A Case of Acute Pulmonary Embolus after mRNA SARS-CoV-2 Immunization.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a critical strategy to overcome the COVID-19 pandemic. Multiple SARS-CoV-2 vaccines have been developed in a rapid timeframe to combat the pandemic. While generally safe and effective, rare cases of venous thromboembolism (VTE) have been reported after two adenovirus-based vaccines, the AstraZeneca ChAdOx1 nCoV-19 vaccine and the Janssen Ad.26.COV2.S vaccine, as well as after the Pfizer-BioNTech BNT162b2 mRNA vaccine. Here, we present the case of a patient who developed acute pulmonary emboli (PE) shortly after his second dose of the Moderna mRNA-1273 SARS-CoV-2 vaccine. We report the results of an extensive thrombophilia workup that was normal except for the identification of positive lupus anticoagulant (LA) signals. It is our goal to contribute to the body of knowledge regarding SARS-CoV-2 vaccines and encourage vaccine adverse event reporting so that clinicians can have a full appreciation and awareness of the possible adverse events related to these critical vaccines.

Reducing Blood Loss by Changing to Small Volume Tubes for Laboratory Testing.

OBJECTIVE: To reduce diagnostic blood loss by using small volume tubes for routine laboratory testing throughout the hospital, as blood loss from laboratory testing can be substantial for patients and may lead to hospital-acquired anemia. PATIENTS AND METHODS: Diagnostic blood loss was evaluated in hospitalized patients between April 1, 2017, and June 1, 2018. The preintervention, during intervention, and postintervention mean diagnostic blood loss per hospitalized patient was compared across the floors and for each type of tube for hematology, basic metabolic panel, and coagulation tests. Mean hemoglobin levels, blood transfusions per hospitalized patient, and percent redraws were also compared. RESULTS: The total volume of blood drawn for all the 3 tests decreased across each implementation phase; however, only patients admitted to the transplant and critical care (T/CC) units had increased hemoglobin levels. In addition, there was a significant reduction in transfusions across implementation phases. The incidence risk ratio for transfusion reduced even more in patients admitted to the T/CC units. Finally, there was no significant difference in the overall percent redraws across all the units. CONCLUSION: The use of small volume tubes in exchange for standard sized tubes markedly decreased diagnostic blood loss by 25.7% in all the units and 22.9% in the T/CC units. Also, the number of transfusions decreased across units, with the greatest decrease in the T/CC units. An increase in mean hemoglobin levels was observed specifically in patients admitted to the T/CC units, with no corresponding change in percent redraws across all the units.

Platelet Function Analyzer 100 and Brain Natriuretic Peptide as Biomarkers in Obstructive Hypertrophic Cardiomyopathy.

To test dual blood biomarkers compared with electrocardiogram (ECG) for hypertrophic cardiomyopathy (HC) screening, we performed 3 analyses and cut-point assessments. First, we measured platelet function analyzer (PFA)-100 (n = 99) and normalized B-type natriuretic peptide (BNP) or NT-proBNP (BNP/upper limit of normal [ULN], n = 92) in 64 patients with HC and 29 normal controls (NCs). Second, from the regression equation between PFA and gradient (r = 0.77), we derived estimated PFA in a population of 189 patients with functional class I HC in whom measured BNP/ULN and ECG were available, and calculated single and dual biomarker sensitivity and specificity compared with ECG. Finally, we compared BNP/ULN in class I patients based on mutation and familial history status. In 42 patients with obstructive HC versus NCs, there was a slight overlap of PFA and BNP/ULN, but for the product of PFA × BNP/ULN, there was near-complete separation of values. Among patients with class I obstructive HC, estimated PFA × BNP/ULN had a sensitivity of 93% and a specificity of 100%; in latent and nonobstructive HC, sensitivity dropped to 61% and 72%; for ECG in obstructive, latent, and nonobstructive HC, sensitivity was 71%, 34%, and 67%. Functional class I patients with positive (n = 28) and negative (n = 36) sarcomere mutations and a positive (n = 71) or a negative (n = 109) family history had significant elevations of BNP/ULN versus NC, with no between-group differences. In conclusion, PFA and BNP were highly associated with obstructive HC and could potentially be used for screening; BNP was not uniquely elevated in patients with familial versus nonfamilial or mutation-positive versus mutation-negative HC.

