Robert W. Maitta - Academia.edu (original) (raw)

Papers by Robert W. Maitta

Research paper thumbnail of Pathological Mechanisms and Novel Testing Methods in Thrombotic Thrombocytopenic Purpura

Biomedicines, Mar 11, 2024

Research paper thumbnail of Editorial: Transfusion medicine and blood, volume II

Frontiers in medicine, May 21, 2024

Research paper thumbnail of Apheresis collection of mononuclear cells for chimeric‐antigen receptor therapies

European Journal of Haematology, Aug 1, 2023

Research paper thumbnail of Challenges Facing Transfusion Practices

Transfusion Medicine has rapidly evolved in the last few decades to become a medical discipline t... more Transfusion Medicine has rapidly evolved in the last few decades to become a medical discipline taking the spotlight as new clinical trials and literature on the appropriate use of blood components become available. In light of these rapid changes, challenges in the coming years are becoming more apparent to professionals in the field, which will likely affect clinical practices throughout disciplines. For this reason, approaches that take into account blood donations in the setting of more conservative and judicious use of blood components is paramount to have a sustainable blood supply that can meet the demands of a population that will likely require more components as a growing proportion of older recipients become more susceptible to diseases requiring transfusion support. However, this needs to be done in a background of practices based on the strongest available evidence in the medical literature to avoid the pitfalls that misuse of blood components or lack of understanding of the complexities of transfusion can bring about. Therefore, rather than this being only a Transfusion Medicine challenge, it represents a major Medical challenge.

Research paper thumbnail of Impact of Lenalidomide on Hematopoietic Myeloid and Erythroid Progenitors: Peripheral Stem Cell Collection May Not be Affected

Biology of Blood and Marrow Transplantation, Mar 1, 2017

P < .04). (Figure 1A). Also, the ratio of CD34 cells to Plt was higher in the first day of collec... more P < .04). (Figure 1A). Also, the ratio of CD34 cells to Plt was higher in the first day of collection in comparison to subsequent days (2.57 vs. 2.12, P < .045) (Figure 1B). The total number of collected CD34 cells was inversely correlated with collected Plt in pts who had more than one-day collection. Mean time to neutrophil and platelet engraftment was not statistically different between Plt High vs. Plt Low (10. 21 vs. 11.49, days P = .09; 19.95 vs. 20.9 days, P = .16, respectively). Median progression free survival was not different between the two groups with a median follow up of 30 months (27.7 vs. 25.7 months, P = .23). Conclusion: Although there was a trend towards faster engraftment with Plt High than Plt Low , it did not reach statistical significance. Further studies paired with pertinent platelet and megakaryocyte assays are needed to delineate the possible influence of platelets on CD34 homing and engraftment (Figures 2, 3).

Research paper thumbnail of Absolute Immature Platelet Counts Suggest Platelet Production Suppression during Complicated Relapsing Thrombotic Thrombocytopenic Purpura

Acta Haematologica, Nov 25, 2020

Absolute immature platelet counts (A-IPC) aid in diagnosis and treatment follow-up in thrombotic ... more Absolute immature platelet counts (A-IPC) aid in diagnosis and treatment follow-up in thrombotic thrombocytopenic purpura (TTP). A-IPC was used to follow a patient on mycophenolate mofetil (MMF) maintenance therapy treated with a prolonged therapeutic plasma exchange (TPE) regimen for relapsing TTP. On admission, the platelet (PLT) count was 95 × 109/L declining to 14 × 109/L in 5 days. Daily TPE was initiated for suspected TTP, and MMF was discontinued. A-IPC and PLT count were 1 × 109/L and 14 × 109/L, respectively, prior to first TPE. A-IPC improved to 3.2 × 109/L with 1 TPE, and on day 5, A-IPC and PLT count were 7.5 × 109/L and 218 × 109/L, respectively. On day 6, A-IPC and PLT count decreased to 4.8 × 109/L and 132 × 109/L further worsening to 0.4 × 109/L and 13 × 109/L, respectively. ADAMTS13 activity remained &lt;5% with an inhibitor; counts did not recover. Initial improvement followed by rapidly declining A-IPC despite therapy suggested production suppression. In TTP, A-IPC may aid in establishing early therapy effects over PLT production.

Research paper thumbnail of Current state of apheresis technology and its applications

Transfusion and Apheresis Science, Oct 1, 2018

Research paper thumbnail of Alloimmunisation rates of sickle cell disease patients in the United States differ from those in other geographical regions

Transfusion Medicine, May 20, 2016

Comparison of the alloimmunisation rates of patients with sickle cell disease in the Unites State... more Comparison of the alloimmunisation rates of patients with sickle cell disease in the Unites States versus other countries.

