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Objectives: We report a case of an 83 year old man who developed oxaliplatin immuneinduced syndrome (OIIS) after his 19th cycle of FOLFOX (5FU, leucovorin, oxaliplatin). When oxaliplatin was omitted from his next cycle of chemotherapy he continues to show signs of drug-induced immune thrombocytopenia (DITP) and was found to have drug-dependent, platelet-reactive antibodies (DDPA) to leucovorin and palonosetron as well as oxaliplatin. Methods: The patient was admitted for monitoring but required no transfusions and thrombocytopenia resolved without treatment during his first admission. Drug-dependent antibody testing was performed on his blood by the Blood Center of Wisconsin (Diagnostic Laboratories; Milwaukee, WI). Results: No RBC or platelet IgG or IgM antibodies were detected in the absence of any drugs, but upon addition of palonosetron, leucovorin, or oxaliplatin, the tests became strongly positive for anti-RBC IgG and anti-platelet IgG antibodies. Discussion: Repeated administration of oxaliplatin can result in drug-induced immune thrombocytopenia (DITP) or autoimmune hemolytic anemia (AIHA). This phenomenon has recently been termed OIIS and may additionally include Evan's syndrome or thrombotic microangiopathy (TMA). Here we describe a patient who developed OIIS with drugdependent, platelet-reactive antibodies (DDPA) to leucovorin and palonosetron. To our knowledge, these two drugs have never been described in the literature as a cause of DDPA. We suggest that OIIS in addition to oxaliplatin-induced thrombocytopenia may be associated with the development of DDPAs to other drugs causing clinically significant thrombocytopenia which is important to recognize and manage with discontinuation of provoking agents. [ABSTRACT FROM AUTHOR]

Anti-Jk3 is a rare alloantibody to a high-prevalence antigen primarily seen in individuals of Polynesian descent and is associated with a handful of well-established variants of the SLC14A1 gene. We report a case of the Jk null phenotype, associated with formation of anti-Jk3, in a patient of non-Polynesian descent. This patient, a 51-year-old woman self-described as of Jamaican and Scottish ancestry, presented to our hospital for oncologic care. The patient's blood sample typed as blood group A, D+. All screening and panel reagent red blood cells showed reactivity, ranging from 2 to 4+; autocontrol and direct antiglobulin test were both negative. Antigen phenotyping revealed Jk(a-b-), leading to suspicion for anti-Jk3, which was subsequently confirmed by our immunohematology reference laboratory. Given her reported familial background, testing of the SLC14A1 gene was performed, revealing that the patient was heterozygous for the single nucleotide variant (SNV) at c.838G>A in exon 8 and therefore carries both JK*01 and JK*02 alleles that encode Jk a and Jk b , respectively. However, the patient was found to be heterozygous for several additional SNVs: c.28G>A in exon 3; c.191G>A, c.226G>A, and c.303G>A in exon 4; and c.757T>C in exon 7. The patient's Jk(b-) phenotype can be explained by coinheritance of c.838A with c.191G>A, which defines null allele JK*02N.09. Coinheritance of SNVs c.28G>A and c.838G with rare SNV c.757C that is predicted to cause a non-conservative amino acid change (p.S253P) likely accounts for the complete serologic absence of Jk a and the ability to form anti-Jk3 in this case. This finding would represent a new JK*01 null allele. This evaluation illustrates the importance of genetic analysis in identifying the factors preventing a high-prevalence antigen from being expressed, particularly when discovered outside of an expected racial or ethnic group., Anti-Jk3 is a rare alloantibody to a high-prevalence antigen primarily seen in individuals of Polynesian descent and is associated with a handful of well-established variants of the SLC14A1 gene. We report a case of the Jk null phenotype, associated with formation of anti-Jk3, in a patient of non-Polynesian descent. This patient, a 51-year-old woman self-described as of Jamaican and Scottish ancestry, presented to our hospital for oncologic care. The patient’s blood sample typed as blood group A, D+. All screening and panel reagent red blood cells showed reactivity, ranging from 2 to 4+; autocontrol and direct antiglobulin test were both negative. Antigen phenotyping revealed Jk(a–b–), leading to suspicion for anti-Jk3, which was subsequently confirmed by our immunohematology reference laboratory. Given her reported familial background, testing of the SLC14A1 gene was performed, revealing that the patient was heterozygous for the single nucleotide variant (SNV) at c.838G>A in exon 8 and therefore carries both JK*01 and JK*02 alleles that encode Jk a and Jk b , respectively. However, the patient was found to be heterozygous for several additional SNVs: c.28G>A in exon 3; c.191G>A, c.226G>A, and c.303G>A in exon 4; and c.757T>C in exon 7. The patient’s Jk(b–) phenotype can be explained by coinheritance of c.838A with c.191G>A, which defines null allele JK*02N.09. Coinheritance of SNVs c.28G>A and c.838G with rare SNV c.757C that is predicted to cause a non-conservative amino acid change (p.S253P) likely accounts for the complete serologic absence of Jk a and the ability to form anti-Jk3 in this case. This finding would represent a new JK*01 null allele. This evaluation illustrates the importance of genetic analysis in identifying the factors preventing a high-prevalence antigen from being expressed, particularly when discovered outside of an expected racial or ethnic group.

