Faculty Bibliography

BACKGROUND:Patients with sickle cell disease (SCD) frequently undergo prophylactic red blood cell (RBC) exchange transfusion and simple transfusion (RCE/T) to prevent complications of disease, such as stroke. These treatment procedures are performed with a target hemoglobin S (HbS) of ≤30%, or a goal of maintaining an HbS level of <30% immediately prior to the next transfusion. However, there is a lack of evidence-based instructions for how to perform RCE/T in a way that will result in an HbS value <30% between treatments. PRINCIPAL OBJECTIVE/UNASSIGNED:To determine whether targets for post-treatment HbS (post-HbS) or post-treatment HCT (post-HCT) can help to maintain an HbS <30% or <40% between treatments. MATERIALS AND METHODS/METHODS:We performed a retrospective study of patients with SCD treated with RCE/T at Montefiore Medical Center from June 2014 to June 2016. The analysis included patients of all ages, and data including 3 documented parameters for each RCE/T event: post-HbS, post-HCT, and follow-up HbS (F/u-HbS), which is the pre-treatment HbS prior to the next RCE/T. Generalized linear mixed model was used for estimating the association between post-HbS or post-HCT levels and F/u-HbS <30%. RESULTS:Based on our results, targeting post-HbS ≤10% was associated with higher odds of having events of F/u-HbS <30% between monthly treatments. Targeting post-HbS ≤15% was associated with higher odds of events of F/u-HbS < 40%. As compared to post-HCT ≤30%, a post-HCT >30%-36% did not contribute to more F/u-HbS <30% or HbS <40% events. CONCLUSIONS:For patients with SCD undergoing regular RCE/T for stroke prevention, a post-HbS ≤10% can be used as a goal to help maintain an HbS <30% for 1 month, and a post-HbS ≤15% allowed patients to maintain HbS <40%.

OBJECTIVE:Heightened inflammation, dysregulated immunity, and thrombotic events are characteristic of hospitalized COVID-19 patients. Given that platelets are key regulators of thrombosis, inflammation, and immunity they represent prime candidates as mediators of COVID-19-associated pathogenesis. The objective of this study was to understand the contribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the platelet phenotype via phenotypic (activation, aggregation) and transcriptomic characterization. APPROACH AND RESULTS/UNASSIGNED:In a cohort of 3915 hospitalized COVID-19 patients, we analyzed blood platelet indices collected at hospital admission. Following adjustment for demographics, clinical risk factors, medication, and biomarkers of inflammation and thrombosis, we find platelet count, size, and immaturity are associated with increased critical illness and all-cause mortality. Bone marrow, lung tissue, and blood from COVID-19 patients revealed the presence of SARS-CoV-2 virions in megakaryocytes and platelets. Characterization of COVID-19 platelets found them to be hyperreactive (increased aggregation, and expression of P-selectin and CD40) and to have a distinct transcriptomic profile characteristic of prothrombotic large and immature platelets. In vitro mechanistic studies highlight that the interaction of SARS-CoV-2 with megakaryocytes alters the platelet transcriptome, and its effects are distinct from the coronavirus responsible for the common cold (CoV-OC43). CONCLUSIONS:Platelet count, size, and maturity associate with increased critical illness and all-cause mortality among hospitalized COVID-19 patients. Profiling tissues and blood from COVID-19 patients revealed that SARS-CoV-2 virions enter megakaryocytes and platelets and associate with alterations to the platelet transcriptome and activation profile.

BACKGROUND:MELD score-based liver transplant allocation was implemented as a fair and objective measure to prioritize patients based upon disease severity. Accuracy and reproducibility of MELD is an essential assumption to ensure fairness in organ access. We hypothesized that variability or bias in laboratory methodology between centers could alter allocation scores for individuals on the transplant waiting list. METHODS:Aliquots of 30 patient serum samples were analyzed for creatinine, bilirubin, and sodium in all transplant centers within United Network for Organ Sharing (UNOS) region 9. Descriptive statistics, intraclass correlation coefficients (ICC), and linear mixed effects regression were used to determine the relationship between center, bilirubin and calculated MELD-Na. RESULTS:The mean MELD-Na score per sample ranged from 14 to 38. The mean range in MELD-Na per sample was 3 points, but 30% of samples had a range of 4-6 points. Correlation plots and intraclass correlation coefficient analysis confirmed bilirubin interfered with creatinine, with worsening agreement in creatinine at high bilirubin levels. Center and bilirubin were independently associated with creatinine reported in mixed effects models. Unbiased hierarchical clustering suggested samples from specific centers have consistently higher creatinine and MELD-Na values. CONCLUSIONS:Despite implementation of creatinine standardization, centers within one UNOS region report clinically significant differences in MELD-Na on an identical sample, with differences of up to 6 points in high MELD-Na patients. The bias in MELD-Na scores based upon center choice within a region should be addressed in the current efforts to eliminate disparities in liver transplant access.

