Immature platelet counts in transfused platelet units given to neonates.

BACKGROUND: Immature platelets, young and large platelets recently released from the bone marrow, have gained interest over the last decade as a clinically informative variable during thrombocytopenic presentations. These immature platelets are found in all donated platelet units, however, the role, if any, that these younger platelets play post transfusion is not known. It has also been reported that the immune response can affect responses to platelet transfusions. Thus, we looked at PLT increments in a cohort of neonates receiving platelet transfusions in our neonatal intensive care unit. METHODS: During a twelve-month period, platelet transfusions received by neonates born and not discharged from our institution at time of transfusion were retrospectively analyzed. In the study period a total of 33 patients received either a single or multiple transfusions during their hospitalization, for a total of 100 transfusion events. RESULTS: The cohort was mostly premature neonates with a mean gestational age of 29.6 weeks. The units transfused appeared to have a broad range of absolute immature platelet counts (A-IPC) but overall, it was similar between those receiving single or multiple transfusions. Considering that platelet count was similar among aliquots transfused, it appeared that count increments were influenced by higher A-IPC content of the aliquot especially among 2nd trimester and 3rd trimester premature neonates. Patients with higher baseline platelet count (PLT) tended to receive a single transfusion aliquot while those receiving multiple transfusions had lower baseline PLT (p = 0.0022). Looking at aliquot dose, regardless if receiving a single or multiple transfusions, younger patients received incrementally higher dose (ml/kg) with each transfusion. CONCLUSIONS: A-IPC in platelet aliquots transfused to neonates may influence post-transfusion PLT. Full effect of A-IPC in platelet aliquots may not be seen since irradiation of units may hamper immature platelets viability and function. Further research is needed to determine if A-IPC plays an active role to limit the need for further transfusions of patients receiving transfusions.

National pilot of entrustable professional activities in pathology residency training.

Entrustable professional activities (EPAs) are observable clinical skills and/or procedures that have been introduced into medical education at the student and resident levels in most specialties to determine readiness to advance into residency or independent practice, respectively. This publication describes the process and outcomes of a pilot study looking at the feasibility of using two anatomic pathology and two clinical pathology EPAs in pathology residency in 6 pathology residency programs that volunteered for the study. Faculty development on EPAs and their assessment was provided to pilot program faculty, and EPA assessment tools were developed and used by the pilot programs. Pre- and post-study surveys were given to participating residents, faculty, and program directors to gauge baseline practices and to gather feedback on the EPA implementation experience. Results demonstrated overall good feasibility in implementing EPAs. Faculty acceptance of EPAs varied and was less than that of program directors. Residents reported a significant increase in the frequency with which faculty provided formative assessments that included specific examples of performance and specific ways to improve, as well as increased frequency with which faculty provided summative assessments that included specific ways to improve. EPAs offered the most benefit in setting clear expectations for performance of each task, for providing more specific feedback to residents, and in increasing Program director's understanding of resident strengths abilities and weaknesses.

Comparison of absolute immature platelet count to the PLASMIC score at presentation in predicting ADAMTS13 deficiency in suspected thrombotic thrombocytopenic purpura.

INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) demands rapid initiation of therapeutic plasma exchange to avoid severe complications associated with it. ADAMTS13 activity <10% defines TTP, however, this is a send-out test at most institutions. We have previously reported our experience looking at absolute immature platelet counts (A-IPC) in TTP patients. Thus, we compared A-IPC on admission to the PLASMIC score to predict ADAMTS13 deficiency. MATERIALS AND METHODS: Of seventy-two patients identified, 52 met inclusion criteria. All patients were suspected of new-onset TTP and had A-IPC on admission. Of these patients, 25/52 were later shown to have ADAMTS13 <10%, defined as TTP group, and 27/52 had ADAMTS13 >10% and are henceforth classified as non-TTP. RESULTS: Patients with TTP were found to have A-IPC below reference range (<1.5 × 109/L) and responded to therapy as shown by fold-increases in A-IPC (p < 0.0001), neither seen in non-TTP patients. A-IPC had a significant correlation with ADAMTS13 deficiency (p = 0.0001) with high sensitivity, specificity, positive and negative predictive values. Comparison of A-IPC to PLASMIC score indicated that the former identified all TTP patients compared to PLASMIC score even in patients obtaining scores of 4 and 5. Finally, Receiver Operating Characteristic curves showed A-IPC had area under the curve of 0.986. CONCLUSIONS: A-IPC below reference range and A-IPC fold-increases were only observed in TTP patients. There was strong association between A-IPC and ADAMTS13 deficiency and A-IPC predicted patients with ADAMTS13 deficiency. Future larger studies are needed to determine ways to apply findings in suspected TTP patients.

