Potential of Dried Blood Self-Sampling for CyclosporineC2Monitoring in Transplant Outpatients

Background. Close therapeutic drug monitoring of Cyclosporine (CsA) in transplant outpatients is a favourable procedure to maintain the long-term blood drug levels within their respective narrow therapeutic ranges. Compared to basal levels (C0), CsA peak levels (C2) are more predictive for transplant rejection. However, the application ofC2levels is hampered by the precise time of blood sampling and the need of qualified personnel. Therefore, we evaluated a newC2self-obtained blood sampling in transplant outpatients using dried capillary and venous blood samples and compared the CsA levels, stability, and clinical practicability of the different procedures.Methods. 55 solid organ transplant recipients were instructed to use single-handed sampling of each 50μL capillary blood and dried blood spots by finger prick using standard finger prick devices. We used standardized EDTA-coated capillary blood collection systems and standardized filter paper WS 903. CsA was determined by LC-MS/MS. The patients and technicians also answered a questionnaire on the procedure and sample quality.Results. TheC0andC2levels from capillary blood collection systems (C0[ng/mL]:114.5±44.5;C2:578.2±222.2) and capillary dried blood (C0[ng/mL]:175.4±137.7;C2:743.1±368.1) significantly(P<.01)correlated with the drug levels of the venous blood samples (C0[ng/mL]:97.8±37.4;C2:511.2±201.5). The correlation atC0wasρcap.-ven.= 0.749, andρdried blood-ven= 0.432; atC2: ρcap.-ven.= 0.861 andρdried blood-ven= 0.711. The patients preferred the dried blood sampling because of the more simple and less painful procedure. Additionally, the sample quality of self-obtained dried blood spots for LC-MS/MS analytics was superior to the respective capillary blood samples.Conclusions.C2self-obtained dried blood sampling can easily be performed by transplant outpatients and is therefore suitable and cost-effective for close therapeutic drug monitoring.

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Self-sampling of capillary blood for serological testing of SARS-CoV-2 by COVID-19 IgG ELISA

10.1101/2020.09.25.20183459 ◽

2020 ◽

Author(s):

Lottie Brown ◽

Rachel Louise Byrne ◽

Alice Fraser ◽

Sophie I Owen ◽

Ana I Cubas Atienzar ◽

...

Keyword(s):

Large Scale ◽

Venous Blood ◽

Dried Blood Spots ◽

Capillary Blood ◽

Blood Collection ◽

Serological Testing ◽

Perfect Agreement ◽

Blood Samples ◽

Large Scale Testing ◽

Feasible Alternative

Serological testing is emerging as a powerful tool to progress our understanding of COVID-19 exposure, transmission and immune response. Large-scale testing is limited by the need for in-person blood collection by staff trained in venepuncture. Capillary blood self-sampling and postage to laboratories for analysis could provide a reliable alternative. Two-hundred and nine matched venous and capillary blood samples were obtained from thirty nine participants and analysed using a COVID-19 IgG ELISA to detect antibodies against SARS-CoV-2. Thirty seven out of thirty eight participants were able to self-collect an adequate sample of capillary blood (≥50 μl). Using plasma from venous blood collected in lithium heparin as the reference standard, matched capillary blood samples, collected in lithium heparin-treated tubes and on filter paper as dried blood spots, achieved a Cohen′s kappa coefficient of >0.88 (near-perfect agreement). Storage of capillary blood at room temperature for up to 7 days post sampling did not affect concordance. Our results indicate that capillary blood self-sampling is a reliable and feasible alternative to venepuncture for serological assessment in COVID-19.

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Self-sampling of capillary blood for SARS-CoV-2 serology

Scientific Reports ◽

10.1038/s41598-021-86008-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lottie Brown ◽

Rachel L. Byrne ◽

Alice Fraser ◽

Sophie I. Owen ◽

Ana I. Cubas-Atienzar ◽

...