Research paper thumbnail of Alpha synuclein in hematopoiesis and immunity

Heliyon, Oct 1, 2019

Parkinson's disease (PD) is the second most common neurodegenerative condition and intracellular ... more Parkinson's disease (PD) is the second most common neurodegenerative condition and intracellular deposition of Lewy bodies in the substantia nigra (SN), which can cause dopaminergic neuronal death, is the hallmark of this syndrome. α-synuclein (syn) is a small protein expressed mainly in neurons but can also be found in a number of tissues. It can be present as a soluble monomer under normal physiological conditions, but can be toxic in its oligomeric or fibrillary forms. Most of the available literature has focused on the effects of α-syn pathology in the mechanisms leading to PD. However, the normal functions of α-syn still remain to be fully elucidated. Notably, α-syn in the hematopoietic system seems to mediate important functions as indicated by anemia and incomplete cell maturation when this protein is absent. This review will summarize basic genetic and structural findings, and critical information that suggests an essential role of α-syn in the development and activation of the hematopoietic system and immunity.

Research paper thumbnail of Chronic red cell exchange in sickle cell patients with iron overload may not affect mortality

Frontiers in Medicine, Sep 27, 2022

Chronic red cell exchange in sickle cell patients with iron overload may not a ect mortality. Fro... more Chronic red cell exchange in sickle cell patients with iron overload may not a ect mortality. Front. Med. :. doi: .

Research paper thumbnail of Use of a whole‐cell ELISA to detect additional antibodies in setting of suspected heparin‐induced thrombocytopenia

European Journal of Haematology, Jun 13, 2019

Objectives:Type II heparin-induced thrombocytopenia (HIT) is mediated by formation of antibodies ... more Objectives:Type II heparin-induced thrombocytopenia (HIT) is mediated by formation of antibodies to platelet factor 4 (PF4)-heparin complexes. We evaluated anti-PF4-heparin negative samples for presence of additional anti-platelet and anti-red blood cell (RBC) antibodies using whole-cell platelet/ RBC ELISAs we developed.Methods:Seventy-three samples tested for anti-PF4-heparin by ELISA were included: 62 tested negative, 9 tested positive, and 2 had equivocal results. Plasma specimens from healthy donors were used as controls.Results:100% (9/9) anti-PF4 positive samples had anti-platelet antibodies detected by whole-cell platelet ELISA. 42.2% (27/64) anti-PF4-heparin negative samples were negative for anti-platelet and anti-RBC antibodies. 32.8% (21/64) negative samples showed reactivity to both platelets and RBC; 12.5% (8/64) negative samples were each reactive with either platelet or RBC ELISA respectively. Additionally, two samples that tested equivocal by anti-PF4-heparin ELISA had antibodies to both platelets and RBC by whole-cell ELISA.Conclusions: Our study suggests that patients with thrombocytopenia testing negative for anti-PF4-heparin may still harbor antibodies to platelets. However, additional research is needed to determine the significance of these antibodies. Nevertheless, these findings may encourage clinicians to further investigate patients with possible immune-mediated etiologies of thrombocytopenia and anemia.

Research paper thumbnail of The Safety of the Blood Supply--Time to Raise the Bar

The New England Journal of Medicine, Aug 27, 2015

To the Editor: In their Perspective article on pathogen-reduction technology (PRT) (May 14 issue)... more To the Editor: In their Perspective article on pathogen-reduction technology (PRT) (May 14 issue),1 Snyder et al. praise the value of this technology. However, they omit a discussion of concerns about the safety and efficacy of PRT, stating that “Numerous studies demonstrate little substantive negative effect from pathogen reduction on plasma proteins or platelets.” A study in the Netherlands was terminated because of increased bleeding complications in the PRT group,2 and a U.S. study documented five fatal cases of the acute respiratory distress syndrome in the PRT group (1.6%) versus none in the control group.3 Furthermore, PRT fails to inactivate some pathogens, such as the hepatitis E virus. Among bacterial pathogens, PRT was not 100% effective against high levels of certain Klebsiella pneumoniae strains and spore-forming Bacillus cereus.4 A further challenge to PRT is its high cost. The use of “at-issue” tests that are approved by the Food and Drug Administration (FDA) to detect bacterial contamination, one of which has been shown to be highly effective in a clinical study,5 is not promoted. The potential for PRT to improve safety and prevent the transmission of infection needs to be tempered by these considerations.

Research paper thumbnail of Absolute immature platelet count helps differentiate thrombotic thrombocytopenic purpura from hypertension-induced thrombotic microangiopathy

Transfusion and Apheresis Science, Aug 1, 2014

ADAMTS13 activity measurement is used in the diagnostic algorithm of thrombotic thrombocytopenic ... more ADAMTS13 activity measurement is used in the diagnostic algorithm of thrombotic thrombocytopenic purpura (TTP), but results may not be available before initiation of therapeutic plasma exchange (TPE). The immature platelet fraction (%-IPF) and the calculated absolute immature platelet count (A-IPC) represent a test of real-time thrombopoiesis, and can be performed in most laboratories using automated analyzers. Here we report on using A-IPC kinetics to exclude idiopathic TTP in a patient with severe hypertension, thrombocytopenia, and acute renal failure, which was confirmed by a normal ADAMTS13. The complete resolution of thrombocytopenia occurred once blood pressure was controlled favoring a diagnosis of hypertension-induced thrombotic microangiopathy.

