Early Convalescent Plasma for High-Risk Outpatients with Covid-19.

BACKGROUND: Early administration of convalescent plasma obtained from blood donors who have recovered from coronavirus disease 2019 (Covid-19) may prevent disease progression in acutely ill, high-risk patients with Covid-19. METHODS: In this randomized, multicenter, single-blind trial, we assigned patients who were being treated in an emergency department for Covid-19 symptoms to receive either one unit of convalescent plasma with a high titer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or placebo. All the patients were either 50 years of age or older or had one or more risk factors for disease progression. In addition, all the patients presented to the emergency department within 7 days after symptom onset and were in stable condition for outpatient management. The primary outcome was disease progression within 15 days after randomization, which was a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization. Secondary outcomes included the worst severity of illness on an 8-category ordinal scale, hospital-free days within 30 days after randomization, and death from any cause. RESULTS: A total of 511 patients were enrolled in the trial (257 in the convalescent-plasma group and 254 in the placebo group). The median age of the patients was 54 years; the median symptom duration was 4 days. In the donor plasma samples, the median titer of SARS-CoV-2 neutralizing antibodies was 1:641. Disease progression occurred in 77 patients (30.0%) in the convalescent-plasma group and in 81 patients (31.9%) in the placebo group (risk difference, 1.9 percentage points; 95% credible interval, -6.0 to 9.8; posterior probability of superiority of convalescent plasma, 0.68). Five patients in the plasma group and 1 patient in the placebo group died. Outcomes regarding worst illness severity and hospital-free days were similar in the two groups. CONCLUSIONS: The administration of Covid-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of Covid-19 did not prevent disease progression. (SIREN-C3PO ClinicalTrials.gov number, NCT04355767.).

Using redox potential as a feasible marker for banked blood quality and the state of oxidative stress in stored red blood cells.

BACKGROUND: Stored red blood cells (RBCs) may undergo oxidative stress over time, with functional changes affecting oxygen delivery. Central to these changes are oxidation-reduction (redox) reactions and redox potential (RP) that must be maintained for cell function. RP imbalance can lead to oxidative stress that may contribute to storage lesions. This study's purpose was to identify changes in RP over time in banked RBCs, and among RBCs of similar age. METHODS: Multiple random RBC segments from RBC units were tested (n = 32), ranging in age from 5 to 40 days, at 5-day intervals. RP was recorded by measuring open circuit potential of RBCs using nanoporous gold electrodes with Ag/AgCl reference. RP measures were also performed on peripheral venous blood from 10 healthy volunteers. RP measures were compared between RBC groups, and with volunteer blood. RESULTS: Stored RBCs show time-dependent RP increases. There were significant differences in Day 5 RP compared to all other groups (p ≤ 0.005), Day 10-15 vs. ages ≥ Day 20 (p ≤ 0.025), Day 20-25 vs. Day 40 (p = 0.039), and all groups compared to healthy volunteers. RP became more positive over time suggesting ongoing oxidation as RBCs age; however, storage time alone was not predictive of RP measured in a particular unit/segment. CONCLUSIONS: There are significant differences in RP between freshly stored RBCs and all others, with RP becoming more positive over time. However, storage time alone does not predict RP, indicating RP screening may be an important measure of RBC oxidative stress and serve as an RBC quality marker.

Red blood cell alloimmunization and minor red blood cell antigen phenotypes in transfused Ghanaian patients with sickle cell disease.