Red blood cell (RBC) alloimmunization is more common in patients with sickle cell disease (SCD) than in any other studied patient population. The high prevalence of RBC alloimmunization is multi-factorial, likely involving the chronic hemolysis and inflammatory status of SCD itself, the transfusion burden of patients, and the RH genetic diversity of patients and blood donors, among other reasons. Antibody evanescence, or the decrease of RBC alloantibodies below levels detectable by blood bank testing, occurs frequently with fewer than 30% of alloantibodies estimated to be detected by current screening practices. Evanescence increases the likelihood that a patient with SCD will have a delayed hemolytic transfusion reaction upon future RBC exposure, with previously undetected alloantibodies coming roaring back in an anamnestic manner after exposure to the cognate RBC antigen. A subset of patients having delayed hemolytic transfusion reactions go on to experience hyperhemolysis; some but not all cases of hyperhemolysis are associated with previously evanescent RBC alloantibodies. There is an increasing appreciation of the association between RBC alloantibodies and RBC autoantibodies, as well as involvement of the alternative complement pathway in some instances of hyperhemolysis. A case report in this manuscript describes a highly alloimmunized patient with SCD who experiences a delayed hemolytic transfusion reaction with bystander hemolysis due to a previously evanescent, complement binding anti-M RBC alloantibody. Additional studies, including those involving multiple centers and countries, are needed to further understand RBC alloimmunization in patients with SCD and to develop strategies to prevent or mitigate potentially life-threatening hemolytic transfusion reactions., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Transfused red blood cells, platelets, or coagulation factors have the capacity to induce alloantibodies, which once formed, can be a clinical barrier to future transfusion therapy and/or transplantation. Large observational studies over the last 50 years have characterized some of the general properties of transfusion induced alloimmunization, which appear to vary to a considerable extent from what is generally observed for human responses to other immunogens, such as microbial pathogens and vaccines. Transfused cells and factor only induce immune responses in the minority of recipients. There are data to suggest that differences in the unit may play a role. However, there are clearly differences in recipient biology, as once a recipient makes one antibody they are much more likely to make additional antibodies; indeed, recipients have been categorized as "responder" and "non-responder" by the field. Recent mechanistic studies have begun to define potential causes for such differences in alloimmunization from patient to patient, but much progress needs to be made to understand how, why, and in whom alloimmunization occurs. This review gives a general background on immunology in the context of transfusion, summarizes recent progress in the field, and discusses future directions for exploration. Particular attention is paid to the general concept that the human immune system is melded by the wide range of antigens encountered in our environment, and that the effects of such on the immune system may have a profound effect upon response to transfused cells., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

We report on two instances of familial recurrence of Angelman syndrome which, from pedigree analysis, appear incompatible with currently known mechanisms of inheritance of this disorder. In these two families, deletion-positive Angelman syndrome has recurred in cousins. Several established mechanisms for deletion-positive familial recurrence have been ruled out. In each family, molecular cytogenetic studies show typical chromosome 15 deletions, and DNA methylation analysis verifies the maternal origin of the deleted chromosomes in all four individuals. Since the mothers of the affected individuals in each family are not known to be related, these recurrences appear to be secondary to coincidental, de novo events. This conclusion is consistent with direct and indirect estimates of the population frequency of Angelman syndrome.

Prometaphase chromosome study of 12 persons with an established diagnosis of the Angelman syndrome demonstrated that 5 had a 15q12 deletion appearing similar to that commonly observed in the Prader-Willi syndrome. Phenotype-karyotype correlation did not show any obvious clinical differences between those with and those without the deletion and no clinical overlap between Angelman and Prader-Willi syndrome was apparent. Our survey suggests that 15q12 deletions are frequent in Angelman syndrome but presence of the deletion does not appear to distinguish different clinical phenotypes. Experience with the cytogenetic study of Prader-Willi syndrome predicts that considerable complexity will emerge between the presence of 15 chromosome abnormalities and clinical expression of Angelman syndrome.

We report on a 4-year-old girl with Angelman syndrome who has an apparent de-novo del(15) (q11q13) originating from a maternally derived chromosome. Her mother had severe brachycephaly, sensorineural hearing loss, speech impediment, and mild ataxia. CT brain scans showed an enlarged foramen magnum in the mother and daughter but magnetic resonance imaging (MRI) showed no brainstem abnormality in either. This family demonstrates that some Angelman syndrome cases may be dominantly transmitted with variable expression and associated with abnormal or cytogenetically apparently normal chromosome 15.