Research paper thumbnail of Implementing an Integrated Approach in Pediatric Stem Cell Collections: An Improvement Project

Transplantation and Cellular Therapy, Mar 1, 2022

Research paper thumbnail of New Concepts in Transfusion Medicine

Medical knowledge continues to increase as the explosion of molecular and genetic discoveries tri... more Medical knowledge continues to increase as the explosion of molecular and genetic discoveries tries to outpace technological breakthroughs affecting all clinical settings. Transfusion Medicine and transfusion practices are not exempt from this deluge of new information influencing not only the ways in which we see blood but also how and when to utilize blood components. In recent years a number of clinical trials are shedding light and leading to the development of new guidelines to help clinicians in making evidence-based decisions while stressing the importance of proper blood utilization. Likewise, new concepts are emerging in Transfusion Medicine, which may change the way we use and even manufacture blood components in the coming years. From the development of cells in vitro/ex vivo that in the future can potentially be applied to human transfusion support to working on how to extend shelf-life of platelets, these new concepts likely will affect blood utilization and transfusion. This chapter will attempt to present some of these developments and introduce the reader to areas of current research.

Research paper thumbnail of Transfusion-Related Immunomodulation

Elsevier eBooks, 2020

Abstract Blood transfusions are common practice across medical disciplines. With the advent of in... more Abstract Blood transfusions are common practice across medical disciplines. With the advent of increased testing, blood components continue being made safer, and they are currently the safest they have ever been. This is not always the case. One entity that has been the reason for concern in the literature for the better part of the last 4 decades is what has been termed as “transfusion-related immunomodulation.” This entity encompasses processes by which the transfused blood leads to changes to the immune responses of the recipient causing a number of possible sequelae. The goal of this chapter is to shed some light at this entity and present the current data indicating the potential elements within blood responsible for either the activation of inflammatory responses or immunosuppression and, in some cases, changes to a recipient's gene expression.

Research paper thumbnail of Comparison of BIOMED-2 Versus Laboratory-Developed Polymerase Chain Reaction Assays for Detecting T-Cell Receptor-γ Gene Rearrangements

The Journal of Molecular Diagnostics, Mar 1, 2010

Detecting clonal T-cell receptor (TCR)-␥ gene rearrangements (GRs) is an important adjunct test f... more Detecting clonal T-cell receptor (TCR)-␥ gene rearrangements (GRs) is an important adjunct test for diagnosing T-cell lymphoma. We compared a recently described assay (BIOMED-2 protocol) , which targets multiple variable (V) gene segments in two polymerase chain reaction (PCR) reactions (multi-V) , with a frequently referenced assay that targets a single V gene segment in four separate PCR reactions (mono-V). A total of 144 consecutive clinical DNA samples were prospectively tested for T-cell clonality by PCR using laboratory-developed mono-V and commercial multi-V primer sets for TCR-␥ GR. The combination of TCR-␤ , mono-V TCR-␥ and multi-V TCR-␥ detected more clonal cases (68/144 , 47%) than any individual PCR assay. We detected clonal TCR-␤ GR in 47/68 (69%) cases. Using either mono-V or multi-V TCR-␥ primers , the sensitivities for detecting clonality were 52/68 (76%) or 51/68 (75%). Using both mono-V and multi-V TCR-␥ primers improved the sensitivity for detecting clonality , 60/68 (88%). Combining either mono-V or multi-V TCR-␥ primers with TCR-␤ primers also improved the sensitivity , 64/68 (94%). Significantly , TCR-␥ V11 GRs could only be detected using the mono-V-PCR primers. We conclude that using more than one T-cell PCR assay can enhance the overall sensitivity for detecting T-cell clonality.

Research paper thumbnail of <scp>Anti‐CD20</scp> therapeutic options in immune‐mediated thrombotic thrombocytopenic purpura

British Journal of Haematology, Apr 26, 2022

How to cite this article: Maitta RW. Anti-CD20 therapeutic options in immune-mediated thrombotic ... more How to cite this article: Maitta RW. Anti-CD20 therapeutic options in immune-mediated thrombotic thrombocytopenic purpura.

