Recombinant Factor VII (Activated) for Haemorrhagic Complications of Severe Sepsis Treated with Recombinant Protein C (Activated)

SummaryThe mechanisms behind dietary effects on fasting coagulant activity of factor VII (FVII: C) are not clarified. In the present study of 15 young volunteers, two experimental diets differing in composition of saturated fatty acids (C18:0 [diet S] or C12:0 + C14:0 [diet ML]) were served for 3 weeks each. Fasting blood samples were collected before and after the dietary regimen and analysed for triglycerides, FVII:C, and protein concentrations of FVII, FII, FX, protein C, CRP, albumin, fibrinogen, and F1+2. FVII:C was significantly reduced on diet S compared with diet ML. This was accompanied by a decrease in FVII protein, F1+2 and the vitamin K-dependent proteins FII, FX, and protein C. In contrast, no changes were observed in triglycerides, FVII:C/FVII: Ag, albumin and CRP. Fibrinogen was increased on diet S compared with diet ML. Our findings suggest that the change in fasting FVII:C was part of a general change in concentrations of vitamin K-dependent proteins.

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Updates on role of human recombinant activated protein C in patients with sepsis and severe sepsis: Changed scenario after PROWESS SHOCK trial

Indian Journal of Anaesthesia ◽

10.4103/0019-5049.104597 ◽

2012 ◽

Vol 56 (6) ◽

pp. 597 ◽

Cited By ~ 2

Author(s):

Aparna Shukla

Keyword(s):

Severe Sepsis ◽

Protein C ◽

Activated Protein C ◽

Shock Trial

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HAEMOSTATIC CHANGES INDUCED BY TWO LOW DOSE TRIPHASIC ORAL CONTRACEPTIVES

10.1055/s-0038-1643825 ◽

1987 ◽

Author(s):

S J Machin ◽

I J Mackie ◽

K Walshe ◽

M D Gillmer

Keyword(s):

Oral Contraceptives ◽

Protein C ◽

Low Dose ◽

Factor Vii ◽

Cycle Period ◽

Factor Xii ◽

Factor X ◽

Combined Oral Contraceptives ◽

First Time ◽

Protein C Activity

The haemostatic system was investigated in 26 women taking cyclically administered triphasic combined oral contraceptives for the first time during their first six cycles. Fourteen women received Logynon (mean dose 32.4μg ethinyloestradiol, 92pg progestagen) and 12 received SHD 415G (Schering) which contains a mean dosage of 32.4μg ethinyloestradiol and 78pg gestodene, a recently developed progesterone. The Logynon group showed a significant increase (p<0.005) in fibrinogen (pre-mean 284.4 g/1; after 1 cycle 347.3 g/1, after 6 cycles 318.6 g/1) , factor VII (65.8 u/1 to 73.9 u/1 to 83.2 u/1), factor XII (1.74 u/1 to 2.41 u/1, to 2.25 u/1), plasminogen (100.9 u/1 to 135.1 u/1 to 126.3 u/1); decrease in ATIII (115.9 u/1 to 103.1 u/1 to 93.4 u/1) but no significant change in factor X (98.4 u/1 to 108.9 u/1 to 102.4) or protein C (0.85 u/1 to 0.88 u/1 to 0.94 u/1) activity. The SHD 415G group showed similar changes with an increase in fibrinogen (247.9 g/1 to 330.8 g/1 to 373 .1 g/1), factor VII (63.1 u/1 to 73.1 u/1 to 90.3 u/1, factor X (98.3 u/1 to 112.0 u/1 to 124.4 u/1), factor XII (1.46 u/1, to 1.93 u/1, to 2.03 u/1), plasminogen (110.8 u/1 to 125.4 u/1 to 136.7 u/1); decrease in ATIII (113.1 u/1 to 96.3 u/1 to 89.7 u/1), but no change in protein C (0.84 u/1 to - 0.78 u/1 to 0.85 u/1) activity. These changes were apparent after the first cycle of therapy and the differences were maintained over the six cycle period. There was no increase in protein C activity despite changes in the other vitamin K dependent proteins factors VII and X. Both low oestrogen dose triphasic pills caused similar prothrombotic changes which were not modified by the new progesterone, gestodene.

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FXa Inhibition and Coagulation Changes During DVT Prophylaxis by Enoxaparin Over the Course of a 15-Day Follow-Up in Septic Patients

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029609345686 ◽

2009 ◽

Vol 16 (5) ◽

pp. 584-590 ◽

Cited By ~ 7

Author(s):

Zuzana Zenáhlíková ◽

Jan Kvasnička ◽

Zuzana Kudrnová ◽

Magda Sudrová ◽

Radka Brzežková ◽

...

