Combined factor V/VIII deficiency: A case report including levels of factor V and factor VIII coagulant and antigen as well as protein C inhibitor

1985 ◽  
Vol 20 (4) ◽  
pp. 401-407 ◽  
Author(s):  
Janet M. Brown ◽  
Nancy R. Selik ◽  
Mary Jo Voelpel ◽  
Eberhard F. Mammen
Keyword(s):  
Case Report ◽  
Factor Viii ◽  
Protein C ◽  
Factor V ◽  
Protein C Inhibitor

scholarly journals Normal titer of functional and immunoreactive protein-C inhibitor in plasma of patients with congenital combined deficiency of factor V and factor VIII

Blood ◽  
1983 ◽  
Vol 62 (6) ◽  
pp. 1266-1270 ◽  
Author(s):  
K Suzuki ◽  
J Nishioka ◽  
S Hashimoto ◽  
T Kamiya ◽  
H Saito
Keyword(s):  
Factor Viii ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V ◽  
Amidolytic Activity ◽  
Normal Plasma ◽  
Coagulant Activity ◽  
Protein C Inhibitor ◽  
Combined Deficiency ◽  
Good Agreement

Protein-C inhibitor (PCI) is a newly described plasma inhibitor directed against a vitamin-K-dependent serine protease, activated protein-C, which is involved in the inactivation of factor V and factor VIII. Marlar and Griffin have reported that PCI activity is absent in the plasma of patients with congenital combined factor V/VIII deficiency. We have measured the levels of PCI in the plasma of seven unrelated patients with this disorder using both functional and immunologic methods. The rate at which the amidolytic activity of activated protein-C was neutralized in the patients' plasma was essentially identical to that observed in normal plasma. The titer of PCI antigen, as measured by an electroimmunoassay using a monospecific anti-PCI serum, was 5.3 +/- 1.6 micrograms/ml in the patients' plasma and was not significantly different from that of normal plasma (5.3 +/- 2.7 micrograms/ml, n = 30). The levels of factor-V-related antigen, factor V coagulant antigen, and factor VIII coagulant antigen were low in all patient plasma and were in good agreement with their respective coagulant activity. Our results do not appear to support the hypothesis that combined factor V/VIII defect is due to a lack of PCI.

Combined factor V and factor VIII deficiency with normal protein C and protein C inhibitor. A family study

2009 ◽  
Vol 34 (5) ◽  
pp. 401-405 ◽  
Author(s):  
Khalifa A. Rahim Adam ◽  
Fath Al Rahman A. El Seed ◽  
Zein A. Karrar ◽  
A.M.A. Gader
Keyword(s):  
Factor Viii ◽  
Protein C ◽  
Family Study ◽  
Factor V ◽  
Factor Viii Deficiency ◽  
Protein C Inhibitor

scholarly journals Normal titer of functional and immunoreactive protein-C inhibitor in plasma of patients with congenital combined deficiency of factor V and factor VIII

Blood ◽  
1983 ◽  
Vol 62 (6) ◽  
pp. 1266-1270 ◽  
Author(s):  
K Suzuki ◽  
J Nishioka ◽  
S Hashimoto ◽  
T Kamiya ◽  
H Saito
Keyword(s):  
Factor Viii ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V ◽  
Amidolytic Activity ◽  
Normal Plasma ◽  
Coagulant Activity ◽  
Protein C Inhibitor ◽  
Combined Deficiency ◽  
Good Agreement

Abstract Protein-C inhibitor (PCI) is a newly described plasma inhibitor directed against a vitamin-K-dependent serine protease, activated protein-C, which is involved in the inactivation of factor V and factor VIII. Marlar and Griffin have reported that PCI activity is absent in the plasma of patients with congenital combined factor V/VIII deficiency. We have measured the levels of PCI in the plasma of seven unrelated patients with this disorder using both functional and immunologic methods. The rate at which the amidolytic activity of activated protein-C was neutralized in the patients' plasma was essentially identical to that observed in normal plasma. The titer of PCI antigen, as measured by an electroimmunoassay using a monospecific anti-PCI serum, was 5.3 +/- 1.6 micrograms/ml in the patients' plasma and was not significantly different from that of normal plasma (5.3 +/- 2.7 micrograms/ml, n = 30). The levels of factor-V-related antigen, factor V coagulant antigen, and factor VIII coagulant antigen were low in all patient plasma and were in good agreement with their respective coagulant activity. Our results do not appear to support the hypothesis that combined factor V/VIII defect is due to a lack of PCI.