Keyword(s):

Large Scale ◽

Venous Blood ◽

Dried Blood Spots ◽

Capillary Blood ◽

Blood Collection ◽

Perfect Agreement ◽

Blood Samples ◽

Large Scale Testing ◽

Feasible Alternative ◽

Lateral Flow Tests

AbstractSerological testing is emerging as a powerful tool to progress our understanding of COVID-19 exposure, transmission and immune response. Large-scale testing is limited by the need for in-person blood collection by staff trained in venepuncture, and the limited sensitivity of lateral flow tests. Capillary blood self-sampling and postage to laboratories for analysis could provide a reliable alternative. Two-hundred and nine matched venous and capillary blood samples were obtained from thirty nine participants and analysed using a COVID-19 IgG ELISA to detect antibodies against SARS-CoV-2. Thirty eight out of thirty nine participants were able to self-collect an adequate sample of capillary blood (≥ 50 µl). Using plasma from venous blood collected in lithium heparin as the reference standard, matched capillary blood samples, collected in lithium heparin-treated tubes and on filter paper as dried blood spots, achieved a Cohen’s kappa coefficient of > 0.88 (near-perfect agreement, 95% CI 0.738–1.000). Storage of capillary blood at room temperature for up to 7 days post sampling did not affect concordance. Our results indicate that capillary blood self-sampling is a reliable and feasible alternative to venepuncture for serological assessment in COVID-19.

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Dried Blood Spot Analysis Suitable for Therapeutic Drug Monitoring of Voriconazole, Fluconazole, and Posaconazole

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00707-13 ◽

2013 ◽

Vol 57 (10) ◽

pp. 4999-5004 ◽

Cited By ~ 36

Author(s):

Kim C. M. van der Elst ◽

Lambert F. R. Span ◽

Kai van Hateren ◽

Karin M. Vermeulen ◽

Tjip S. van der Werf ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Sampling Method ◽

Fungal Infections ◽

Venous Blood ◽

Blood Sampling ◽

Dried Blood Spot ◽

Therapeutic Drug ◽

Venous Blood Sampling ◽

Blood Spot

ABSTRACTInvasive aspergillosis and candidemia are important causes of morbidity and mortality in immunocompromised and critically ill patients. The triazoles voriconazole, fluconazole, and posaconazole are widely used for the treatment and prophylaxis of these fungal infections. Due to the variability of the pharmacokinetics of the triazoles among and within individual patients, therapeutic drug monitoring is important for optimizing the efficacy and safety of antifungal treatment. A dried blood spot (DBS) analysis was developed and was clinically validated for voriconazole, fluconazole, and posaconazole in 28 patients. Furthermore, a questionnaire was administered to evaluate the patients' opinions of the sampling method. The DBS analytical method showed linearity over the concentration range measured for all triazoles. Results for accuracy and precision were within accepted ranges; samples were stable at room temperature for at least 12 days; and different hematocrit values and blood spot volumes had no significant influence. The ratio of the drug concentration in DBS samples to that in plasma was 1.0 for voriconazole and fluconazole and 0.9 for posaconazole. Sixty percent of the patients preferred DBS analysis as a sampling method; 15% preferred venous blood sampling; and 25% had no preferred method. There was significantly less perception of pain with the DBS sampling method (P= 0.021). In conclusion, DBS analysis is a reliable alternative to venous blood sampling and can be used for therapeutic drug monitoring of voriconazole, fluconazole, and posaconazole. Patients were satisfied with DBS sampling and had less pain than with venous sampling. Most patients preferred DBS sampling to venous blood sampling.

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An Assessment of Dried Blood-Spot Technology for Identifying Iron Deficiency

Blood ◽

10.1182/blood.v92.5.1807 ◽

1998 ◽

Vol 92 (5) ◽

pp. 1807-1813 ◽

Cited By ~ 38

Author(s):

James D. Cook ◽

Carol H. Flowers ◽

Barry S. Skikne

Keyword(s):

