A Probable Interaction between Warfarin and the Antiretroviral TRIO Study Regimen

2012 ◽  
Vol 46 (11) ◽  
pp. e34-e34 ◽  
Author(s):  
Michelle D Liedtke ◽  
Amulya Vanguri ◽  
R Chris Rathbun
Keyword(s):  
Drug Interaction ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Dose Requirement ◽  
Vein Thrombosis ◽  
Warfarin Dose Requirement ◽  
Recurrent Deep Vein Thrombosis ◽  
The Mean ◽  
Deep Vein ◽  
Probable Interaction

OBJECTIVE: To report a probable drug interaction between the antiretroviral TRIO regimen (ritonavir-boosted darunavir, etravirine, and raltegravir) and warfarin in an HIV-infected patient. CASE SUMMARY: In January 2010, a 50-year-old transgender female with HIV infection and recurrent deep vein thrombosis began treatment with the TRIO study regimen. Treatment had been maintained with warfarin for the past 5 years and emtricitabine monotherapy for the preceding 22 months. Emtricitabine was discontinued when the TRIO regimen was started. The mean weekly warfarin dose while the patient was receiving emtricitabine monotherapy was 13.3 mg (95% CI 12.7 to 13.8), with a mean international normalized ratio (INR) of 2.8 (95% CI 2.5 to 3.1). Following the initiation of the TRIO regimen, the mean weekly warfarin dose was increased to 19.3 mg (95% CI 18.5 to 20.1) and was maintained over the ensuing 71 weeks with a mean INR of 2.6 (95% CI 2.2 to 3.0). DISCUSSION: Information on the effect of newer antiretrovirals on warfarin metabolism, as well as the collective contribution of combination antiretroviral therapy including multiple agents that may alter warfarin metabolism, is limited. We predicted that warfarin dose requirements would change upon initiation of the TRIO regimen. Given the variability in INR that can occur with chronic warfarin treatment, weekly warfarin doses were averaged during emtricitabine monotherapy (90 weeks) and TRIO regimen (71 weeks) periods. Mean weekly warfarin doses increased by 45% (p < 0.001) following initiation of the TRIO regimen. Mean INR results for the 2 time periods were not significantly different, demonstrating that stable anticoagulation was maintained. The Horn drug interaction probability scale score to assess causation indicated a probable interaction. CONCLUSIONS: An increased weekly warfarin dose requirement is predicted when warfarin is used concurrently with the antiretroviral TRIO regimen. Increased INR monitoring is prudent when the combination is administered.

scholarly journals Vitamin K antagonists in children with heart disease: height and VKORC1 genotype are the main determinants of the warfarin dose requirement

Blood ◽  
2012 ◽  
Vol 119 (3) ◽  
pp. 861-867 ◽  
Author(s):  
Caroline Moreau ◽  
Fanny Bajolle ◽  
Virginie Siguret ◽  
Dominique Lasne ◽  
Jean-Louis Golmard ◽  
...  
Keyword(s):  
Vitamin K ◽  
Dose Response ◽  
Maintenance Dose ◽  
Vitamin K Antagonists ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Individual Variability ◽  
Dose Requirement ◽  
Warfarin Dose Requirement ◽  
Main Determinants

Abstract Managing vitamin K antagonist (VKA) therapy is challenging in children because of a narrow therapeutic range and wide inter- and intra-individual variability in dose response. Only a few small studies have investigated the effect of nongenetic and genetic factors on the dose response to VKAs in children. In a cohort study including 118 children (median age 9 years; range, 3 months-18 years) mostly with cardiac disease, we evaluated by multivariate analysis the relative contribution of nongenetic factors and VKORC1/CYP2C9/CYP4F2 genotypes on warfarin (n = 83) or fluindione (n = 35) maintenance dose and the influence of these factors on the time spent within/above/below the range. The results showed that height, target international normalized ratio and VKORC1 and CYP2C9 genotypes were the main determinants of warfarin dose requirement, accounting for 48.1%, 4.4%, 18.2%, and 2.0% of variability, respectively, and explaining 69.7% of the variability. Our model predicted the warfarin dose within 7 mg/wk in 86.7% of patients. None of the covariates was associated with the time spent above or below the international normalized ratio range. Whether this model predicts accurately the effective maintenance dose is currently being investigated.