The Diagnosis and Clinical Manifestations of Activated Protein C Resistance: A Case Report and Review of the Literature

1996 ◽  
Vol 1 (4) ◽  
pp. 275-280 ◽  
Author(s):  
Howard Daniel Hoerl ◽  
Aldo Tabares ◽  
Kandice Kottke-Marchant
Keyword(s):  
Case Report ◽  
Protein C ◽  
Activated Protein C ◽  
Clinical Manifestations ◽  
Factor V Leiden ◽  
Laboratory Diagnosis ◽  
Factor V ◽  
Review Of The Literature ◽  
Activated Protein C Resistance ◽  
Genetic Anomaly

Activated protein C resistance (APCR) is a recently discovered, medically important cause of venous thrombosis. More than 95% of cases are due to factor V Leiden (FVL), a mutated form of factor V that is resistant to degradation by activated protein C. The prevalence of this disorder, which is inherited in an autosomal dominant fashion, is approximately 5% among asymptomatic people of European heritage. In addition, 20 to 60% of patient cohorts with previous thrombosis demonstrate APCR, making it the most common known genetic cause of abnormal thrombophilia. Current laboratory techniques available for diagnosis include functional assays, such as the APC ratio, as well as DNA-based tests that detect the specific genetic anomaly responsible for FVL. A case report is presented, along with a review of the literature highlighting epidemiology, pathogenesis, clinical features and methods for laboratory diagnosis.

scholarly journals Proteolytic inactivation of human factor VIII procoagulant protein by activated human protein C and its analogy with factor V

Blood ◽  
1984 ◽  
Vol 63 (2) ◽  
pp. 486-489 ◽  
Author(s):  
CA Fulcher ◽  
JE Gardiner ◽  
JH Griffin ◽  
TS Zimmerman
Keyword(s):  
Factor Viii ◽  
Protein C ◽  
Human Factor ◽  
Activated Protein C ◽  
Light Chains ◽  
Factor V ◽  
Human Factor Viii ◽  
Thrombin Activation ◽  
A Site ◽  
Polypeptide Chains

Abstract Purified human factor VIII procoagulant protein (VIII:C) was treated with purified human activated protein C (APC) and the loss of VIII:C activity correlated with proteolysis of the VIII:C polypeptides. APC proteolyzed all VIII:C polypeptides with mol wt = 92,000 or greater, but not the doublet at mol wt = 79–80,000. These results and our previous thrombin activation studies of purified VIII:C, are analogous with similar studies of factor V and form the basis for the following hypothesis: activated VIII:C consists of heavy and light chain polypeptides [mol wt = 92,000 and mol wt = 79–80,000 (or 71–72,000), respectively] which are similar in Mr to the heavy and light chains of activated factor V. Thrombin activates VIII:C and V by generating these polypeptide chains from larger precursors and APC inactivates both molecules by cleavage at a site located in the heavy chain region of activated VIII:C and V.