BACKGROUND: The routine pretransfusion investigations in Southern Ghana involve only ABO-D blood group typing and ABO compatibility testing without screening for irregular red blood cell (RBC) antibodies. The prevalence and specificities of RBC antibodies and frequencies of most minor blood group antigens in transfused patients with sickle cell disease (SCD) in Ghana are not known and are the objectives of this study. STUDY DESIGN AND METHODS: This was a cross-sectional study that investigated transfused patients with SCD for the presence of irregular RBC antibodies and Rhesus, Kell, Duffy, Kidd, and Ss antigens. RESULTS: From a total of 154 patients (median age, 9 years), 10 patients (6.5%) possessed 13 antibodies, predominantly against D, C, and E antigens. In three patients, the antibodies (anti-D, anti-D + C, and anti-C + e) were against antigens they possessed by serology. Genotyping showed that two of these patients had variant RHCE genes that encode for weak and partial e antigens and one patient had a partial RHC gene. Frequencies of most RBC antigens were comparable with frequencies established among the African American population; however, K-k- and Jk(a-b-) phenotypes were more frequent and were present in 21% and 17% of patients, respectively. CONCLUSION: The prevalence of RBC alloimmunization in transfused Ghanaian patients with SCD was 6.5% and the majority of antibodies were against antigens of the Rh system. Our findings stress the need to include pretransfusion testing for RBC antibodies in patients with SCD, to improve transfusion safety.

Potential of Three Ethnomedicinal Plants as Antisickling Agents.

Sickle cell disease (SCD) is a genetic blood disorder that affects the shape and transportation of red blood cells (RBCs) in blood vessels, leading to various clinical complications. Many drugs that are available for treating the disease are insufficiently effective, toxic, or too expensive. Therefore, there is a pressing need for safe, effective, and inexpensive therapeutic agents from indigenous plants used in ethnomedicines. The potential of aqueous extracts of Cajanus cajan leaf and seed, Zanthoxylum zanthoxyloides leaf, and Carica papaya leaf in sickle cell disease management was investigated in vitro using freshly prepared 2% sodium metabisulfite for sickling induction. The results indicated that the percentage of sickled cells, which was initially 91.6% in the control, was reduced to 29.3%, 41.7%, 32.8%, 38.2%, 47.6%, in the presence of hydroxyurea, C. cajan seed, C. cajan leaf, Z. zanthoxyloides leaf, and C. papaya leaf extracts, respectively, where the rate of polymerization inhibition was 6.5, 5.9, 8.0, 6.6, and 6.0 (×10-2) accordingly. It was also found that the RBC resistance to hemolysis was increased in the presence of the tested agents as indicated by the reduction of the percentage of hemolyzed cells from 100% to 0%. The phytochemical screening results indicated the presence of important phytochemicals including tannins, saponins, alkaloids, flavonoids, and glycosides in all the plant extracts. Finally, gas chromatography-mass spectrometry analysis showed the presence of important secondary metabolites in the plants. These results suggest that the plant extracts have some potential to be used as alternative antisickling therapy to hydroxyurea in SCD management.

Coagulation status after therapeutic plasma exchange using citrate in kidney transplant recipients.

BACKGROUND: Therapeutic plasma exchange (TPE) is increasingly used for treatment of antibody-mediated rejection (AMR) after solid organ transplants. There is concern that TPE may increase risk of bleeding, although data are limited. After TPE, clot-based coagulation tests may not accurately represent the levels of coagulation factors due to the effect of citrate. We investigated protein levels of fibrinogen using antigen detection method (FibAg) and correlated results with a clot-based fibrinogen activity test (Fib). STUDY DESIGN AND METHODS: Nine kidney transplant recipients who received TPE for AMR were investigated. Fib, FibAg, prothrombin time/international normalized ratio (PT/INR), partial thromboplastin time (PTT), coagulation factor X chromogenic activity (CFX), and ionized calcium (iCa) were measured at pre- and post-TPE and 1, 3, 6, 9, 24, and 48 hours after the first TPE. RESULTS: Mean Fib/FibAg ratio before TPE was 1.08; therefore, all Fib values were normalized (n) by dividing by 1.08. Overall, the mean normalized Fib (nFib)/FibAg ratio at post-TPE was 0.89 and returned to close to 1.0 at 6 hours after the first TPE. Decreases in nFib, FibAg, and CFX and increases in PT/INR and PTT post-TPE were observed. The lowest Fib, FibAg, CFX, platelet, and iCa levels were still at levels that would be considered sufficient for hemostasis at all time points. CONCLUSION: The mean nFib/FibAg ratio after TPE was 0.89 and normalized in 6 hours, which demonstrates a persistent effect of citrate for up to 6 hours. Therefore, similar data observed in clot-based tests of PT/INR and PTT may be falsely elevated up to 6 hours after TPE due to the citrate effect.