Neonatal and pediatric blood bank practice in the United States: Results from the AABB pediatric transfusion medicine subsection survey.

BACKGROUND: There are limited standards guiding the selection and processing of blood components specific for neonatal and pediatric transfusions. Therefore, blood banks (BBs) and transfusion services must create their own policies and procedures. STUDY DESIGN AND METHODS: The American Association of Blood Banks (AABB) Pediatric Transfusion Medicine Subsection Committee developed a 74-question survey to capture neonatal and pediatric BB practices in the United States. RESULTS: Thirty-five centers completed the survey: a response rate 15.8%. Responses indicated that most carry a mixed inventory of red blood cells (RBCs); 94.2% allow more than one type of RBC product for small-volume (SV) and large-volume (LV) transfusions to neonatal and pediatric patients. Many had storage age thresholds for RBCs transfused to neonates (SV = 60%, LV = 67.7%) but not older pediatric patients. The use of Group O for nonurgent RBC transfusion in neonates was common (74.2%). Responses related to special processing of RBCs and platelets indicated that 100% RBC and platelets are leukocyte-reduced (LR) for neonates and 97% for non-neonates. Irradiation of RBCs and platelets was commonly performed for neonatal transfusion (88.6%). Providing cytomegalovirus (CMV) seronegative products, volume reduction, and washing were variable. All centers transfused single-donor apheresis platelets; 20% allowed pathogen reduction (PR). The majority of centers have strategies limiting the amount of incompatible plasma transfused; however, few titrate ABO isoagglutinins in plasma-containing products (20% for platelets and 9.1% for plasma). CONCLUSIONS: Variability exists in BB practice for neonatal and pediatric transfusion. Future studies are needed to understand and define best BB practices in these patient populations.

Absolute Immature Platelet Counts Suggest Platelet Production Suppression during Complicated Relapsing Thrombotic Thrombocytopenic Purpura.

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 <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.

Immature platelet dynamics correlate with ADAMTS13 deficiency and predict therapy response in immune-mediated thrombotic thrombocytopenic purpura.

INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) requires prompt initiation of therapeutic plasma exchange (TPE) to avoid significant morbidity and mortality. ADAMTS13 activity testing defines TTP, however, at most institutions this is a send-out test and therapy is often initiated prior to measurement availability. We describe our experience looking at absolute immature platelet counts (A-IPC) in patients suspected with TTP at presentation and in response to therapy. MATERIALS AND METHODS: Forty-eight patients treated for suspected TTP with A-IPC measure on admission and during hospitalization met inclusion criteria. Of these patients, sixteen had new-onset TTP (ADAMTS13 < 10%), ten were relapsing patients (first diagnosis prior to study period), and 22 were classified as non-TTP (ADAMTS13 ≥ 10%). RESULTS: Patients with ADAMTS13 deficiency (TTP) had A-IPC different from those without deficiency. A-IPC of 1-2 × 109/L at presentation had high sensitivity and specificity with a negative predictive value of 95.5 to 100%. Two-to-three-fold increases in A-IPC from count prior to TPE initiation was limited to ADAMTS13 deficient patients who was the group responding to therapy. Increases were higher in patients with new disease onset compared to relapsing patients (p = 0.018). Likewise, relapsing patients' A-IPC appeared dependent upon platelet count at time of relapse. A-IPC predicted and correlated with ADAMTS13 deficiency in new-onset TTP (p = 0.0002). CONCLUSIONS: Only patients with A-IPC-fold increases responded to TPE with platelet count normalization. Our results represent a proof of concept that A-IPC measurements can supplement ADAMTS13 testing and determine response to TPE. Future studies are needed to establish ways to apply these findings in the setting of suspected TTP.

