ABSTRACT In fetal/neonatal alloimmune thrombocytopenia (FNAIT), platelets are destroyed by maternal antibodies directed against fetal/neonate antigens. Thrombocytopenia can be severe and lead to ...intracranial hemorrhage (ICH) in about 10% of cases. Although three types of antigen groups, presented on platelets ABO blood group antigens, human leukocyte antigens (HLA) and human platelet antigens (HPA) are known to be implicated in immune platelet destruction, antibodies against HPA are most commonly involved in FNAIT and hence are the target of extensive research. Awareness of FNAIT by physicians as well as the availability of the most sensitive diagnostic methods capable of detecting a wide range of antibodies are crucial for the diagnosis of FNAIT and the prevention of severe thrombocytopenia and its bleeding risks in subsequent pregnancies.
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a common cause of severe thrombocytopenia in newborns. Intracranial bleeding may lead to severe neurological sequelae and mortality. Current ...management of pregnancies at risk is suboptimal. Prenatal FNAIT diagnosis commonly requires invasive procedures and therapy is associated with a high treatment burden. The present review explores advances in the field and their potential contribution to modification of the diagnostic and therapeutic landscape. Topics addressed include the role of noninvasive prenatal testing using fetal cell free DNA, insights into novel and prospective therapeutic options achieved through the development of murine models of FNAIT as well as the forecast for the progress in pregnancy risk stratification through advancement in the investigation of biological characteristics of alloantibodies and their association with the risk of fetal bleeding.
BACKGROUND
Intravenous immunoglobulin (IVIG) has known efficacy in various hematologic conditions, including immune thrombocytopenic purpura.
STUDY DESIGN AND METHODS
We present the clinical course ...of a patient with splenic marginal zone lymphoma, who developed acute thrombocytopenia on three consecutive episodes, with nadir counts of 27 × 109, 50 × 109, and 9 × 109/L, upon administration of Intratect IVIG for hypogammaglobulinemia. An immunofluorescence test applying flow cytometry and monoclonal antibody immobilization of platelet antigens (MAIPA) assay were used to evaluate the reaction between IgG present in the IVIG preparations and the patient's or healthy donors' platelets (PLTs).
RESULTS
A strong direct binding reaction was observed between the patient's PLTs and Intratect IgG using both methods. A similar reaction failed to materialize with controls. Binding was not antigen specific according to MAIPA.
CONCLUSIONS
This is the first reported case of thrombocytopenia as a possible adverse effect of IVIG.
Divergent views remain regarding the safety of treating anemia with red blood cell (RBC) transfusion in patients with acute coronary syndrome (ACS). We used a prospective database to study effect of ...RBC transfusion in patients with acute myocardial infarction (MI; n = 2,358). Cox regression models were used to determine the association between RBC transfusion and 6-month outcomes, incorporating transfusion as a time-dependent variable. The models adjusted for baseline variables, propensity for transfusion, and nadir hemoglobin previous to the transfusion. One hundred ninety-two patients (8.1%) received RBC transfusion. Six-month mortality rates were higher in patients receiving transfusion (28.1% vs 11.7%, p <0.0001). The adjusted hazard ratio (HR) for mortality was 1.9 in transfused patients (95% confidence interval CI 1.3 to 2.9). Interaction between RBC transfusion and nadir hemoglobin with respect to mortality (p = 0.004) was significant. Stratified analyses showed a protective effect of transfusion in patients with nadir hemoglobin ≤8 g/dL (adjusted HR 0.13, 95% CI 0.03 to 0.65, p = 0.013). By contrast, transfusion was associated with increased mortality in patients with nadir hemoglobin >8 g/dL (adjusted HR 2.2, 95% CI 1.5 to 3.3; p <0.0001). Similar results were obtained for the composite end point of death/MI/heart failure (p for interaction = 0.04). In conclusion, RBC transfusion in patients with acute MI and hemoglobin ≤8 g/dL may be appropriate. The increased mortality observed in transfused patients with nadir hemoglobin above 8 g/dL underscores the clinical difficulty of balancing risks and benefits of RBC transfusion in the setting of ACS.