Comparison of two leukocytapheresis protocols in a case of idiopathic hypereosinophilic syndrome.

BACKGROUND: Hypereosinophilic syndrome (HEOS) is rare, and the efficacy of leukocytapheresis in this context is unclear. We here report the successful treatment of a patient with idiopathic HEOS with four leukocytapheresis procedures using two protocols. CASE: A 4-year-old female presented with cardiac and respiratory dysfunction, and WBC of 225 K/µL with 96% eosinophils. Leukocytapheresis was started after initiation of methylprednisolone and hydroxyurea. She received two leukocytapheresis with polymorphonuclear cell (PMN) protocol, followed by initiation of imatinib therapy, then two leukocytapheresis with mononuclear cell (MNC) protocol. After the fourth leukocytapheresis, her WBC decreased to 69 K/µL with 82% eosinophils. She was discharged on hospital day 21 under stable condition with WBC of 22 K/µL with 86% eosinophils. WBC count and eosinophil percentage continued to decrease, and were 6.4 K/µL and 52% by 2 weeks and 3.9 K/µL and 4.9% by 3 months after discharge, respectively. FINDINGS: WBC and absolute eosinophil (aEO) counts decreased by an average of 29.0 and 30.4% per leukocytapheresis, respectively. Normalized to estimated blood volume, procedures with PMN and MNC protocols changed, on average, WBC by -10.7 and -12.1%, aEO by -10.4 and -13.4%, platelet by -8.1 and -19.2%, and fluid balance by -129 and -47 mL, respectively. CONCLUSION: Leukocytapheresis was effective in decreasing WBC and aEO counts in HEOS, with PMN and MNC protocols achieving similar reductions. However, PMN protocol resulted in greater negative fluid balance and MNC protocol resulted in greater platelet loss. J. Clin. Apheresis 31:481-489, 2016. © 2015 Wiley Periodicals, Inc.

Efficacy of plasmapheresis on donor-specific antibody reduction by HLA specificity in post-kidney transplant recipients.

BACKGROUND: Donor-specific antibodies (DSAs) to HLA antigens can cause acute antibody-mediated rejection (AMR) after kidney transplantation (Txp). Therapeutic plasma exchange (TPE) has been used for AMR treatment; however, DSA reduction rates are inconsistent. We investigated DSA reduction rates by HLA specificity and clinical outcome. STUDY DESIGN AND METHODS: Sixty-four courses of TPE for 56 kidney Txp recipients with high DSA were investigated. Dates of TPE procedures and Txp, patients' age, sex, race, creatinine (Cr), and mean fluorescent intensity (MFI) of DSA were retrieved. MFI reduction rate after one to three TPE and four to six TPE procedures were calculated by HLA DSA specificity in each patient, and the mean reduction rates were compared. The relationship of TPE treatment, MFI or Cr improvement rate, and graft age was also investigated. RESULTS: Patients received a mean 6.0 TPE procedures. Most received intravenous immunoglobulin after TPE and immunosuppressives. Forty-two cases (65.6%) had DSA to HLA Class I and 54 cases (84.4%) to Class II, including 32 cases (50.0%) to both. Mean MFI reduction rates after one to three TPE and four to six TPE procedures were 25.7 and 37.1% in HLA Class I, 25.1 and 34.2% in Class II, and 14.3 and 19.9% in DR51-53. The mean Cr improvements at the end of TPE and 3 and 6 months after TPE were 3.41, -0.37, and -0.72%, respectively. CONCLUSION: Six TPE procedures decreased DSA more than three TPE procedures, but reduction rate was lower by the second three TPE procedures than the first three TPE procedures. Although the mean Cr improvement was minimal, the treatment has good potential to stop further deterioration of kidney function. Better Cr improvement rate is correlated with the graft age.

