Delayed Plasmodium falciparum Malaria in Pregnant Patient with Sickle Cell Trait 11 Years after Exposure, Oregon, USA.

Delayed Plasmodium falciparum malaria in immigrants from disease-endemic countries is rare. Such cases pose a challenge for public health because mosquitoborne transmission must be rigorously investigated. We report a case of delayed P. falciparum malaria in a pregnant woman with sickle cell trait 11 years after immigration to the United States.

Investigation of Apparent Solid Phase-Only Red Cell Serologic Reactivity: Clinical and Laboratory Correlations.

BACKGROUND: Solid phase red cell adherence is a sensitive platform for blood group antibody detection, but non-specific reactions may occur. The aim of this study was to define the clinical characteristics of patients with these reactions and their associated laboratory findings. METHODS: An 8-month retrospective review of a regional blood bank database was performed. One hundred and seventy-three patients were identified with apparent nonspecific solid phase (NSP) reactivity. Serologic findings were recorded, and each patient's electronic health record was interrogated. RESULTS: NSP reactivity was the most common positive finding in the laboratory. Of 173 patients with NSP, 167 had documented concurrent tube testing. Of these, 165 were negative, one demonstrated nonspecific reactivity, and one anti-Lea was identified. Most positive solid phase antibody screens had negative panel testing, with fewer cases of pan-reactivity or sporadic reactivity. Follow-up testing was either negative (85.5%) or demonstrated NSP reactivity (14.5%). No new blood group antibodies were identified. Most patients were female (72.8%), with pregnancy being the leading diagnosis (35.8%); however, this mirrored the distribution of cases received in the laboratory. When pregnant patients were excluded, female and male patients had the same average age, and the gender distribution and the primary diagnoses of NSP patients mirrored those of all patients evaluated. CONCLUSIONS: Solid phase antibody detection is known to be sensitive, but nonspecific reactions are relatively common. Compared to other studies, the evolution of NSP to clinically significant antibodies was not seen, female patients did not have a predilection for NSP reactivity, and NSP was not associated with certain diagnoses.

Novel NMP split liver model recapitulates human IRI and demonstrates ferroptosis modulators as a new therapeutic strategy.

BACKGROUND: Almost 9%of deceased donor livers are discarded as marginal donor livers (MDL) due to concern of severe ischemia reperfusion injury (IRI). Emerging data supports ferroptosis (iron regulated hepatocellular death) as an IRI driver, however lack of robust preclinical model limits therapeutic testing. In this manuscript we describe the development of a novel rigorous internal control system utilizing normothermic perfusion of split livers to test ferroptosis regulators modulating IRI. METHODS: Upon institutional approval, split human MDLs were placed on our normothermic perfusion machine, Perfusion Regulated Organ Therapeutics with Enhanced Controlled Testing (PROTECT), pumping arterial and portal blood. Experiment 1 compared right (UR) and left (UL) lobes to validate PROTECT. Experiment 2 assessed ferroptosis regulator Deferoxamine in Deferoxamine Agent Treated (DMAT) vs. No Agent Internal Control (NAIC) lobes. Liver serology, histology, and ferroptosis genes were assessed. RESULTS: Successful MDL perfusion validated PROTECT with no ALT or AST difference between UR and UL (∆ALT UR: 235, ∆ALT UL: 212; ∆AST UR: 576, ∆AST UL: 389). Liver injury markers increased in NAIC vs. DMAT (∆ALT NAIC: 586, ∆ALT DMAT: -405; ∆AST NAIC: 617, ∆AST DMAT: -380). UR and UL had similar expression of ferroptosis regulators RPL8,HO-1 and HIFα. Significantly decreased intrahepatic iron (p = .038), HO-1 and HIFα in DMAT (HO-1 NAIC: 6.93, HO-1 DMAT: 2.74; HIFαNAIC: 8.67, HIFαDMAT: 2.60)and no hepatocellular necrosis or immunohistochemical staining (Ki67/Cytokeratin-7) differences were noted. CONCLUSION: PROTECT demonstrates the therapeutic utility of a novel normothermic perfusion split liver system for drug discovery and rapid translatability of therapeutics, driving a paradigm change in organ recovery and transplant medicine. Our study using human livers, provides preliminary proof of concept for the novel role of ferroptosis regulators in driving IRI.

