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.

In Vivo Studies On The Inhibition Of Coagulation By A Heparin Analogue

1981 ◽  
Author(s):  
U Schmitz-Huebner ◽  
F Asbeck ◽  
J van de Loo
Keyword(s):  
Plasma Sample ◽  
Anticoagulant Activity ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
At Iii ◽  
In Vivo Effects ◽  
Higher Doses ◽  
Free Plasma

SSHA, a semi-synthetic heparin analogue belonging to the chondroitin family, was reported to induce considerable anti-Xa activity in vivo being practically inactive in vitro. In a study designed to elucidate further the in vivo effects of this drug, SSHA and sodium heparin from porcine intestinal mucosa were injected subcutaneously into six volunteers on separate occasions over a period of three days in a cross-over trial. Before injection and 2,4,6,8 hours afterwards, the heparin-like activity was measured by means of the APTT, the anti -Xa clotting test and two chromogenic substrate assays. The results show that SSHA mediates both anti-Xa and antithrombin activities in vivo. A comparison between the effects of SSHA and heparin is problematical, due to the heterogeneity of different heparin preparations. Low doses of the analogue (45 mg s.c.) induce proportionally higher and longer lasting anti-Xa activities than higher doses (90 mg s.c.). In an attempt to identify the mediator involved in the anticoagulant activity induced by SSHA in vivo, antithrombin III AT III) was removed from a plasma sample of one the subjects obtaining SSHA injections by immunosorption using Sepharose IVb coupled with antibodies against AT III. The AT III free plasma obtained was found to be devoid of heparin-like activity in the anti-Xa clotting test but it maintained its anticoagulant activity in the APTT assay. When purified AT III was added to this plasma its anti-Xa activity was largely restored. In conclusion, the inhibitory effect of SSHA on coagulation seems to involve at least two mechanisms: a direct one which does not depend on AT III and an indirect one, induced in vivo and mediated by AT III.

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.

A Patient With Remote Heparin-Induced Thrombocytopenia and Antiphospholipid Syndrome Requiring Cardiopulmonary Bypass: Do Current Guidelines Apply?

2018 ◽  
Vol 23 (2) ◽  
pp. 256-260 ◽  
Author(s):  
Warsame Ibrahim ◽  
Hunter Nakia ◽  
Miller Stephen ◽  
Spiess Bruce ◽  
Whitson Bryan ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Unfractionated Heparin ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Artery Bypass ◽  
Inhibitory Effect ◽  
Heparin Induced Thrombocytopenia ◽  
History Of ◽  
Complex Decision Making

Anticoagulation for cardiopulmonary bypass (CPB) is required to prevent acute disseminated intravascular coagulation and clot formation within the bypass circuit. Unfractionated heparin is the standard anticoagulant for CPB due to its many advantages and long history of successful use. However, heparin has the unique drawback of triggering Heparin-PF4 (PF4) antibodies potentially leading to heparin-induced thrombocytopenia (HIT). We have limited data regarding reformation of antibodies if a patient has had a prior (remote) antibody production or full HIT. Patients with antiphospholipid antibodies undergoing CPB with unfractionated heparin have a high complication rate, even in the absence of HIT. Antiphospholipid antibodies have a multifaceted, cumulatively inhibitory effect on the normal anticoagulation armamentarium in vivo. Even more concerning is the possibility that antiphospholipid syndrome and HIT may be synergistic. We report a patient with risk factors for both thromboembolic (remote history of HIT and antiphospholipid syndrome) and hemorrhagic complications who underwent an aortic valve replacement and coronary artery bypass grafting on CPB using bivalirudin. We discuss the complex decision making regarding anticoagulant for CPB, particularly with regard to American College of Chest Physicians guidelines.

The Effects of Heparin and Annexin V on Fibrin Accretion after Injury in the Jugular Veins of Rabbits

1993 ◽  
Vol 69 (03) ◽  
pp. 227-230 ◽  
Author(s):  
J Van Ryn-McKenna ◽  
H Merk ◽  
T H Müller ◽  
M R Buchanan ◽  
W G Eisert
Keyword(s):  
Vessel Wall ◽  
Thrombin Generation ◽  
Antithrombin Iii ◽  
Specific Effect ◽  
Annexin V ◽  
Inhibitory Effect ◽  
Jugular Veins ◽  
Prothrombinase Complex ◽  
Wall Injury

SummaryWe compared the relative abilities of unfractionated heparin and annexin V to prevent fibrin accretion onto injured jugular veins in vivo. Heparin was used to accelerate the inhibition of thrombin by antithrombin III, and annexin V was used to inhibit the assembly of the prothrombinase complex on phospholipid surfaces, thereby blocking thrombin generation. Rabbit jugular veins were isolated in situ, a 2 cm segment was injured by perfusing it with air, and then blood flow was re-established. Five minutes later, each rabbit was injected with heparin (20 U/kg) or annexin V (0.3 mg/kg) and then with 125I-fibrinogen. The amount of 125I-fibrin accumulation onto each injured vessel wall segment was measured 4 h later. Each injured vessel was completely deendothelialized as a result of the air perfusion as demonstrated by electron microscopy. 125I-fibrin accretion onto the injured jugular veins was enhanced 2.4-fold as compared to the uninjured veins in sham-operated animals. Heparin treatment did not reduce fibrin accretion, whereas, annexin V treatment decreased fibrin accretion by 60%, p <0.05. This latter effect was achieved without sustained circulating anticoagulation. Additional experiments confirmed that the inhibitory effect of annexin V on fibrin accretion was associated with a surface specific effect, since more annexin V bound to the injured jugular vein segments as compared to the non-injured jugular veins. We conclude that, i) mild vessel wall injury (selective de-endothelialization) in veins results in a thrombogenic vessel wall; ii) the thrombogenecity of which is not inhibited by prophylactic doses of heparin; but iii) is inhibited by annexin V, which binds to injured vessel wall surface, and inhibits thrombin generation independently of antithrombin 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.

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 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.

Heparin-Affinity of Antithrombin III in a Family With Congenital Antithrombin III Deficiency

1979 ◽  
Author(s):  
G. Sas ◽  
D. Bánhegyi ◽  
I. Petö
Keyword(s):  
Affinity Chromatography ◽  
Antithrombin Iii ◽  
Normal Person ◽  
Agarose Gel ◽  
Functional Methods ◽  
At Iii ◽  
Antithrombin Iii Deficiency ◽  
Heparin Affinity

We found a new thrombophilic family with antithrombin III/ AT-III / deficiency. In the members of this family both immunologic and functional methods revealed similarly decreased levels of AT-III. Gelfiltration displayed identical size of AT-III molecule of patient and normal alike. On the basis of tnese findings we assumed that in this family normal AT-III is produced Dut only in diminished quantity. Experiments on the heparin-affinity of AT-III did not support this assumption. The AT-III of the proposita migrated slower than that of normal person in the heparinized agarose gel. In the course of the heparin-affinity chromatography the AT-III of the proposita could be eluted at lower salt concentrations than normal AT-III.Thus we conclude that even in the case of “true” AT-III deficiency the molecule might have some qualitative deviation from normal.

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