Anti-PF4 positivity and platelet activation after Ad26.COV2·S vaccination in Brazil.

INTRODUCTION: The Ad26.COV2·S (Janssen/Johnson & Johnson) COVID-19 vaccine, has been rarely associated with vaccine-induced immune thrombocytopenia and thrombosis (VITT). We investigated the prevalence of anti-PF4 antibody positivity, thrombocytopenia, D-dimer elevation, plasmatic thromboinflammatory markers, and platelet functional assays following Ad26.COV2·S vaccination in Rio de Janeiro, Brazil. METHODS: From July to September 2021, participants were assessed prior, 1, and 3 weeks post-vaccination. Platelet count and D-dimer were measured at each visit and anti-PF4 at week 3. A positive anti-PF4 prompted retrospective testing of the sample from week 0. Individuals with new thrombocytopenia or elevated D-dimer, positive anti-PF4, and 38 matched controls without laboratory abnormalities were evaluated for plasmatic p-selectin, tissue factor, and functional platelet activation assays. RESULTS: 630 individuals were included; 306 (48.57%) females, median age 28 years. Forty-two (6.67%) presented ≥1 laboratory abnormality in week 1 or 3. Five (0.79%) had thrombocytopenia, 31 (4.91%) elevated D-dimer, and 9 (1.57%) had positive anti-PF4 at week 3. Individuals with laboratory abnormalities and controls showed a slight increase in plasmatic p-selectin and tissue factor. Ten individuals with laboratory abnormalities yielded increased surface expression of p-selectin, and their ability to activate platelets in a FcγRIIa dependent manner was further evaluated. Two were partially inhibited by high concentrations of heparin and blockage of FcγRII with IV.3 antibody. Plasma obtained before vaccination produced similar results, suggesting a lack of association with vaccination. CONCLUSIONS: Vaccination with Ad26.COV2·S vaccine led to a very low frequency of low-titer positive anti-PF4 antibodies, elevation of D-dimer, and mild thrombocytopenia, with no associated clinically relevant increase in thromboinflammatory markers and platelet activation.

A case report of vaccine-induced immune thrombotic thrombocytopenia (VITT) with genetic analysis.

The emergence of the rare syndrome called vaccine-induced immune thrombocytopenia and thrombosis (VITT) after adenoviral vector vaccines, including ChAdOx1 nCov-19, raises concern about one's predisposing risk factors. Here we report the case of a 56-year-old white man who developed VITT leading to death within 9 days of symptom onset. He presented with superior sagittal sinus thrombosis, right frontal intraparenchymal hematoma, frontoparietal subarachnoid and massive ventricular hemorrhage, and right lower extremity arterial and venous thrombosis. His laboratory results showed elevated D-dimer, C-reactive protein, tissue factor, P-selectin (CD62p), and positive anti-platelet factor 4. The patient's plasma promoted higher CD62p expression in healthy donors' platelets than the controls. Genetic investigation on coagulation, thrombophilia, inflammation, and type I interferon-related genes was performed. From rare variants in European or African genomic databases, 68 single-nucleotide polymorphisms (SNPs) in one allele and 11 in two alleles from common SNPs were found in the patient genome. This report highlights the possible relationship between VITT and genetic variants. Additional investigations regarding the genetic predisposition of VITT are needed.

Clinical Presentation of Parvovirus B19 Infection in Adults Living with HIV/AIDS: A Case Series.

Parvovirus B19 (B19V) infection varies clinically depending on the host's immune status. Due to red blood cell precursors tropism, B19V can cause chronic anemia and transient aplastic crisis in patients with immunosuppression or chronic hemolysis. We report three rare cases of Brazilian adults living with human immunodeficiency virus (HIV) with B19V infection. All cases presented severe anemia and required red blood cell transfusions. The first patient had low CD4+ counts and was treated with intravenous immunoglobulin (IVIG). As he remained poorly adherent to antiretroviral therapy (ART), B19V detection persisted. The second patient had sudden pancytopenia despite being on ART with an undetectable HIV viral load. He had historically low CD4+ counts, fully responded to IVIG, and had undiagnosed hereditary spherocytosis. The third individual was recently diagnosed with HIV and tuberculosis (TB). One month after ART initiation, he was hospitalized with anemia aggravation and cholestatic hepatitis. An analysis of his serum revealed B19V DNA and anti-B19V IgG, corroborating bone marrow findings and a persistent B19V infection. The symptoms resolved and B19V became undetectable. In all cases, real time PCR was essential for diagnosing B19V. Our findings showed that adherence to ART was crucial to B19V clearance in HIV-patients and highlighted the importance of the early recognition of B19V disease in unexplained cytopenias.

