Antithrombin-III-Mangel und Thrombophilie

1985 ◽  
Vol 05 (04) ◽  
pp. 127-133
Author(s):  
E. Thaler
Keyword(s):  
Autosomal Dominant ◽  
Antithrombin Iii ◽  
Maligne Tumoren ◽  
Sich Eine ◽  
At Iii ◽  
Chirurgische Eingriffe

IV. Zusammenfassende BetrachtungenIm ersten Teil der Übersichtsarbeit wurden vier pathogenetisch unterschiedliche Formen eines vergleichbar schweren AT-III-Mangels vorgestellt.Am besten läßt sich anhand des angeborenen, autosomal dominant vererbten AT-III-Mangels die Beziehung zwischen niedrigen Plasma-ATIII-Spiegeln und Thromboserisiko ableiten, da es sich hier um eine isolierte Störung handelt. Das Hämostasegleichgewicht ist hier einseitig durch eine geringere Gerinnungshemmung gestört. Als Ausdruck dieses Ungleichgewichts resultieren fast ausschließlich schwere venöse thromboembolische Ereignisse, jedoch gelegentlich erst nach jahrzehntelangerLatenz. Eine weitere wichtige Erkenntnis ist, wenn AT III nicht substituiert wird, die Unwirksamkeit einer Behandlung mit Heparin bei thromboembolischen Ereignissen, jedoch eine volle prophylaktische Wirksamkeit peroraler Antikoagulantien vom Kumarintyp, offenbar durch eine Wiederherstellung des hämostatischen Gleichgewichts auf niedrigerem Niveau.Ein hämostatisches Gleichgewicht auf niedrigerem Niveau scheint auch bei der fortgeschrittenen Leberzirrhose vorzuliegen, da trotz schwerem ATIII-Mangel das Thromboserisiko nicht erhöht ist. Dieses Gleichgewicht ist aber leichter störbar, auf relativ geringe gerinnungsfördernde Stimuli reagieren diese Patienten gehäuft mit einer VK.Am Beispiel des schweren nephrotischen Syndroms, bei welchem das Hämostasegleichgewicht zuungunsten des AT III und zugunsten gerinnungsfördernder Faktoren verändert ist, läßt sich eine im Vergleich zum angeborenen AT-III-Mangel wesentlich höhere Thromboseneigung nachweisen.Bei der Septikämie mit vergleichbar schwerem AT-III-Mangel ist über das Thromboserisiko zu wenig bekannt. Nach bisherigen Erkenntnissen herrscht hier die klinisch und therapeutisch nicht weniger relevante DIG mit ihren sehr komplexen Hämostaseveränderungen vor.Im folgenden Teil der Arbeit wurde auf einige Zustände mit evidenter Thromboseneigung eingegangen, bei denen nicht sicher eine Beziehung zu einem entsprechend schweren AT-III-Mangel gefunden werden konnte, wie die Einnahme östrogenhaltiger Kontrazeptiva, größere chirurgische Eingriffe und maligne Tumoren. Interessanterweise ist bei diesen Zuständen eine Prophylaxe oder Therapie mit Heparin zumeist wirksam.

Inherited Antithrombin III Deficiency and Thrombo-Embolism

1975 ◽  
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.

Antithrombin III “Northwick Park”: A Variant Antithrombin with Normal Affinity for Heparin but Reduced Heparin Cofactor Activity

1985 ◽  
Vol 53 (03) ◽  
pp. 314-319 ◽  
Author(s):  
D J Howarth ◽  
Diana Samson ◽  
Yvonne Stirling ◽  
M J Seghatchian
Keyword(s):  
Venous Thrombosis ◽  
Fast Moving ◽  
Autosomal Dominant ◽  
Antithrombin Iii ◽  
Two Dimensional ◽  
Antithrombin Activity ◽  
The Family ◽  
At Iii ◽  
History Of ◽  
Cofactor Activity

SummaryFurther studies have been carried out in a previously reported family with congenital antithrombin III (AT III) deficiency due to an abnormal variant of AT III (AT III Northwick Park). The variant has been identified in five members of the family, three of whom had a history of venous thrombosis. Inheritance followed an autosomal dominant pattern. The affected family members have reduced levels of antithrombin heparin cofactor (41–67%) and progressive antithrombin activity (44–62%) but normal levels of immunoreactive AT III (91–162%). Two dimensional immunoelectrophoresis (2 DIE) of AT III in the absence of heparin revealed an abnormal fast-moving peak in addition to the normal peak but 2 DIE in the presence of heparin appeared normal. Further studies confirmed that the abnormal AT III binds completely to heparin but has no heparin cofactor or progressive antithrombin activity. These results would be consistent with a mutation affecting the binding site for thrombin.

