Recombinant ADAMTS13 for Immune Thrombotic Thrombocytopenic Purpura.

In patients with immune thrombotic thrombocytopenic purpura (iTTP), autoantibodies against the metalloprotease ADAMTS13 lead to catastrophic microvascular thrombosis. However, the potential benefits of recombinant human ADAMTS13 (rADAMTS13) in patients with iTTP remain unknown. Here, we report the clinical use of rADAMTS13, which resulted in the rapid suppression of disease activity and complete recovery in a critically ill patient whose condition had proved to be refractory to all available treatments. We also show that rADAMTS13 causes immune complex formation, which saturates the autoantibody and may promote its clearance. Our data support the role of rADAMTS13 as a novel adjunctive therapy in patients with iTTP.

Emergency transfusion with whole blood versus packed red blood cells: A study of 1400 patients.

BACKGROUND: Low-titer group O whole blood (LTOWB) is increasingly used for emergency transfusion. We studied whether initial release of LTOWB compared with packed red blood cells (pRBCs) reduced overall blood requirements for patients needing emergency transfusion. Secondary outcomes examined included survival and non-lethal adverse clinical outcomes. STUDY DESIGN AND METHODS: A retrospective, single-center, before-versus-after study compared patients transfused with emergency-release, uncrossmatched pRBC followed by component therapy (2016-2019) versus patients transfused with emergency-release, uncrossmatched LTOWB followed by component therapy (2019-2022). RESULTS: Outcomes were available for 602 patients in the pRBC group versus 749 in the whole blood group. The two groups were similar for age, sex, race, estimated blood volume, ABO blood groups, and underlying diagnosis. Use of LTOWB was associated with increased blood product use at 24 h (4.0 (2.0-12.0) in pRBC group versus 6.5 (4.2-12.7) in LTOWB group, p < .0001) and at 7 days (5.5 (3.0-13.0) in pRBC group versus 7.3 (4.3-14.3) in LTOWB group, p < .0001). Initial use of LTOWB was not associated with improved 24 h or 30 day survival nor lower incidence of non-lethal adverse clinical outcomes compared with pRBC. DISCUSSION: Our study showed a statistically significant increase in total blood use and blood acquisition costs for patients receiving initial emergency transfusion with LTOWB compared with pRBC. The initial use of LTOWB offered no advantage over component therapy for 30 day survival or selected non-lethal adverse outcomes.

Aberrant expression of HMB45 and negative PRAME expression in halo nevi.

BACKGROUND: Traditionally, most cutaneous nevi show a gradient of HMB45 (human melanoma black 45) and negative PRAME (preferentially expressed antigen in melanoma) immunostaining, while melanomas often show irregularly positive, diffusely positive or completely negative HMB45 expression, and PRAME immunopositivity. However, we have occasionally observed benign halo nevi with loss of HMB45 gradient, raising diagnostic consideration for melanoma. The purpose of this study was to elucidate the expression pattern of HMB45 and PRAME in nevi with the halo phenomenon (NHP). METHODS: PRAME and HMB45 staining patterns in 20 cases of NHP and 16 cases of conventional nevi were evaluated using light microscopy. An HMB45 gradient was defined as immunopositivity in only superficial melanocytes. HMB45 aberrant expression consisted of superficial and deep immunopositivity. RESULTS: Aberrant HMB45 expression was observed in 10 of 20 NHP (50%). A gradient of HMB45 staining was seen in most conventional nevi, with only one showing focal weak expression in the deep dermis (6.3%). All cases of NHP and conventional nevi showed essentially negative immunostaining by PRAME. CONCLUSION: Aberrant HMB45 expression in NHP is not uncommon and may be a diagnostic pitfall. Negative PRAME immunostaining may be a reassuring finding to help differentiate halo nevus from malignant melanoma.

Post-scabietic nodules: Mimicker of infantile indeterminate cell histiocytosis and potential diagnostic pitfall.

