Protein C activity value as a prognostic factor in sepsis-induced disseminated intravascular coagulation

Abstract This study was undertaken to determine the levels of protein C antigen and activity and protein C inhibitor in sequential plasma samples of disseminated intravascular coagulation (DIC) patients. Our normal range for both protein C antigen and activity is 70 to 130 U/dL, and protein C inhibitor is 65 to 135 U/dL. A decreased level of protein C activity was found in 96% of the plasma samples from individuals with DIC; the protein C antigen was decreased in 73%. The inhibitor of protein C was decreased in all samples. Analysis of serial samples from patients with DIC reveals that protein C activity and antigen and protein C inhibitor decrease progressively during the initial stages of DIC and remain at a low level for 24 to 48 hours before gradually returning toward normal in nonfatal cases. The protein C activity decreases in parallel with protein C inhibitor and is lower than protein C antigen. In a fatal case of DIC, protein C activity and protein C inhibitor rapidly decreased to undetectable levels; however, protein C antigen was gradually decreasing but still detectable at time of death. In DIC, a discrepancy initially occurs between the activity and antigen of protein C, suggesting a complex with the inhibitor or other inactive forms of protein C. Protein C appears to play a major role in the control of DIC.

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Protein C activity levels in endotoxin-induced disseminated intravascular coagulation in a dog model

Thrombosis Research ◽

10.1016/0049-3848(89)90062-5 ◽

1989 ◽

Vol 55 (3) ◽

pp. 297-307 ◽

Cited By ~ 11

Author(s):

Renee M Madden ◽

Michael Ward ◽

Richard A Marlar

Keyword(s):

Disseminated Intravascular Coagulation ◽

Protein C ◽

Activity Levels ◽

Intravascular Coagulation ◽

Dog Model ◽

Protein C Activity

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Serial studies of protein C and its plasma inhibitor in patients with disseminated intravascular coagulation

Blood ◽

10.1182/blood.v66.1.59.bloodjournal66159 ◽

1985 ◽

Vol 66 (1) ◽

pp. 59-63

Author(s):

RA Marlar ◽

J Endres-Brooks ◽

C Miller

Keyword(s):

Disseminated Intravascular Coagulation ◽

Protein C ◽

Fatal Case ◽

Plasma Samples ◽

Normal Range ◽

C Protein ◽

Intravascular Coagulation ◽

Protein C Inhibitor ◽

Serial Samples ◽

Protein C Activity

This study was undertaken to determine the levels of protein C antigen and activity and protein C inhibitor in sequential plasma samples of disseminated intravascular coagulation (DIC) patients. Our normal range for both protein C antigen and activity is 70 to 130 U/dL, and protein C inhibitor is 65 to 135 U/dL. A decreased level of protein C activity was found in 96% of the plasma samples from individuals with DIC; the protein C antigen was decreased in 73%. The inhibitor of protein C was decreased in all samples. Analysis of serial samples from patients with DIC reveals that protein C activity and antigen and protein C inhibitor decrease progressively during the initial stages of DIC and remain at a low level for 24 to 48 hours before gradually returning toward normal in nonfatal cases. The protein C activity decreases in parallel with protein C inhibitor and is lower than protein C antigen. In a fatal case of DIC, protein C activity and protein C inhibitor rapidly decreased to undetectable levels; however, protein C antigen was gradually decreasing but still detectable at time of death. In DIC, a discrepancy initially occurs between the activity and antigen of protein C, suggesting a complex with the inhibitor or other inactive forms of protein C. Protein C appears to play a major role in the control of DIC.

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Safety of plasma-derived protein C for treating disseminated intravascular coagulation in adult patients with active cancer

American Journal of Hematology ◽

10.1002/ajh.22238 ◽

2012 ◽

Vol 87 (2) ◽

pp. 230-232 ◽

Cited By ~ 1

Author(s):

Alessandra Malato ◽

Giorgia Saccullo ◽

Lucio Lo Coco ◽

Clementina Caracciolo ◽

Simona Raso ◽

...