Homozygous Variant of Antithrombin III that Lacks Affinity for Heparin, AT III Kumamoto

1989 ◽  
Vol 61 (01) ◽  
pp. 020-024 ◽  
Author(s):  
Kenji Okajima ◽  
Hidetsugu Ueyama ◽  
Youichiro Hashimoto ◽  
Yasuto Sasaki ◽  
Keiko Matsumoto ◽  
...  
Keyword(s):  
Affinity Chromatography ◽  
Autosomal Dominant ◽  
Antithrombin Iii ◽  
Factor Xa ◽  
Heparin Cofactor Ii ◽  
At Iii ◽  
Antifactor Xa ◽  
Cofactor Activity ◽  
Inhibition Of Thrombin ◽  
Plasma Heparin

SummaryAbnormal antithrombin III (AT III) was found in the plasma of a 31-year-old female who suffered from recurrent thrombotic episodes. Heparin cofactor activity was 28% of normal and undetectable when measured by inhibition of thrombin and factor Xa (F. Xa), while both progressive antithrombin and antifactor Xa activities were normal. The concentration of plasma AT III antigen was 37 mg/dl. Analysis by crossed-immunoelec- trophoresis (CIE) in the presence of heparin and affinity chromatography on heparin-Sepharose revealed that the propositus’ AT III did not bind to heparin. When heparin cofactor II (HC II) was removed from propositus’ plasma, heparin cofactor activity of AT III was not detected. Thus, HC II seemed to account for the plasma heparin cofactor activity found in the presence of thrombin. The patient’s parents and three of her brothers demonstrated qualitative abnormality of AT III; heparin cofactor activity was 30-50% of normal levels in the presence of both thrombin and F. Xa. These findings indicate that the propositus’ AT III lacks affinity for heparin and the mode of its inheritance seems to be autosomal dominant and, hence, the propositus would be a homozygote. For this variant, the name of AT III Kumamoto is proposed.

Molekularbiologische Grundlagen und Diagnostik der hereditären Defekte von Antithrombin III, Protein C und Protein S

2002 ◽  
Vol 22 (02) ◽  
pp. 57-66
Author(s):  
I. Witt
Keyword(s):  
Protein C ◽  
Antithrombin Iii ◽  
Protein S ◽  
Klinische Relevanz ◽  
At Iii

ZusammenfassungDie enormen Fortschritte in der Molekularbiologie in den letzten Jahren ermöglichten sowohl die Aufklärung der Nukleotidsequenzen der Gene für Antithrombin III (AT III), Protein C (PROC) und Protein S (PROS) als auch die Identifizierung zahlreicher Mutationen bei hereditären Defekten dieser wichtigen Inhibitoren des plasmatischen Gerinnungssystems. Da die Gene für AT III (13,8 kb) und PROC (11,2 kb) nicht groß und relativ leicht zu analysieren sind, gibt es bereits umfangreiche »databases« der Mutationen (50, 73). Für AT III sind 79 und für PROC 160 unterschiedliche Mutationen beschrieben.Sowohl beim AT-III-Mangel als auch beim Protein-C-Mangel hat die Mutationsaufklärung neue Erkenntnisse über die Struktur-Funktions-Beziehung der Proteine gebracht. Beim Protein-C-Mangel steht die klinische Relevanz der DNA-Analyse im Vordergrund, da die Diagnostik des Protein-C-Mangels auf der Proteinebene nicht immer zuverlässig möglich ist.Das Protein-S-Gen ist für die Analytik schwer zugänglich, da es groß ist (80 kb) und außerdem ein Pseudogen existiert. Es sind schon zahlreiche Mutationen bei Patienten mit Protein-S-Mangel identifiziert worden. Eine Database ist bisher nicht publiziert. Die klinische Notwendigkeit zur Mutationsaufklärung besteht ebenso wie beim Protein-C-Mangel. Es ist zu erwarten, dass zukünftig die Identifizierung von Mutationen auch beim Protein-S-Mangel beschleunigt vorangeht.