Haemophilia and thrombophilia

2003 ◽  
Vol 23 (01) ◽  
pp. 36-40 ◽  
Author(s):  
C. Escuriola ◽  
K. Kurnik ◽  
R. Schobess ◽  
S. Horneff ◽  
A. Kosch ◽  
...  
Keyword(s):  
Risk Factors ◽  
Factor Viii ◽  
Protein C ◽  
Methylenetetrahydrofolate Reductase ◽  
Haemorrhagic Stroke ◽  
Type I ◽  
Haemophilia A ◽  
Factor V ◽  
Severe Haemophilia ◽  
Prothrombotic Risk Factors

SummaryFor the study presented here 135 pediatric PUP patients with haemophilia consecutively admitted to German pediatric haemophilia treatment centers were investigated. In addition to factor VIII activity, the factor V (FV) G1691A mutation, the factor II (FII) G20210A variant, methylenetetrahydrofolate reductase (MTHFR) T677T genotype, elevated lipoprotein a (Lp a), antithrombin, protein C, and protein S were investigated. 103 out of 122 HA patients (FVIII activity <1%) were suffering from severe HA. The prevalence of prothrombotic risk factors in children with severe haemophilia A (HA) did not differ from previously reported data: FV GA 5.8%, FII GA 3.9%, MTHFR TT 10%, elevated Lp a 7%, protein C type I deficiency 1.1%. The first symptomatic bleeding leading to diagnosis of severe haemophilia occurred with a median age of 1.6 years (range: 0.5-7.1 years) in children carrying prothrombotic risk factors compared to non-carriers (0.9 years (0.1-4.0; p = 0.01). Two patients presenting with neonatal stroke due to elevated Lp a and the FII GA variant showed haemorrhagic stroke transformation triggered by severe haemophilia. In addition, when haemophilia A was corrected by administration of factor VIII concentrates eight out of 25 children with central lines in place developed catheter-related thrombosis. Conclusion: The data of this multicentre cohort study demonstrate that the clinical phenotype of severe haemophilia A in childhood is clearly influenced by the coinheritance of prothrombotic risk factors.

COAGULATION, FIBRINOLYSIS AND PLATELET FUNCTION DURING COUMARIN THERAPY

1987 ◽  
Author(s):  
D A Taberner ◽  
J M Thomson ◽  
L Poller
Keyword(s):  
Factor Viii ◽  
Protein C ◽  
T Test ◽  
Factor Vii ◽  
Factor V ◽  
Factor X ◽  
Complex Activity ◽  
Oral Anticoagulant Treatment ◽  
Protein C Activity ◽  
Paired T Test

The inactivation of factors VIII:C, V:C and fast acting TPA inhibitor by activated Protein C indicates that oral anticoagulation is more than simple reduction of prothrombin complex activity. To investigate these changes, six patients were studied after stopping oral anticoagulant treatment. Protein C activity and C antigen, Factors VIII:C, VIII:vWFAg, V:C, V:Ag, X:C, VII:C, fibrinogen and TPA activity were measured during long-term nicoumalone therapy (duration of therapy 8-96 months, mean 28 months), and after discontinuation on days 2, 4, 8, 10, 15, 30 and 42.The INR on the last day of therapy ranged between 2.0 - 3.3, (mean 2.6). Protein C activity and antigen and factor X became normal by day 8; factor II by day 10. Factor VII activity peaked on day 8, falling to resting levels by day 30. Factor VIII parameters remained high throughout, whereas Factor V antigen showed no significant change. Factor V activity was not quantifiable untill day 8 because of non-parallelism (? PIVKA effect), but was higher on day 8 than day 42 (p < 0.002 paired “t” test) . The higher levels of factor V activity could be protein C dependent, but the high factor VIII appears unrelated. Fibrinogen levels were higher on coumarin treatment (p < 0.05 paired “t” test) and took 30 days to fall to resting level. The effect of Protein C on TPA inhibitor would be expected to increase the activity of TPA, but this activity remained unchanged. Raised fibrinogen levels did not, therefore, appear to be mediated by the effect of protein C on fibrinolysis. Fibrinogen levels in plasma influence ADP induced platelet aggregation which is known to be increased in patients receiving coumarin drugs. In conclusion, patients on coumarin treatment, in addition to showing a reduction in protein C activity, also have higher fibrinogen levels and increased platelet aggregability all of which may be undesirable.

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