Impact of multidisciplinary engagement in a quality improvement blood conservation protocol for craniosynostosis.

OBJECTIVE: Patients undergoing open cranial vault remodeling for craniosynostosis frequently experience substantial blood loss requiring blood transfusion. Multiple reports in the literature have evaluated the impact of individual blood conservation techniques on blood transfusion rates during craniosynostosis surgery. The authors engaged a multidisciplinary team and assessed the impact of input from multiple stakeholders on the evolution of a comprehensive quality improvement protocol aimed at reducing or eliminating blood transfusion in patients undergoing open surgery for craniosynostosis. METHODS: Over a 4-year period from 2012 to 2016, 39 nonsyndromic patients were operated on by a single craniofacial plastic surgeon. Initially, no clear blood conservation protocol existed, and specific interventions were individually driven. In 2014, a new pediatric neurosurgeon joined the craniofacial team, and additional stakeholders in anesthesiology, transfusion medicine, critical care, and hematology were brought together to evaluate opportunities for developing a comprehensive blood conservation protocol. The initial version of the protocol involved the standardized administration of intraoperative aminocaproic acid (ACA) and the use of a cell saver. In the second version of the protocol, the team implemented the preoperative use of erythropoietin (EPO). In addition, intraoperative and postoperative resuscitation and transfusion guidelines were more clearly defined. The primary outcomes of estimated blood loss (EBL), transfusion rate, and intraoperative transfusion volume were analyzed. The secondary impact of multidisciplinary stakeholder input was inferred by trends in the data obtained with the implementation of the partial and full protocols. RESULTS: Implementing the full quality improvement protocol resulted in a 66% transfusion-free rate at the time of discharge compared to 0% without any conservation protocol and 27% with the intermediate protocol. The administration of EPO significantly increased starting hemoglobin/hematocrit (11.1 g/dl/31.8% to 14.7 g/dl/45.6%, p < 0.05). The group of patients receiving ACA had lower intraoperative EBL than those not receiving ACA, and trends in the final-protocol cohort, which had received both preoperative EPO and intraoperative ACA, demonstrated decreasing transfusion volumes, though the decrease did not reach statistical significance. CONCLUSIONS: Patients undergoing open calvarial vault remodeling procedures benefit from the input of a multidisciplinary stakeholder group in blood conservation protocols. Further research into comprehensive protocols for blood conservation may benefit from input from the full surgical team (plastic surgery, neurosurgery, anesthesiology) as well as additional pediatric subspecialty stakeholders including transfusion medicine, critical care, and hematology.

Immature Platelet Dynamics in Immune-Mediated Thrombocytopenic States.

A major challenge encountered by clinicians is differentiating presentations characterized by significant thrombocytopenia due to overlapping clinical symptoms and signs in the setting of ambiguous laboratory results. Immature platelets represent the youngest platelets that can be measured in peripheral blood by current hematology analyzers. These young platelets are larger, with higher RNA content recently released from the bone marrow. Thrombocytopenic presentations caused directly or indirectly by immune responses can lead to compensatory bone marrow responses seeking to normalize the platelet count; thus obtaining absolute immature platelet counts may be informative while triaging patients. Over the last decade, their use has expanded beyond being an early biomarker of bone marrow reconstitution post-hematopoietic stem cell transplantation to being used to establish bone marrow responses to infection and thrombocytopenias due to immune etiologies. Its accessibility as part of more detailed platelet indices obtained with routine laboratories makes it a promising option to understand the bone marrow's real-time response to disease states characterized by thrombocytopenia. This review will look at the immature platelet count as a biomarker, while presenting current attempts trying to understand how it could be used in thrombocytopenias occurring secondary to a given immune etiology.

Dynamic changes in absolute immature platelet count suggest the presence of a coexisting immune process in the setting of thrombotic thrombocytopenic purpura.