Keyword(s):

Severe Sepsis ◽

Protein C ◽

Factor Xa ◽

Inclusion Criteria ◽

C Reactive Protein ◽

Once Daily ◽

Reactive Protein ◽

Factor Xa Inhibition ◽

The Mean

The objective of our study was to examine the changes in coagulation parameters and inflammatory reaction over the course of 15 days in patients with severe sepsis. We tried to identify mechanisms by which sepsis-induced pathophysiological changes may influence the effectiveness of subcutaneously (SC) administered enoxaparin 40 mg once daily. A total of 16 patients (8 men, 8 women; age 35-83 years) meeting the inclusion criteria of severe sepsis were enrolled in this study. The follow-up was performed on days 1, 2, 3, 6, 9, 12, and 15 of hospitalization at the intensive care unit (ICU). Blood coagulation (activated partial thromboplastin time [aPTT], prothrombin time [PT], fibrinogen, antithrombin (AT), protein C [PC], D-dimer, fragment 1.2 [F1.2], factor Xa [FXa] inhibition) and inflammatory reactants (interleukin 6 [IL-6], C-reactive protein [CRP], orosomucoid, α-1-antitrypsin) were tested. The mean FXa inhibition was 0.17 (±0.17) IU/mL. The arbitrarily established range of FXa inhibition for prophylaxis, 0.2 to 0.4 IU/mL, was reached in 22 cases (20%), while in 74 cases (68%), it was below and in 13 cases (12%) above the aforementioned range. Factor Xa inhibition positively correlated with AT (r = .42; P < .001) and PC (r = .45; P < .001) activities. A negative correlation was found between the FXa inhibition and α-1-antitrypsin concentrations (r = —.33; P = .01) but only in the subgroup with α-1-antitrypsin concentrations ≥2.2 g/L. We confirmed that in most patients with sepsis, the prophylaxis with enoxaparin did not lead to the required FXa inhibition. The inhibition of FXa by enoxaparin depends mainly on the AT and PC activities.

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Enhancement of Vitamin-K-Dependent Protein Function by Modification of the Î³-Carboxyglutamic Acid Domain Studies of Protein C and Factor VII

Trends in Cardiovascular Medicine ◽

10.1016/s1050-1738(99)00024-9 ◽

1999 ◽

Vol 9 (6) ◽

pp. 162-167 ◽

Cited By ~ 15

Author(s):

G Nelsestuen

Keyword(s):

Vitamin K ◽

Protein Function ◽

Protein C ◽

Factor Vii ◽

Carboxyglutamic Acid ◽

Dependent Protein ◽

Acid Domain

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A Thrombomodulin Promoter Gene Polymorphism, rs2239562, Influences Both Susceptibility to and Outcome of Sepsis

Frontiers in Medicine ◽

10.3389/fmed.2021.762198 ◽

2022 ◽

Vol 8 ◽

Author(s):

Eizo Watanabe ◽

Osamu Takasu ◽

Youichi Teratake ◽

Teruo Sakamoto ◽

Toshiaki Ikeda ◽

...

Keyword(s):

Severe Sepsis ◽

Protein C ◽

Validation Cohort ◽

University Hospital ◽

Coagulation Cascade ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Functional Polymorphisms ◽

Promoter Gene ◽

Control Study

Objective: Disseminated intravascular coagulation plays a key role in the pathophysiology of sepsis. Thrombomodulin is essential in the protein C system of coagulation cascade, and functional polymorphisms influence the human thrombomodulin gene (THBD). Therefore, we conducted a multicenter study to evaluate the influence of such polymorphisms on the pathophysiology of sepsis.Methods: A collaborative case-control study in the intensive care unit (ICU) of each of five tertiary emergency centers. The study included 259 patients (of whom 125 displayed severe sepsis), who were admitted to the ICU of Chiba University Hospital, Chiba, Japan between October 2001 and September 2008 (discovery cohort) and 793 patients (of whom 271 patients displayed severe sepsis), who were admitted to the five ICUs between October 2008 and September 2012 (multicenter validation cohort). To assess the susceptibility to severe sepsis, we further selected 222 critically ill patients from the validation cohort matched for age, gender, morbidity, and severity with the patients with severe sepsis, but without any evidence of sepsis.Results: We examined whether the eight THBD single nucleotide polymorphisms (SNPs) were associated with susceptibility to and/or mortality of sepsis. Higher mortality on severe sepsis in the discovery and combined cohorts was significantly associated with the CC genotype in a THBD promoter SNP (−1920*C/G; rs2239562) [odds ratio [OR] 2.709 (1.067–6.877), P = 0.033 and OR 1.768 (1.060–2.949), P = 0.028]. Furthermore, rs2239562 SNP was associated with susceptibility to severe sepsis [OR 1.593 (1.086–2.338), P = 0.017].Conclusions: The data demonstrate that rs2239562, the THBD promoter SNP influences both the outcome and susceptibility to severe sepsis.

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