BACKGROUND: The study aimed to evaluate the agreement of prescribed drug dosages with renal dosing recommendations and describe adverse drug events (ADEs) contributing to hospital admissions of patients with chronic kidney disease (CKD). METHODS: This cross-sectional study focused on CKD patients admitted to University Hospital Hradec Králové, with an estimated glomerular filtration rate below 60 ml/min. The necessity for renal dosage adjustments was determined using the Summary of Product Characteristics (SmPC). For medications requiring renal dosage adjustment according to SmPC, agreement between the prescribed and recommended renal dosage was assessed. ADEs were adjudicated using the OPERAM drug-related hospital admissions adjudication guide. RESULTS: Of 375 CKD patients, 112 (30%, 95% CI 25-34) were prescribed drug dosages in disagreement with SmPC renal dosage recommendations. Perindopril, metformin, and ramipril were most frequently dosed in disagreement with SmPC. ADE-related hospital admissions occurred in 20% (95% CI 16-24) of CKD patients. CONCLUSION: CKD patients are often prescribed medication dosages in disagreement with SmPC renal dosing recommendations. Besides explicit factors, treatment goals, feasibility of monitoring and alternative treatment must be weighed when assessing drug and dosage appropriateness. Gastrointestinal bleeding was the most frequent ADE that contributed to hospital admissions of CKD patients.
The aim of this study was to determine the thrombogenicity of lupus anticoagulant (LA) antibodies using a modified thrombin generation assay (TGA) with the addition of activated protein C (APC) in a group of 85 patients with LA-positive samples. Of these, 58 patients had clinical manifestations of antiphospholipid syndrome (APS) according to the Sydney criteria classification, i.e., each patient had thrombosis or foetal loss, and 27 patients did not show any clinical manifestations of APS. A comparison of the two groups' TGA results revealed statistically significant differences (Fisher's test p = 0.0016). The group of patients exhibiting clinical manifestations of APS showed higher thrombogenicity in 56.9% of patients, while the group of patients not yet exhibiting clinical manifestations of APS showed higher thrombogenicity in 25.9% of patients. There were no significant differences in the specificity of the TGA test between the groups of patients exhibiting similar clinical manifestations. Receiver operating characteristic curve analysis showed a more significant relationship (p = 0.0060) for TGA than for LA titre (p = 0.3387). These data suggest that the determination of LA thrombogenicity with the TGA assay leads to an increased prediction of the manifestation of a thromboembolic event. Our findings appear to be particularly relevant for the prediction of thrombotic events in patients with laboratory-expressed APS and no clinical manifestations.
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
Úvod: Ropeginterferon alfa-2b (RopegIFN) prokázal účinnost a bezpečnost u pacientů s pravou polycytémií v multicentrických randomizovaných studiích PROUD-PV a CONTINUATION-PV. Během 4.–5. roku terapie byl prokázán jednoznačný benefit terapie RopegIFN ve srovnání s nejlepší dostupnou terapií, a to jak ve smyslu dosažení kompletní hematologické remise onemocnění, tak i výrazného snížení mutační alelické zátěže JAK2V617F. Materiál a metodika: Retrospektivní neintervenční analýza byla provedena u celkem 14 pacientů s Ph negativními myeloproliferacemi (Ph-MPN) léčených RopegIFN na Interní hematologické a onkologické klinice (IHOK) v období od května 2020 do července 2022. Hodnocena byla data týkající se délky terapie, dávkování, efektu a tolerance terapie. Výsledky: Medián délky terapie v souboru byl 266 dní. Léčeno bylo celkem 14 pacientů, z toho 11 s pravou polycytémií (79 %), 2 s esenciální trombocytémií (14 %) a 1 se sekundární myelofibrózou po pravé polycytémii (7 %). Medián dávky RopegIFN byl 150 μg. Dosažení kompletní hematologické remise bylo u 11 pacientů (79 %). Terapie byla během doby sledování ukončena u 2 pacientů (14 %). Nežádoucí účinky byly zaznamenány u 6 pacientů (43 %), tromboembolická příhoda byla dokumentována u jednoho pacienta (7 %). Závěr: Naše analýza prvotních zkušeností s terapií RopegIFN potvrdila jeho velmi dobrý efekt na kontrolu hematokritu a zároveň výbornou toleranci u pacientů s Ph-MPN.
Background: Ropeginterferon alfa-2b demonstrated efficacy and safety in patients with polycythaemia vera in the PROUD-PV and CONTINUATION-PV multicentric randomised studies. These studies reported the superior effect of ropeginterferon alfa-2b in attaining haematological and molecular remission during the fourth and fifth year of therapy. Patients and Methods: A total of 14 Ph-MPN patients treated with ropeginterferon alfa-2b at our Dept. of Internal Medicine – Haematology and Oncology were analysed from May 2020 to July 2022. Therapy duration, dosing, effect, and tolerance were evaluated. Results: Therapy median duration was 266 days. 14 patients in total were treated; 11 had polycythaemia vera (79%), 2 had essential thrombocythemia (14%), and one patient had secondary myelofibrosis post polycythaemia vera (7%). The median ropeginterferon alfa 2-b dose was 150 μg. Complete haematological remission was attained in 11 (79%) patients. Two patients (14%) had to discontinue treatment. During therapy, six patients (43%) suffered adverse events; only one patient (7%) developed a thromboembolic event. Conclusion: Our initial experience has confirmed the promising effect of ropeginterferon alfa 2-b on haematocrit control and its excellent tolerance among patients.