Sonographische Untersuchung von Mammatumoren der Hündin

2005 ◽  
Vol 33 (01) ◽  
pp. 23-26
Author(s):  
C. Marquardt ◽  
E. Burkhardt ◽  
K. Failing ◽  
H. Bostedt ◽  
A. Wehrend
Keyword(s):  
Maligne Tumoren ◽  
Sich Eine ◽  
Klinische Relevanz ◽  
Who Klassifikation

Zusammenfassung Gegenstand: In der Studie sollte überprüft werden, ob anhand der sonographischen Untersuchung von kaninen Mammatumoren eine präoperative Zuordnung zu den drei Dignitätsklassen benigne Tumoren, Tumoren mit niedrigem und höherem Malignitätsgrad möglich ist. Material und Methode: 90 Tumoren wurden präoperativ sonographisch untersucht und einer dieser Dignitätsklassen zugeordnet. Die sonographische Prädiktion wurde mit der nach den Vorgaben der WHO-Klassifikation durchgeführten histopathologischen Charakterisierung verglichen, wobei allerdings die Gruppe der malignen Mischtumoren beibehalten wurde. Ergebnisse: Bei 77,4% der benignen und 91,9% der Tumoren von höherem Malignitätsgrad ergab sich eine korrekte präoperative Einschätzung. Diese gelang nur bei 45,5% der Neoplasien mit niedrigem Malignitätsgrad. Insbesondere bei Tumoren mit einem Durchmesser von unter 2 cm war die präoperative Dignitätseinschätzung häufig falsch. Schlussfolgerung und klinische Relevanz: Die Sonographie eignet sich, um präoperativ die Dignität kaniner Mammatumoren einzuschätzen. Grenzen findet dieses Verfahren, wenn es sich um kleine Tumoren oder Neoplasien mit niedrigem Malignitätsgrad handelt. Insbesondere kleine maligne Tumoren zeigen sonographisch häufiger Charakteristika einer benignen Neoplasie.

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.

Antithrombin III and Heparin Cofactor II in Patients with Chronic Renal Failure Undergoing Regular Hemodialysis

1987 ◽  
Vol 57 (03) ◽  
pp. 263-268 ◽  
Author(s):  
P Toulon ◽  
C Jacquot ◽  
L Capron ◽  
M -O Frydman ◽  
D Vignon ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Plasma Proteins ◽  
Antithrombin Iii ◽  
Vascular Wall ◽  
Relative Increase ◽  
Heparin Cofactor Ii ◽  
Normal Ranges ◽  
At Iii ◽  
Regular Hemodialysis

SummaryHeparin enhances the inhibition rate of thrombin by both antithrombin III (AT III) and heparin cofactor II (HC II). We studied the activity of these two plasma proteins in patients with chronic renal failure (CRF) undergoing regular hemodialysis as their heparin requirements varied widely. In 77 normal blood donors, normal ranges (mean ± 2 SD) were 82-122% for AT III and 65-145% for HC II. When compared with these controls 82 dialyzed CRF patients had a subnormal AT III activity and a significantly (p <0.001) lower HC II activity. To evaluate the effect of hemodialysis we compared AT III, HC II and total proteins in plasma before and after dialysis in. 24 patients (12 with normal and 12 with low basal HC II activity). AT III and HC II activities significantly (p <0.001) increased in absolute value. When related to total plasma proteins, in order to suppress the influence of hemoconcentration induced by dialysis, AT III decreased significantly (p <0.01) whereas HC II increased slightly but significantly (p <0.01) in the 12 patients with low initial HC II activity. The decrease of AT III induced by heparin administrated during dialysis is likely to account for this relative decrease of AT III activity. A modification of the distribution of both HC II and heparin between the vascular wall and the circulating blood is evoked to explain the relative increase in HC II activity and the need for higher heparin dosage in patients with low HC II levels.

