PROTHROMBIN AND ANTITHROMBIN III IN PATIENTS WITH HEPATOCELLULAR CARCINOMA

1987 ◽  
Author(s):  
G Leone ◽  
V De Stefano ◽  
R Ferrelli ◽  
C Barone ◽  
C Garufi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antithrombin Iii ◽  
Previous History ◽  
Extensive Study ◽  
Normal Range ◽  
Normal Pattern ◽  
At Iii ◽  
History Of ◽  
Large Peak ◽  
Plasma Absorption

Prothrombin (F.II) and antithrombin III (AT III) levels were measured in 11 patients (mean age 61 years) with hepatocellular carcinoma; F.II antigen (Ag) mean levels (Laurell) were 1.39±0.53 U/ml and F.II activity (Ac) (clotting method) 0.9±0.21 U/ml; AT III Ag mean levels (radial immunodiffusion) were 1.18±0.32 U/ml and AT III heparin cofactor (HC) (amidolytic method) 1.15±0.31 U /ml. In 5 patients F.II Ag was higher than 1.2 U/ml; no patient had F.II Ag lower than 0.8 U/ml (normal range 0.7-1.2 U/ml). F.II Ac was in the normal range in all patients. In 4 patients both AT III Ag and HC were higher than 1.2 U/ml; no patient had AT III Ag and HC lower than 0.8 U/ml (normal range 0.75-1.2 U/ml). Seven patients had a long history of liver cirrhosis and 2 of them sho wed AT III Ag and HC of 1.8 U/ml; one of these two patients had F.II Ag and Ac around 1.00 U/ml, whereas the other had F.II Ag 2.4 U/ml and F.II Ac 1.2 U/ml. In these two patients a prelimina ry more extensive study was performed. In both subjects AT III plasma crossed immunoelectrophoresis was normal in the presence and absence of heparin and AT III crossed immunoelectrofocusing (CIEF) showed a normal pattern of 6 peaks (pH 5.2-4.6) and two additional small peaks at pH 4.5 and 5.4. In the patient with in creased F.II Ag the CIEF of plasma prothrombin showed a large peak with asymmetric branches at pH 5.2-4.9, as in the control, and a large additional peak at pH 5.9; after plasma absorption with Al(OH), the F.II CIEF pattern showed only the abnormal peek. We conclude that in patients with hepatocellular carcinoma F.II and AT III are normal, independently of previous history of cirrhosis; moreover, in agreement with previous studies (N.Engl.J. Med. 310,1427,1984), an abnormal prothrombin, which we demonstra ted characterizable by the CIEF, can be synthesized.

A NEW ASYMPTOMATIC TYPE III VARIANT OF ANTITHROMBIN III WITH DECREASE HEPARIN COFACTOR ACTIVITY : AT III AMIENS

1987 ◽  
Author(s):  
B ROUSSEL ◽  
J DIEVAL ◽  
S GROSS ◽  
J F CLAISSE ◽  
J DELOBEL
Keyword(s):  
Factor Xa ◽  
Normal Range ◽  
Normal Pattern ◽  
Type Iii ◽  
Crossed Immunoelectrophoresis ◽  
At Iii ◽  
History Of ◽  
Routine Laboratory Examination ◽  
Slow Moving ◽  
Cofactor Activity

A qualitative abnormality of AT III suggested by the discrepancy between a normal level of AT III antigen (0,33 g/1) and a decreased heparin cofactor activity (60 % of normal) was discovered in a 37 years old woman during a routine laboratory examination for oral contraceptive. The propositus was asymptomatic as she did not developpe any thrombo-embolic disease during three previous pregnancies. There was no familial history of thrombo-embolism. The AT III level measured by radial immuno-diffusion was within the normal range. The progressive anti factor lia and anti factor Xa activities (chromogenic substrates CBS 3 447 and CBS 3 139) were normal (92 % and 100 %). Plasma and serum crossed immunoelectrophoresis (CIE) showed a normal pattern. In the presence of heparin, anti factor Xa and anti factor Xa activities were decreased (60 % and 45 %); Plasma and serum crossed immunoelectrophoresis showed an abnormal slow moving peak exhibiting the inhability of the molecule to bind completely to heparin. CIE with various other glycosaminoglycans are on experiments.Familial study revealed that the daughter of the propositus was carrying the same molecular abnormality.We conclude that AT III Amiens is an hereditary type III variant.

