Nicholas Bandarenko
· Associate Professor of PathologyDuke University · Pathology
Active 1994–2020
About
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Research topics
- Business
- Medical emergency
- Medicine
- Surgery
Selected publications
UNC Libraries · 2020-11-05 · 7 citations
articleOpen accessWe sought to describe clinical and laboratory findings for a large cohort of patients with thienopyridine-associated thrombotic thrombocytopenic purpura (TTP).
UNC Libraries · 2020-10-30
articleOpen accessValproic acid and intensified antiretroviral therapy may deplete resting CD4+ T-cell HIV infection. We tested the ability of valproic acid to deplete resting CD4+ T-cell infection in patients receiving standard antiretroviral therapy.
Management of Blood Product Market Withdrawals - A Single Institution's Process and Experience.
2020
- Medicine
- Business
- Medical emergency
OBJECTIVE: While lookback investigations follow specific Food and Drug Administration (FDA) requirements, the management of blood product market withdrawals from suppliers varies widely. Follow-up data are limited, prompting this analysis of the types and reasons for recipient notification and their outcomes. METHODS: A single institution retrospective review of market withdrawal and lookback files from 2012-2015 included product type, reason, FDA category, notification, and turnaround time. Descriptive statistics and chi-square analysis were performed. RESULTS: Over 4 years, 796/229,549 (0.35%) blood components were implicated in supplier notifications, including market withdrawals (84.3%) and lookbacks (15.7%). Seventy-nine cases resulted in patient notification. 97% of patient notifications were achieved within 3 months. Plasma with human leukocyte antigen antibodies was the most common reason for withdrawal (20.5%). Category 1 notifications were the most commonly reported by this transfusion service, apart from in 2015 when category 4 notifications were highest. Over four years, the proportion of notifications by category remained relatively stable. CONCLUSIONS: Market withdrawal investigations involve significant effort to review, document, and appropriately notify. Standardized management and centralized reporting of recipient notification of market withdrawals may improve this process.
Transfusion · 2016-04-22 · 5 citations
articleBACKGROUND: Recent animal studies suggest that transfusion of plasma from young donors reverses age-related neurologic and cardiac changes in older recipients. Associations between age of blood product donors and corresponding outcomes in recipients have not been studied in humans. Therefore, our primary objective was to examine this relationship between donor age and recipient outcomes among patients that received plasma during and after coronary artery bypass grafting (CABG) surgery. STUDY DESIGN AND METHODS: This retrospective cohort included patients undergoing CABG surgery who received plasma during or after surgery. All plasma units transfused were evenly divided into tertiles based on the plasma donor age (17-37, 38-50, and 51-86 years), and CABG patients receiving all perioperative plasma within a single donor tertile were studied. Patient demographics and outcomes including mortality, length of stay (LOS), and acute kidney injury (AKI) were measured. RESULTS: Overall, 1306 patients (24% of 5339) received American Red Cross plasma perioperatively, with a median dose of 2 units. In a multivariate model of 1-year mortality, transfusion of a greater number of plasma units (p = 0.0007) and EuroSCORE (p < 0.0001) were significantly associated with patient mortality while donor age was not. There was no difference in mortality between patients receiving plasma from donors in the youngest, middle, or oldest age tertile (10.2 and 8.1% vs. 7.8%, respectively, p = 0.76). Other outcomes, including rates of AKI or LOS, were also independent of plasma donor age. CONCLUSIONS: We did not observe an association between donor age and recipient outcomes among patients who received plasma perioperatively while undergoing CABG surgery.
Transfusion · 2016-11-23 · 13 citations
articleBACKGROUND Randomized trials, for example, RECESS, comparing “young” (median, 7‐day) versus “middle‐aged” (median, 28‐day) red blood cells (RBCs), showed no difference in outcome. These data are important; however, they do not inform us about the safety and effectiveness of the oldest RBCs, which some patients receive. It may not be feasible to conduct a clinical trial randomizing patients to receive the oldest blood. Therefore, we propose strenuous exercise (VO 2 max testing) as a model to study the relative efficacy to increase oxygen delivery to tissue of different RBC products, for example, extremes of storage duration. STUDY DESIGN AND METHODS In this pilot study, eight healthy subjects had 2 units of leukoreduced RBCs collected by apheresis in AS‐3 using standard methods. Subjects were randomized to receive both (2) units of their autologous RBCs at either 7 or 42 days after blood collection. VO 2 max testing on a cycle ergometer was performed 2 days before (Monday) and 2 days after (Friday) the transfusion visit (Wednesday). This design avoids confounding effects on intravascular volume from the 2‐unit blood transfusion. The primary outcome was the difference in VO 2 max between Friday and Monday (delta VO 2 max). RESULTS VO 2 max increased more in the 7‐day RBC arm (8.7 ± 6.9% vs. 1.9 ± 6.5%, p = 0.202 for comparison between arms). Exercise duration (seconds) increased in the 7‐day RBC arm (8.4 ± 1.7%) but actually decreased in the 42‐day arm (−2.6 ± 3.6%, p = 0.002). CONCLUSIONS This pilot study suggests that VO 2 max testing has potential as a rigorous and quantitative in vivo functional assay of RBC function. Our preliminary results suggest that 42‐day RBCs are inferior to 7‐day RBCs at delivering oxygen to tissues.