- Klíčová slova
- Ph negativní myeloproliferativní onemocnění, ropeginterferon alfa‐2 b,
- MeSH
- interferon alfa-2 farmakologie terapeutické užití MeSH
- interferony farmakologie terapeutické užití MeSH
- lidé MeSH
- myeloproliferativní poruchy * farmakoterapie MeSH
- polycythaemia vera * farmakoterapie MeSH
- randomizované kontrolované studie jako téma MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
Antiphospholipid syndrome (APS) is a hypercoagulable state accompanied by the presence of heterogeneous antiphospholipid antibodies (aPL), which nonspecifically affect hemostasis by the presence of lupus anticoagulans (LA), anticardiolipin antibodies (aCL), antibodies against β2-glycoprotein-I (anti-β2GPI), but also non-criteria antibodies such as antibodies against β2-glycoprotein-I domain I (anti-DI), anti-phosphatidylserine/prothrombin (anti-PS/PT), anti-annexin V, and many others. The main target of the antibodies is the activated protein C (APC) system, the elimination of which can manifest itself as a thrombotic complication. The aim of this study was to determine the thrombogenicity of antibodies using a modified protein C-activated thrombin generation assay (TGA) on a group of 175 samples suspected of APS. TGA was measured with/without APC and the ratio of both measurements was evaluated (as for APC resistance), where a cut-off was calculated ≤4.5 (90th percentile) using 21 patients with heterozygous factor V Leiden mutation (FV Leiden heterozygous). Our study demonstrates the well-known fact that multiple positivity of different aPLs is a more severe risk for thrombosis than single positivity. Of the single antibody positivity, LA antibodies are the most serious (p value < 0.01), followed by aCL and their subgroup anti-DI (p value < 0.05). Non-criteria antibodies anti-annexin V and anti-PT/PS has a similar frequency occurrence of thrombogenicity as LA antibodies but without statistical significance or anti-β2GPI1 positivity. The modified TGA test can help us identify patients in all groups who are also at risk for recurrent thrombotic and pregnancy complications; thus, long-term prophylactic treatment is appropriate. For this reason, it is proving increasingly beneficial to include the determination antibodies in combination with modified TGA test.
- MeSH
- antifosfolipidové protilátky MeSH
- antifosfolipidový syndrom * komplikace MeSH
- antikardiolipinové protilátky MeSH
- beta-2-glykoprotein I MeSH
- fosfatidylseriny MeSH
- lidé MeSH
- protein C MeSH
- protrombin MeSH
- těhotenství MeSH
- thrombin MeSH
- trombóza * etiologie MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
The deficiency of natural anticoagulants-antithrombin (AT), protein C (PC), and protein S (PS)-is a highly predisposing factor for thrombosis, which is still underdiagnosed at the genetic level. We aimed to establish and evaluate an optimal diagnostic approach based on a high-throughput sequencing platform suitable for testing a small number of genes. A fast, flexible, and efficient method involving automated amplicon library preparation and target sequencing on the Ion Torrent platform was optimized. The cohort consisted of a group of 31 unrelated patients selected for sequencing due to repeatedly low levels of one of the anticoagulant proteins (11 AT-deficient, 13 PC-deficient, and 7 PS-deficient patients). The overall mutation detection rate was 67.7%, highest in PC deficiency (76.9%), and six variants were newly detected-SERPINC1 c.398A > T (p.Gln133Leu), PROC c.450C > A (p.Tyr150Ter), c.715G > C (p.Gly239Arg) and c.866C > G (p.Pro289Arg), and PROS1 c.1468delA (p.Ile490fs) and c.1931T > A (p.Ile644Asn). Our data are consistent with those of previous studies, which mostly used time-consuming Sanger sequencing for genotyping, and the indication criteria for molecular genetic testing were adapted to this process in the past. Our promising results allow for a wider application of the described methodology in clinical practice, which will enable a suitable expansion of the group of indicated patients to include individuals with severe clinical findings of thrombosis at a young age. Moreover, this approach is flexible and applicable to other oligogenic panels.
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: The effect of direct oral anticoagulants (DOAC) on laboratory tests dependent on the production of their targets, factor IIa and factor Xa, is a well-known problem and can cause both false positive and negative results. In particular, the situation in patients who develop lupus anticoagulant (LA) antibodies is highly complex. To evaluate the effectiveness of DOAC therapy in lupus-positive patients, 31 samples were enrolled in this retrospective study. All patient samples were spiked with three types of DOAC (dabigatran, DABI; rivaroxaban, RIVA; and apixaban, API) in a concentration that significantly influenced the screening test for LA and thus can mask the presence of LA. Subsequently, the DOAC was always unbound by the DOAC-Stop procedure. DOAC levels before and after binding were determined by functional assays, followed by liquid chromatography coupled with mass spectrometry (LC-MS) analysis. METHODS: The determination of DOAC levels was performed by direct thrombin assay and determination of anti-Xa activity with specific calibration as functional tests for DABI and xabans (API and RIVA). To determine concentration levels of API, DABI, and RIVA, our in-house LC-MS method was used. RESULTS: The results of LA-positive samples show significant differences between functional tests and the LC-MS method both before and after DOAC binding. CONCLUSIONS: The acute findings of the presence of LA-type antibodies fundamentally affects the determination of DOAC by functional tests, and in this case, it is necessary to use LC-MS analysis to determine the true value. If patients treated with DOAC develop LA of medium and higher titers, we do not recommend checking DOAC levels with functional tests.
- Publikační typ
- časopisecké články MeSH