Research paper thumbnail of Immature platelets in COVID‐19 infection

British Journal of Haematology, Jul 11, 2021

Pandemics have become more frequent events beginning in the latter part of the 20 century due to ... more Pandemics have become more frequent events beginning in the latter part of the 20 century due to the brevity of time needed to travel between distant regions of the world. The current COVID-19 or SARS-CoV-2 pandemic exemplifies the challenges facing healthcare delivery systems and health practitioners across the world, not only to treat, but also to use every available tool to diagnose and predict those patients more likely to develop complications related to the infection. Attempts to treat have included looking at old approaches of passive immunity in the form of COVID-19 convalescent plasma (CCP), to help those battling the disease despite limited knowledge of its potential efficacy. Unfortunately, the use of CCP has shown in randomised clinical trials, limitedto-no survival benefit to recipients, even when the plasma contained high antibody titres. It is in this climate that, along with basic science research, observational studies of COVID-19 patients can offer additional information of ways in which they could be risk-stratified. Thromboembolic complications related to COVID-19 infection cause in-hospital challenges in a significant number of such patients and are, thus, responsible for substantial mortality. In this setting, platelets in some COVID-19 patients establish not only a prothrombotic, but also a proinflammatory milieu in which a number of coagulation irregularities occur, as shown by prolongation of prothrombin and activated partial thromboplastin times as well as concomitant thrombocytopenia. This suggests that analysing platelets more closely could be a clinical approach to determining patients who are at greater risk. Along these lines, reports indicating that remaining platelets of COVID19 patients are more prone to respond to agonists in a background of a higher mean platelet volume, which is a reflection of a higher number of larger platelets in circulation and higher expression of P selectin, argue that looking at immature platelets is a logical step towards understanding platelet count changes in COVID-19 patients. Immature platelets represent the youngest platelets newly released into circulation that are larger and with a greater content of ribonucleic acids compared to mature circulating platelets. It is these differences that are readily detectable by current modern hematology analysers with fluorescence capability that is reported as a percentage of the total platelet count, the immature platelet fraction (IPF). These are equivalent to the reticulated platelets reported by different analysers. Importantly, testing for immature platelets does not delay results of a complete blood count since they can be obtained at the same time. This immature platelet count (IPC) is currently of interest in the literature in several clinical settings where platelet count disorders lead to production changes in the bone marrow. Consequently, in consumptive processes the marrow can either produce a higher number of immature platelets in response to thrombocytopenia or fail to respond, as seen in marrow failure or diseases where compensation is impaired. It is with this in mind that the work of Welder et al. describing their findings looking at the interplay of lower platelet counts in COVID-19 patients and immature platelets at time of hospital admission, how they quantitatively changed when patients required subsequent intensive care unit (ICU) admission with or without ventilator support, and when disease severity resulted in death, is an interesting and promising report. Parameters, including comorbidities that could also be predictive of disease outcomes, were also analysed by these investigators. Utilising a large cohort of 678 patients of whom the vast majority 658 (97%) required hospitalization due to the infection and received dexamethasone, they saw that increases in the IPF was predictive of patients who would end up requiring longer hospitalization (5 8% vs. 4 7%). This increase appeared not to be relevant to ethnicity or age. Furthermore, peak increases in IPF and IPC were also predictive of those patients who required ICU admission and longer duration of ventilator support. Finally, IPF increases also predicted those patients succumbing to disease Correspondence: Robert W. Maitta, Case Western Reserve University, Cleveland, USA. E-mail: robert.maitta@case.edu commentary

Research paper thumbnail of Adverse events during apheresis: A 10‐year experience at a tertiary academic medical center

Journal of Clinical Apheresis, Apr 5, 2019

Background: Apheresis can be associated with adverse events (AEs). Available studies published on... more Background: Apheresis can be associated with adverse events (AEs). Available studies published on apheresis-associated AEs lack uniformity of data. Unfortunately, there is no common database in the United States (US) to report apheresis-associated AEs. We evaluated our institutional incidence of apheresis-associated AEs and compared it with published literature. Study design and methods: We conducted a 10-year retrospective study of apheresis procedures and associated AEs at our facility, a tertiary academic medical center, from 2007 to 2016. Concurrently, a literature search was conducted on AEs associated with apheresis procedures. Twenty-eight studies including data from US and other countries' facilities were analyzed. Results: The overall AE incidence was 6.9% (396/5684 procedures). Frequency of AEs associated with therapeutic plasma exchange (TPE) was higher (8.5%, P < .0001) compared to other apheresis procedures. Significant correlation between number of TPE and AEs (Spearman rho [r s ] = 0.7, P = .002) was encountered. Furthermore, there was a significant decrease over time of moderate and severe AEs (r s = −0.64, P = .04 and r s = −0.83, P = .003 respectively). Comparison of our institutional AEs (6.9%) to data from other countries (9.8%) and US (22.6%) indicated a significant difference (P < .0001). Conclusion: Overall our incidence of AEs was significantly lower than current published literature. Incidence of AEs published in other countries is significantly lower than US rates. Differences in incidence of AEs emphasize need for uniform reporting and stratification of AEs and development of a common database to report AEs. Therefore, we propose a grading rationale in order to standardize reporting of AEs.