Keyword(s):

Disseminated Intravascular Coagulation ◽

Protein C ◽

Adult Patients ◽

Intravascular Coagulation ◽

Active Cancer

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Recurrent Thromboembolism, Disseminated Intravascular Coagulation, and Coumarin-induced Skin Necrosis Associated with Protein C Deficiency

Pathology - Research and Practice ◽

10.1016/s0344-0338(88)80127-4 ◽

1988 ◽

Vol 183 (3) ◽

pp. 308-313 ◽

Cited By ~ 2

Author(s):

J.T. Lie

Keyword(s):

Disseminated Intravascular Coagulation ◽

Skin Necrosis ◽

Protein C ◽

Protein C Deficiency ◽

Intravascular Coagulation

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Purpura Fulminans in a Chinese Boy With Congenital Protein C Deficiency

PEDIATRICS ◽

10.1542/peds.77.5.670 ◽

1986 ◽

Vol 77 (5) ◽

pp. 670-676

Author(s):

Patrick Yuen ◽

Alfred Cheung ◽

Hsiang Ju Lin ◽

Faith Ho ◽

Jun Mimuro ◽

...

Keyword(s):

Disseminated Intravascular Coagulation ◽

Protein C ◽

Purpura Fulminans ◽

Fresh Frozen Plasma ◽

Protein C Deficiency ◽

Intravascular Coagulation ◽

The Family ◽

Fresh Frozen ◽

Frozen Plasma ◽

Congenital Protein C Deficiency

Severe and recurrent purpura fulminans developed in a Chinese boy at one day of age. Results of coagulation studies performed on the patient during attacks were compatible with the diagnosis of disseminated intravascular coagulation. Subsequent investigations have revealed that the patient is homozygous and that his parents are heterozygous for protein C deficiency. Cryoprecipitate and fresh frozen plasma induced a remission, and administration of warfarin has been successful in preventing recurrence of attacks for as long as 8 months without infusion of any plasma components. None of the family members who are heterozygous for protein C deficiency have had thrombotic episodes.

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Endothelial Dysfunction Is Associated with Mortality and Severity of Coagulopathy in Patients with Sepsis and Disseminated Intravascular Coagulation

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029619852163 ◽

2019 ◽

Vol 25 ◽

pp. 107602961985216 ◽

Cited By ~ 7

Author(s):

Amanda Walborn ◽

Matthew Rondina ◽

Michael Mosier ◽

Jawed Fareed ◽

Debra Hoppensteadt

Keyword(s):

Disseminated Intravascular Coagulation ◽

Protein C ◽

High Mobility ◽

Severity Of Illness ◽

Endothelial Activation ◽

Endothelial Damage ◽

Intravascular Coagulation ◽

Angiopoietin 2 ◽

Von Willebrand ◽

Relationship Of

The role of the endothelium in sepsis-associated disseminated intravascular coagulation (DIC) is multifaceted and may contribute substantially to disease severity and outcome. The purpose of this study was to quantify measures of endothelial function, including markers of activation (endocan, Angiopoietin-2 [Ang-2], and von Willebrand Factor), endogenous anticoagulants (tissue factor pathway inhibitor and protein C), and damage-associated factors (High Mobility Group Box 1 [HMGB-1]) in the plasma of patients with sepsis and DIC, and to determine the relationship of these factors with severity of illness and outcome. Plasma samples were collected from 103 adult patients with sepsis within 48 hours of intensive care unit admission. Biomarker levels were measured using commercially available, standardized methods. Disseminated intravascular coagulation was diagnosed according to the International Society of Thrombosis and Hemostasis scoring algorithm. Twenty-eight-day mortality was used as the primary end point. In this study, endothelial damage and dysfunction were associated with the severity of coagulopathy and mortality in DIC patients. Loss of the endogenous anticoagulant protein C and elevation in the vascular regulator Ang-2 were associated with the development of overt DIC. In addition to Ang-2 and protein C, endocan, a biomarker of endothelial activation, and HMGB-1, a mediator of endothelial damage and activation, were significantly associated with mortality. This underscores the contribution of the endothelium to the pathogenesis of sepsis-associated DIC.

