Effect of Vitamin K in Critically Ill Patients

Study Overview
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Brief Summary
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Critically ill patients with spontaneously prolonged pro-thrombin time, where administration of intravenous administration of phytomenadione (vitamin K) has been ordered by the treating physician will be identified. After signed informed consent baseline samples will be collected. Phytomenadione will be given and 24 hours after administration new blood samples will be collected. Several different advanced coagulation and vitamin K-assays will be performed before and 24 hours after vitamin K administration.

Detailed Description
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Vitamin K-deficiency is common in the peri-operative and intensive care setting. It is often seen in patients with prolonged prothrombin complex (PK-INR). A prolonged (PK-INR) is sometimes treated with intravenous vitamin K, even in non-warfarin treated or non-liver failure patients. Despite the development of this practice the knowledge about how intravenously given vitamin K affects routine coagulation status and other advanced laboratory coagulations assays is rare. The aim of this study is to investigate the effects of intravenously administered vitamin K on routine coagulation status and on advanced coagulation and vitamin K-assays in post-operative- and critically ill patients with prolonged PK-INR. Patients with spontaneously prolonged PK-INR are routinely given intravenous vitamin K but it is largely unknown how this procedure affects the included coagulation assays. This research project may contribute to increased knowledge concerning effects of intravenously given vitamin K in critical ill patients with spontaneous coagulopathies. Since spontaneous coagulopathy is frequently occurring in critically ill and postoperative patients due to various underlying conditions and current evidence for vitamin K administration is based on scarce evidence more research in this area is motivated.

Official Title
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Effect of Vitamin K in Critically Ill Patients With Spontaneously Increased Pro-thrombin Time Measured With Routine Coagulation Tests and Advanced Coagulation- and Vitamin K-assays

Conditions
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Coagulation Factor Deficiency, Coagulopathy, Consumption, Vitamin K Deficiency

Intervention / Treatment
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* Drug: Phytomenadione


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Critically ill patients at the postoperative care unit or at the intensive care unit with a prothrombin complex (PK-INR) > 1.2 during office hours who are ordered parenteral phytomenadione 10 mg will be eligible for inclusion Exclusion Criteria: Warfarin treatment Treatment with novel oral anticoagulants Hepatocellular carcinoma Liver resection within 6 months Known pre-existing coagulopathy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with increased PK-INR<br>Critically ill patients with spontaneously increased prothrombin complex (PK-INR) who are given phytomenadione intravenously at the discretion of the treating physician | Drug: Phytomenadione<br>* Blood samples will be taken before and after intravenously prescribed phytomenadione is given. Phytomenadione will be given independently of this study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in prothrombin complex (PK-INR) | Prothrombin complex (PK-INR) with Owren and Quick reagents | Before and 24 hours after given phytomenadione | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in concentration of coagulation factors II, VII, IX and X in plasma |  | Before and 24 hours after given phytomenadione | 
| Change in concentration of PIVKA-II in plasma | Protein Induced by Vitamin K Absence or antagonism for factor II (PIVKA-II) | Before and 24 hours after given phytomenadione | 
| Change in concentration of protein C and S in plasma |  | Before and 24 hours after given phytomenadione | 
| Change in concentration of dp-ucMGP in plasma | Dephospho-uncarboxylated Matrix Gla Protein (dp-ucMGP) | Before and 24 hours after given phytomenadione | 
| Change in thrombin generation assay in plasma |  | Before and 24 hours after given phytomenadione | 
| Change in thromboelastometry assay in whole blood | Thromboelastometry using ROTEM with tissue factor activation (EXTEM reagent) | Before and 24 hours after given phytomenadione |