Safety and Efficacy of Intensified Antiplatelet Therapy in Patients Undergoing Neuroendovascular Procedures.

INTRODUCTION: The purpose of this study was to evaluate safety and efficacy of intensified antiplatelet therapy guided by VerifyNow assay P2Y12 reaction unit (PRU) reported values in patients undergoing neuroendovascular procedures. METHODS: An observational, retrospective review was conducted at a single academic tertiary referral center and comprehensive stroke center from December 1, 2012, to August 31, 2014. The primary objective was to determine the prevalence of thromboembolic complications stratified by preprocedural PRU values. Secondary outcomes were assessed by investigating whether the goal PRU value of 190 or less is sufficient to reduce thromboembolic complications on the day of the procedure, and 30- and 90-day postprocedure. RESULTS: There was no statistically significant difference in the overall rate of complications in the two groups (two events in the group with preprocedural PRU values of 190 or more versus seven events in the group with preprocedural PRU values of less than 190, p = 0.668). Furthermore, the rates of thromboembolic events by 90 days were not significantly different in the two groups (one event in the group with preprocedural PRU ≥ 190 versus four events in patients with preprocedural PRU < 190, p = 1). Similarly, there was no statistically significant difference in the rate of hemorrhagic events in the two groups by 90-day postprocedure (one versus three events, p = 0.558). CONCLUSION: The observed rate of thromboembolic and hemorrhagic complications in patients with preprocedural PRU values of less than 190 was not significantly different from the rate observed in patients with preprocedural PRU values of greater than 190. Sources of funding: No external funding used.

Clopidogrel Resistance by P2Y12 Platelet Function Testing in Patients Undergoing Neuroendovascular Procedures: Incidence of Ischemic and Hemorrhagic Complications.

PURPOSE: The purpose of the study was to assess clopidogrel resistance and whether "intensified" antiplatelet therapy guided by platelet inhibition tests during neuroendovascular procedures would reduce ischemic complications. METHODS: We conducted a retrospective review of patients at Mayo Clinic in Jacksonville, Florida, who underwent neuroendovascular (NV) procedures and had P2Y12 platelet function testing from October 1, 2009, to September 30, 2010. The primary end-point was to determine P2Y12 resistance to antiplatelet therapy in patients who underwent NV procedures. Secondary objectives included incidence of hemorrhagic and ischemic events and a correlation between resistance and genetic CYP2C19 testing. RESULTS: 160 patients underwent P2Y12 platelet function tests. Eighty-one patients (81/160, 50.6%) met inclusion criteria. Platelet function tests identified 64 patients (79%) as non-resistant (≥20% P2Y12 inhibition) and 17 (21%) as resistant (<20% inhibition) after initial clopidogrel loading. There was an increased rate of death when a complication occurred in the resistant group by 30 day (17% versus 3%; p=0.059) and 90 day follow-up (23% versus 4%; p=0.032). There was no significant association found between complication and loading dose (p=0.0721). CONCLUSIONS: 21% of patients undergoing NV procedures were resistant to clopidogrel. Intensifying antiplatelet therapy to achieve ≥20% inhibition on platelet function testing did not result in higher numbers of ischemic or hemorrhagic events, but there was a trend toward more death in the resistant group by 30 and 90 days of those experiencing complication(s). AUTHOR JUSTIFICATIONS: Jerah D. Nordeen, Pharm.D.: Primary author Alden V. Patel, Pharm.D.: Contributor of professional content, study design Robert M. Darracott, Pharm.D.: Contributor of professional content, study design Gretchen S. Johns, M.D.: Contributor of professional content, study design Philipp Taussky, M.D.: Contributor of professional content, study design Rabih G. Tawk, M.D.: Contributor of professional content, study design David A. Miller, M.D.: Contributor of professional content, study design William D. Freeman, M.D.: Contributor of professional content, study design Ricardo A. Hanel, MD, PhD: Contributor of professional content, study design. LIST OF ABBREVIATIONS: (NV)neuroendovascular(CYP)cytochrome P-450(PPI)proton pump inhibitors(PCI)percutaneous coronary intervention. LIST OF COMMERCIAL PRODUCTS: Aspirin (Acetylsalicylic Acid) (Bayer Corp, Morristown, NJ, USA) Clopidogrel (Plavix®) (Bristol Myers Squibb/Sanofi Pharmaceuticals, Princeton, NJ, USA) VerifyNow® (Accumetrics Inc., San Diego, CA, USA) Ticlopidine (Ticlid®) (Roche Laboratories, Basel, Switzerland) Prasugrel (Effient®) (Eli Lilly & Co., Indianapolis, IN, USA) Eptifibatide (Integrilin®) (Merck & Co., Inc., Whitehouse Station, NJ, USA) Abciximab (Reopro®) (Janssen Pharmaceuticals, Inc., Titusville, NJ, USA) Tirofiban (Aggrastat®) (MGI Pharma, Inc., Bloomington, MN, USA) Pantoprazole (Protonix®) (Pfizer Inc., New York, NY, USA) Omeprazole (Prilosec®) (Procter and Gamble Pharmaceuticals, Mason, OH, USA) Famotidine (Pepcid®) (McNeil Consumer & Specialty Pharmaceuticals, Fort Washington, PA, USA) Ticagrelor (Brilinta®) (AstraZeneca Pharmaceuticals, Wilmington, NC, USA).