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Decreased plasma activity of antithrombin or protein C is not due to consumption coagulopathy in septic patients with disseminated intravascular coagulation

European Journal Of Haematology ◽

10.1034/j.1600-0609.2001.5790508.x ◽

2001 ◽

Vol 67 (3) ◽

pp. 170-175 ◽

Cited By ~ 43

Author(s):

Hidesaku Asakura ◽

Yasuo Ontachi ◽

Tomoe Mizutani ◽

Minori Kato ◽

Takako Ito ◽

...

Keyword(s):

Disseminated Intravascular Coagulation ◽

Protein C ◽

Consumption Coagulopathy ◽

Intravascular Coagulation ◽

Plasma Activity

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Dysregulation of Inflammatory and Hemostatic Markers in Sepsis Associated Disseminated Intravascular Coagulation.

Blood ◽

10.1182/blood.v120.21.2223.2223 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2223-2223 ◽

Cited By ~ 1

Author(s):

Jawed Fareed ◽

Debra Hoppensteadt ◽

Josephine Cunanan ◽

Michael Mosier ◽

Yutaka Osawa ◽

...

Keyword(s):

Disseminated Intravascular Coagulation ◽

Inflammatory Mediators ◽

Protein C ◽

Control Group ◽

Functional Protein ◽

Double Blind ◽

Intravascular Coagulation ◽

Hemostatic Markers ◽

Circulating Levels ◽

Pai 1

Abstract Abstract 2223 Disseminated intravascular coagulation (DIC) represents a complex pathophysiologic syndrome where marked alterations in the hemostatic system are manifested. As a result several inflammatory mediators are up regulated through multiple mechanisms. The up regulation of inflammatory mediators such as anaphylatoxin C5a (C5a), procalcitonin (PCT), interleukin 6 (IL-6), interleukin 10 (IL-10), myeloperoxidase (MPO), C reactive protein (CRP), and circulating levels of hemostatic markers including protein C inhibitor (PCI), plasminogen activator inhibitor 1 (PAI-1), and protein C (Pr C) were evaluated in 758 subjects enrolled in a randomized, double-blind, placebo-controlled, Phase-2B study evaluating the safety and efficacy of recombinant thrombomodulin (ART-123) in subjects with sepsis and suspected DIC. Thirty healthy male and female volunteers served as the control group. Commercially available ELISA methods were used to measure the various mediators. Marked deviations in the circulating levels of these markers, as compared to controls, were noted as shown in the following table. Compared with controls, subjects in DIC showed an increase in the circulating levels of most inflammatory markers. The levels of PCT, IL-6 and CRP, where considerably higher in the DIC subjects whereas PCI, Pr C and AT exhibited slight decreases. Wide individual variations were present. The PAI-1 levels were also increased in the DIC subjects. These results are tabulated below. These results clearly indicate that inflammation and impairment of fibrinolysis play a key role in the pathogenesis of DIC Parameter Nomal (NHP Mean+SEM) DIC (Baseline Mean+SEM) % Change Protein C (% Ag) 82.5 ± 13.6 47.6 ± 23.7 −42.2% Functional Protein C (%) 83.4 ± 13.2 46.2 ± 29.8 −44.6% PCI (% Inhibition) 130.0 ± 24.6 79.4 ± 105.5 −38.9% PAI-1 (ng/ml) 35.4 ± 10.8 140.6 ± 165.6 297.1% CRP (ug/ml) 2.6 ± 0.4 48.0 ± 14.2 1736.9% C5a (ng/ml) 9.2 ± 3.2 17.2 ± 13.3 85.1% IL-6 (pg/ml) 9.3 ± 3.7 620.3 ± 1883.4 6583.9% IL-10 (pg/ml) 13.9 ± 13.1 130.2 ± 118.6 836.1% MPO (ng/ml) 16.0 ± 4.2 108.1 ± 68.6 574.6% PCT (ng/ml) 0.2 ± 0.13 21.9 ± 43.3 14514.5% Disclosures: Osawa: Asahi Kasei Pharma America Corporation: Employment. Kaul:Asahi Kasei Pharma America Corporation: Employment.

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