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

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.

Inherited Antithrombin III Deficiency and Cerebral Thrombosis in a Child

PEDIATRICS ◽  
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.

scholarly journals Lenvatinib-Induced Destructive Thyroiditis in a Patient With Hepatocellular Carcinoma

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A939-A940
Author(s):  
Anjani Pandya ◽  
Jawairia Shakil
Keyword(s):  
Hepatocellular Carcinoma ◽  
Thyroid Gland ◽  
Thyroid Function ◽  
Kinase Inhibitor ◽  
Previous History ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Peroxidase ◽  
Thyroid Function Tests ◽  
Normal Range ◽  
History Of

Abstract Lenvatinib is an antineoplastic oral agent that acts as a multi-kinase inhibitor against vascular endothelial growth factor (VEGF). This drug is commonly known for its use against radioiodine-refractory differentiated thyroid cancer, but it is also approved for unresectable hepatocellular carcinoma (HCC). Side effects such as fatigue, hypertension, palmar-plantar erythrodysesthesia, diarrhea, decreased appetite, and hypothyroidism are frequently reported adverse effects. However, the incidence of hyperthyroidism is a less known phenomenon. This case describes a patient with HCC on lenvatinib therapy who develops destructive thyroiditis. A 69-year-old man with hepatitis c cirrhosis complicated by progressive hepatocellular carcinoma (Child-Pugh class A6) presented with generalized weakness, unintentional weight loss, heat intolerance, palpitations, and tremors. He had been started on chemotherapy with lenvatinib 12 mg/day four weeks prior to presentation. Endocrinology was consulted due to abnormal thyroid function tests (TFTs). He had no previous history of thyroid function abnormalities or family history of thyroid disease. Laboratory tests revealed a hyperthyroid state [total thyroxine (T4), 14.3 µg/dL (normal range 4.5-11.7); free thyroxine (FT4), 1.9 ng/dL (normal range 0.9-1.7); thyroid-stimulating hormone (TSH), 0.07 µIU/mL (normal range 0.27-4.20), and negativity for antibodies [anti-thyroid peroxidase antibody (TPO Ab), 0.8 IU/mL (normal range 0.0-9.0); thyroglobulin antibody (Tg Ab), < 0.9 IU/mL (normal range 0.0-4.0); thyroid stimulating immunoglobulin (TSI), 90% (normal range < 122)]. Ultrasonography revealed a mildly prominent thyroid gland, a homogenous echo texture, and no suspicious thyroid nodules. In addition, a 99m-technetium (99mTc) scintigraphy demonstrated reduced radioactive uptake that was consistent with thyroiditis. Therefore, this patient was diagnosed with lenvatinib-induced destructive thyroiditis. Palpitations improved with a beta-blocker and the patient was resumed on a lower dose of lenvatinib, 8 mg/day, one week later. About six weeks after the initial dose of lenvatinib, his TFT results normalized. Lenvatinib disrupts cell proliferation which can affect many organs, including the thyroid gland. Although several theories have been proposed, the exact underlying mechanism by which this occurs remains unknown. It is important to note that in addition to hypothyroidism, lenvatinib may also cause hyperthyroidism in the form of a transient destructive thyroiditis. This emphasizes the need to routinely check TFTs prior to the initiation of lenvatinib and throughout the course of therapy.

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

1985 ◽  
Vol 54 (04) ◽  
pp. 744-745 ◽  
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.

Biological Characteristics Op Antithrombin III In An Antithrombin III Deficient Family

1981 ◽  
Author(s):  
S Kondo ◽  
T Matsuo ◽  
Y Ohoki ◽  
O Matsuo
Keyword(s):  
Antithrombin Iii ◽  
Recurrent Thrombosis ◽  
Normal Range ◽  
Japanese Family ◽  
Neutralization Activity ◽  
Normal Value ◽  
Antithrombin Activity ◽  
At Iii ◽  
Molecular Abnormality ◽  
Antifactor Xa