Maintenance plasma exchange treatment for muscle specific kinase antibody positive myasthenia gravis patients.

BACKGROUND: Anti-muscle specific kinase antibody positive myasthenia gravis (MuSK MG) is often characterized by a relatively severe and progressive course, refractoriness to standard myasthenia gravis (MG) medications, and an increased risk of myasthenic crisis. We report here successful management of three MuSK MG patients using maintenance therapeutic plasma exchange (TPE) treatment for up to 4.5 years. MATERIALS: The study was a 5-year retrospective review of all MG patients treated with TPE between 2008 and 2013 at University of Michigan. Inclusion criteria of MuSK MG were positive for anti-MuSK antibodies and a diagnosis of MuSK MG by staff neurologists. Patient data included age, gender, diagnostic testing results, medications, and the dates and response to TPE treatments. RESULTS: A total of 153 MG patients underwent at least one course of TPE between 2008 and 2013. A total of 12 patients (7.8%) were positive for anti-MuSK antibodies. Patients were predominantly female (83.3%) and a median age of onset was 46-years old. Three MuSK MG patients were successfully managed with maintenance TPE. CONCLUSION: Maintenance TPE may be an effective option for MuSK MG patients. The key of successful maintenance treatment at our institution has been to tailor the TPE frequency for each individual, and to modify the treatment interval in conjunction with medical management.

Evaluation of the efficacy and safety of amustaline/glutathione pathogen-reduced RBCs in complex cardiac surgery: the Red Cell Pathogen Inactivation (ReCePI) study-protocol for a phase 3, randomized, controlled trial.

BACKGROUND: Red blood cell (RBC) transfusion is a critical supportive therapy in cardiovascular surgery (CVS). Donor selection and testing have reduced the risk of transfusion-transmitted infections; however, risks remain from bacteria, emerging viruses, pathogens for which testing is not performed and from residual donor leukocytes. Amustaline (S-303)/glutathione (GSH) treatment pathogen reduction technology is designed to inactivate a broad spectrum of infectious agents and leukocytes in RBC concentrates. The ReCePI study is a Phase 3 clinical trial designed to evaluate the efficacy and safety of pathogen-reduced RBCs transfused for acute anemia in CVS compared to conventional RBCs, and to assess the clinical significance of treatment-emergent RBC antibodies. METHODS: ReCePI is a prospective, multicenter, randomized, double-blinded, active-controlled, parallel-design, non-inferiority study. Eligible subjects will be randomized up to 7 days before surgery to receive either leukoreduced Test (pathogen reduced) or Control (conventional) RBCs from surgery up to day 7 post-surgery. The primary efficacy endpoint is the proportion of patients transfused with at least one study transfusion with an acute kidney injury (AKI) diagnosis defined as any increased serum creatinine (sCr) level ≥ 0.3 mg/dL (or 26.5 µmol/L) from pre-surgery baseline within 48 ± 4 h of the end of surgery. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to pathogen-reduced RBCs through 75 days after the last study transfusion. With ≥ 292 evaluable, transfused patients (> 146 per arm), the study has 80% power to demonstrate non-inferiority, defined as a Test group AKI incidence increase of no more than 50% of the Control group rate, assuming a Control incidence of 30%. DISCUSSION: RBCs are transfused to prevent tissue hypoxia caused by surgery-induced bleeding and anemia. AKI is a sensitive indicator of renal hypoxia and a novel endpoint for assessing RBC efficacy. The ReCePI study is intended to demonstrate the non-inferiority of pathogen-reduced RBCs to conventional RBCs in the support of renal tissue oxygenation due to acute anemia and to characterize the incidence of treatment-related antibodies to RBCs.

Infusion of P-Capt prion-filtered red blood cell products demonstrate acceptable in vivo viability and no evidence of neoantigen formation.

