Endogenous or exogenous coagulation factor level and the response to activated protein C

Gennari, Laura C.; Blanco, Alicia N.; Dominguez, María Paula; Grosso, Silvia; Lazzari, M.A.

doi:10.1016/j.thromres.2005.07.022

Cited by 6 publications

(4 citation statements)

References 25 publications

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“…Saenko et al [13] demonstrated that LRP1 contributes to the clearance, internalization and degradation of FVIII. Indeed, increased FVIII levels were shown to be due to an impaired effect of activated PC [21]. LRP1-deficient mice [16] showed increased FVIII plasma levels and a slower FVIII clearance, which underlines the crucial role of LRP1 for FVIII half-life.…”

Section: Introductionmentioning

confidence: 95%

“…Furthermore, protein C (PC), an important regulator of coagulation, is known to proteolytically cleave the heavy chain of FVIII [20], following activation to activated PC. Indeed, increased FVIII levels were shown to be due to an impaired effect of activated PC [21]. Up to now, neither the influence of LRP1 nor of PC on FVIII PK has been studied in haemophilia patients.…”

Section: Introductionmentioning

confidence: 99%

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Parameters influencing FVIII pharmacokinetics in patients with severe and moderate haemophilia A

et al. 2015

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In haemophilia A patients factor VIII (FVIII) recovery and half-life can vary substantially. There are parameters known to modulate FVIII pharmacokinetics (PK), but they explain only about 34% of the variability. The aim of this study was to identify new parameters that influence FVIII PK and thus to expand the current knowledge. FVIII PK were determined in 42 haemophilia A patients (37 severe, 5 moderate) without inhibitor. Patients' characteristics and laboratory parameters were evaluated for an association with FVIII PK. We analysed plasma levels of low-density lipoprotein receptor-related protein 1 (LRP1) and protein C (PC) activity, which had been hypothesized to influence FVIII activity. Furthermore, four variations in intron 6 of the LRP1 gene, which had been shown to influence LRP1, were investigated. FVIII half-life differed widely from 6.2 to 20.7 h, with a median of 10.0 h. Patients with blood group O had shorter FVIII half-life compared to patients with non-O blood group (median FVIII half-life 9.0 h vs. 10.4 h, P = 0.018). Age was significantly associated with FVIII half-life (r = 0.32, P = 0.035). Besides age, also VWF antigen (r = 0.52, P < 0.001) and blood group (r = -0.37, P = 0.015) was associated with FVIII half-life. No correlation was found with FVIII- or LRP1-genotype, LRP1 or PC concentrations. Our data showed large differences in FVIII PK between individual patients and revealed age, blood group and VWF levels as important determining factors for FVIII half-life. FVIII genotype or levels of LRP1 or PC had no influence on FVIII PK.

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Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Parameters influencing FVIII pharmacokinetics in patients with severe and moderate haemophilia A

et al. 2015

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“…Another mechanism in OC-induced thrombotic tendency- especially with third-generation OCs- is the reduction in plasma sensitivity to activated protein C (APC) [ 17 , 20 – 23 ]. Protein C is a precursor of the anticoagulant pathway, which is activated by the thrombin-thrombomodulin (TM) complex formation at the endothelial cell surface.…”

Section: Introductionmentioning

confidence: 99%

The effects of oral contraceptive usage on thrombin generation and activated protein C resistance in Saudi women, with a possible impact of the body mass index

et al. 2018

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Background and objectivesThe effect of oral contraceptive (OC) usage on coagulation has been studied worldwide. However, no such studies have been conducted in Saudi Arabia on Saudi women using OCs. The aim of this study was to investigate the effects of OC-induced changes of thrombin generation (TG) in the absence and presence of activated protein C (APC) or thrombomodulin (TM) in Saudi women.MethodsA total of 115 adult women, 47 on oral contraception (OC users) and 68 controls (not using OCs) were recruited from the obstetrics-gynecology outpatient clinic in Saudi Arabia. OCs that were used in this study include the following: Marvelon, Gynera, Cerrazetem, Yasmine, Microlut, Gracial and Diane. The plasma calibrated automated thrombinography (CAT) was used to determine TG which was expressed as endogenous thrombin potential (ETP; nM/min), lag time (min), peak (nM) and time-to-peak (ttpeak; min). In the presence of TM or APC, TG parameters were expressed relative to the parameters in the absence of TM or APC.Results and conclusionAs in other populations, our study demonstrated that OC usage induced prothrombotic changes in plasma of Saudi women, including resistance to the inhibitory actions of TM and APC. More specifically, OC usage in our population predominantly influenced TG and APC/TM sensitivity in overweight and obese individuals, a finding that needs confirmation in large cohort studies. The effects of APC and TM on TG parameters showed a positive association, and the correlation coefficients were higher in OC users for both ETP and peak values.

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“…Later, APC resistance was also shown to occur in the absence of the mutation. This condition, which, in the majority of cases, was associated with increased plasma levels of procoagulant proteins (prothrombin and factor VIII) or decreased levels of the anticoagulant, protein S [42,43], appeared to be an independent risk factor for VT [44].…”

Section: Risk Factors For Vtmentioning

confidence: 99%

Dignity in Health and Social Care for Older Europeans: Implications of a European Project

Tadd

Bayer

2006

Aging Health

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The use of oral contraceptives is associated with an increased risk of venous thrombosis. It is now generally accepted that women who use oral contraceptives that contain so-called third-generation progestins (desogestrel or gestodene) are exposed to a twofold higher risk of venous thrombosis than women who use oral contraceptives that contain the second-generation progestin levonorgestrel. Coagulation studies demonstrated that oral contraceptives increase the plasma level of prothrombin, decrease the level of protein S and induce acquired activated protein C resistance. The changes in hemostatic parameters can explain why women who use oral contraceptives are exposed to an increased risk of venous thrombosis and why the risk is further increased in third-generation oral contraceptive users.

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Endogenous or exogenous coagulation factor level and the response to activated protein C

Cited by 6 publications

References 25 publications

Parameters influencing FVIII pharmacokinetics in patients with severe and moderate haemophilia A

Parameters influencing FVIII pharmacokinetics in patients with severe and moderate haemophilia A

The effects of oral contraceptive usage on thrombin generation and activated protein C resistance in Saudi women, with a possible impact of the body mass index

Dignity in Health and Social Care for Older Europeans: Implications of a European Project

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