From Prof. Jeanne Isabel, Northern Illihois University, a long-time friend and colleague. Hi George, a colleague who works at a cancer center has a patient on hydrocortisone (not sure how much) and her prothrombin time and international normalized ratio (PT/INR) were elevated to 54 s/4.9. she is on Coumadin and last time her INR was in the therapeutic range. She did not have symptoms to correlate with the elevated results. would the hydrocortisone cause this? Thanks.
Hi, Jeanne, and thank you. Yes, the oral and injectable cortisols, including prednisone, prednisolone, cortisone, and hydrocortisone unpredictably interfere with Coumadin, sometimes prolonging the PT and raising the INR. This exposes the patient to a bleeding risk, and it is necessary to adjust the Coumadin dosage. If there are signs of bleeding the physician may wish to give oral or intravenous vitamin K, and if there is serious bleeding. four-factor prothrombin compex concentrate (KCentra), which appears to be recommended over fresh frozen plasma, according to a recent publication by Dr. Ravi Sarode:
Sarode Circulation 2013 4-factor PCC
I hope this helps your colleague. Geo.
A prospective cohort study assessed 10 patients who were on
A prospective cohort study assessed 10 patients who were on stable oral anticoagulation therapy with either fluindione (n = 8) or acenocoumarol (n = 2) and who were given pulse doses of intravenous methylprednisolone 500-1000 mg. Prior to corticosteroid therapy, the mean INR was 2.75 (range 2.02-3.81), and the mean INR following methylprednisolone administration was 8.04 (range 5.32-20), at a mean duration of 92.7 hours (range 29-156). Two additional analyses were performed to exclude an independent effect of methylprednisolone on the INR. A control group, which consisted of 5 patients without concurrent anticoagulation, was reported to have a stable PT after methylprednisolone was administered. In vitro analysis was conducted by adding methylprednisolone to plasma samples of patients being treated with fluindione, and the resulting INRs were not influenced. The 2 anticoagulants evaluated in this study, acenocoumarol and fluindione, are coumarin-like drugs, but are less commonly used than warfarin.
The 15% of patients with extreme INR elevations generate gre
The 15% of patients with extreme INR elevations generate great concern because when the INR is greater than 5, the risk of hemorrhage markedly increases. For this reason, early monitoring of patients’ warfarin therapy following initiation of a corticosteroid is warranted to reduce the risk for extreme INR elevations and potential bleeding complications.
Here is another Czech article:
http://www.ncbi.nlm.nih.gov/
Here is another Czech article:
http://www.ncbi.nlm.nih.gov/pubmed/22716170
Glucocorticoids impair integrity of vessels and bleeding usually occurs due to this mechanism. Considering that glucocorticoids have impact on genetic transcription at the nucleus and consequent protein translations (factor biosynthesis) in addition to warfarin strong dependency to liver metabolic enzymes, finding an exact mechanism of interaction seems very challenging. Increasing or sometimes decreasing of INR has been reported after co-administration of warfarin and glucocorticoids. Interestingly enough co-administration of warfarin and glucocorticoids is not very uncommon, for instance in immune-dependent thrombotic events such as anti-phospholipid syndrome.
Thank you for your interpretation, VadimKo.
Thank you for your interpretation, VadimKo.
The exact mechanism of the interaction between warfarin and
The exact mechanism of the interaction between warfarin and oral corticosteroids is unknown but may be due to altered liver metabolism of warfarin by corticosteroids. Methylprednisolone, prednisone, and warfarin are substrates for metabolism by the CYP3A4 isoenzyme pathway. The inhibition of warfarin metabolism potentially occurs as a result of competitive binding at CYP3A4. In addition to the CYP3A4 pathway, warfarin is also a substrate for the CYP1A2, 2D6, and 2C9 isoenzyme pathways. Possible rationales for the variable patient responses are genetic deficiencies and/or inhibition of one cytochrome P450 isoenzyme, leading to varying compensation of warfarin metabolism through a different isoenzyme pathway. According to Kaufman, another theorized mechanism is the increased availability of warfarin through a transient increase in serum pH that occurs as a consequence of corticosteroid therapy. The alkalosis diminishes protein binding of warfarin, thereby increasing its serum availability. From Hazlewood KA, et al. Effect of oral corticosteroids on chronic warfarin therapy. Ann Pharmacother. 2006; 40:21016.
http://www.medscape.com/viewarticle/553030_4
what’s the mechanism of cortisols interfering with Coumadin?
what’s the mechanism of cortisols interfering with Coumadin?
Dowd MB, et al. Empiric warfarin dose adjustment with predni
Dowd MB, et al. Empiric warfarin dose adjustment with prednisone therapy. A randomized, controlled trial. J Thromb Thrombolysis. 2011; 31:4727. http://www.ncbi.nlm.nih.gov/pubmed/21161329