Effect of CYP2C9 *11/*11 genotype on initial and long-term warfarin dose requirement and therapeutic response

2020 ◽  
Vol 21 (18) ◽  
pp. 1271-1277
Author(s):  
Alison LH Quinn ◽  
Shubha Bhat ◽  
James C Lee
Keyword(s):  
Therapeutic Response ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Term Treatment ◽  
Dose Requirement ◽  
Long Term Treatment ◽  
Warfarin Dose Requirement ◽  
Short And Long Term ◽  
Load Dose

The warfarin dose requirement and therapeutic response of a 42-year-old African–American male with genotype CYP2C9 *11/*11, VKORC1 -1639GG and CYP4F2 433Val/Val anticoagulated for ischemic stroke is described herein. Warfarin was dosed according to the institution’s personalized medicine program recommendations of a 10 mg mini-load dose, followed by dose decreases to 4–6 mg/day through discharge. Stable international normalized ratio was achieved after eight doses, with good overall long-term maintenance of therapeutic international normalized ratio over several years with warfarin doses of 3.1–4.3 mg/day. This case report sheds further light on the clinical impact of CYP2C9 *11/*11 on warfarin dose requirements, short- and long-term treatment response and practical considerations for warfarin management in suspected carriers of rare variant CYP2C9 alleles.

Increased Warfarin Requirements during Concurrent Dicloxacillin Therapy

2012 ◽  
Vol 28 (5) ◽  
pp. 197-200 ◽  
Author(s):  
Kelsey N Kohman ◽  
Rebecca L Dunn ◽  
Winter J Smith
Keyword(s):  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Heparin Therapy ◽  
Probability Scale ◽  
Vein Thrombosis ◽  
Therapeutic Anticoagulation ◽  
History Of ◽  
Lost To Follow Up ◽  
Deep Vein

Objective: To report on a patient who required increased dosages of warfarin to achieve therapeutic anticoagulation while taking dicloxacillin. Case Summary: A 60-year-old woman was hospitalized for an infected lymphocele and cellulitis. Based on microbiology results, dicloxacillin 500 mg by mouth 4 times daily was initiated to complete 14 days of treatment. Concurrently, a deep vein thrombosis was diagnosed by computed tomography angiography. Enoxaparin 100 mg subcutaneously twice daily and warfarin 5 mg by mouth daily were initiated with an international normalized ratio (INR) goal of 2–3. The patient had a history of a supratherapeutic INR while on warfarin 5 mg daily. Throughout the 20-day hospitalization, her warfarin dose was steadily increased in an attempt to achieve a therapeutic INR. Required doses ranged from 7.5 to 15 mg daily. Two days after discontinuation of dicloxacillin and with administration of a 15-mg warfarin boost, the INR was therapeutic at 2.3. Enoxaparin was discontinued and the patient was discharged on warfarin 7.5 mg daily. Upon clinic follow-up 5 days after discharge, the INR was supratherapeutic at 3.3 and the warfarin dose was decreased. The patient was then lost to follow-up. Discussion: This interaction between warfarin and dicloxacillin has been described in the literature; however, the mechanism responsible remains unknown. In all cases reported, increased warfarin requirements appeared after several days of dicloxacillin therapy and slowly disappeared after dicloxacillin discontinuation. This case differs from previously reported cases because it demonstrates warfarin resistance associated with dicloxacillin and a subsequent new initiation of warfarin therapy. The Naranjo probability scale and the Horn Drug Interaction Probability Scale both rate this interaction as probable. Conclusions: Patients taking dicloxacillin who are initiated on warfarin may require a longer duration of concurrent low-molecular-weight heparin therapy, as well as higher doses of warfarin, and may take longer to achieve a therapeutic INR.