Iron Deficiency ◽

Transferrin Receptor ◽

Venous Blood ◽

Dried Blood Spots ◽

Epidemiologic Studies ◽

Capillary Blood ◽

Deficiency Anemia ◽

Blood Samples ◽

Blood Spots ◽

American Society

Abstract The present study was undertaken to assess the feasibility of using ferritin and transferrin receptor measurements on dried capillary blood spots to identify iron deficiency (ID) in public health surveys. Measurements on serum and blood spots prepared from venous blood were performed in 71 healthy subjects, 41 of whom were iron-replete and 30 who had ID, either without (n = 20) or with (n = 10) anemia. Parallel measurements were performed on hemolyzed whole blood and washed hemolyzed red blood cells to assess the erythrocyte contribution of ferritin and transferrin receptor to dried blood samples. The concentration of ferritin in dried blood samples was threefold higher than serum assays due to the release of ferritin from hemolyzed erythrocytes, which diminished the usefulness of ferritin measurements for detecting ID. On the other hand, there was negligible erythrocyte contribution to the measurement of transferrin receptor in dried blood spots. The most sensitive parameter in dried blood spots was the ratio of receptor/ferritin, which was suitable for identifying iron-deficiency anemia (IDA), but less reliable than serum assays for detecting milder ID without anemia. We conclude that tandem measurements of serum ferritin and transferrin receptor in dried blood spots can be used to facilitate the identification of IDA in epidemiologic studies. © 1998 by The American Society of Hematology.

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Real-life isoniazid and rifampicin plasma concentrations in children: a tool for therapeutic drug monitoring of tuberculosis

BMC Infectious Diseases ◽

10.1186/s12879-021-06764-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chiara Tersigni ◽

Giulia Boiardi ◽

Lorenzo Tofani ◽

Elisabetta Venturini ◽

Carlotta Montagnani ◽

...

Keyword(s):

Plasma Concentration ◽

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Venous Blood ◽

Plasma Concentrations ◽

Age Groups ◽

Real Life ◽

Therapeutic Drug ◽

Blood Samples ◽

Drug Concentrations

Abstract Background Low plasma levels of first-line antitubercular drugs can be counted among the main causes of poor response to antitubercular therapy, and therapeutic drug monitoring has been proposed as a method to promote tailored treatments for both child and adult patients. The main aim of the study was to evaluate serum concentrations of isoniazid (INH) and rifampicin (RIF) and to investigate reasons for sub-therapeutic plasma concentrations in order to fix dosages. Methods Children with TB were prospectively enrolled from January to August 2019. Two venous blood samples were collected (the first at least 15 days after the beginning of antitubercular treatment, and the second between 1 and 8 weeks later). Plasma concentrations were determined by a validated high-performance liquid chromatography method. Results In all, 45 children were included. Seventy blood samples for INH plasma concentration were collected between 120 and 240 min after drug intake. Adjusting for dose (mg/kg/day) and time of INH administration, when considering three different age groups (≤ 2 years, 2–12 years, > 12 years), a statistically significant lower INH plasma concentration was observed in younger children compared to the older age groups in the multivariate analysis (p < 0.001 and p < 0.001). A total of 68 blood samples were evaluated for RIF concentrations. Both for INH and RIF a statistically significant lower plasma concentration was also observed in adolescents (p < 0.001). Fifteen children (15/45, 33%) presented drug concentrations under the referral therapeutic range. Conclusions Based on our findings, monitoring patients’ drug plasma concentrations in children under 2 years of age and in adolescents can make treatment more patient-tailored.

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Developing a Nationwide Infrastructure for Therapeutic Drug Monitoring of Targeted Oral Anticancer Drugs: The ON-TARGET Study Protocol

Cancers ◽

10.3390/cancers13246281 ◽

2021 ◽

Vol 13 (24) ◽

pp. 6281

Author(s):

Anna Mc Laughlin ◽

Eduard Schmulenson ◽

Olga Teplytska ◽

Sebastian Zimmermann ◽

Patrick Opitz ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Anticancer Drugs ◽

