Empirically Reduced Dosages of Tinzaparin in Patients with Moderate-to-Severe Renal Insufficiency Lead to Inadequate Anti-Xa Levels

Abstract

Background: Due to the higher molecular weight of tinzaparin, the low molecular weight heparin (LMWH) is less dependent on renal excretion than other LMWH preparations. However, several international guidelines recommend the same preemptive dosage reduction for all therapeutic dose LMWHs prescribed in renal insufficient patients, to ensure that there is no accumulation of anticoagulant activity and increased risk of bleeding. This study is aimed at assessing whether a preemptive dosage reduction of tinzaparin in all renal insufficient patients (comprising 25% reduction in patients with Modification of Diet in Renal Disease - estimated glomerular filtration rate (MDRD-eGFR) 30-60 mL/min/1.73 m² and 50% reduction in patients with MDRD-eGFR <30 mL/min/1.73 m²) leads to adequate anti-Xa levels. Methods: We selected the anti-Xa levels of in-hospital patients (≥18 years) with moderate-to-severe renal insufficiency (MDRD-eGFR <60 mL/min/1.73 m²), on therapeutic dosages of tinzaparin. Anti-Xa levels were measured using a chromogenic assay. Results: Preemptive dosage reduction resulted in a median anti-Xa activity of 0.50 IU/mL (interquartile range [IQR] 0.38-0.60). In 92.3% of patients the anti-Xa level was below the target anti-Xa level of >0.85 IU/mL for therapeutic indications. Unadjusted dosages led to a median anti-Xa activity of 0.74 IU/mL (IQR 0.56-0.92). The preemptive dosage reduction was significantly associated with anti-Xa activity below therapeutic range (p = 0.007). No difference in anti-Xa activity was observed between patients with moderate (0.71 IU/mL, IQR 0.61-0.95) versus severe (0.65 IU/mL, IQR 0.41-1.06) renal insufficiency in whom an unadjusted dose had been administered (p = 0.77). None of the anti-Xa levels were above the upper margin of the presumed therapeutic range of 2.0 IU/mL. Conclusion: In renal insufficient patients, the preemptive dosage reduction of tinzaparin leads to inadequate anti-Xa levels.

Dosage reduction of low weight heparin in patients with renal dysfunction: Effects on anti-Xa levels and clinical outcomes

“…Dalteparin (6000 Dalton) has a similar molecular weight as tinzaparin (6500 Dalton) and has a higher molecular weight than nadroparin (4300 Dalton) or enoxaparin (4500 Dalton) [ 27 , 28 ]. Our finding that a dosage reduction in dalteparin for patients with eGFR below the 60 ml/min/1.73m 2 resulted in adequate anti-Xa levels in 12% of the patients was in line with the finding of a previous study that showed adequate anti-Xa levels in only 8% of tinzaparin users [ 25 ].…”

“…Therefore, these studies recommended pre-emptive dose reductions of enoxaparin in patients with decreased kidney function. In contrast to enoxaparin, previous studies did not find an association between decreased kidney function and increased anti-Xa levels for tinzaparin [22][23][24][25].…”

Anticoagulation in patients with sepsis. Pathophysiology and common pitfalls

“…12 Dicha determinación puede no correlacionarse adecuadamente con las propiedades antitrombóticas de la HBPM que se esté estudiando ni con el riesgo de sangrado del paciente, ya que las heparinas poseen otros efectos al implicarse en la función plaquetaria y el mecanismo de inhibición de liberación de factor tisular por parte del endotelio. 2,13 Sin embargo, al no poder emplear las pruebas de anticoagulación estándares como el TTPA para la monitorización de las HBPM, la determinación de anti-Xa es, tal vez, la más adecuada dentro de las disponibles en la actualidad. 2…”

Efficacy and tolerance of selective and non-selective factor Xa inhibitors in the prevention of thrombosis in kidney disease in patients with systemic lupus erythematosus and antiphospholipid syndrome

“…Результаты фармакокинетических испытаний свидетельствуют об ассоциации между КК и показателем аХа. За небольшим исключением [17,18], большинство авторов выявили корреляцию между снижением СКФ и нарастанием аХа [9]. В нашем исследовании также наблюдалась зависимость уровня аХа от КК у больных АФСн.…”

“…Однако доказательства этих рекомендаций противоречивы. Результаты недавних исследований показали, что уменьшение дозы тинзапарина на 25 или 50% у больных со среднетяжелой и тяжелой ХПН соответственно привело к достижению адекватного терапевтического уровня аХа только в 7,7% случаев [17].…”