Autoimmune Hemolytic Anemia in Children: Laboratory Investigation, Disease Associations, and Treatment Strategies.

Autoimmune hemolytic anemia is a relatively uncommon pediatric clinical condition. As such, the evaluation and management of these cases can be challenging for even the most seasoned pediatrician. In this review, the 3 major forms of autoimmune hemolytic anemia in children will be discussed: warm autoimmune hemolytic anemia, cold agglutinin disease, and paroxysmal cold hemoglobinuria. After a general description of the laboratory approach to these entities, the pathophysiology of these disease processes, including important disease associations, will be described, and treatment strategies will be discussed. This will provide the reader with a rational approach to identifying and managing pediatric patients with these uncommon autoimmune conditions.

Rapid establishment of a COVID-19 convalescent plasma program in a regional health care delivery network.

BACKGROUND: COVID-19 convalescent plasma (CCP) represents an appealing approach to the treatment of patients with infections due to SARS-CoV-2. We endeavored to quickly establish a sustainable CCP transfusion program for a regional network of health care facilities. STUDY DESIGN AND METHODS: A regional collaborative group was activated to address the issues necessary to implementing a CCP transfusion program and making the program sustainable. A wide range of health care providers including physicians (critical care, infectious disease, transfusion medicine), nurses, pharmacists, laboratorians, and information technology (IT) specialists were required to make the program a success. RESULTS: The CCP implementation team initially consisted of four members but quickly grew to a group of nearly 20 participants based on different issues related to program implementation. Overall, six major implementation "themes" were addressed: (a) registration of individual hospitals and principal investigators with a national investigational new drug research protocol; (b) collaboration with a regional blood donor center; (c) targeted recruitment of convalesced donors; (d) IT issues related to all aspects of CCP ordering, distribution, and transfusion; (e) prioritization of patients to receive CCP; and (f) evaluation of CCP products including antibody characteristics and patient response to therapy. CONCLUSION: Within 4 weeks of initiation, CCP was successfully transfused at multiple hospitals in our regional health care delivery system. A program infrastructure was established that will make this program sustainable into the future. This approach has broader implications for the success of multi-institutional programs requiring rapid implementation.

Successful plasma exchange in a 34-year-old woman with diabetic ketoacidosis and a thrombotic microangiopathy.

Thrombotic microangiopathy (TMA) associated with diabetic ketoacidosis (DKA) is a rare complication reported in the pediatric setting. We report a case of an adult patient with new-onset DM, DKA, and TMA who was treated successfully with therapeutic plasma exchange (TPE). The patient underwent five procedures and experienced quick recovery in her platelet count and a near-normalization of her LDH. Within 3 days, ADAMTS13 activity was reported at 40.7% (>66.8%). After a protracted hospital course, mostly focused on treating the patient's bilateral hemorrhagic chemosis, the patient was discharged on hospital day 30. TMA is associated with a spectrum of diseases such as TTP and sepsis but, to our knowledge, it has not been reported in the setting of DKA in an adult patient. Evidence supports that metabolic alterations associated with DKA and its treatment disrupt basal hemostatic mechanisms and promote a thrombotic state. Although ADAMTS13 activity was only moderately decreased, our patient responded rapidly to TPE, with a striking increase and stabilization of her PLT count that was durable beyond discharge. As reported recently, patients who have TMA with ADAMTS13 activity levels >10% have a range of diagnoses, presentations, and outcomes. Although the underlying microangiopathic process is incompletely understood, these patients may respond well to TPE, as was seen in this case.

Severe Warm Autoimmune Hemolytic Anemia in a 7-Month-Old Infant Associated With a Mycoplasma Pneumoniae Infection.