Acute promyelocytic leukemia in a long-standing HIV-positive patient: Case report and literature review.

The use of antiretroviral therapy has drastically improved the life quality and prognosis of people living with the human immunodeficiency virus (HIV). The risk of acute myeloid leukemia (AML) currently does not appear to be significantly increased compared to the general population. Acute promyelocytic leukemia (APL), infrequent in people with HIV, is a distinct subtype of AML with unique molecular pathogenesis, clinical manifestations, and treatment. Herein we describe a fatal case of APL hypogranular variant in an HIV-positive patient presenting with hyperleukocytosis. Also, we conducted a literature review of the ten cases reported so far.

Generalized Edema and Pseudothrombocytopenia After ChAdOx1 nCoV-19 COVID-19 Vaccination: A Case Report.

Reports of side effects of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are increasing worldwide. Capillary leak syndrome and vaccine-induced immune thrombotic thrombocytopenia are very rare but life-threatening adverse events that should be identified early and treated. However, isolated thrombocytopenia can indicate pseudothrombocytopenia. In certain people, ethylenediaminetetraacetic acid (EDTA) induces an in vitro platelet aggregation, resulting in misleading underestimation of platelet counts. It is essential to recognize pseudothrombocytopenia to prevent diagnostic errors, overtreatment, anxiety, and unnecessary invasive procedures. We present a case who developed generalized edema and persistent pseudothrombocytopenia after the first dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca).

Anti-Chido/Rodgers antibodies in a patient with infectious disease / Anticuerpos anti-Chido/Rodgers en paciente con enfermedad infecciosa

Introduction: Red cell alloimmunization is an immune response against foreign red cell antigens, usually occurring due to sensibilization in blood transfusions and pregnancies. The Chido (Ch) and Rodgers (Rg) antigens are present in about 96-98 percent of the population in general. Patients who have antibodies against antigens of high frequency in the population are a problem for transfusion medicine. Objectives: To describe the case of a patient diagnosed with AIDS and invasive cancer of the rectum with a recent hospitalization for lower gastrointestinal bleeding and anemia with the presence of anti-Ch and anti-Rg and the difficulties and solutions found for handling the case. Case presentation: Anti-Ch and anti-Rg have not been found to cause a hemolytic transfusion reaction (HTR) or hemolytic disease of the fetus and newborn (HDFN). However, the clinical presentation and laboratory findings including the immunohematological workups concerning the reaction are discussed, with a special emphasis on the benefit of identifying such an antibody and providing a compatible blood unit for transfusion support of the patient. Conclusions: When an antibody against a high-frequency erythrocyte antigen is identified in African or American-descent, anti-Ch or anti-Rg should be considered and that transfusion tests should not be delayed due to its clinical importance(AU)

Introducción: La aloinmunización de glóbulos rojos es una respuesta inmune frente a antígenos de glóbulos rojos extraños, que pueden ocurrir por sensibilización en transfusiones de sangre y embarazos. Los antígenos Chido (Ch) y Rodgers (Rg) están presentes en aproximadamente el 96-98 por ciento de la mayoría de la población. Los pacientes que tienen anticuerpos contra antígenos de alta frecuencia poblacional son un problema para la medicina transfusional. Objetivos: Describir caso de un paciente diagnosticado de AIDS y cáncer invasivo de recto con hospitalización reciente por hemorragia digestiva baja y anemia con presencia de anti-Ch y anti-Rg y las dificultades y soluciones encontradas para el manejo del caso. Presentación de caso: No se ha encontrado que Anti-Ch y anti-Rg causen reacciones hemolíticas transfusionales y enfermedad hemolítica del recién nacido. Sin embargo, se discuten la presentación clínica y los hallazgos de laboratorio, incluidos los estudios inmunohematológicos con respecto a la reacción, con especial énfasis en el beneficio de identificar dicho anticuerpo y obtener una unidad de sangre para transfusión que respalde al paciente con respecto a proporcionar una unidad compatible. Conclusiones: Cuando se identifica anticuerpos contra un antígeno eritrocitario de alta frecuencia, en afrodescendientes o americanos, se deben considerar Anti-Ch o anti-Rg y no retrasar las pruebas de transfusión por su importancia clínica(AU)