Management of Gardner–Diamond syndrome with therapeutic plasma exchange
Journal of Clinical Apheresis · 2016-08-17 · 7 citations
letterSenior authorRandomized study of washing 40‐ to 42‐day‐stored red blood cells
Transfusion · 2014-04-16 · 34 citations
articleOpen accessBACKGROUND: Pretransfusion washing of red blood cells (RBCs) stored for a longer duration may have theoretical advantages but few data exist to support this practice. In many hospital settings, use of a point-of-care cell washer could conceivably be used to quickly wash allogeneic RBCs before transfusion. The purpose of this preliminary study was to compare a point-of-care device with a common blood bank device for washing longer-stored RBCs. STUDY DESIGN AND METHODS: Forty RBC units stored for 40 to 42 days were randomized to washing with the COBE 2991 device (Terumo BCT; FDA-cleared for washing stored RBCs) or the Cell Saver Elite (Haemonetics; FDA-cleared point-of-care device for processing and washing fresh autologous shed whole blood). Supernatant and unit RBCs from unwashed (baseline) and washed blood were assayed for potassium, lactate, intracellular ATP, percentage of RBC recovery, cell-free hemoglobin, RBC microparticles, and RBCs were examined for susceptibility to hemolysis by physical stress. RESULTS: Both devices recovered a high percentage of RBCs and efficiently removed extracelluar potassium. Washing with the Elite resulted in significant increases in cell-free Hb, percent hemolysis, and RBC microparticle production, whereas washing with the COBE 2991 did not (fold Δ = 2.1 vs. 1.0, 4.6 vs. 1.2, 2.0 vs. 1.1, respectively; p < 0.05). Hemolysis induced by physical stress was not altered by washing. CONCLUSION: Although point-of-care washing of longer-stored RBCs is appealing, these preliminary data suggest that transfusion of washed, longer-stored units could result in potentially greater exposure to plasma free Hb. More data are needed before this practice can be routinely recommended.
Early Human Development · 2014-03-02 · 65 citations
articleOpen accessBritish Journal of Haematology · 2013-03-27 · 26 citations
letterOpen accessThrombotic thrombocytopenic purpura (TTP) is a life-threatening generalized disorder. The classic TTP ‘pentad’ is thrombocytopenia, microangiopathic hemolytic anemia (MAHA), renal impairment, neurological symptoms, and fever (Amorosi & Ultmann, 1966). Laboratory studies identified deficiency of plasma ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 motifs 13) activity (ADAMTS13:AC) among some TTP patients (Furlan et al, 1998; Tsai & Lian, 1998). ADAMTS13 cleaves the peptide bond between Thy1605 and Met1606 in the A2 domain of von Willebrand factor (VWF) subunit. VWF is released into the plasma as unusually large VWF multimers (UL-VWFMs), which are degraded into smaller size VWF multimers by ADAMTS13. In the late 1990's, studies in the United States identified 117 cases of TTP that developed after initiation of the thienopyridine, ticlopidine; although at that time, ADAMTS13 activity levels were not widely available (Bennett et al, 1999; Steinhubl et al, 1999). A study of seven patients in the United States with ticlopidine-associated TTP found that all seven had severe deficiency of ADAMTS13 activity and five had detectable antibodies to ADAMTS13 activity (Tsai et al, 2000). We now report on 22 individuals from Japan with ticlopidine-induced TTP and compare these findings to those from the United States. Ticlopidine was the primary anti-platelet agent in Japan from 1989 to 2006. Since 1998, our laboratory at Nara Medical University has been a nationwide referral centre in Japan for thrombotic microangiopathies (TMAs), including TTP (Fujimura & Matsumoto, 2010). The study protocol was approved by the Ethics Committee of Nara Medical University Hospital. TTP diagnostic criteria were: microangiopathic haemolytic anaemia (haemoglobin ≤120 g/l), Coombs test negative, undetectable serum haptoglobin (<1 μmol/l), more than 2 fragmented red cells (schistocytes) in a microscopic field with ×100 magnification, increased serum lactate dehydrogenase (LDH) above institutional baseline, thrombocytopenia (platelet count ≤100 × 109/l), absence of evidence for disseminated intravascular coagulation and no other identifiable cause of TTP. Additional information on fever ≥37°C; and central nervous system and renal function data were abstracted. Patients were included if, in addition to criteria for idiopathic TTP, the patient had received ticlopidine prior to TTP onset. Before therapeutic plasma exchange or plasma infusion was initiated, whole blood samples (five ml) were withdrawn from each patient and placed into plastic tubes containing 1/10 volume of 3·2% sodium citrate. Plasma was separated by centrifugation at 3000 g for 15 min at 4°C, kept in aliquots at −80°C until testing, and sent to our laboratory with clinical information. Until