A 7-month-old female infant had clinical and laboratory evidence of severe warm autoimmune hemolytic anemia. She also had clinical evidence of an upper respiratory tract infection with molecular detection of Mycoplasma pneumoniae. Although reticulocytopenic initially, she responded to red blood cell transfusion, steroids, and intravenous immunoglobulin and remains well today. With the increasing use of multiplex respiratory viral and bacterial pathogen detection systems, the rare association described in this report may prove to be more common than previously thought and may provide insight into the pathogenesis and clinical consequences of red blood cell autoantibodies.

Three Rwandan Children With Massive Splenomegaly and Epstein-Barr Virus-associated Lymphoproliferative Disorders: Case Presentations and the Literature Review.

This report describes 3 Rwandan children with massive splenomegaly and pancytopenia who underwent splenectomy. Each was diagnosed with Epstein-Barr virus-associated lymphoproliferative disorder (EBV LPD) based on lymphocyte morphology, lymphocyte immunophenotype, and the results of EBV in situ hybridization studies. The differential diagnosis of splenomegaly, with a special emphasis on the sub-Saharan African context, is discussed along with EBV and associated disorders. These cases serve as a call to consider EBV LPD in the differential diagnosis of splenomegaly in children in whom common causes have been ruled out.

Warm reactive autoantibodies detected by solid phase technology: Patient characteristics, laboratory features, and clinical significance.

OBJECTIVES: This study focused on the serology, clinical characteristics, and hemolytic potential of warm reactive autoantibodies detected by solid phase red cell adherence. METHODS: Ninety-seven patients with warm autoantibodies were evaluated. Serologic characteristics included the strength of solid phase reactivity, the results of tube-based ancillary testing, direct antiglobulin test and eluate results, and an assessment for contemporaneous alloantibodies. Clinical characteristics of the patients included age, sex, and primary diagnosis. Each patient was also assessed for evidence of hemolysis. RESULTS: Most of the 97 study patients were female (63.9%), and the average age was 66 years. Hematologic disorders were the most common diagnosis. A majority (70.1%) of the warm autoantibodies had 3 to 4+ reaction strengths, and approximately 90% had negative testing with at least 1 test tube method. There was an even distribution of direct antiglobulin test reaction strengths, with 74% reactive with anti-immunoglobulin G only. Alloantibodies were identified in 20% of patients. Evidence of hemolysis was identified in only 13 patients (13.4%). CONCLUSIONS: Warm reactive autoantibodies are more likely to be hemolytic, have strongly reactive indirect and direct antiglobulin tests, remain reactive in tube-based ancillary testing methods, and are seen primarily in patients with hematologic disorders.

Severe Hemolytic Disease of the Newborn due to Anti-Dia.

Dia is a low-frequency member of the Diego blood group system, which is comprised of 23 antigens. The Diego blood group antigens are found on the erythroid membrane glycoprotein band 3, the red cell anion exchanger (AE1). The behavior of anti-Dia in pregnancy can only be surmised by rare, published case reports. This is a case report of severe hemolytic disease of the newborn due to a high-titer maternal anti-Dia immune response. The neonate's mother was monitored throughout pregnancy with Dia antibody titers. In the third trimester, her antibody titer abruptly rose to 32. Her fetus was emergently delivered and was found to be jaundiced at birth with a hemoglobin/hematocrit of 5 g/dL/15.9% and a neonatal bilirubin of 14.6 mg/dL. With simple transfusion, intensive phototherapy, and two doses of intravenous immunoglobulin, the neonate's condition normalized quickly. He was discharged from the hospital after 8 days in excellent condition. Anti-Dia is uncommonly encountered in both transfusion services and obstetric practices. Although very rare, anti-Dia can be associated with cases of severe hemolytic disease in newborns.

Carfilzomib-Induced Thrombotic Microangiopathy: Focus on Pathogenesis.

Drug-induced thrombotic microangiopathies present in similar fashion but have varied pathogenic mechanisms. Carfilzomib is an irreversible proteasome inhibitor. Since its initial approval as a single agent for the treatment of relapsed or refractory multiple myeloma in 2012, there have been increasing reports of carfilzomib-induced thrombotic microangiopathy. However, the mechanism of this disease process is not fully understood. Without treatment, there is a high likelihood of end-organ damage, especially in the kidneys, and death. In recent reports, the lifesaving role of eculizumab, a terminal complement inhibitor, in managing and further preventing end-stage renal disease has been described. In this article, we present a case of carfilzomib-induced thrombotic microangiopathy in a patient with multiple myeloma and discuss the pathogenesis of thrombotic microangiopathy in this setting.