Drug Monitoring ◽

Drug Exposure ◽

Plasma Concentrations ◽

Blood Sampling ◽

Therapeutic Drug ◽

Study Phase ◽

Blood Samples ◽

Drug Concentrations

Exposure-efficacy and/or exposure-toxicity relationships have been identified for up to 80% of oral anticancer drugs (OADs). Usually, OADs are administered at fixed doses despite their high interindividual pharmacokinetic variability resulting in large differences in drug exposure. Consequently, a substantial proportion of patients receive a suboptimal dose. Therapeutic Drug Monitoring (TDM), i.e., dosing based on measured drug concentrations, may be used to improve treatment outcomes. The prospective, multicenter, non-interventional ON-TARGET study (DRKS00025325) aims to investigate the potential of routine TDM to reduce adverse drug reactions in renal cell carcinoma patients receiving axitinib or cabozantinib. Furthermore, the feasibility of using volumetric absorptive microsampling (VAMS), a minimally invasive and easy to handle blood sampling technique, for sample collection is examined. During routine visits, blood samples are collected and sent to bioanalytical laboratories. Venous and VAMS blood samples are collected in the first study phase to facilitate home-based capillary blood sampling in the second study phase. Within one week, the drug plasma concentrations are measured, interpreted, and reported back to the physician. Patients report their drug intake and toxicity using PRO-CTCAE-based questionnaires in dedicated diaries. Ultimately, the ON-TARGET study aims to develop a nationwide infrastructure for TDM for oral anticancer drugs.

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Finger-Prick Blood Sampling for Therapeutic Drug Monitoring

Therapeutic Drug Monitoring ◽

10.1097/ftd.0000000000000746 ◽

2020 ◽

Vol 42 (3) ◽

pp. 512-513

Author(s):

Brenda C. M. de Winter ◽

Matthijs de Hoog ◽

Nienke J. Vet ◽

Joke H. Dunk-Craaijo ◽

Birgit C. P. Koch ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Blood Sampling ◽

Therapeutic Drug ◽

Finger Prick

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Volumetric Microsampling of Capillary Blood Spot vs Whole Blood Sampling for Therapeutic Drug Monitoring of Tacrolimus and Cyclosporin A: Accuracy and Patient Satisfaction

The Journal of Applied Laboratory Medicine ◽

10.1093/jalm/jfaa005 ◽

2020 ◽

Vol 5 (3) ◽

pp. 516-530

Author(s):

Michael M Mbughuni ◽

Maria A Stevens ◽

Loralie J Langman ◽

Yogish C Kudva ◽

William Sanchez ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Cyclosporin A ◽

Drug Monitoring ◽

Whole Blood ◽

Solid Phase ◽

Venous Blood ◽

Therapeutic Drug ◽

Blood Collection ◽

Clinical Validation ◽

Transplant Patients

Abstract Background Immunosuppressant therapeutic drug monitoring (TDM) usually requires outpatient travel to hospitals or phlebotomy sites for venous blood collection; however Mitra® Microsampling Device (MSD) sampling could allow self-collection and shipping of samples to a laboratory for analysis. This study examined the feasibility of using volumetric microsampling by MSD for TDM of tacrolimus (TaC) and cyclosporin A (CsA) in transplant patients, along with their feedback on the process. Methods MSD was used to collect TaC and CsA from venous (VB) or capillary (CB) blood. The MSDs were rehydrated, extracted, and analyzed using on-line solid phase extraction coupled to tandem mass spectrometry (SPE-MS/MS). We report an abbreviated method validation of the MSD including: accuracy, precision, linearity, carry-over, and stability using residual venous whole blood (VB) samples. Subsequent clinical validation compared serially collected MSD + CB against VB (200 µL) from transplant patients. Results Accuracy comparing VB vs. MSD+VB showed high clinical concordance (TaC = 89% and CsA = 98%). Inter- and intra-precision was ≤11.5 %CV for TaC and CsA. Samples were stable for up to 7 days at room temperature with an average difference of <10%. Clinical validation with MSD+CB correlated well with VB for CsA (slope = 0.95, r2 = 0.88, n = 47) and TaC (slope = 0.98, r2 = 0.82, n = 49). CB vs. VB gave concordance of 94% for CsA and 79% for TaC. A satisfaction survey showed 82% of patients preferred having the capillary collection option. Conclusion Transplant patients favored having the ability to collect capillary samples at home for TaC/CsA monitoring. Our results demonstrate good concordance between MSD+CB and VB for TaC and CsA TDM, but additional studies are warranted.

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