Management of antithrombin III deficiency in pregnancy: a representative case and a literature review

The work is aimed at discussing pregnancy management for the most thrombogenic genetic thrombophilia - antithrombin III (AT-III) deficiency. A detailed analysis of the literature and clinical case of pregnancy management in a patient with AT-III deficiency, pulmonary embolism and habitual history of miscarriage has been performed and presented. Patients with AT-III deficiency are at high risk for developing thrombotic and obstetric complications even despite using therapeutic doses of anticoagulants. Indications for use and modes of administration of AT-III concentrate have not been currently defined clearly. Monitoring therapy with low molecular weight heparin is largely complicated because a test for determining anti-Xa activity is AT-III-dependent. In addition to standard methods for controlling antithrombotic therapy, we used tests characterizing the dynamic blood clot parameters: thromboelastography and thrombin generation test. The peak risk resulting in both thrombotic and hemorrhagic complications in such patients occurs during period of labor and the postpartum period, when a change in the regimen of anticoagulant therapy is required with its temporary withdrawal and additional administration of AT-III concentrate.

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Antithrombin III and Hypercoagulability in Smokers

10.1055/s-0039-1680834 ◽

1977 ◽

Author(s):

R. Losito ◽

D. Nathan ◽

H. Gattiker ◽

B. Longpré

Keyword(s):

Factor Viii ◽

Thrombin Generation ◽

Antithrombin Iii ◽

Intravascular Coagulation ◽

Coagulation Tests ◽

At Iii ◽

History Of ◽

Generation Test

It is known that various coagulation tests such as the thromboplastin generation test (TGT), thrombin generation (TG), levels of factor VIII or antithrombin III have been found to be abnormal in individuals with intravascular coagulation or having an increased tendancy to thrombosis. The aim of this study was to evaluate the role of the TGT, TG, factor VIII and antithrombin III assays in the diagnosis of possible mild intravascular coagulation in patients undergoing cardiac catheterization who had a history of smoking. In addition to these four tests, a routine coagulogram was performed for a total of 13 tests. It appeared that smokers had more abnormal tests (7.3/patient) than the controls (3.3/patient). The greatest association was between TGT and TG (29.6%) and TG and AT-III (25.9%). If by definition, hypercoagulability is present where 3 or more of these 4 mentioned tests were abnormal, then five patients were found to be in this category; all, except one, formed clots. In the patients (50) with a history of smoking, a third were found to have the TGT and the TG abnormal; however, the most striking observation in this group was in the antithrombin III where it was noted to be low in forty-five percent of the patients compared to the controls (patients having catheterization and were non-smokers) whose antithrombin III was found to be decreased in only five percent of the individuals. It is concluded that determination of antithrombin III may be of more importance in assisting the detection of hypercoagulability, especially in the smoking population, than the TGT, TG, or factor VIII.

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Inherited Antithrombin III Deficiency and Cerebral Thrombosis in a Child

PEDIATRICS ◽

10.1542/peds.65.1.125 ◽

1980 ◽

Vol 65 (1) ◽

pp. 125-131

Author(s):

Daniel R. Ambruso ◽

Linda J. Jacobson ◽

William E. Hathaway

Keyword(s):

Antithrombin Iii ◽

Index Case ◽

Cerebral Thrombosis ◽

Recurrent Thrombosis ◽

Normal Pattern ◽

Crossed Immunoelectrophoresis ◽

Warfarin Sodium ◽

At Iii ◽

History Of ◽

Antithrombin Iii Deficiency

Identification of a family affected by antithrombin III-heparin cofactor (AT-III) deficiency was made after diagnosis of the index case, a 15-year-old boy who suffered cerebral thrombosis. The proband had a two-year history of recurrent thrombosis involving the lower extremities. His mother and sister were also affected. Studies showed a decreased biological activity (AT-IIIc) and antigen (AT-IIIag) by the Laurell technique in the proband (AT-IIIc = 0.32, AT-IIIag = 46%), his sister (AT-IIIc = 0.29, AT-IIIag = 47%), and his mother (AT- IIIc = 0.41, AT-IIIag 56%). Crossed immunoelectrophoresis (CIE) of the affected individuals' plasma in agarosecontaining heparin demonstrated a normal pattern of migration. Treatment with warfarin sodium (Coumadin) resulted in an increase in activity in two of three affected family members, and in antigen in all three. Anticoagulant therapy did not affect the pattern of AT-III on CIE. This family represents a quantitative deficiency in antithrombin III. A review of the reported cases of antithrombin III deficiency indicates that individuals with this disorder may have thromboembolic disease in childhood.

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The Prevalence of Hereditary Antithrombin-III Deficiency in Patients with a History of Venous Thromboembolism

Thrombosis and Haemostasis ◽

10.1055/s-0038-1660123 ◽

1985 ◽

Vol 54 (04) ◽

pp. 744-745 ◽

Cited By ~ 29

Author(s):

R Vikydal ◽

C Korninger ◽

P A Kyrle ◽

H Niessner ◽

I Pabinger ◽

...