Hyperhemolysis Syndrome Following Red Cell Exchange in a Newly Diagnosed Sickle Cell Disease Patient With Spinal Cord Infarction.

Hyperhemolysis syndrome (HS) is a rare red blood cell (RBC) transfusion reaction that shares similarities with other hemolytic transfusion reactions. Because of this, it is important to recognize key presenting clinical and laboratory features in order to guide therapy. In this case report, a patient with a sickling hemoglobinopathy who developed HS is presented. The atypical nature of this case resides in the clinical presentation of paraplegia secondary to spinal cord infarction, increasingly complex blood group serological findings, and multiple RBC exchanges prior to the HS reaction. Once the patient was diagnosed with probable HS, approximately 4 weeks into her clinical course, RBC transfusion (including exchange transfusion) was withheld. Instead, corticosteroids and erythropoietin were initiated without complication. The patient remained stable with this treatment modality until her care was transferred to a hospital with a comprehensive sickle cell center. This case highlights the need to withhold transfusion in HS patients, barring exceptional circumstances, and the efficacy of initiating immunomodulatory and erythropoiesis stimulating therapies.

Resolution of an unexpected ABO typing discrepancy in a 9-month-old patient with juvenile myelomonocytic leukemia.

In the post-hematopoietic transplant period, the components of the ABO blood type (antigen testing of erythrocytes and plasma antibody testing) can provide important insights into a patient's immunologic status.

Recombinant polymeric IgG anti-Rh: a novel strategy for development of direct agglutinating reagents.

Anti-Rh alloantibodies are used in research and clinic laboratories to define the Rh antigenic profile of human blood samples. IgM anti-Rh antibodies directly agglutinate Rh-positive RBCs. Anti-Rh antibodies of the IgG isotype bind to Rh antigens with a higher intrinsic affinity than IgM and sensitize RBCs, but do not induce direct hemagglutination. The aim of this work was to produce IgG anti-Rh possessing direct hemagglutinating properties of IgM. To achieve this goal, recombinant antibody technology was used to construct genes encoding Ig light and heavy chains that will form polymers with anti-Rh specificity. Expression vectors and liposome-mediated DNA transfer were used to generate transfectomas secreting human recombinant IgG3 anti-Rh. ELISA, SDS-PAGE, and hemagglutination were used to identify and characterize the recombinant antibody produced. Thus, a recombinant polymeric IgM-like IgG3 anti-Rh antibody was produced that directly agglutinates RBCs with specificity identical to that of the parent non-agglutinating IgG. The results obtained suggest that the technology used here to generate polymeric IgM-like IgG3 anti-Rh antibodies can be applied to produce Rh blood typing reagents. This approach might also be used to develop reagents for which cell surface antigen binding and agglutination or aggregation is required.

Hemolytic disease of the fetus and newborn due to anti-Ge3: combined antibody-dependent hemolysis and erythroid precursor cell growth inhibition.

The Gerbich (Ge) antigens are a collection of high-incidence antigens carried on the red blood cell membrane glycoproteins, glycophorins C and D. Antibodies against these antigens are uncommon, and there have been only rare case reports of hemolytic disease of the fetus and newborn due to anti-Ge. In this case report, we present a neonate with severe anemia and hyperbilirubinemia due to anti-Ge3. Routine and special laboratory studies undertaken in this case suggested two mechanisms for the patient's hemolysis and persistent anemia. Antibody-dependent hemolysis was associated with early-onset hyperbilirubinemia, anemia, and a mild reticulocytosis, and inhibition of erythroid progenitor cell growth was associated with late anemia and normal bilirubin and reticulocyte values. Though rare, anti-Ge3 can be a dangerous antibody in pregnancy. Affected neonates may require intensive initial therapy and close follow-up for at least several weeks after delivery.