Vitamin K & Liver Disease

Liver : Normal Physiology

• Liver has a crucial role in hemostasis in which it synthesize all the coagulation factos with the exception of von Willebrand factor.
• It also synthesize inhibitors of coagulation 9antithrombin, protein C, and protein S and proteins of the fibrinolytic system 9plaminogen and α-antiplasmin).
• It is also involved in the clearance of activated clotting factors from circulation.

Liver Disease & Hemostasis

• The complex nature of haemostasis in patients with liver disease can result in bleeding and/or thrombosis.
• Patients with end-stage-liver disease (ESLD) do not suffer only from procoagulant deficiency; there is also a lack of natural anticoagulants (i.e. proteins C and S) and profibrinolytics.

Bleeding Risk Assessment in ESLD

• Bleeding risk assessment is imperative in ESLD patients before any intervention is considered.
• However, conventional coagulation tests such as for the international normalized ratio (INR) or the activated partial thromboplastin time (aPTT) only poorly reflect the pathophysiological changes in advanced liver cirrhosis. 
• Patients in advanced stages of liver disease develop thrombosis despite pathological procoagulation profiles.
• Still, INR and aPTT are predictive for procoagulation factor deficiency, but they are not sensitive for decreased protein C and S activity.

When to give Vitamin K?

• In most patients, intervention is not in the setting of asymptomatic laboratory changes.
• An exception is that, vitamin K is given to patients with suspected deficiency, including any patients with suspected poor nutrition and cirrhosis, as well as those with cholestatic disease, diarrheal illness, or antibiotic use.
• There is little evidence regarding the efficacy of administering vitamin K; however, toxicities are also negligible.
• A typical dose of vitamin K in this setting is 10 mg orally per day for three days, or 10 mg intravenously as a single dose for individuals who cannot take vitamin K orally or who may not adequately absorb vitamin K (eg, ascites, gut edema).  

Vitamin K in ESLD Adults

• A study quoted that the replacement of vitamin K-dependent coagulation factors in patients with ESLD differs from the reversal of oral vitamin K antagonists. 
• Patients with vitamin K antagonists require 1 IU/kg PCC to increase the prothrombin time (PT) time by 1%, while patients with ESLD require 1.6 IU/kg to achieve the same increase.

Vitamin K in Acute Liver Failure Adults

• Vitamin K (5-10 mg subcutaneously) should be administered routinely, since vitamin K deficiency has been reported in patients with ALF.
• In another study, in acute liver patient for control of coagulopathy is recommended with the adminstration of intravenous vitamin K (2–10 mg). 

Vitamin K in Liver Failure Peadiatric

• Oral vitamin K supplementation is usually adequate to prevent severe vitamin K deficiency-associated coagulopathy.
• Children are given 2.5 - 5 mg/day although supplementation three times per week is often adequate to prevent coagulopathy.

Reference: 

1. Uptodate 
2. E. D. Nel and A. J. Terblanche, “Nutritional support of children with chronic liver disease,” vol. 105, no. 7, 2015.
3. W. M. Lee, A. M. Larson, and R. Todd Stravitz, “The Management of Acute Liver Failure,” 2011.
4. D. A. Kelly, “Managing liver failure,” Postgrad. Med. J., vol. 78, no. 925, pp. 660–667, Nov. 2002.
5. F. H. Saner, R. K. Gieseler, H. Akiz, A. Canbay, and K. Görlinger, “Delicate Balance of Bleeding and Thrombosis in End-Stage Liver Disease and Liver Transplantation,” Digestion, vol. 88, no. 3, pp. 135–144, 2013.