In the familial AT III deficiency of a Japanese family, the propositus (a-39-yr old female) and her mother had episodes of recurrent thrombosis and their AT III levels as measured immunologically and biologically were below the normal value. In the plasma of her brother, the AT III concentration as measured immunologically was half of the normal value, but his biological antithrombin activity was within the normal range. The progressive antithrombin activity and antifactor Xa activity of plasma samples in this familial AT III deficiency were within the normal range. Measurements of the rate of thrombin neutralization activity revealed that the brother’s plasma was in the normal range, but the plasma of the propositus and of her mother showed rates of thrombin neutralization activity which were somewhat below the normal value. The rate of thrombin neutralization activity per mg protein of AT III was highest in the plasma of the brother, and became slower in the mother, propositus, and pooled normal plasma in that order. In the plasma of this familial AT III deficiency, the rate of Xa neutralization activity was much slower than the normal value. It is postulated that since the antithrombin of the brother of the propositus was found to react as normal in the neutralization of thrombin, he does not have episodes of thrombosis. Such characteristic hyperfunction of antithrombin in the plasma of the brother may be due to some molecular abnormality of AT III within this hereditary deficient family.

AT III Barcelona: A Familial Quantitative-Qualitative AT III Deficiency

1988 ◽  
Vol 59 (01) ◽  
pp. 013-017 ◽  
Author(s):  
E Grau ◽  
J Fontcuberta ◽  
J Félez ◽  
I de Diego ◽  
R Soto ◽  
...  
Keyword(s):  
Antithrombin Iii ◽  
Normal Range ◽  
Affinity Adsorption ◽  
Crossed Immunoelectrophoresis ◽  
At Iii ◽  
Spanish Family ◽  
Slow Moving ◽  
Cofactor Activity ◽  
Ph Range ◽  
Thrombotic Tendency

SummaryA quantitative and qualitative deficiency of antithrombin III (AT III) was found in four members of a Spanish family with thrombotic tendency. In all affected members, levels of AT III antigen and activity (heparin cofactor activity) were reduced to 50% of the normal range. When crossed immunoelectrophoresis (CIE) was performed in the presence of heparin, an abnormal slow-moving peak was found. Crossed immunoelectrofocusing (CIEF) from normal and affected individuals showed that normal AT III migrated between pH 4.9–5.3 while the AT III under study was asymetrically distributed between two pH ranges: 4.9–5.3 and 4.6–4.8. Affinity adsorption of affected members’ plasma to heparin-sepharose beads revealed one population of AT III in the supernatant corresponding to the abnormal AT III, devoid of heparin cofactor activity and showing a peak between pH range: 4.6–4.8 in CIEF.Our data supports the view that a quantitative-qualitative deficiency was present in the heterozygous state in all the affected family members. Both normal and abnormal ATIII were present in plasma of the affected individuals. This abnormal ATIII was characterized by a lack of affinity for heparin. This familial ATIII deficiency was named ATIII Barcelona.

scholarly journals Antithrombin III and Hypercoagulability in Smokers

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.

Homozygous Variant of Antithrombin III : AT III Fontainebleau

1986 ◽  
Vol 56 (01) ◽  
pp. 018-022 ◽  
Author(s):  
C Boyer ◽  
M Wolf ◽  
J Vedrenne ◽  
D Meyer ◽  
M J Larrieu
Keyword(s):  
Antithrombin Iii ◽  
Oral Anticoagulant Therapy ◽  
Low Molecular Weight ◽  
Normal Amount ◽  
Homozygous State ◽  
Normal Range ◽  
At Iii ◽  
Cofactor Activity ◽  
Intracardiac Thrombosis ◽  
Tunisian Family

SummaryA qualitative defect of antithrombin III (AT III) was demonstrated in four members of a large Tunisian family by the discrepancy between a normal amount of antigen and decreased or absent heparin cofactor activity. The propositus, a 3-year-old girl, died from massive intracardiac thrombosis despite oral anticoagulant therapy. Heparin cofactor activity measured in the presence of thrombin or F. Xa was undetectable in her plasma. Anti-F. Xa activity was also absent when using low molecular weight heparin or a synthetic pentasaccharide, representing the binding site to AT III. The lack of affinity of the propositus AT III for heparin was demonstrated by two-dimensional immunoelectrophoresis and chromatography on heparin-Sepha-rose. The parents, first cousins, and the sister of the propositus also demonstrated a qualitative abnormality of AT III, with levels of heparin cofactor activity close to 50% of the normal range. Our data support the view that the abnormal protein was present at the heterozygous state in the parents and sister and at the homozygous state in the propositus. None of the affected family members had thrombotic episodes, except for the propositus. The name of AT III Fontainebleau is proposed for this variant.

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