Features of Thrombi and Diagnostic Accuracy of Impedance Plethysmography in Symptomatic and Asymptomatic Deep Vein Thrombosis

1993 ◽  
Vol 70 (02) ◽  
pp. 266-269 ◽  
Author(s):  
Giancarlo Agnelli ◽  
Benilde Cosmi ◽  
Stefano Radicchia ◽  
Franca Veschi ◽  
Enrico Boschetti ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Diagnostic Accuracy ◽  
High Sensitivity ◽  
Impedance Plethysmography ◽  
Surveillance Programme ◽  
Vein Thrombosis ◽  
Asymptomatic Patients ◽  
High Prevalence ◽  
The Mean ◽  
Deep Vein

SummaryImpedance plethysmography (IPG) has high sensitivity and specificity in patients with symptomatic deep vein thrombosis (DVT) while it fails to detect asymptomatic DVT. The aim of this study was to determine whether the features of thrombi such as location, size and occlusiveness could explain the different accuracy of IPG in symptomatic and asymptomatic DVT patients. One-hundred and seventeen consecutive outpatients with a clinical suspicion of DVT and 246 consecutive patients undergoing hip surgery were admitted to the study. In symptomatic patients IPG was performed on the day of referral, followed by venography, while in asymptomatic patients IPG was performed as a surveillance programme, followed by bilateral venography.A venography proved DVT was observed in 37% of the symptomatic patients and 34% of the asymptomatic limbs. A significantly higher proportion of proximal DVTs was found in symptomatic patients than in asymptomatic patients (78% vs 46%; p = 0.001). The mean Marder score, taken as an index of thrombus size, was significantly higher in symptomatic patients than in asymptomatic patients (19.0 vs 9.6; p = 0.0001). A significantly higher proportion of occlusive DVTs was observed in symptomatic than in asymptomatic patients (69% vs 36%; p = 0.001).We conclude that the unsatisfactory diagnostic accuracy of IPG in asymptomatic DVT is due to the high prevalence of distal, small and non occlusive thrombi. Such thrombi are unlikely to cause a critical obstruction of the venous outflow and therefore to produce a positive IPG.

Pre-operative Plasma Levels of Thrombin-Antithrombin III Complexes Correlate with the Development of Venous Thrombosis after Major Hip or Knee Surgery

1995 ◽  
Vol 74 (02) ◽  
pp. 602-605 ◽  
Author(s):  
Jeffrey S Ginsberg ◽  
Patrick Brill-Edwards ◽  
Akbar Panju ◽  
Ameen Patel ◽  
Joanne McGinnis ◽  
...  
Keyword(s):  
Antithrombin Iii ◽  
Tertiary Care ◽  
Knee Surgery ◽  
Referral Centre ◽  
Study Objective ◽  
Cut Points ◽  
Vein Thrombosis ◽  
Major Orthopedic Surgery ◽  
The Mean ◽  
Deep Vein

SummaryStudy objective. To determine whether levels of thrombin-antithrombin III (TAT) in plasma, taken two weeks pre-operatively, predict the development of deep vein thrombosis (DVT) in patients undergoing major hip or knee surgery.Design. Prospective cohort.Setting. Tertiary-care referral centre, university-affiliated hospital.Patients. Ninety eight consecutive patients undergoing elective hip or knee surgery.Intervention. All eligible consenting patients were seen in a preoperative clinic two weeks prior to surgery and had blood taken for measurement of plasma TAT level. After surgery, they received a combination of unfractionated heparin 5000 Units 12-hourly subcutaneously, and antiembolism stockings (TEDS), as prophylaxis against DVT. Contrast venography was performed prior to discharge, and according to the results, patients were classified as having proximal (popliteal and/or more proximal) DVT (n = 12), calf DVT (n = 7) or no DVT (n = 79).Measurements and Results. The mean TAT level was significantly higher in patients who developed DVT (5.7 μg/l) than in those who did not (4.1 μg/l), p = 0.035. Using cut-points of 3.5 and 5.5 μg/l for the TAT level, patients could be categorized as high, intermediate, and low risk for the development of DVT. The proportion of patients with TAT levels of ≥3.5μg/l who developed calf or proximal DVT was significantly higher than the proportion of patients with TAT levels of <3.5 μg/l who developed calf or proximal DVT (p = 0.02). The proportion of patients with TAT levels >5.5 μg/l who developed proximal DVT was significantly higher than the proportion of patients with TAT levels of ≤5.5 μg/l who developed proximal DVT (p = 0.03).Conclusions. This study demonstrates that pre-operative TAT levels correlate with the risk of developing DVT after major orthopedic surgery. Further studies are needed to determine the reason(s) for this observation and whether rational recommendations about prophylaxis and screening for DVT can be made based on the results of a pre-operative TAT level.