Research paper thumbnail of Pathological Mechanisms and Novel Testing Methods in Thrombotic Thrombocytopenic Purpura

Biomedicines, Mar 11, 2024

Research paper thumbnail of Editorial: Transfusion medicine and blood, volume II

Frontiers in medicine, May 21, 2024

Research paper thumbnail of Apheresis collection of mononuclear cells for chimeric‐antigen receptor therapies

European Journal of Haematology, Aug 1, 2023

Research paper thumbnail of Challenges Facing Transfusion Practices

Transfusion Medicine has rapidly evolved in the last few decades to become a medical discipline t... more Transfusion Medicine has rapidly evolved in the last few decades to become a medical discipline taking the spotlight as new clinical trials and literature on the appropriate use of blood components become available. In light of these rapid changes, challenges in the coming years are becoming more apparent to professionals in the field, which will likely affect clinical practices throughout disciplines. For this reason, approaches that take into account blood donations in the setting of more conservative and judicious use of blood components is paramount to have a sustainable blood supply that can meet the demands of a population that will likely require more components as a growing proportion of older recipients become more susceptible to diseases requiring transfusion support. However, this needs to be done in a background of practices based on the strongest available evidence in the medical literature to avoid the pitfalls that misuse of blood components or lack of understanding of the complexities of transfusion can bring about. Therefore, rather than this being only a Transfusion Medicine challenge, it represents a major Medical challenge.

Research paper thumbnail of Impact of Lenalidomide on Hematopoietic Myeloid and Erythroid Progenitors: Peripheral Stem Cell Collection May Not be Affected

Biology of Blood and Marrow Transplantation, Mar 1, 2017

P < .04). (Figure 1A). Also, the ratio of CD34 cells to Plt was higher in the first day of collec... more P < .04). (Figure 1A). Also, the ratio of CD34 cells to Plt was higher in the first day of collection in comparison to subsequent days (2.57 vs. 2.12, P < .045) (Figure 1B). The total number of collected CD34 cells was inversely correlated with collected Plt in pts who had more than one-day collection. Mean time to neutrophil and platelet engraftment was not statistically different between Plt High vs. Plt Low (10. 21 vs. 11.49, days P = .09; 19.95 vs. 20.9 days, P = .16, respectively). Median progression free survival was not different between the two groups with a median follow up of 30 months (27.7 vs. 25.7 months, P = .23). Conclusion: Although there was a trend towards faster engraftment with Plt High than Plt Low , it did not reach statistical significance. Further studies paired with pertinent platelet and megakaryocyte assays are needed to delineate the possible influence of platelets on CD34 homing and engraftment (Figures 2, 3).

Research paper thumbnail of Absolute Immature Platelet Counts Suggest Platelet Production Suppression during Complicated Relapsing Thrombotic Thrombocytopenic Purpura

Acta Haematologica, Nov 25, 2020

Absolute immature platelet counts (A-IPC) aid in diagnosis and treatment follow-up in thrombotic ... more Absolute immature platelet counts (A-IPC) aid in diagnosis and treatment follow-up in thrombotic thrombocytopenic purpura (TTP). A-IPC was used to follow a patient on mycophenolate mofetil (MMF) maintenance therapy treated with a prolonged therapeutic plasma exchange (TPE) regimen for relapsing TTP. On admission, the platelet (PLT) count was 95 × 109/L declining to 14 × 109/L in 5 days. Daily TPE was initiated for suspected TTP, and MMF was discontinued. A-IPC and PLT count were 1 × 109/L and 14 × 109/L, respectively, prior to first TPE. A-IPC improved to 3.2 × 109/L with 1 TPE, and on day 5, A-IPC and PLT count were 7.5 × 109/L and 218 × 109/L, respectively. On day 6, A-IPC and PLT count decreased to 4.8 × 109/L and 132 × 109/L further worsening to 0.4 × 109/L and 13 × 109/L, respectively. ADAMTS13 activity remained &lt;5% with an inhibitor; counts did not recover. Initial improvement followed by rapidly declining A-IPC despite therapy suggested production suppression. In TTP, A-IPC may aid in establishing early therapy effects over PLT production.

Research paper thumbnail of Current state of apheresis technology and its applications

Transfusion and Apheresis Science, Oct 1, 2018

Research paper thumbnail of Alloimmunisation rates of sickle cell disease patients in the United States differ from those in other geographical regions

Transfusion Medicine, May 20, 2016

Comparison of the alloimmunisation rates of patients with sickle cell disease in the Unites State... more Comparison of the alloimmunisation rates of patients with sickle cell disease in the Unites States versus other countries.