Severe Antithrombin III Deficiency in an Infant Associated with Multiple Arterial and Venous Thromboses

1976 ◽  
Vol 36 (03) ◽  
pp. 495-502 ◽  
Author(s):  
Geoffrey Mendelsohn ◽  
Edward D. Gomperts ◽  
Dennis Gurwitz
Keyword(s):  
Antithrombin Iii ◽  
Adult Life ◽  
Rare Condition ◽  
Male Infant ◽  
Liver Cells ◽  
Liver Pathology ◽  
Fixed Tissue ◽  
Formalin Fixed Tissue ◽  
First Case ◽  
At Iii

SummaryInherited antithrombin III (AT-II, heparin cofactor) deficiency is a rare condition, presenting with thrombotic disease in adult life. This paper reports an 8 months old South African Black male infant with multiple large vessel venous and arterial thromboses, and E. coli septicaemia. This was associated with an extremely low plasma AT-II level. Micronodular cirrhosis and intracytoplasmic hyaline globules in the liver cells were present. These globules were eosinophilic, and PAS-positive after diastase. They measured approximately 5 μ to 30 μ in diameter, occurred singly in the liver cells and were located mainly in the periportal areas. The histological findings in the liver are similar to those observed in α1-antitrypsin (AAT) deficiency in which the intracytoplasmic globules represent accumulation of altered AAT. Immunochemical studies carried out on formalin fixed tissue failed to detect cross reaction material with anti-α1 antitrypsin or anti-AT III antiserum. This is the first case report of AT-III deficiency presenting in infancy. It is also the first case associated with distinctive liver pathology.The available data presented are insufficient to distinguish between an inborn defect and acquired causes of the severely depressed AT-III plasma level and the distinctive liver pathology.

Predictive Value of Decreasing Antithrombin III in Deep-Vein Thrombosis

1980 ◽  
Vol 44 (03) ◽  
pp. 135-137 ◽  
Author(s):  
Thorkild Lund Andreasen
Keyword(s):  
Deep Vein Thrombosis ◽  
Predictive Value ◽  
Coronary Care Unit ◽  
Antithrombin Iii ◽  
Predictive Values ◽  
Vein Thrombosis ◽  
At Iii ◽  
Coronary Care ◽  
Time Of Admission ◽  
Deep Vein

SummaryAntithrombin III (At-III) was measured at the time of admission and two days later in 131 patients laid up in a coronary care unit. The patients were examined for deep-vein thrombosis (DVT) clinically and by means of 125I-fibrinogen scanning. 19 patients developed DVT. In 11 subjects with and 25 without DVT At-III decreased more than 10%. And in 7 with and 17 without DVT At-III decreased more than 15%. One person with DVT had subnormal At-III. By using decrease of At-III or subnormal initial At-III to predict DVT the following predictive value (PV) were found. Decrease ≤ 10%, PV pos.= 0.32 and PV neg. = 0.93. Decrease ≤ 15%, PV pos. = 0.32 and PV neg. = 0.90. The positive predictive values obtained were too low to let decreasing At-III give occasion for prophylactic anticoagulant treatment.

Reactivity of a Hereditary Abnormal Antithrombin III Fraction in the Inhibition of Thrombin and Factor Xa

1980 ◽  
Vol 44 (02) ◽  
pp. 092-095 ◽  
Author(s):  
T H Tran ◽  
C Bondeli ◽  
G A Marbet ◽  
F Duckert
Keyword(s):  
Antithrombin Iii ◽  
Factor Xa ◽  
Heparin Binding ◽  
Thrombin Inhibition ◽  
Superficial Thrombophlebitis ◽  
Heparin Concentration ◽  
Heparin Binding Site ◽  
At Iii ◽  
The Difference ◽  
Inhibition Of Thrombin

SummaryTwo different AT-III fractions were purified from the plasma of a patient with recurrent superficial thrombophlebitis. The abnormal AT-III fraction (A-AT) was compared to the normal AT-III fraction (N-AT) in the inhibition of thrombin and factor Xa. Without heparin, both inactivate proteases in a similar manner and at the same rate. However, at low heparin concentration the thrombin inhibition proceeds more slowly with A-AT than with N-AT. At high heparin concentration the difference between A-AT and N-AT becomes very small. The inhibition of factor Xa follows a similar pattern. It is suggested that the heparin binding site of A-AT differs from that of N-AT resulting in a decreased heparin cofactor activity.

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