Background: According to the AABB, a pre-transfusion sample must be obtained within 3 days of transfusion if a patient has been transfused or pregnant in the preceding 3 months. Despite this safeguard, high risk patients (i.e. those recently transfused with a history of pregnancy or transfusion) may develop antibody during this 3 day window. To avoid issuing incompatible red blood cells (RBCs) to these patients, a new antibody screen (ABS) sample should be drawn and tested shortly before anticipated transfusion.
Aim(s): We report a case of a 60 y/o man who presented to the ED (hospital day 0, HD0) with a post-fall intracranial hemorrhage and multiple fractures. Anti-E and anti-Jka were identified after admission on a new specimen prior to current specimen expiration (<3 days).
Method(s): Specimen #1 (S1) was sent on HD0 for Type & ABS (T&S) and crossmatch (XM) of 2 RBCs. ABS and immediate spin XM were negative; there was no patient history. By HD9, he had 4 negative T&S specimens (HD0: S1; HD2: S2&3; HD6: S4) and had been transfused 4 RBCs (HD2: 2; HD5: 2) via electronic XM (EXM). At 1730 hr on HD9, 2 RBCs were requested and could have been issued via EXM since S4 was not expiring until midnight. However, given recent transfusions, BB staff first called the patient's nurse to review history. Patient was uncommunicative, but had scars suggesting past trauma or surgery. S5 was requested and received at 1801 hr.
Result(s): S5 showed anti-E and anti-Jk^a in plasma and eluate. His hemoglobin/hema-tocrit (H/H) decreased from 10.2 (14.0-17.5 g/dL)/30.1 (41.5-50.4%) on HD6 to 6.9/20.6 on HD9. During this period, he underwent several surgeries without unexpected bleeding, documented jaundice or dark urine. Two E-Jk(a-) RBCs were transfused on HD9, which he tolerated well with an increase of hemoglobin from 6.9 g/dL to 8.6 g/dL. He did well post transfusion with stable H/H between 8.1/24.2.0 to 8.5/25.3. He was discharged on HD19. Repeat ABS on S4 was negative. Of the 4 RBCs transfused before S5, one was E+ and four Jk(a+). The family reported that he was injured 20 years prior and had been admitted to 3 hospitals, but was unaware of transfusion. Hospital #1 (H1) reported admissions 20 years ago (2 RBCs transfused) and 4 years ago; all ABS were negative. H2 admission was 5 years ago with positive ABS and inconclusive workup. H3 admission 4 years ago showed negative ABS. Summary/Conclusions: The patient developed a significant antibody response in less than 3 days from the specimen collection, likely a secondary immune response to sensitization from a transfusion 20 years earlier. A new specimen was requested prior to transfusion even though the existing sample (which was ABS Negative) had not expired. This approach identified new antibodies, preventing transfusion of incompatible RBCs, and a potentially serious hemolytic transfusion reaction. This case suggests that for high-risk patients, ABS more frequently than every 3 days may be beneficial. It is important to increase clinicians' and laboratorians' awareness of this issue

Objectives/UNASSIGNED:In the United States, minimum standards for quality control (QC) are specified in federal law under the Clinical Laboratory Improvement Amendment and its revisions. Beyond meeting this required standard, laboratories have flexibility to determine their overall QC program. Methods/UNASSIGNED:We surveyed chemistry and immunochemistry QC procedures at 21 clinical laboratories within leading academic medical centers to assess if standardized QC practices exist for chemistry and immunochemistry testing. Results/UNASSIGNED:We observed significant variation and unexpected similarities in practice across laboratories, including QC frequency, cutoffs, number of levels analyzed, and other features. Conclusions/UNASSIGNED:This variation in practice indicates an opportunity exists to establish an evidence-based approach to QC that can be generalized across institutions.

To compare utilization of CT pulmonary angiogram (CTA) for diagnosis of pulmonary embolism (PE) in an emergency department (ED) with unstructured CT ordering to published rates of CT positivity in other EDs including those employing decision support and to identify pathways for improved utilization via collaboration with our pathology and ED colleagues. Two hundred seventeen patients over a 2.5-month time period who received a CTA for PE were reviewed with exclusion of pediatric patients and all sub-optimal, non-diagnostic, or equivocal scans; 21 were excluded leaving a sample of 196 patients. The rate of PE diagnosis and association of PE positivity with selected factors (D-dimer testing) was assessed. The percentage of cases positive for PE was 10.7 % (21/196) which is similar to the frequently published rate of 10 % in other emergency departments including settings that have studied the use of decision support. D-dimer testing was performed in 40.3 % of cases. In 29.6 % (58/196) of subjects, D-dimer was positive, 10.7 % (21/196) was negative, and 59.7 % (117/196) was not assessed. Prevalence of PE among D-dimer negative (0 %, 0/21) was lower versus positive D-dimer (12.1 %, 7/58) and unknown D-dimer patients (12.0 %, 14/117). D-dimer had 100 % (21/21) negative predictive value for the diagnosis of PE. While this suggests that D-dimer is useful to rule-out PE, due to the small number of patients with PE, the 95 % confidence intervals are wide and the post-test likelihood of PE could be as high as 14 %. The rate of CT positivity for PE in an ED with unstructured CT ordering is similar to that in other published series including as series in which decision support was used. While D-dimer had high negative predictive value, large studies are needed to confirm this high sensitivity and potentially increase its use in ruling out PE without CT and to reduce CT ordering particularly in patients with sufficiently low clinical pre-test probability of PE.

Glucose obtained from unprocessed blood samples can decrease by 5%-7% per hour due to glycolysis. This study compared the impact of glucose degradation on measured glucose values by examining two different collection methods. For the first method, blood samples were collected in tubes containing sodium fluoride (NaF), a glycolysis inhibitor. For the second method, blood samples were collected in tubes containing a clot activator and serum gel separator and were centrifuged to separate the serum and plasma 20 minutes after sample collection. The samples used in the two methods were collected during the same blood draw and were assayed by the clinical laboratory 2-4 hours after the samples were obtained. A total of 256 pairs of samples were analyzed. The average glucose reading for the centrifuged tubes was significantly higher than the NaF tubes by 0.196 +/- 0.159 mmol/L (P < 0.01) or 4.2%. This study demonstrates the important role collection methods play in accurately assessing glucose levels of blood samples collected in the field, where working environment may be suboptimal. Therefore, blood samples collected in the field should be promptly centrifuged before being transported to clinical labs to ensure accurate glucose level measurements.