls and this activation was not suppressed by low doses of heparin (10 u./kg) as in the controls.These findings indicate that antithrombin III acts chiefly in the regulation balance of the early stages of hemostasis and thrombosis.

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