The Influence of CYP2C9 and VKORC1 Gene Polymorphisms on Optimal Warfarin Doses After Heart Valve Replacement

Medicina ◽  
2011 ◽  
Vol 47 (1) ◽  
pp. 4 ◽  
Author(s):  
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Keyword(s):  
Valve Replacement ◽  
Heart Valve ◽  
Heart Surgery ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Heart Valve Replacement ◽  
Warfarin Dosage ◽  
Individualize Treatment ◽  
The Impact ◽  
Vkorc1 Gene

A clinical effect of warfarin depends on highly polymorphic drug-metabolizing (CYP2C9) and drug-target (VKORC1) enzymes. The objective of this study was to investigate the impact of CYP2C9*2, CYP2C9*3, and VKORC1 (G-1639A) polymorphisms on the variability of warfarin dosage requirements in Lithuanian patients after heart valve replacement. Materials and Methods. The study included 83 patients with a mean age of 65.2 years (SD, 13.31) after heart valve replacement with an achieved stable international normalized ratio of 2–3.5. The restriction fragment length polymorphism method was used to identify polymorphisms of VKORC1 and CYP2C9. Results. Daily warfarin dosage significantly correlated with weight (r=0.4087) and height (r=0.3883) of the patients. Patients younger than 60 years required significantly higher daily warfarin dosages than older patients. Two-thirds (66.3%) of the patients had the wild-type (WT) CYP2C9* 1/*1 genotype; 38.6% and 54.2% of the patients had WT VKORC1 (G/G) and VKORC1 (G/A) genotypes, respectively. WT CYP2C9*1/*1 genotype was associated with a higher daily warfarin dosage (5.84 mg [SD, 2.84]) as compared to other CYP2C9 genotypes. Carriers of WT VKORC1 (G/G) required a higher warfarin dose as compared to (A/A) carriers (6.20±2.78 mg and 3.75±1.40 mg, respectively; P=0.04). Patients having CYP2C9*1/*1 or 1/*2 in combination with VKORC1 (G/G) or (G/A) genotypes required the highest daily warfarin dosage in comparison to other combinations of genotypes. Conclusions. The Lithuanian study sample is characterized by high a frequency (92.8%) of VKORC1 G/G and G/A genotypes that determines a higher warfarin-loading dose. Analysis of combined CYP2C9 and VKORC1 gene variants allows the prediction of warfarin dosage. These results can be used to individualize treatment with warfarin in the field of heart surgery in Lithuania.

De Ritis ratio as a significant prognostic factor of international normalized ratio ≥4 in the initial 10 days of warfarin therapy

2019 ◽  
Vol 13 (18) ◽  
pp. 1599-1607
Author(s):  
Yide Cao ◽  
Ganyi Chen ◽  
Huangshu Li ◽  
Yafeng Liu ◽  
Zhonghao Tao ◽  
...  
Keyword(s):  
Valve Replacement ◽  
Heart Valve ◽  
Warfarin Therapy ◽  
Anticoagulation Therapy ◽  
International Normalized Ratio ◽  
Heart Valve Replacement ◽  
Significant Prognostic Factor ◽  
Replacement Surgery ◽  
The Relationship ◽  
Valve Replacement Surgery

Aim: To assess the relationship between the De Ritis ratio on admission and warfarin sensitivity in the initial 10 days of anticoagulation therapy. Methods: We retrospectively reviewed data from 906 patients who underwent heart valve replacement surgery. Results: A De Ritis ratio of 1.19 was identified as the optimal cutoff according to the ROC curve. Patients with a high De Ritis ratio achieved an international normalized ratio (INR) ≥4 more easily and earlier than those with a low De Ritis ratio in the initial 10 days of warfarin therapy. Multivariate analysis showed that a high De Ritis ratio was an independent predictor of an INR ≥4 (HR: 2.567; p < 0.001). Conclusion: A De Ritis ratio ≥1.19 on admission was significantly associated with an INR ≥4 in the initial 10 days of warfarin therapy among patients underwent heart valve replacement surgery.

scholarly journals Hypoxic encephalopathy after heart valve replacement: etiology and pathogenesis, diagnostic criteria and treatment

2015 ◽  
Vol 17 (2) ◽  
pp. 62
Author(s):  
V. G. Postnov
Keyword(s):  
Valve Replacement ◽  
Heart Valve ◽  
Heart Surgery ◽  
Cerebral Metabolism ◽  
Intensive Therapy ◽  
Heart Valve Replacement ◽  
Glycerol Solution ◽  
Hypoxic Encephalopathy ◽  
Replacement Surgery ◽  
Valve Replacement Surgery

Reviewed in this paper are modern approaches in the intensive therapy of acute hypoxic encephalopathy developing in a number of occasions after the heart valve replacement surgery. The study is based on the results of neurological, neuropsychological and neurophysiological (EEG) examinations of 240 patients who underwent heart valve replacement surgery under cardiopulmonary bypass conditions complicated later by the development of hypoxic encephalopathies of varying severity and who received complex intensive care. Relying on many years of experience in the treatment of heart surgery patients in whom manifestations of encephalopathy developed in the early postoperative period, or were delayed, we have formulated the following algorithms of therapy. (1) Maintenance of normal blood gas: Hb>100 g/L, pH 7.45, PaCO2 35 mmHg. (2) Maintenance of hemodynamics: ABPsystolic>90 mmHg. (3) Supplying fluids and electrolytes: isoosmolar infusion solutions, adding of KCl and MgSO4 to the infusion. (4) Antiedemic therapy: 15% mannitol or 40% glycerol solution. (5) If necessary (in case of psychomotor agitation, seizures), short-acting barbiturates (sodium thiopental), neuroleptics (haloperidol), propofol. No benzodiazepines in case of psychoses (6) Cerebral metabolism stimulation (not earlier than 48 hours after surgery) with cholinomimetics, nootropics, cerebral blood flow protectors. Cholinomimetics are allowed on the first day after surgery. This algorithm and the above-mentioned groups of drugs, especially central cholinomimetics, allow for correcting the neurocognitive impairment in the discussed group of patients quickly and effectively.

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