BACKGROUND: Transmission of variant Creutzfeldt-Jacob disease (vCJD) is a major concern in blood transfusion. The P-Capt filter has been shown to remove around 4 log ID(50) prion infectivity from prion-spiked human red blood cells (RBCs). STUDY DESIGN AND METHODS: Two independent, single-center, randomized, open-label studies were designed to analyze the safety of P-Capt-filtered RBCs. RBCs prepared from leukoreduced whole blood from 43 eligible subjects were randomly assigned to P-Capt filtration and/or storage in plasma or SAGM and stored for 28 or 42 days. Stored RBCs were analyzed for in vivo 24-hour recovery, hemolysis, metabolic variables, blood group antigen expression, neoantigen formation, and safety after autologous infusion. RESULTS: Mean P-Capt filtration times for leukoreduced RBCs were 41 (SAGM) to 51 (plasma) minutes. Thirteen of 14 subjects receiving P-Capt-filtered RBCs had 24-hour RBC recoveries of 75% or more after 42-day storage, with a mean hemolysis of less than 0.6%. No loss of RBC antigen expression or formation of neoantigens was observed. In both studies, RBCs had white blood cell counts of less than 1 × 10(6)/unit after leukofiltration. P-Capt prion filtration provided an additional greater than 0.8 log leukoreduction. No serious or unexpected adverse events were observed after infusion of P-Capt-filtered full-volume RBC units. CONCLUSIONS: P-Capt-filtered, stored RBCs demonstrated acceptable viability and no detectable neoantigen expression, immunogenic responses. or safety issues after infusion of a complete unit. The additional filtration time and modest reduction in RBC content are within acceptable levels for implementation in countries with transfusion transmission of vCJD.

Anti-A and anti-B titers in pooled group O platelets are comparable to apheresis platelets.

BACKGROUND: Although uncommon, acute hemolytic transfusion reactions (AHTRs) have been reported after transfusion of group O single-donor apheresis platelets (SDPs) to group A, B, and AB recipients. Current methods for identifying "high-titer" SDPs include tube and gel methods. The risk of a high-titer unit is considered low with group O, poststorage, pooled platelet concentrates (PPLTs); however, data regarding anti-A and anti-B titers in PPLTs are lacking. STUDY DESIGN AND METHODS: Anti-A and anti-B titers were determined in 185 PPLTs by direct agglutination using manual gel and tube methods. PPLTs tested included 124 group O PPLTs, 25 group A PPLTs, 26 group B PPLTs, and 10 PPLTs containing a mix of either groups O plus A or groups O plus B (mixed PPLTs). The reciprocal of the highest dilution giving macroscopic agglutination was considered the agglutinin titer. RESULTS: Mean anti-A and anti-B titers in group O PPLTs were, respectively, 16 and 8 by tube and 64 and 32 by gel (p < 0.0001). Gel titers were one to two dilutions higher than tube and sensitive to reagent red cell lots. With the use of at least 64 as a critical titer, 60 percent of group O PPLTs tested by gel would be considered high-titer. In mixed PPLTs, the addition of one non-group O PLT significantly decreased or neutralized the corresponding anti-A or anti-B (p < 0.0001). CONCLUSION: Anti-A and anti-B titers in group O PPLTs are comparable to those reported in group O SDPs and significantly lower than titers reported in AHTR. A critical direct agglutinin titer of 64 for identifying high-titer units by gel is too low and should be increased to 128 or higher.

Molecular Pathology in Transfusion Medicine: New Concepts and Applications.

Virtually all the red blood cell and platelet antigen systems have been characterized at the molecular level. Highly reliable methods for red blood cell and platelet antigen genotyping are now available. Genotyping is a useful adjunct to traditional serology and can help resolve complex serologic problems. Although red blood cell and platelet phenotypes can be inferred from genotype, knowledge of the molecular basis is essential for accurate assignment. Genotyping of blood donors is an effective method of identifying antigen-negative and/or particularly rare donors. Cell-free DNA analysis provides a promising noninvasive method of assessing fetal genotypes of blood group alloantigens.