Research paper thumbnail of Alpha synuclein in hematopoiesis and immunity

Heliyon, Oct 1, 2019

Parkinson's disease (PD) is the second most common neurodegenerative condition and intracellular ... more Parkinson's disease (PD) is the second most common neurodegenerative condition and intracellular deposition of Lewy bodies in the substantia nigra (SN), which can cause dopaminergic neuronal death, is the hallmark of this syndrome. α-synuclein (syn) is a small protein expressed mainly in neurons but can also be found in a number of tissues. It can be present as a soluble monomer under normal physiological conditions, but can be toxic in its oligomeric or fibrillary forms. Most of the available literature has focused on the effects of α-syn pathology in the mechanisms leading to PD. However, the normal functions of α-syn still remain to be fully elucidated. Notably, α-syn in the hematopoietic system seems to mediate important functions as indicated by anemia and incomplete cell maturation when this protein is absent. This review will summarize basic genetic and structural findings, and critical information that suggests an essential role of α-syn in the development and activation of the hematopoietic system and immunity.

Research paper thumbnail of Chronic red cell exchange in sickle cell patients with iron overload may not affect mortality

Frontiers in Medicine, Sep 27, 2022

Chronic red cell exchange in sickle cell patients with iron overload may not a ect mortality. Fro... more Chronic red cell exchange in sickle cell patients with iron overload may not a ect mortality. Front. Med. :. doi: .

Research paper thumbnail of Use of a whole‐cell ELISA to detect additional antibodies in setting of suspected heparin‐induced thrombocytopenia

European Journal of Haematology, Jun 13, 2019

Objectives:Type II heparin-induced thrombocytopenia (HIT) is mediated by formation of antibodies ... more Objectives:Type II heparin-induced thrombocytopenia (HIT) is mediated by formation of antibodies to platelet factor 4 (PF4)-heparin complexes. We evaluated anti-PF4-heparin negative samples for presence of additional anti-platelet and anti-red blood cell (RBC) antibodies using whole-cell platelet/ RBC ELISAs we developed.Methods:Seventy-three samples tested for anti-PF4-heparin by ELISA were included: 62 tested negative, 9 tested positive, and 2 had equivocal results. Plasma specimens from healthy donors were used as controls.Results:100% (9/9) anti-PF4 positive samples had anti-platelet antibodies detected by whole-cell platelet ELISA. 42.2% (27/64) anti-PF4-heparin negative samples were negative for anti-platelet and anti-RBC antibodies. 32.8% (21/64) negative samples showed reactivity to both platelets and RBC; 12.5% (8/64) negative samples were each reactive with either platelet or RBC ELISA respectively. Additionally, two samples that tested equivocal by anti-PF4-heparin ELISA had antibodies to both platelets and RBC by whole-cell ELISA.Conclusions: Our study suggests that patients with thrombocytopenia testing negative for anti-PF4-heparin may still harbor antibodies to platelets. However, additional research is needed to determine the significance of these antibodies. Nevertheless, these findings may encourage clinicians to further investigate patients with possible immune-mediated etiologies of thrombocytopenia and anemia.

Research paper thumbnail of The Safety of the Blood Supply--Time to Raise the Bar

The New England Journal of Medicine, Aug 27, 2015

To the Editor: In their Perspective article on pathogen-reduction technology (PRT) (May 14 issue)... more To the Editor: In their Perspective article on pathogen-reduction technology (PRT) (May 14 issue),1 Snyder et al. praise the value of this technology. However, they omit a discussion of concerns about the safety and efficacy of PRT, stating that “Numerous studies demonstrate little substantive negative effect from pathogen reduction on plasma proteins or platelets.” A study in the Netherlands was terminated because of increased bleeding complications in the PRT group,2 and a U.S. study documented five fatal cases of the acute respiratory distress syndrome in the PRT group (1.6%) versus none in the control group.3 Furthermore, PRT fails to inactivate some pathogens, such as the hepatitis E virus. Among bacterial pathogens, PRT was not 100% effective against high levels of certain Klebsiella pneumoniae strains and spore-forming Bacillus cereus.4 A further challenge to PRT is its high cost. The use of “at-issue” tests that are approved by the Food and Drug Administration (FDA) to detect bacterial contamination, one of which has been shown to be highly effective in a clinical study,5 is not promoted. The potential for PRT to improve safety and prevent the transmission of infection needs to be tempered by these considerations.

Research paper thumbnail of Absolute immature platelet count helps differentiate thrombotic thrombocytopenic purpura from hypertension-induced thrombotic microangiopathy

Transfusion and Apheresis Science, Aug 1, 2014

ADAMTS13 activity measurement is used in the diagnostic algorithm of thrombotic thrombocytopenic ... more ADAMTS13 activity measurement is used in the diagnostic algorithm of thrombotic thrombocytopenic purpura (TTP), but results may not be available before initiation of therapeutic plasma exchange (TPE). The immature platelet fraction (%-IPF) and the calculated absolute immature platelet count (A-IPC) represent a test of real-time thrombopoiesis, and can be performed in most laboratories using automated analyzers. Here we report on using A-IPC kinetics to exclude idiopathic TTP in a patient with severe hypertension, thrombocytopenia, and acute renal failure, which was confirmed by a normal ADAMTS13. The complete resolution of thrombocytopenia occurred once blood pressure was controlled favoring a diagnosis of hypertension-induced thrombotic microangiopathy.