Abstract Background and Objectives Spontaneous massive foetomaternal haemorrhage (SM‐FMH) is a rare yet critical condition that poses substantial risk to foetal health and survival. Existing data ...indicate that many cases may be undiagnosed. The current study aimed to investigate and validate the utility of identifying mixed field red blood cell (RBC) agglutination during maternal blood typing as a diagnostic aid for SM‐FMH. Materials and Methods Retrospective analysis of medical records from neonates born at our tertiary, university‐affiliated medical centre between 2016 and 2023 was performed. Diagnosis of SM‐FMH was based on neonates born with severe anaemia (haematocrit HCT <15%) within the first 24 h post‐delivery with positive maternal Kleihauer–Betke (KB) test. Maternal ABO/Rhesus D (RhD) blood typing results were scrutinized with the primary objective of assessing the ability to identify dual RBC populations in cases clinically diagnosed with SM‐FMH. Results Among 29,192 neonates studied, a mere 0.02% (5 cases) exhibited severe SM‐FMH. Notably, a mixed field RBC agglutination was discerned in 80% (4/5) of these cases. Conclusion This study underscores the significance of detecting mixed field RBC agglutination during antepartum maternal ABO/RhD blood typing as a potential indicator for SM‐FMH. Increased awareness among blood bank technology specialists and obstetricians regarding these laboratory findings could prove instrumental in saving foetal lives.
Checkpoint inhibitors effectively enhance the natural immune response against cancer, but they are also known to induce a unique spectrum of immune-related adverse events. Here, we report the first ...case of isolated neutropenia subsequent to nivolumab therapy. Prominent activated T-cells were found in the patient's serum and bone marrow alongside evidence of maturational defects in neutrophil precursors. Antineutrophil antibodies were not detected despite reliable testing techniques. A T-cell-mediated response is probable, consistent with the established mechanism for the development of other immune-related toxicities. Awareness of this rare and severe side effect reinforces the importance of early diagnosis and prompt initiation of proper treatment.
Introduction: Patients with acute myeloid leukemia (AML) are treated with intensive chemotherapeutic protocols. They are known to suffer from protracted pancytopenia and need prolonged transfusion ...support. Despite the administration of leukocyte-reduced and irradiated blood products, long-term transfusion dependency predisposes these patients to alloimmunization to both leukocyte (HLA) and platelet (HPA) antigens, leading to immune platelet transfusion refractoriness, which is a major risk factor for bleeding-associated morbidity and mortality, to longer hospitalizations and higher inpatient hospital costs. The published incidence of immune platelet refractoriness in patients with hematologic malignancies ranges between 7% and 34%. The Rambam Health Care Campus is the only tertiary care medical center in Northern Israel providing services to over 2 million citizens. This population is highly heterogeneousin terms of ethnic and religious background and has a relatively high birth rate (3.2 versus 1.75 in other developed countries). The majority of AML patients in the region are treated at the Rambam Department of Hematology. To the best of our knowledge, the incidence of alloimmunization to platelet antigens and immune platelet refractoriness in this population has never been studied. The aims of the current study were: to estimate the incidence of immune platelet transfusion refractoriness among AML patients in Northern Israel, to define the onset of alloimmunization during the treatment course and to evaluate the efficacy of antibody screening by platelet immunofluorescent test (PIFT) as a follow-up tool to predict the risk for alloimmunization and immune platelet transfusion refractoriness in these patients.
Methods: Newly diagnosed AML patients were screened every two weeks for two months since diagnosis and throughout induction therapy for the presence of anti-HPA and anti-HLA antibodies using flow cytometry (PIFT assay). Antibodies were identified by the monoclonal-specific immobilization of platelet antigens (MAIPA) assay. Clinical parameters of patients were consecutively registered. Patients received platelet transfusions according to the institutional transfusion policy, including continuous platelet increment monitoring. Blood counts and platelet transfusion requirements were followed weekly; platelet refractoriness was determined when no increment (defined as an increase <5x109 platelets/L after a single transfusion of 3x1011 platelets) was documented following two consecutive platelet transfusions.
Results: One hundred newly diagnosed AML patients (56 males and 44 females; age range 25-60 years) of various ethnic origins were included in the analysis. Platelet refractoriness was revealed in 49 (49%) patients (20 males and 29 females). Forty four (44%) patients developed anti-HLA and/or anti-HPA antibodies, 32/44 (73%) were females, 27 of them with more than two children. Immune platelet refractoriness was revealed in 34/49 (69%) refractory patients (8 males and 26 females); 13/34 (38%) had anti-HPA with (11) or without (2) anti-HLA antibodies and 21/34 (62%) had only anti-HLA antibodies. The average period from the beginning of treatment to antibody appearance was 26 days. The PIFT was found to be a sensitive, specific and efficient method for screening and detection of all anti-platelet antibodies, while MAIPA was found to be the preferred method for anti-platelet antibody identification.
Conclusions: Women with more than two children were found to have a significantly higher risk to develop alloantibodies and transfusion refractoriness. Our findings demonstrating a higher incidence of immune platelet refractoriness compared to that reported in the literature may be attributed to the increased prevalence of multiparous women inhabiting our region. Routine antibody screening by PIFT appears to be an efficient tool for early detection of alloimmunized patients.
No relevant conflicts of interest to declare.
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