Challenges in achieving a target international normalized ratio for deep vein thrombosis among HIV-infected patients with tuberculosis: a case series

Abstract

BackgroundTuberculosis (TB) and HIV are among the risk factors for deep vein thrombosis (DVT). There are several challenges in the management of DVT patients with TB-HIV co-infection including drug-drug interactions and non-adherence due to pill burden.MethodsHIV infected patients starting treatment for TB were identified and followed up two weekly. Cases of DVT were diagnosed with Doppler ultrasound and patients were initiated on oral anticoagulation with warfarin and followed up with repeated INR measurements and warfarin dose adjustment.ResultsWe describe 7 cases of TB and HIV-infected patients in Uganda diagnosed with DVT and started on anticoagulation therapy. Their median age was 30 (IQR: 27–39) years and 86 % were male. All patients had co-medication with cotrimoxazole, tenofovir, lamivudine and efavirenz and some were on fluconazole. The therapeutic range of the International Normalization Ratio (INR) was difficult to attain and unpredictable with some patients being under-anticoagulated and others over-anticoagulated. The mean Time in Therapeutic Range (TTR) for patients who had all scheduled INR measurements in the first 12 weeks was 33.3 %. Only one patient among those with all the scheduled INR measurements had achieved a therapeutic INR by 2 weeks. Four out of seven (57 %) of the patients had at least one INR above the therapeutic range which required treatment interruption. None of the patients had major bleeding.ConclusionWe recommend more frequent monitoring and timely dose adjustment of the INR, as well as studies on alternative strategies for the treatment of DVT in TB-HIV co-infected patients.

Improving anticoagulation in sub-Saharan Africa -- what are the challenges, and how can we overcome them?

“…[106] In a Ugandan case series, patients concomitantly prescribed rifampicin, antiretroviral therapy, and warfarin had highly labile INRs and warfarin dose requirements, and it was not possible to predict the course of INR results in any individual patient. [107] In Kenya, VTE patients with advanced HIV and tuberculosis required a median 8 additional clinic visits to achieve or maintain a therapeutic INR. [108] Despite widespread herbal medicine use in SSA [109,110] there is very little data on how this influences anticoagulation.…”

A cross-sectional evaluation of five warfarin anticoagulation services in Uganda and South Africa

“…The burden of HIV and tuberculosis (TB) is high in sub-Saharan Africa [6]. Patients on warfarin who are HIV positive and/or have TB require multiple concomitant medicines, which may interact with warfarin and complicate warfarin dosing and dose adjustment [7].…”

Comparison of the therapeutic dose of warfarin in HIV-infected and HIV-uninfected patients: a study of clinical practice

“…ARV drugs have variable effects on warfarin blood levels, some causing an increase in levels and some a decrease. Sekaggya et al 17 demonstrated this in a case series of HIV-infected patients being treated for tuberculosis. Jong et al 4 demonstrated lower levels of the von Willebrand factor, factor VIII, D-dimer and endogenous thrombin potential in HIV-infected patients on ARV drugs.…”

“…The development of a warfarin dosing algorithm for HIV-infected persons would be difficult and complex because of the multiple influences that may be operating. 14 17 These include genetic factors, the hypercoagulable state, pertinent infections and malignancies, and the effect of multiple drugs on the cytochrome P450 2C9 system. These diverse effects on warfarin dosage are probably reflected in the wide range of SD in this study as shown in figure 1 .…”