March 2005, ADAMTS13:AC was determined by classic VWF multimer (VWFM) assay with a detection limit of 3% of the normal control (Furlan et al, 1996; Kinoshita et al, 2001). Thereafter, a chromogenic ADAMTS13-act-enzyme-linked immunosorbent assay (ELISA) with a detection limit of 0·5% of the normal control was developed, and replaced the VWFM assay. Plasma ADAMTS13 inhibitor (ADAMTS13:INH) titres were analysed either by classic VWFM assay or chromogenic ADAMTS13-act-ELISA using heat-inactivated plasmas at 56°C for 30 min. A total of 22 ticlopidine-associated TTP patients fulfilled the inclusion criteria (Table 1). Age at diagnosis ranged from 41 to 89 years, with the median age of onset of 69 years. Females accounted for 45·5% of the cohort. Ticlopidine had been administered for a median of 27·5 d (range, 14–35 d) but was discontinued after a clinical diagnosis of TTP was made. Median values for hemoglobin were 83 (60–146) g/l, platelets 9·5 (3–57) × 109/l, and serum creatinine 132·6 (35–380) μmol/l. Abnormal neurological findings were noted in 63·6%. All of the patients had <5% ADAMTS13:AC activity and detectable inhibitors to ADAMTS13 at the time of presentation. ADAMTS13:INH titres were 0·5 to <1·0 Bethesda units (BU)/ml in 4·5% of the patients, 1·0 to <2·0 BU/ml in 13·5%, 2·0 to <5·0 BU/ml in 45·5%, 5·0 to <10 BU/ml in 18·2%, and 4·5% of the patients had ADAMTS13:INH titres of ≥10 BU/ml. Mortality during the acute TTP episode was 9·0%. Mortality was highest among persons 60 years of age or older (10·0% vs. 0·0%). Therapeutic plasma exchange was performed in 72·7%, at a median of 3 d after the onset of TTP (range 1–5 d), and the TTP resolved at a median of 8 d (range 3–28 d). Among four patients whose TTP cleared after 20 or more days of therapeutic plasma exchange, ADAMTS13:INH titres were 2,4·4, 17, and 20 BU/ml. Among 12 patients whose TTP resolved with therapeutic plasma exchange at <20 d, none had ADAMTS13:INH titres >4 BU/ml. Both ticlopidine-associated TTP deaths did not receive therapeutic plasma exchange. To our knowledge, this is the first study to report detailed characteristics of ticlopidine-associated TTP among patients outside of the United States. Our findings, from a cohort of ticlopidine-associated TTP patients in Japan, identified severe ADAMTS13 deficiency and antibodies to ADAMTS13 in 100% of these 22 individuals. A decade earlier, severe ADAMTS13 deficiency was reported in 100% of seven patients with ticlopidine-associated TTP in the Uni ted States and antibodies to ADAMTS13 in five of these patients (Bennett et al, 1999; Tsai et al, 2000). While ticlopidine-induced TTP is undoubtedly a rare disease, it is reassuring that the original observations reported from the United States have been independently replicated in Japan (Bennett et al, 1999; Steinhubl et al, 1999). Limitations of our study should be identified. Follow-up ended at the time of hospital discharge, which prevented us from reporting on relapse rates. Ticlopidine is rarely used today, having been replaced by clopidogrel in 1999 because of safety concerns. Our research has shown that clopidogrel, unlike ticlopidine, does not lead to ADAMTS13 antibody formation and deficiency of ADAMTS13 activity and the rare cases of clopidogrel-associated TTP are not responsive to therapeutic plasma exchange. Also, very little is known about TTP associated with prasugrel (the newest thienopyridine), despite 14 cases of prasugrel-associated TTP having been reported to the Food and Drug Administration in 2009 and 2010 (Jacob et al, 2012). Careful pharmacovigilance to identify severe adverse drug reactions developing among small numbers of persons can serve as important warning signals for potentially serious adverse drug events internationally. This work was supported in part by grants-in-aid from the National Heart Lung and Blood Institute (1R01 HL–096 717 to (CLB)) and (P01-HL074124-project 3 to (XLZ)); the National Cancer Institute (R01 CA102713 , 1R01CA165609-01A1, and 1R01HL71650-01 to (CLB) and1K01CA134554-01 to (JMM) and 1R01CA165609-01A1 to (ZQ)); the Ministry of Health, Labour, and Welfare of Japan (YF), the Takeda Science Foundation (YF); and the Centers for Disease Control and Prevention (DD000014 (TLO)). We also thank Ms. Ayami Isonishi for her excellent technical assistance for assaying ADAMTS13 activity and inhibitors.
Posttransfusion thrombocytopenia: a cautionary tale of female group <scp>AB</scp> plasma
Transfusion · 2013-09-01
letter
Frequent coauthors
- 55 shared
Dilip K. Pandey
Okinawa Institute of Science and Technology Graduate University
- 52 shared
Anaadriana Zakarija
Northwestern University
- 51 shared
Charles L. Bennett
- 48 shared
Paul R. Yarnold
Optimal Solutions (United States)
- 47 shared
June M. McKoy
- 45 shared
Hau C. Kwaan
- 44 shared
Benjamin Kim
- 41 shared
Richard J. Kowalsky
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