Keyword(s):

Venous Thrombosis ◽

Antithrombin Iii ◽

Positive Family History ◽

Normal Range ◽

The Family ◽

History Of ◽

Antithrombin Iii Deficiency ◽

Recurrent Venous Thrombosis ◽

Antithrombin Iii Activity ◽

Slight Deficiency

SummaryAntithrombin-III activity was determined in 752 patients with a history of venous thrombosis and/or pulmonary embolism. 54 patients (7.18%) had an antithrombin-III activity below the normal range. Among these were 13 patients (1.73%) with proven hereditary deficiency. 14 patients were judged to have probable hereditary antithrombin-III deficiency, because they had a positive family history, but antithrombin-III deficiency could not be verified in other members of the family. In the 27 remaining patients (most of them with only slight deficiency) hereditary antithrombin-III deficiency was unlikely. The prevalence of hereditary antithrombin-III deficiency was higher in patients with recurrent venous thrombosis.

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

10.1055/s-0038-1665841 ◽

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.

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NEUTRALIZING EFFECT OF PLATELET FACTOR 4 OR HISTIGINE-RICH GLYCOPROTEIN AGAINST LOW MOLECULAR WEIGHT HEPARIN AND UNFRACTIONATED HEPARIN

10.1055/s-0038-1643499 ◽

1987 ◽

Author(s):

K Takahashi ◽

M Niwa ◽

N Sakuragawa

Keyword(s):

Molecular Weight ◽

Low Molecular Weight Heparin ◽

Antithrombin Iii ◽

Platelet Factor 4 ◽

Low Molecular Weight ◽

Bleeding Tendency ◽

Human Origin ◽

Platelet Factor ◽

At Iii ◽

Antifactor Xa

Purpose: Low molecular weight(LMW) heparin shows stronger antifactor Xa(F-Xa) and weaker anti-thrombin(TH) activities compared with unfractionated(UF) heparin, and shows less bleeding tendency in the cases of clinical use. Platelet factor 4(Pf-4) and histidine-rich glycoprotein(HRG) neutralize heparin. We investigated on the heparin neutralizing effects of them to both kinds of heparinMaterials and methods: LMW heparin(Kabi and Pharmuka) and UF heparin(Novo) were used. Antithrombin III(AT-III), HRG(human origin ) and pf-4( bovine origin ) were purified by our methodsTH(Green-Cross) and F-Xa(Sigma) were used. Reaction mixtures for anti-TH or anti-F-Xa were as follows: 1 vol of AT-III( 0.1 U/ml)+ 1 vol of heparin( 10 ug/ml)+l vol of pf-4 or HRG(varied)→incubated for 5 min→+l vol of TH(5 U/ml) or F-Xa( 7 nKat/ml)→incubated for 5 min→ + S-2238 or S-2222→ recorded at 405 nm.Results: (1) Pf-4 showed the equivalent anti-TH effect on both kinds of heparin, and 3 ug of pf-4 neutralized 1 ug of heparinOn F-Xa neutralizing effect, 13 ug of pf-4 neutralized 1 ug of UF heparin, but could not neutralize LMW heparin. (2) HRG showed the same results on anti-TH effect of both kinds of heparin, but could not neutralize the anti-F-Xa effect of LMW heparin on the same amount of HRG which neutralized that of UF heparin. Conclusion: Anti-F-Xa effect of. LMW heparin could not be easily neutralized by pf-4 or HRG compared with that of UF heparin.

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

10.1055/s-0039-1684713 ◽

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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Antithrombin III Deficiency in a Japanese Family

10.1055/s-0039-1684570 ◽

1979 ◽

Author(s):

M. Nakagawa ◽

T. Kawamura ◽

H. Tsuji ◽

Y. Okajima ◽

S. Urano ◽

...

Keyword(s):

Antithrombin Iii ◽

Sinus Thrombosis ◽

Elevated Serum ◽

Peptic Ulcers ◽

Autosomal Dominant Disorder ◽

Japanese Family ◽

Vein Thrombosis ◽

Chromogenic Assay ◽

History Of ◽

Antithrombin Iii Deficiency

Antithrombin III has been reported to be decreased in the cases of several thrombotic disorders and the decreased Antithrombin III is known to induce the hypercoagulable state. This study was started from the 28 year-old male patient who developed the superior sagital sinus thrombosis after appendectomy and it was followed by deep vein thrombosis of extremities. Antithrombin III level was 19 mg/dl and activity was 68% by the progressive antithrombin assay and other laboratory examinations were within normal range excepts for the elevated serum lipids. Antithrombin III was assayed for his family members in three consecutive generations by single radial immunodifusion method, coagulation assay, and chromogenic assay. Four out of eight members were confirmed to have low Antithrombin III level and activity ranging from 59%-68% of normal values, although the two of this four members had no history of thrombosis. Mother of this propositus is deceased, but it was suspected of having the defect of Antithrombin III. History of peptic ulcers were found in all members of this family. The inheritance pattern of Antithrombin III deficiency was characteristic of an autosomal dominant disorder.