Indexes of von Willebrand factor as biomarkers of aortic stenosis severity (from the Biomarkers of Aortic Stenosis Severity [BASS] study).

We correlated von Willebrand factor (VWF) activity indexes and brain natriuretic peptide (BNP) with measures of aortic stenosis (AS) severity, bleeding, symptoms, and freedom from death or aortic valve replacement. Patients with AS (n = 66 [16 mild, 20 moderate, and 30 severe]) and aortic valve replacement (n = 21) were assessed with VWF antigen, VWF latex agglutination immunoturbidic activity, platelet function analyzer collagen plus adenosine diphosphate (PFA-CADP), VWF multimer ratio, and BNP level after echocardiography. In patients with AS, the mean gradient correlated with BNP (Spearman r = 0.29, p = 0.02), VWF latex agglutination immunoturbidic activity/VWF antigen ratio (r = -0.41, p <0.001), PFA-CADP (r = 0.49, p <0.001), and VWF multimer ratio (r = -0.76, p <0.001). The area under the curve for detection of severe AS was 0.62 (95% confidence interval [CI] 0.48 to 0.77) by elevated BNP, 0.81 (95% CI 0.69 to 0.92) by PFA-CADP closure time, 0.69 (95% CI 0.55 to 0.82) by VWF latex agglutination immunoturbidic activity/VWF antigen ratio, and 0.86 (95% CI 0.76 to 0.95) by VWF multimer ratio. For the VWF multimer ratio, a threshold of 0.15 yielded a sensitivity and specificity for severe AS of 77% and positive predictive value of 74%. Bleeding (in 14%) was associated with a prolonged PFA-CADP time and reduced VWF latex agglutination immunoturbidic activity/VWF antigen ratio. Symptoms were associated with elevated BNP and low Duke Activity Status Index score. In 66 patients with AS, freedom from death (n = 4) or aortic valve replacement (n = 22) was associated with PFA-CADP (p = 0.003), VWF high-molecular-weight multimers (p = 0.009), and VWF latex agglutination immunoturbidic activity/VWF antigen ratio (p <0.001) but not BNP (p = 0.32). In severe AS versus aortic valve replacement, the PFA-CADP and VWF multimer ratio differed (p <0.001), but BNP and the VWF latex agglutination immunoturbidic activity/VWF antigen ratio did not. In conclusion, the VWF activity indexes were associated with AS severity and bleeding and were predictive of cardiovascular outcomes.

Infantile Alexander's disease: serial neuroradiologic findings.

Serial neuroimaging studies in Alexander's disease were obtained on an African-American girl who died at 4z\x years of age. She presented with macrocephaly, psychomotor retardation, spasticity, a seizure disorder, and hydrocephalus. A thorough metabolic evaluation of defined leukodystrophies, including Krabbe's disease, adrenoleukodystrophy, metachromatic leukodystrophy, Canavan's disease, and Leigh disease, was negative. A diagnosis of Alexander's disease was made based on the clinical features and ruling out all other possible causes. It was confirmed by pathologic findings of numerous subpial, subependymal, and perivascular Rosenthal fibers throughout the entire cerebrum. Interestingly, autopsy also identified the stenotic sylvian aqueduct owing to Rosenthal fiber accumulation, explaining the origin of hydrocephalus. The evolution of magnetic resonance imaging findings appears to be unique in this disease.