Indeterminate cell histiocytosis (ICH) is an extremely rare disease and little is known about its etiology. Patients usually present with nodular, dermal proliferations of indeterminate cells, which characteristically resemble Langerhans cells but lack Birbeck granules. The clinical course is highly variable, ranging from spontaneous regression to rapid progression with reports of extracutaneous involvement, subsequent acute myeloid leukemias, and associated B-cell lymphomas. Rare cases of ICH-like reactions have been reported in the setting of scabies infestations as well as in patients who had been bitten by ticks and mosquitos. We present a successfully treated case of indeterminate cell-rich post scabietic nodules in an otherwise healthy 8-month-old boy and review the literature on similar cases. Clinical context is essential for correct interpretation of these indolent ICH-mimicking lesions, and to avert unnecessary patient anxiety and aggressive management.

Melanocytic aggregates with unique morphology associated with regression of basal cell carcinoma.

BACKGROUND: Spontaneous regression of basal cell carcinomas (BCC) is a well-documented phenomenon. In practice, we have observed melanocytic aggregates associated with BCC at various stages of regression showing unique morphologic features. METHODS: Fourteen cases featuring melanocytic aggregates were retrospectively identified through a pathology database search. Clinical and histopathologic features were systematically evaluated, and additional immunohistochemical studies were performed. Melanocyte density within tumor nodules was compared to a group of control BCCs. RESULTS: All cases showed BCC at various stages of regression with associated melanocytic aggregates, as highlighted by Melan-A and SOX10 immunostains. Three of 14 cases (21.4%) had only dermal melanocytic nests, while 11 (78.6%) had both junctional and dermal nests. The melanocytic aggregates all had similar asymmetrical architecture and lacked maturation. The melanocytes were small, uniform, bland, and had minimal cytoplasm. Their nuclei were overlapping and hyperchromatic, and had inconspicuous nucleoli. None of the melanocytic aggregates stained for BRAFV600E by immunohistochemistry. No patient developed a recurrent or metastatic melanocytic lesion (median follow-up 42 months). Melanocyte density was higher in the case series than in the control BCCs (P = 0.0008). CONCLUSION: We described the unique morphology of melanocytic aggregates associated with BCC regression.

Bacterial screening of apheresis platelets with a rapid test: a 113-month single center experience.

BACKGROUND: The 2016 Food and Drug Administration draft guidance describes the use of a rapid test (RT) to enhance platelet transfusion safety and availability. This study reports a 113-month experience of screening of apheresis platelets (APs) by RT. STUDY DESIGN AND METHODS: From July 2008 to October 2015, all APs underwent an RT on Day 4. Day 6 and 7 units were transfused with transfusion medicine physician approval. Any units remaining on Day 8 had a second RT performed. From November 2015 to November 2017, APs underwent an RT on Day 5 with a repeat RT on Days 6 and 7. During both periods, positive RTs underwent confirmatory testing with culture when repeat testing was positive. RESULTS: A total of 9009 APs underwent an RT on Day 4 or 5. Of these, 45 (0.5%) were RT positive, with no true positives. A total of 754 underwent a second RT on Day 8, with no positives. Since November 2015, 1152 platelets have undergone a second RT on Day 6; 391 have undergone a third RT on Day 7. Of these, five (0.4%) were RT positive on Day 6, with no true positives. There were no septic transfusion reactions identified by passive surveillance at our institution during either study period. CONCLUSION: To date, we have not detected any true positives after performing 11,306 tests on 9009 APs. A total of 1906 underwent testing twice, and 391 underwent testing three times. We did not identify any conversions from negative to positive on repeat testing.

Emperipolesis and S100 expression may be seen in cutaneous xanthogranulomas: A multi-institutional observation.

Cutaneous Rosai-Dorfman disease (RDD) can be difficult to distinguish from other non-Langerhans cell histiocytoses, particularly xanthogranuloma (XG). Pathologists use S100 immunoreactivity, abundant plasma cells, and the presence of emperipolesis to distinguish RDD from XG. However, S100 expression has been reported in XG and, in practice, we have occasionally observed emperipolesis in cases that were otherwise clinically and pathologically consistent with XG. We present 10 cases of XG with emperipolesis and variable S100 immunoreactivity. Histologically, 7 cases were most in keeping with XG, and a histologic differential of XG versus RDD was raised in the remaining 3 cases. All 10 cases were clinically consistent with XG. Notably, none of these cases showed abundant plasma cells. Nine cases showed variable S100 immunostaining, ranging from focal/weak expression, to focal/strong, diffuse/moderate, and diffuse/strong expression. Histiocytes in all cases were CD68 positive and CD1a negative. We conclude that emperipolesis and S100 expression in a skin biopsy cannot reliably distinguish XG from cutaneous manifestations of RDD. Clinical correlations are essential, as are histologic clues to a diagnosis of classic XG that include an abundance of foamy mononuclear cells, Touton giant cells, and an absence of pale-stained histiocytes, abundant plasma cells, fibrosis, or vascular proliferation.

