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.

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

1994 ◽  
Vol 14 (04) ◽  
pp. 199-208
Author(s):  
Irene 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 RPOC 160 unterschiedliche Mutationen beschrieben.Sowohl beim AT-Ill-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.

Patients with APC Resistance Compared with Those with Other Clotting Inhibitor Deficiencies Show Later Onset of Venous Thrombosis During Oral Contraception

1995 ◽  
Vol 1 (4) ◽  
pp. 274-276 ◽  
Author(s):  
Antonio Girolami ◽  
Paolo Simioni ◽  
Sandra Zanardi ◽  
Luigi Scarano ◽  
Bruno Girolami
Keyword(s):  
Deep Vein Thrombosis ◽  
Protein C ◽  
Antithrombin Iii ◽  
Activated Protein C ◽  
Protein S ◽  
Oral Contraception ◽  
Vein Thrombosis ◽  
Apc Resistance ◽  
At Iii ◽  
Deep Vein

The prevalence of deep vein thrombosis in female patients with antithrombin III (AT III), protein C, or protein S deficiency who are on oral contraception has been compared with that of patients with activated protein C (APC) resistance. In the latter case the prevalence was lower (36.4%) than in the AT III deficiency group (71.4%) but similar to that seen in the protein C and protein S group (25%).' Furthermore, venous thrombosis occurred with APC resistance much later than with AT III, protein C, or protein S defects. The time lag between onset of oral contraception and thrombosis (~16 cycles) was not statistically different from that seen in a group of women who were known to have no antithrombin III, protein C, or protein S defects. It appears that as far as the interaction with oral contraception is concerned APC resistance is a much less severe condition compared with other clotting inhibitor defects. Key Words: Oral contraceptive—Activated protein C resistance—Deep vein thrombosis.

Hämostaseologische Risikoindikatoren im Verlauf der tiefen Venenthrombose und ihre Beziehung zur Entzündungsreaktion (CRP)

1995 ◽  
Vol 15 (02) ◽  
pp. 109-116
Author(s):  
O. Anders ◽  
H. Auel ◽  
C. Burstein ◽  
H. Ehrensberger ◽  
V. Hossmann ◽  
...  
Keyword(s):  
Protein C ◽  
Antithrombin Iii ◽  
Protein S ◽  
C Protein ◽  
At Iii

ZusammenfassungIn dieser Studie sollte bei Patienten mit tiefer Venenthrombose im Verlauf des akuten Ereignisses und bei ambulanter Nachuntersuchung die Beziehung zwischen bekannten hämostaseologischen Risikoindikatoren der Thrombophilie und der Akute-Phase-Reaktion untersucht werden. 73 Patienten mit phlebographisch gesicherter Venenthrombose wurden am Tag der Klinikaufnahme, am zweiten Tag und bei Entlassung aus dem Krankenhaus untersucht, bei 63 Patienten erfolgte eine ambulante Nachuntersuchung nach Abklingen der akuten Symptomatik. Bestimmt wurden die Parameter Plasminogenaktivator-Inhibitor (PAI), Ristocetin-Kofaktor, Plasminogen, Antithrombin III (AT III), Protein C, Protein S, Fibrinogen und C-reaktives Protein (CRP). Es zeigte sich ein deutlicher Abfall der bei 90% der Patienten pathologisch erhöhten CRP-Werte vom Zeitpunkt der Klinikaufnahme bis zur Entlassung aus dem Krankenhaus, 1/3 der Patienten hatte auch zum Zeitpunkt der ambulanten Nachuntersuchung noch erhöhte CRP-Konzehtrationen >0,5 mg/dl. Diese Patienten hatten eine Häufigkeit pathologisch erhöhter Werte von Fibrinogen (84,2%) und Ristocetin-Kofaktor (47,4%) wie zum Zeitpunkt der Akutveränderung bei Klinikaufnahme. Bei 2/3 der Patienten konnte bei der ambulanten Nachuntersuchung anhand unauffälliger CRP-Werte <0,5 mg/dl eine Akute-Phase-Reaktion ausgeschlossen werden. Diese Patienten hatten zu 49% pathologisch erhöhte Fibrinogenwerte, zu 41 % pathologisch erhöhte PAI-Werte und zu 25% pathologisch erhöhte Ristocetin-Kofaktor-Werte; 39% dieser Patienten mit normalem CRP hatten gleichzeitige Erhöhungen von zwei der drei Parameter Fibrinogen, Ristocetin-Kofaktor und PAI.Fibrinogen, Ristocetin-Kofaktor und PAI sind auch als Risikoindikatoren arterieller Thrombosen bekannt. Dies führt zu dem Schluß, daß der Pathomechanismus und die Risikokonstellation bezüglich thromboembolischer Ereignisse zwischen arteriellem und venösem System ähnlicher sind als bisher angenommen.CRP hat sich nach den vorliegenden Ergebnissen als prognostisch wichtiger Risikomarker bei der tiefen Venenthrombose erwiesen. Die vorgelegten Daten können Hinweise darauf geben, daß die Entzündungsreaktion im Pathomechanismus der tiefen Venenthrombose eine kausale und nicht nur sekundäre Rolle spielt. Die prospektive Bedeutung dieser Ergebnisse muß noch durch weitere Untersuchungen geklärt werden.