Metastatic ductal carcinoma of the breast to the thyroid gland diagnosed with fine needle aspiration: A case report with emphasis on morphologic and immunophenotypic features.

Metastases to the thyroid are uncommon [<0.2% of thyroid fine needle aspirations (FNA)]. Of metastases to the thyroid, breast carcinoma is relatively common. The diagnosis of metastasis to the thyroid has important therapeutic and prognostic implications. To our knowledge, a morphologic and immunophenotypic comparison of metastatic ductal carcinoma of the breast and primary thyroid carcinomas has not been reported. Here, we report the case of a 37-year-old female with a history of metastatic ductal carcinoma of the breast (modified Bloom-Richardson grade 2; ER+, PgR+, HER2+) diagnosed 6 years prior. She developed hoarseness, prompting a CT scan. Multiple thyroid nodules were found, including a 1.5 cm hypoechoic, solid, irregularly-shaped nodule. On FNA, cells were arranged singly and in crowded groups, varied in size and degree of pleomorphism, and exhibited rare nuclear grooves, inconspicuous nucleoli, and rare intracytoplasmic lumina with no nuclear pseudoinclusions or colloid (Figs. 1A and B). These findings raised the differential of papillary thyroid carcinoma (Fig. 1C), follicular neoplasm (Fig. 1D), medullary carcinoma (Fig. 1E), parathyroid (Fig. 1F), and metastatic breast carcinoma. Immunostaining for GATA-3 (+), ER (+), PAX-8 (-), and TTF-1 (-) was consistent with metastatic breast carcinoma (Fig. 2). We conclude that metastatic breast carcinoma to the thyroid may morphologically mimic primary thyroid carcinoma on FNA; a panel of immunomarkers, such as GATA-3, hormonal marker(s), PAX-8, and TTF-1, may be useful in some cases. GATA-3 immunostaining for metastatic breast carcinoma was helpful in our case and has not been previously reported in a thyroid metastasis sampled by FNA. Diagn. Cytopathol. 2016;44:530-534. © 2016 Wiley Periodicals, Inc.

Pathophysiology of hemolytic transfusion reactions.

Hemolytic transfusion reactions (HTR) are systemic reactions provoked by immunologic red blood cell (RBC) incompatibility. Clinical and experimental observations of such reactions indicate that they proceed through phases of humoral immune reaction, activation of phagocytes, productions of cytokine mediators, and wide-ranging cellular responses. HTR have many features in common with the systemic inflammatory response syndrome (SIRS). Knowledge of the pathophysiologic mechanisms in HTR suggest that newer biological agents that target complement intermediates or proinflammatory cytokines may be effective agents in the treatment of severe HTRs.

Noninvasive prenatal RHD genotyping by real-time polymerase chain reaction using plasma from D-negative pregnant women.

OBJECTIVE: Prenatal noninvasive determination of fetal Rh status is an important aid to the management of hemolytic disease of the fetus and newborn. We performed real-time polymerase chain reaction on fetal DNA derived from maternal plasma to determine fetal Rh status. STUDY DESIGN: Cell-free plasma DNA from 98 D-negative pregnant women was tested for the presence of exons 4, 5, and 10 of RHD. The presence of fetal DNA was confirmed by detection of SRY or biallelic insertion/deletion polymorphisms in the maternal plasma and buffy coat. RESULTS: Seventy-two D-positive infants and 26 D-negative infants were determined by serologic studies. All 3 RHD exon sequences were detected in 68 of 72 mothers of D-positive infants. The presence of fetal DNA in mothers of D-negative infants was confirmed in all 10 boys and in 14 of 16 girls. CONCLUSION: Fetal RHD genotyping in this study correctly predicted fetal Rh status in 92 of 98 (94%) cases.

Packed red blood cells are an abundant and proximate potential source of nitric oxide synthase inhibition.