Application of Standardized Residual Component Culture Criteria for Suspected Septic Transfusion Reactions Would Increase the Component Culturing Rate at a Single Academic Medical Center.

OBJECTIVES: The 2019 SCARED study developed the Biomedical Excellence for Safer Transfusion (BEST) criteria in an effort to standardize the decision to culture residual units in the context of suspected septic transfusion reactions (STRs). The goal of this study was to apply the BEST criteria to determine the effect on the transfusion reaction decision to culture. METHODS: This retrospective, single-center, cross-sectional study assessed adult transfusion reactions identified in calendar years 2013 to 2020. Reactions following transfusion of RBCs, platelets, and plasma were included, and the decisions to culture following strict application of BEST criteria were compared with decisions to culture in actual practice. RESULTS: In total, 1,068 transfusion reactions were reported and 200 (19%) suspected STRs were cultured, all with negative results; 303 (28%) reactions would have been cultured per strict application of the BEST criteria. Concordance between actual culture decision and BEST criteria recommendation was 62% for cultured components and 79% for components that were not cultured. CONCLUSIONS: BEST criteria provide objective recommendations of when to culture residual units implicated in suspected STRs, but strict application of these criteria may result in increased culture rates. Clinical correlation to aid in the decision to culture is recommended.

Risk of ABO-Incompatible Plasma From Non-ABO-Identical Components.

The last several decades have seen significant changes in the approach to resuscitation of bleeding patients. These include the adoption of ABO-incompatible plasma transfusion in the form of group A plasma and/or low titer group O whole blood for trauma patients of unknown ABO group. Studies to date have examined the impact of these practices on patient outcomes and clinical markers of hemolysis in recipients of ABO-incompatible plasma compared to those for whom the plasma is ABO-compatible. Risk for increased mortality and/or overt hemolysis appear to be low among recipients of ABO-incompatible plasma; however, nearly all of studies are retrospective and most have focused only on adult trauma patients so results may not be generalizable to other bleeding patients. Work continues to evaluate the role of various titer thresholds in decreasing hemolytic risk and opportunities remain to improve our understanding of anti-A and anti-B antibody interactions with complement/endothelium and identify strategies to minimize risk.

Diagnostic and prognostic value of glucose transporters in melanocytic lesions.

We have previously reported increased glucose transporter 1 (GLUT1) expression in melanoma compared to benign nevi, associated with a significantly lower survival rate. GLUT1 upregulation was highly specific for distinguishing melanoma from benign nevi, yet poorly sensitive, likely because of expression of other GLUT isoforms. The purpose of this study was to evaluate GLUT2 and GLUT3, as melanoma biomarkers. A tissue microarray, consisting of 91 primary melanomas, 18 melanoma metastases, and 56 nevi, was examined using GLUT2 and GLUT3 immunohistochemistry. A semiquantitative scoring method was used to determine the percentage of positive tumor cells and staining intensity. GLUT2 was negative in all melanomas and benign nevi examined. Increased GLUT3 expression was more frequent in melanoma than in nevi (P < 0.0001), and in metastatic melanoma than in primary melanomas (P < 0.001). Of melanoma cases, 85.3% expressed either GLUT1 or GLUT3 or both, 39.4% of melanoma cases coexpressed GLUT1 and GLUT3, 17.4% of melanoma cases only expressed GLUT1, 28.4% of melanoma cases only expressed GLUT3, and 14.7% of melanoma cases were negative for both markers. Patients whose melanoma exhibited a high level of GLUT3 had significantly lower survival rates than those with low GLUT3 expression (P = 0.002). Evaluating both GLUT1 and GLUT3 increased the diagnostic value by increasing the sensitivity while the specificity remained high. In conclusion, GLUT2 was not expressed in melanocytes. GLUT3 expression was upregulated in melanoma compared with nevi, especially in those with worse prognosis. Similar to GLUT1, GLUT3 may serve as a useful diagnostic and prognostic marker.