Role of Platelets in Recurrent Deep Vein Thrombosis

1975 ◽  
Author(s):  
K. K. Wu ◽  
R. W. Barnes ◽  
J. C. Hoak
Keyword(s):  
Deep Vein Thrombosis ◽  
Oral Anticoagulant Therapy ◽  
Additional Patient ◽  
Ratio Method ◽  
Vein Thrombosis ◽  
Platelet Survival ◽  
Platelet Aggregate ◽  
Recurrent Deep Vein Thrombosis ◽  
Platelet Aggregates ◽  
Deep Vein

To evaluate the role that platelets play in the pathogenesis of recurrent deep vein thrombosis (DVT), a platelet count ratio method was used for the detection of platelet aggregates and an aggregometric technique was used to measure spontaneous aggregation (SPA) in 27 patients with idiopathic recurrent DVT. Seventeen patients were found to have decreased platelet aggregate ratios (mean 0.63±SEM 0.02) which were significantly lower than those of normals (0.90 ±0.02, p < 0.01). Twelve of the 17 patients had SPA. The mean platelet survival half-time of 5 patients with increased platelet aggregates was 2.9 days±0.49, significantly decreased from that of normals (4.2 ±0.10, p < 0.05). Platelet survival values were normal in patients with normal platelet aggregate ratios. Five patients who failed to improve on oral anticoagulant therapy responded to aspirin and dipyridamole with normalization of platelet aggregates and disappearance of SPA. An additional patient responded to sulfinpyrazone. When the drug was discontinued, pulmonary embolus recurred. These findings suggest that recurrent DVT may involve heterogeneous groups of patients and platelets may play an important pathogenetic role in some of them. The approach to the problem with this panel of 3 tests appears useful in the selection of patients for treatment with antiplatelet agents.

scholarly journals COAGULOGRAM INDICES IN PATIENTS WITH DEEP VEIN TROMBOSIS, DEPENDING ON THE METHOD OF TREATMENT

2020 ◽  
pp. 81-85
Author(s):  
Ya. M. Popovich ◽  
V. V. Rusin
Keyword(s):  
Deep Vein Thrombosis ◽  
Surgical Treatment ◽  
Anticoagulant Therapy ◽  
Quantitative Estimation ◽  
Treatment Method ◽  
International Normalized Ratio ◽  
Average Concentration ◽  
Vein Thrombosis ◽  
Mechanical Removal ◽  
Deep Vein

Summary. Despite a satisfactory number of research which dedicated on coagulogram changes in patients with DVT, they are rarely used in clinical practice for the diagnosis of thrombosis, more often for the correction of anticoagulant therapy. The aim of research. Estimate the changes of coagulogram indices in patients with deep vein thrombosis, depending on the type of treatment performed. Materials and methods. Has been performed the quantitative estimation of coagulogram indices in 721 patients with deep vein thrombosis. Depending on the treatment method, the patients were divided into two groups: І – 382 (53 %) patients, which performed the surgical treatment with the following prescription the anticoagulant therapy; ІІ – 339 (47 %) patients, which performed only the anticoagulant therapy. Results. Has been observed more expression of hypocoagulation in patients of I group for the essesment the most of the coagulogram indices: the level of D-dimer was 14.1 % lower than in II group, the average concentration of thrombocyte was 7.8 %, the prothrombin index was 7.1 %, the international normalized ratio by 3.8 %, the level of hematocrit by 2.4 %, platelet count by 1.9 % lower than in patients ІІ group. More expression the prolongation of activated thromboplastin time, activated recalcification time and prothrombin time for 37.9 %, 10.6 % and 4.8 %, respectively, was observed in I group compared with the patients II group. At the same time, the level of fibrinogen in the I group was 9.1 % higher compared with the patients II group. Conclusions. Hypocoagulation changes of haemostasis in patients which performed the surgical treatment for deep vein thrombosis, compared to patients with isolated anticoagulant therapy, suggest that mechanical removal of thrombotic masses promotes faster normalization of indices hemostasis.

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