Research paper thumbnail of Implementing an Integrated Approach in Pediatric Stem Cell Collections: An Improvement Project

Transplantation and Cellular Therapy, Mar 1, 2022

Research paper thumbnail of New Concepts in Transfusion Medicine

Medical knowledge continues to increase as the explosion of molecular and genetic discoveries tri... more Medical knowledge continues to increase as the explosion of molecular and genetic discoveries tries to outpace technological breakthroughs affecting all clinical settings. Transfusion Medicine and transfusion practices are not exempt from this deluge of new information influencing not only the ways in which we see blood but also how and when to utilize blood components. In recent years a number of clinical trials are shedding light and leading to the development of new guidelines to help clinicians in making evidence-based decisions while stressing the importance of proper blood utilization. Likewise, new concepts are emerging in Transfusion Medicine, which may change the way we use and even manufacture blood components in the coming years. From the development of cells in vitro/ex vivo that in the future can potentially be applied to human transfusion support to working on how to extend shelf-life of platelets, these new concepts likely will affect blood utilization and transfusion. This chapter will attempt to present some of these developments and introduce the reader to areas of current research.

Research paper thumbnail of Transfusion-Related Immunomodulation

Elsevier eBooks, 2020

Abstract Blood transfusions are common practice across medical disciplines. With the advent of in... more Abstract Blood transfusions are common practice across medical disciplines. With the advent of increased testing, blood components continue being made safer, and they are currently the safest they have ever been. This is not always the case. One entity that has been the reason for concern in the literature for the better part of the last 4 decades is what has been termed as “transfusion-related immunomodulation.” This entity encompasses processes by which the transfused blood leads to changes to the immune responses of the recipient causing a number of possible sequelae. The goal of this chapter is to shed some light at this entity and present the current data indicating the potential elements within blood responsible for either the activation of inflammatory responses or immunosuppression and, in some cases, changes to a recipient's gene expression.

Research paper thumbnail of Comparison of BIOMED-2 Versus Laboratory-Developed Polymerase Chain Reaction Assays for Detecting T-Cell Receptor-γ Gene Rearrangements

The Journal of Molecular Diagnostics, Mar 1, 2010

Detecting clonal T-cell receptor (TCR)-␥ gene rearrangements (GRs) is an important adjunct test f... more Detecting clonal T-cell receptor (TCR)-␥ gene rearrangements (GRs) is an important adjunct test for diagnosing T-cell lymphoma. We compared a recently described assay (BIOMED-2 protocol) , which targets multiple variable (V) gene segments in two polymerase chain reaction (PCR) reactions (multi-V) , with a frequently referenced assay that targets a single V gene segment in four separate PCR reactions (mono-V). A total of 144 consecutive clinical DNA samples were prospectively tested for T-cell clonality by PCR using laboratory-developed mono-V and commercial multi-V primer sets for TCR-␥ GR. The combination of TCR-␤ , mono-V TCR-␥ and multi-V TCR-␥ detected more clonal cases (68/144 , 47%) than any individual PCR assay. We detected clonal TCR-␤ GR in 47/68 (69%) cases. Using either mono-V or multi-V TCR-␥ primers , the sensitivities for detecting clonality were 52/68 (76%) or 51/68 (75%). Using both mono-V and multi-V TCR-␥ primers improved the sensitivity for detecting clonality , 60/68 (88%). Combining either mono-V or multi-V TCR-␥ primers with TCR-␤ primers also improved the sensitivity , 64/68 (94%). Significantly , TCR-␥ V11 GRs could only be detected using the mono-V-PCR primers. We conclude that using more than one T-cell PCR assay can enhance the overall sensitivity for detecting T-cell clonality.

Research paper thumbnail of <scp>Anti‐CD20</scp> therapeutic options in immune‐mediated thrombotic thrombocytopenic purpura

British Journal of Haematology, Apr 26, 2022

How to cite this article: Maitta RW. Anti-CD20 therapeutic options in immune-mediated thrombotic ... more How to cite this article: Maitta RW. Anti-CD20 therapeutic options in immune-mediated thrombotic thrombocytopenic purpura.