OBJECTIVE: We determined, for packed red blood cells (PRBC) and fresh frozen plasma, the maximum content, and ability to release the endogenous nitric oxide synthase (NOS) inhibitors asymmetric dimethylarginine (ADMA) and monomethylarginine (LNMMA). BACKGROUND: ADMA and LNMMA are near equipotent NOS inhibitors forming blood's total NOS inhibitory content. The balance between removal from, and addition to plasma determines their free concentrations. Removal from plasma is by well-characterized specific hydrolases while formation is restricted to posttranslational protein methylation. When released into plasma they can readily enter endothelial cells and inhibit NOS. Fresh rat and human whole blood contain substantial protein incorporated ADMA however; the maximum content of ADMA and LNMMA in PRBC and fresh frozen plasma has not been determined. METHODS: We measured total (free and protein incorporated) ADMA and LNMMA content in PRBCs and fresh frozen plasma, as well as their incubation induced release, using HPLC with fluorescence detection. We tested the hypothesis that PRBC and fresh frozen plasma contain substantial inhibitory methylarginines that can be released chemically by complete in vitro acid hydrolysis or physiologically at 37°C by enzymatic blood proteolysis. RESULTS: In vitro strong-acid-hydrolysis revealed a large PRBC reservoir of ADMA (54.5 ± 9.7 µM) and LNMMA (58.9 ± 28.9 µM) that persisted over 42-d at 6° or -80°C. In vitro 5h incubation at 37°C nearly doubled free ADMA and LNMMNA concentration from PRBCs while no change was detected in fresh frozen plasma. CONCLUSION: The compelling physiological ramifications are that regardless of storage age, 1) PRBCs can rapidly release pathologically relevant quantities of ADMA and LNMMA when incubated and 2) PRBCs have a protein-incorporated inhibitory methylarginines reservoir 100 times that of normal free inhibitory methylarginines in blood and thus could represent a clinically relevant and proximate risk for iatrogenic NOS inhibition upon transfusion.

Exaggerated pigmented granulomatous reaction to the artificial joint implant mimics metastatic melanoma.

Total joint replacement is a common orthopedic procedure. An artificial joint implant may fail due to mechanical mishap and a granulomatous reaction can be induced by the artificial joint debris after the mechanical failure. We report a case of an exaggerated pigmented granulomatous tissue response to metallic artificial joint implant debris in a 72-yr-old male that was mistaken for metastatic melanoma. The mass was soft, pigmented, ill-defined, and located in the right inguinal region. Fine-needle aspiration revealed numerous black-pigment laden cells. The cellular features were frequently obscured by the heavy pigmentation. Occasional cells exhibited atypia and prominent nucleoli. There were also abundant extracellular irregular small black particles dispersed in the background. The diagnosis of melanoma involving a lymph node was made. Since there was no prior history of melanoma, it was presumed that this represented metastatic melanoma from an unknown primary. A subsequent exploration of the groin was performed with the intent to resect the disease. At exploration, the mass was found to be contiguous with the hip joint and the frozen section of the mass revealed no evidence of melanoma. The final tissue diagnosis confirmed the frozen section report and showed a granulomatous reaction. This report underscores the diagnostic dilemma associated with the exaggerated pigmented granulomatous reaction due to an artificial prosthesis.

A case of extravascular hemolysis with Tk-activation.

KEY CLINICAL MESSAGE: A 50-year-old female with ovarian cancer for 4 years presented with abdominal pain. She started antibiotics for possible infection, and developed extravascular hemolysis. All antigen detection tests were negative, but lectin panel suggested Tk-activation. Additional laboratory testing in conjunction with blood bank is essential to investigate rare cause of hemolysis.

Molecular pathology in transfusion medicine.

This article provides an overview of the application of molecular diagnostic methods to red cell and platelet compatibility testing. The advantages and limitations of molecular methods are evaluated compared with traditional serologic methods. The molecular bases of clinically significant red cell and platelet antigens are presented. Current recommendations for reporting molecular assay results and distinctions between genotype and phenotype are discussed.