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Antithrombin III Doses Rounded to Available Vial Sizes in Critically Ill Pediatric Patients

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-22.1.15 ◽

2017 ◽

Vol 22 (1) ◽

pp. 15-21

Author(s):

Winifred M. Stockton ◽

Eimeira Padilla-Tolentino ◽

Carolyn E. Ragsdale

Keyword(s):

Critically Ill ◽

Low Molecular Weight Heparin ◽

Pediatric Patients ◽

Antithrombin Iii ◽

Cost Savings ◽

Pediatric Intensive Care ◽

Acute Illness ◽

Low Molecular Weight ◽

Dose Administration ◽

At Iii

OBJECTIVES Children have decreased levels of antithrombin III (AT III) compared to adults. These levels may be further decreased during acute illness. Administration of exogenous AT III can increase anticoagulant efficacy. The objective of this study was to evaluate AT III doses rounded to available vial sizes compared to partial vial doses in critically ill pediatric patients, including patients receiving extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). METHOD This retrospective review evaluated pediatric patients 0–18 years of age admitted to a 24-bed medical/surgical pediatric intensive care unit between June 1, 2012, and December 31, 2014, who received plasma-derived AT III. Patients received unfractionated heparin, low-molecular-weight heparin, or no anticoagulation. This review included patients who received ECMO and CRRT. RESULTS Eighty doses of AT III were administered to 24 patients (38 full vial size doses and 42 partial vial size doses). The AT III level following dose administration was ≥80% for 26 full vial doses (70%) and 16 partial vial doses (41%; p = 0.010). For patients who received multiple doses of AT III, the median time between doses was 45 hours following full vial doses, and 23 hours following partial vial doses (p = 0.011). Seven patients (29%) had documentation of new or increased bleeding. The median waste prevented from rounding doses to full vial sizes was 363 units. CONCLUSIONS After receiving AT III doses rounded to full vial sizes, patients were more likely to have a therapeutic AT III level and a longer interval between administrations. Rounding AT III doses to full vial sizes reduces waste and can result in cost savings.

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Inherited Deficiency Of Antithrombin III In Two Italian Families. Different Behaviour After Long-Term Anticoagulant Treatment

10.1055/s-0038-1653103 ◽

1981 ◽

Author(s):

C Manotti ◽

M Pini ◽

R Poti ◽

R Quintavalia

Keyword(s):

Antithrombin Iii ◽

Oral Anticoagulants ◽

Immunological Methods ◽

Anticoagulant Treatment ◽

Normal Pattern ◽

Vein Thrombosis ◽

Congenital Deficiency ◽

At Iii ◽

History Of

An inherited deficiency of antithrombin III (AT III), measured with four different, functional and immunological, methods, was found in 8 out of 11 examined members and in 3 out of 11 examined members of two Italian families (D.M. and A. families). Biological activity, measured with Abildgard’s clotting assay and with an amidolytic method, ranged between 17 and 75%. Cross immunoelectrophoresis, with or without heparin, performed in the two propositi and in 1; other relatives, showed a normal pattern of migration.A different behaviour of AT III after anticoagulation with acenocoumarin was seen in two long-term treated subjects. The proposita of the D.M. family, who had a history of recurrent thrombotic accidents, did not show any increase of AT III levels, measured in the first two weeks and after 6 and 12 months of therapy. A significant (about 50%) increase both with the functional and immunological methods was on the contrary observed in the propositus of A. family, who had undergone surgery because of mesenteric vein thrombosis. Until now both patients have been free of thrombotic recurrences.Our findings confirm previous reports of variable effects of oral anticoagulants on AT III levels in subjects with congenital deficiency.

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Inherited Antithrombin III Deficiency and Thrombo-Embolism

10.1055/s-0039-1689223 ◽

1975 ◽

Cited By ~ 1

Author(s):

O. Egeberg

Keyword(s):

Pulmonary Embolism ◽

Platelet Aggregation ◽

Venous Thrombosis ◽

Platelet Function ◽

Autosomal Dominant ◽

Antithrombin Iii ◽

Dominant Inheritance ◽

At Iii ◽

Coagulation Assay ◽

Antithrombin Iii Deficiency

Thrombophilia due to inherited deficiency of blood antithrombin III (AT III, heparin cofactor, anticonvertin) in a Norwegian family was published 1965, Thromb. D. h. 13, 516 & 14, 473. Only a few families with this defect have since then been described in different countries. In another Norwegian family, two sisters, age 42 and 30, and a brother, 35, have had episodes of venous thrombosis and pulmonary embolism from the age of 24–29. Their father suffered from thrombosis and died at 67. The two sisters have blood AT III level about half of normal average, measured with a two-stage coagulation assay. Data from both families are compatible with an autosomal dominant inheritance of the plasma protein deficiency. Venous thrombosis in the families is remarkably often complicated with embolizations; this might also relate to an inadequate platelet function. Platelet aggregation time of PRP with added thrombin or ADP was found prolonged. In coumarin treatment of the patients, AT III assaying gave increased levels.

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