scholarly journals Coagulation Status in Women With Missed Abortion

2021 ◽  
Author(s):  
Shuo Yang ◽  
Dandan Chen ◽  
Junxiong Wang ◽  
Rui Qiao ◽  
Liyan Cui
Keyword(s):  
Platelet Aggregation ◽  
Lupus Anticoagulant ◽  
Protein C ◽  
Antithrombin Iii ◽  
Protein S ◽  
Missed Abortion ◽  
Coagulation Function ◽  
Healthy Pregnancy ◽  
At Iii ◽  
D Dimer

Abstract Background: Missed abortion is a special type of spontaneous miscarriage, as well as a complex and multifactorial reproductive health problem that affects people all over the world. The purpose of this study was to assess the status of coagulation function in a large series of reproductive-age women diagnosed as missed abortion. Likewise, we want to explore the association between coagulation and missed abortions, in order to evaluate whether they could be used as early predictive factors for missed abortions.Methods: A total of 11182 women who suffered from missed abortion from Peking University Third Hospital and 5298 healthy age –matched early pregnancy women were enrolled in our study. Coagulation function test (prothrombin time, activated partial thromboplastin time), fibrinolysis status detection (fibrinogen, D-Dimer), anticoagulation function tests (protein C, protein S and antithrombin III) and lupus anticoagulants (LAC) were examined on an automated coagulation analyzer. In addition, platelet counts were detected by automated hematology analyzer. Platelet aggregation (PAgT) were tested by light transmission aggregometry (LTA). All tests were taken according to standard operating procedures of the instruments.Results: Compared with healthy pregnancy, the level of D-Dimer and platelet count were higher, and the antithrombin III (AT-III) activity was lower(P<0.05). 13.1% patients with missed abortion were positive for LAC, and platelet aggregation was increased in 47.4% patients. There were no significant differences in the levels of PT, aPTT, TT, fibrinogen, protein C and protein S between the patients with missed abortion and healthy pregnancy. Moreover, multivariate logistic regression analysis showed that D-Dimer, dRVVT-R, AT-III and PAgT had significant predictive value for missed abortion.Conclusion: These findings provide evidence of hypercoagulability in patients with missed abortion. Lupus anticoagulant, PAgT and D-Dimer were the strongest predictors of missed abortion. These data suggest that treatment of the lupus anticoagulant and antiplatelet aggregation could be considered in missed abortion.