BACKGROUND: Previous studies have indicated the usefulness of absolute immature platelet counts (A-IPCs) in the management and diagnostic algorithm of thrombotic thrombocytopenic purpura (TTP). Specifically a threefold increase in A-IPC from baseline may be diagnostic of TTP. Here, A-IPC was used to understand a coexisting immune dysregulation complicating TTP treatment. CASE REPORT: A 17-year-old previously healthy female was admitted with altered mental status, petechiae, anemia, thrombocytopenia, and schistocytes on peripheral smear. Daily therapeutic plasma exchange (TPE) and corticosteroids were started for suspected TTP supported by ADAMTS13 activity of less than 5%, inhibitor more than 8, and more than threefold A-IPC increase from baseline post-TPE initiation. Despite daily TPE, the patient had significant and unexpected decreases in platelet (PLT) counts and A-IPCs during her hospital course. After each PLT count decline, response to TPE and immunosuppression led to increasingly prolonged count recovery with subsequent episodes. Decreases in both PLTs and A-IPCs indicated that both mature and immature PLTs were being cleared from circulation. Recovery occurred once A-IPC dynamics indicated restored negative feedback in relation to PLT count. CONCLUSION: Serial monitoring of A-IPC dynamics was indicative of coexisting processes in the setting of ADAMTS13 deficiency. Uncoupling of the expected A-IPC and PLT count seen in TTP suggested the presence of such an immune process in addition to TTP with high ADAMTS13 inhibitor. Monitoring of A-IPC is a clinically valuable, rapid, and noninvasive thrombopoietic measurement when TTP is suspected.

Unexpected Non-Maternally Derived Anti-PP1Pk in an 11-Week-Old Patient.

Alloantibody formation at less than 4 months of age is rare. Most antibodies identified in these patients are maternally derived. Anti-PP1Pk was detected in an 11-week-old infant that was not maternally derived. A multidisciplinary team approach led to appropriate testing, diagnosis, and transfusion management in this critically ill infant.

Comparison of two apheresis systems during hematopoietic progenitor stem cell collections at a tertiary medical center.

BACKGROUND: The Spectra Optia is a newer apheresis system developed based on the COBE Spectra platform. COBE Spectra requires more manual control, while Spectra Optia offers greater automation. The purpose of this study was to compare the two systems during hematopoietic progenitor stem cell (HPSC) collections. STUDY DESIGN AND METHODS: A retrospective review of 41 collections performed in 26 subjects at a tertiary medical center between June 1, 2013, and December 31, 2013, was conducted, 11 with the Spectra Optia and 30 with the COBE Spectra. Six patients underwent two consecutive daily collections, first on the Spectra Optia followed by the COBE Spectra. RESULTS: Procedure run time with the Spectra Optia was considerably longer than with the COBE Spectra (283 ± 11 min vs. 217 ± 2 min, respectively; p < 0.01). Mean CD34+ cell yields with the Spectra Optia were comparable with those of the COBE Spectra. Products collected with the Spectra Optia had less red blood cell contamination. However, platelet (PLT) attrition was greater with the Spectra Optia. Similar results were obtained in patients who were collected on consecutive days in both systems. CONCLUSION: Collections with the Spectra Optia take longer and lead to greater PLT losses during HPSC collections.

Absolute immature platelet count helps differentiate thrombotic thrombocytopenic purpura from hypertension-induced thrombotic microangiopathy.

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.

The mechanisms of action of plasma exchange.

The initial description of therapeutic plasma exchange (TPE) in an animal model was published almost 100 years ago. Since that time, this treatment has been applied to a wide variety of diseases but limited research has been published examining the mechanisms of action of TPE. The therapeutic effects of TPE could include the removal of pathological substances from the blood, such as monoclonal paraproteins and autoantibodies, as well as the replacement of deficient plasma components when plasma is used as a replacement fluid. Beyond these potential mechanisms, other possible mechanisms include possible alterations in lymphocyte proliferation and function that could sensitize these cells to immunosuppressant and chemotherapeutic agents and alterations in the immune system including changes in B and T cell numbers and activation, increased T suppressor function, and alteration in T-helper cell type 1/2 (Th1/Th2) ratio. Much remains unknown about the mechanisms of action of TPE, indicating a need for basic research into this therapy.