Research paper thumbnail of Immature platelets in COVID‐19 infection

British Journal of Haematology, Jul 11, 2021

Pandemics have become more frequent events beginning in the latter part of the 20 century due to ... more Pandemics have become more frequent events beginning in the latter part of the 20 century due to the brevity of time needed to travel between distant regions of the world. The current COVID-19 or SARS-CoV-2 pandemic exemplifies the challenges facing healthcare delivery systems and health practitioners across the world, not only to treat, but also to use every available tool to diagnose and predict those patients more likely to develop complications related to the infection. Attempts to treat have included looking at old approaches of passive immunity in the form of COVID-19 convalescent plasma (CCP), to help those battling the disease despite limited knowledge of its potential efficacy. Unfortunately, the use of CCP has shown in randomised clinical trials, limitedto-no survival benefit to recipients, even when the plasma contained high antibody titres. It is in this climate that, along with basic science research, observational studies of COVID-19 patients can offer additional information of ways in which they could be risk-stratified. Thromboembolic complications related to COVID-19 infection cause in-hospital challenges in a significant number of such patients and are, thus, responsible for substantial mortality. In this setting, platelets in some COVID-19 patients establish not only a prothrombotic, but also a proinflammatory milieu in which a number of coagulation irregularities occur, as shown by prolongation of prothrombin and activated partial thromboplastin times as well as concomitant thrombocytopenia. This suggests that analysing platelets more closely could be a clinical approach to determining patients who are at greater risk. Along these lines, reports indicating that remaining platelets of COVID19 patients are more prone to respond to agonists in a background of a higher mean platelet volume, which is a reflection of a higher number of larger platelets in circulation and higher expression of P selectin, argue that looking at immature platelets is a logical step towards understanding platelet count changes in COVID-19 patients. Immature platelets represent the youngest platelets newly released into circulation that are larger and with a greater content of ribonucleic acids compared to mature circulating platelets. It is these differences that are readily detectable by current modern hematology analysers with fluorescence capability that is reported as a percentage of the total platelet count, the immature platelet fraction (IPF). These are equivalent to the reticulated platelets reported by different analysers. Importantly, testing for immature platelets does not delay results of a complete blood count since they can be obtained at the same time. This immature platelet count (IPC) is currently of interest in the literature in several clinical settings where platelet count disorders lead to production changes in the bone marrow. Consequently, in consumptive processes the marrow can either produce a higher number of immature platelets in response to thrombocytopenia or fail to respond, as seen in marrow failure or diseases where compensation is impaired. It is with this in mind that the work of Welder et al. describing their findings looking at the interplay of lower platelet counts in COVID-19 patients and immature platelets at time of hospital admission, how they quantitatively changed when patients required subsequent intensive care unit (ICU) admission with or without ventilator support, and when disease severity resulted in death, is an interesting and promising report. Parameters, including comorbidities that could also be predictive of disease outcomes, were also analysed by these investigators. Utilising a large cohort of 678 patients of whom the vast majority 658 (97%) required hospitalization due to the infection and received dexamethasone, they saw that increases in the IPF was predictive of patients who would end up requiring longer hospitalization (5 8% vs. 4 7%). This increase appeared not to be relevant to ethnicity or age. Furthermore, peak increases in IPF and IPC were also predictive of those patients who required ICU admission and longer duration of ventilator support. Finally, IPF increases also predicted those patients succumbing to disease Correspondence: Robert W. Maitta, Case Western Reserve University, Cleveland, USA. E-mail: robert.maitta@case.edu commentary

Research paper thumbnail of Adverse events during apheresis: A 10‐year experience at a tertiary academic medical center

Journal of Clinical Apheresis, Apr 5, 2019

Background: Apheresis can be associated with adverse events (AEs). Available studies published on... more Background: Apheresis can be associated with adverse events (AEs). Available studies published on apheresis-associated AEs lack uniformity of data. Unfortunately, there is no common database in the United States (US) to report apheresis-associated AEs. We evaluated our institutional incidence of apheresis-associated AEs and compared it with published literature. Study design and methods: We conducted a 10-year retrospective study of apheresis procedures and associated AEs at our facility, a tertiary academic medical center, from 2007 to 2016. Concurrently, a literature search was conducted on AEs associated with apheresis procedures. Twenty-eight studies including data from US and other countries' facilities were analyzed. Results: The overall AE incidence was 6.9% (396/5684 procedures). Frequency of AEs associated with therapeutic plasma exchange (TPE) was higher (8.5%, P < .0001) compared to other apheresis procedures. Significant correlation between number of TPE and AEs (Spearman rho [r s ] = 0.7, P = .002) was encountered. Furthermore, there was a significant decrease over time of moderate and severe AEs (r s = −0.64, P = .04 and r s = −0.83, P = .003 respectively). Comparison of our institutional AEs (6.9%) to data from other countries (9.8%) and US (22.6%) indicated a significant difference (P < .0001). Conclusion: Overall our incidence of AEs was significantly lower than current published literature. Incidence of AEs published in other countries is significantly lower than US rates. Differences in incidence of AEs emphasize need for uniform reporting and stratification of AEs and development of a common database to report AEs. Therefore, we propose a grading rationale in order to standardize reporting of AEs.