Different Incidence of Venous Thrombosis in Patients with Inherited Deficiencies of Antithrombin III, Protein C and Protein S

1994 ◽  
Vol 71 (01) ◽  
pp. 015-018 ◽  
Author(s):  
G Finazzi ◽  
T Barbui
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Antithrombin Iii ◽  
Protein S ◽  
Total Period ◽  
Total Incidence ◽  
S Deficiency ◽  
At Iii ◽  
Antithrombin Iii Deficiency

SummaryA cohort study was undertaken to compare the incidence of thrombosis in patients with inherited deficiency of Antithrombin III (n = 9), Protein C (n = 36) and Protein S (n = 36). The patients were stratified for schedule of antithrombotic prophylaxis and followed for a total period of 160 patient-years. Seven venous thrombosis were observed for a total incidence of 4.3% pts.-ys. The incidence of thrombosis was not significantly different in patients of different age, sex and schedule of prophylaxis, although there was a trend to a lower incidence in young individuals and in those receiving long-term oral anticoagulation. Patients with AT III deficiency had an higher incidence of thrombosis than patients with Protein C or Protein S deficiency (12 vs. 2.8 vs. 3.3% pts.-ys., p <0.05), despite the fact that they were, on average, younger and more prophylaxed. This study suggests that congenital Antithrombin III deficiency constitutes a greater risk of thrombosis than congenital deficiences of Protein C and Protein S.

The Frequency of Type I Heterozygous Protein S and Protein C Deficiency in 141 Unrelated Young Patients with Venous Thrombosis

1988 ◽  
Vol 59 (01) ◽  
pp. 018-022 ◽  
Author(s):  
C L Gladson ◽  
I Scharrer ◽  
V Hach ◽  
K H Beck ◽  
J H Griffin
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Antithrombin Iii ◽  
Young Patients ◽  
Protein S ◽  
Type I ◽  
Protein S Deficiency ◽  
Protein C Deficiency ◽  
Low Protein ◽  
S Deficiency

SummaryThe frequency of heterozygous protein C and protein S deficiency, detected by measuring total plasma antigen, in a group (n = 141) of young unrelated patients (<45 years old) with venous thrombotic disease was studied and compared to that of antithrombin III, fibrinogen, and plasminogen deficiencies. Among 91 patients not receiving oral anticoagulants, six had low protein S antigen levels and one had a low protein C antigen level. Among 50 patients receiving oral anticoagulant therapy, abnormally low ratios of protein S or C to other vitamin K-dependent factors were presented by one patient for protein S and five for protein C. Thus, heterozygous Type I protein S deficiency appeared in seven of 141 patients (5%) and heterozygous Type I protein C deficiency in six of 141 patients (4%). Eleven of thirteen deficient patients had recurrent venous thrombosis. In this group of 141 patients, 1% had an identifiable fibrinogen abnormality, 2% a plasminogen abnormality, and 3% an antithrombin III deficiency. Thus, among the known plasma protein deficiencies associated with venous thrombosis, protein S and protein C. deficiencies (9%) emerge as the leading identifiable associated abnormalities.

The Influence of Insulin, ß-Estradiol, Dexamethasone and Thyroid Hormone on the Secretion of Coagulant and Anticoagulant Proteins by HepG2 Cells

1995 ◽  
Vol 74 (02) ◽  
pp. 686-692 ◽  
Author(s):  
René W L M Niessen ◽  
Birgit A Pfaffendorf ◽  
Augueste Sturk ◽  
Roy J Lamping ◽  
Marianne C L Schaap ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Protein C ◽  
Protein Production ◽  
Culture Medium ◽  
Protein S ◽  
Cell Protein ◽  
Hepatoma Cell Line ◽  
Factor X ◽  
Factor Ii ◽  
At Iii

SummaryAs a basis for regulatory studies on the influence of hormones on (anti)coagulant protein production by hepatocytes, we examined the amounts of the plasma proteins antithrombin III (AT III), protein C, protein S, factor II, factor X, fibrinogen, and prealbumin produced by the hepatoma cell line HepG2, into the culture medium, in the absence and presence of insulin, β-estradiol, dexamethasone and thyroid hormone. Without hormones these cells produced large amounts of fibrinogen (2,452 ± 501 ng/mg cell protein), AT III (447 ± 16 ng/mg cell protein) and factor II (464 ± 31 ng/mg cell protein) and only small amounts of protein C (50 ± 7 ng/mg cell protein) and factor X (55 ± 5 ng/mg cell protein). Thyroid hormone had a slight but significant effect on the enrichment in the culture medium of the anticoagulant protein AT III (1.34-fold) but not on protein C (0.96-fold) and protein S (0.91-fold). This hormone also significantly increased the amounts of the coagulant proteins factor II (1.28-fold), factor X (1.45-fold) and fibrinogen (2.17-fold). Insulin had an overall stimulating effect on the amounts of all the proteins that were investigated. Neither dexamethasone nor ß-estradiol administration did substantially change the amounts of these proteins.We conclude that the HepG2 cell is a useful tool to study the hormonal regulation of the production of (anti)coagulant proteins. We studied the overall process of protein production, i.e., the amounts of proteins produced into the culture medium. Detailed studies have to be performed to establish the specific hormonal effects on the underlying processes, e.g., transcription, translation, cellular processing and transport, and secretion.

Protein C, protein S and antithrombin III in children with portal vein obstruction

1997 ◽  
Vol 27 (1) ◽  
pp. 132-135 ◽  
Author(s):  
Claire Dubuisson ◽  
Catherine Boyer-Neumann ◽  
Martine Wolf ◽  
Dominique Meyer ◽  
Olivier Bernard
Keyword(s):  
Portal Vein ◽  
Protein C ◽  
Antithrombin Iii ◽  
Protein S ◽  
C Protein ◽  
Portal Vein Obstruction

scholarly journals Thrombophilia And Arterial Ischemic Stroke

2017 ◽  
pp. 45
Author(s):  
A.A. Abrishamizadeh
Keyword(s):  
Ischemic Stroke ◽  
Vitamin K ◽  
Arterial Thrombosis ◽  
Protein C ◽  
Antithrombin Iii ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
C Protein

Ischemic stroke (IS) is a common cause of morbidity and mortality with significant socioeconomic impact especially when it affects young patients. Compared to the older adults, the incidence, risk factors, and etiology are distinctly different in younger IS. Hypercoagulable states are relatively more commonly detected in younger IS patients.Thrombophilic states are disorders of hemostatic mechanisms that result in a predisposition to thrombosis .Thrombophilia is an established cause of venous thrombosis. Therefore, it is tempting to assume that these disorders might have a similar relationship with arterial thrombosis. Despite this fact that 1-4 % of ischemic strokes are attributed to Thrombophillia, this   alone rarely causes arterial occlusions .Even in individuals with a positive thrombophilia screen and arterial thrombosis, the former might not be the primary etiological factor.Thrombophilic   disorders can be broadly divided into inherited or acquired conditions. Inherited thrombophilic states include deficiencies of natural anticoagulants such as protein C, protein S, and antithrombin III (AT III) deficiency, polymorphisms causing resistance to activated protein C(Factor V Leiden mutation), and disturbance in the clotting balance (prothrombin gene 20210G/A variant). Of all the inherited  thrombophilic disorders, Factor V Leiden mutation is perhaps the commonest cause. On the contrary, acquired thrombophilic disorders are more common and include conditions such as the antiphospholipid syndrome, associated with lupus anticoagulant and anticardiolipin antibodies.The more useful and practical approach of ordering various diagnostic tests for the uncommon thrombophilic states tests should be determined by a detailed clinical history, physical examination, imaging studies and evaluating whether an underlying hypercoagulable state appears more likely.The laboratory thrombophilia   screening should be comprehensive and avoid missing the coexisting defect and It is important that a diagnostic search protocol includes tests for both inherited and acquired thrombophilic disorders.Since the therapeutic approach (anticoagulation and thrombolytic therapy) determines the clinical outcomes, early diagnosis of the thrombophilic  disorders plays an important role. Furthermore, the timing of test performance of some of the  thrombophilic  defects (like protein C, protein S, antithrombin III and fibrinogen levels) is often critical since these proteins can behave as acute phase reactants and erroneously elevated levels of these factors may be observed in patients with acute thrombotic events. On the other hand, the plasma levels of vitamin K-dependent proteins (protein C, protein S and APC resistance) may not be reliable in patients taking vitamin K antagonists. Therefore, it is suggested that plasma-based assays for these disorders should be repeated3 to 6 months after the initial thrombotic episode to avoid false-positive results and avoid unnecessary prolonged   anticoagulation therapy. The assays for these disorders are recommended after discontinuation of oral anticoagulant treatment or heparin for at least 2 weeks.    

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