Acquired Amegakaryocytic Thrombocytopenic Purpura: A Review of Therapeutic Options.

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare bone marrow disorder characterized by either a marked decrease or a complete absence of megakaryocytes with the preservation of all other cell lines. To date, more than 60 cases of AATP have been reported in the literature. Due to the rarity of this disease, no standard treatment guidelines have been established, and therapy is based on a handful of case studies and expert opinions. Herein, we provide a comprehensive review of currently utilized therapeutic options for AATP.

Quetiapine-associated thrombocytopenic purpura in a young man with a first episode schizophrenia.

BACKGROUND: We aimed to contribute to the current limited literature addressing quetiapine-associated thrombocytopenia. We report the case of a young man with a first episode schizophrenia who experienced thrombocytopenic purpura following the administration of quetiapine co-prescribed with valproic acid. CASE REPORT: HA is a 19-year-old single man who had no history of systemic or hematologic diseases and no personal psychiatric history. He presented with psychotic symptoms that have been continuously evolving since ten months. His psychiatrist put him on treatment with 400 mg/day of quetiapine and 1500 mg/day of valproic acid over a three-week titration. Twelve days later, the patient developed a sudden onset of thrombocytopenic purpura without fever, which resolved over two weeks after cessation of both drugs. CONCLUSION: Although uncommon and reversible, thrombocytopenia induced by quetiapine can be life-threatening. Clinicians should carefully follow-up the hematological data when prescribing quetiapine. The unnecessary use of valproic acid should be avoided as a first-line treatment for young people with first-episode schizophrenia.

Acquired Amegakaryocytic Thrombocytopenia Misdiagnosed as Immune Thrombocytopenia in a Patient with Seronegative Arthritis: A Case Report.

Acquired amegakaryocytic thrombocytopenia (AATP) is an uncommon cause of severe thrombocytopenia with preserved cells of other lineages, which can present with severe bleeding episodes. We report a case of a 45-year-old male with seronegative arthritis who was diagnosed with idiopathic thrombocytopenic purpura (ITP) and was being treated with steroids for ITP. Despite aggressive treatment, the patient had persistently low levels of platelets. In view of persistent thrombocytopenia, bone marrow biopsy was done and was diagnosed as Acquired Amegakaryocytic Thrombocytopenia (AATP). Patient was successfully treated with cyclosporine. Correct identification of AATP is essential because it can lead to life threatening bleeding manifestations and advance into Aplastic anemia or MDS. How to cite this article: N AM, Rajanna AH, Kamath N. Acquired Amegakaryocytic Thrombocytopenia Misdiagnosed as Immune Thrombocytopenia in a Patient with Seronegative Arthritis: A Case Report. J Assoc Physicians India 2023;71(11):100-102.

Polimorfismos genéticos implicados en el desarrollo de la purpura trombocitopénica inmune / Genetic polymorphisms involved in the development of Immune Thrombocytopenic Purpura

Introducción: los cambios en el ácido desoxirribonucleico se conocen como mutaciones, estas dan lugar a los polimorfismos, los cuales generan variación alélica entre individuos y diversidad de la misma especie. Se ha sugerido que los polimorfismos genéticos en los mediadores inmunitarios desempeñan un papel fundamental en la patogénesis de muchos trastornos autoinmunes, como en la púrpura trombocitopénica inmune, siendo esta el tipo más común de púrpura trombocitopénica y, a menudo, se diagnostica como un tipo de trastorno autoinmune, debido a la destrucción de las plaquetas mediadas por el sistema inmunitario. Objetivo: realizar una revisión bibliográfica sobre el papel de los polimorfismos genéticos y su influencia en el desarrollo de la púrpura trombocitopénica inmune. Métodos: se realizó revisión literaria en inglés y español en PubMed y Elsevier, desde marzo hasta mayo del 2021, con el uso de combinación de palabras clave y términos MeSH, como púrpura trombocitopénica y polimorfismos genéticos. Se realizó análisis y resumen de la literatura encontrada. Conclusión: la púrpura trombocitopénica inmune es considerada como una patología multifactorial, causada por factores ambientales y genéticos, dentro de los cuales se encuentran los polimorfismos para los mediadores inmunitarios que pueden llevar a una exacerbación de la enfermedad o no intervenir en la misma.

Introduction: Changes in deoxyribonucleic acid are known as mutations, these give place to polymorphisms, which generate allelic variation between individuals and provide diversity among same species. Genetic polymorphisms in immune mediators have been suggested to play a key role in the pathogenesis of many autoimmune disorders, such as immune thrombocytopenic purpura, this being the most common type of thrombocytopenic purpura and is often diagnosed as a type of autoimmune disorder, due to the destruction of platelets mediated by the immune system. Objective: To execute a bibliographic review on the role of genetic polymorphisms and their influence on the development of immune thrombocytopenic purpura. Methods: A literary review in English and Spanish was performed in PubMed and Elsevier from March to May 2021, with the use of a combination of keywords and MeSH terms such as Thrombocytopenic Purpura and genetic polymorphisms. Analysis and summary of the literature found was executed. Conclusion: Immune thrombocytopenic purpura is considered a multifactorial pathology, caused by environmental and genetic factors, among which are polymorphisms for immune mediators that can lead to an exacerbation of the disease or not intervene in the same.

Pembrolizumab-Induced Acquired Amegakaryocytic Thrombocytopenia and Successful Combination Treatment With Eltrombopag, Romiplostim and Cyclosporine: A Brief Communication.

Pembrolizumab is a humanized antibody directed against the programmed death-1 receptor on the cell surface, resulting in a T-cell-mediated immune response against tumor cells that can be complicated by immune-related adverse events. Here we present a novel case of pembrolizumab-induced acquired amegakaryocytic thrombocytopenia (AAT) in a patient with metastatic nasopharyngeal carcinoma. AAT is an incredibly rare and challenging entity for which there is no standardized treatment. We discuss our therapeutic approach using a calcineurin inhibitor and thrombopoietin receptor agonists for successful treatment of AAT and resumption of multiagent cytotoxic chemotherapy.

El volumen medioplaquetario: su importancia en la práctica clínica / Mean platelet volume: its importance in clinical practice

Las plaquetas son fragmentos citoplasmáticos anucleados derivados de los megacariocitos que presentan función central, tanto en procesos fisiológicos como la hemostasia, así como también en procesos patológicos como la inflamación, la ateroesclerosis. El tamaño de las plaquetas, medido como volumen medio de plaquetas, es un marcador de reactividad plaquetaria, que proporciona información importante sobre el curso y pronóstico de una variedad de afecciones inflamatorias. El estudio de este marcador se ha utilizado como pronóstico en enfermedades cardiovasculares, preeclampsia y en la púrpura trombocitopénica. El objetivo de este trabajo es revisar los conceptos actuales basados en la evidencia científica relacionados con el volumen plaquetario medio e insistir en su evaluación y significado en la práctica clínica cotidiana(AU)

Platelets are enucleated cytoplasmic fragments derived from megakaryocytes, which have a central function, both in physiological processes such as hemostasis, as well as in pathological processes such as inflammation, atherosclerosis. Platelet size, measured as mean volume of platelets, is a marker of platelet reactivity, providing important information on the course and prognosis of a variety of inflammatory conditions. The study of this marker has been used as a prognostic in cardiovascular diseases, preeclampsia and in thrombocytopenic purpura. The objective of this paper is to review the current concepts based on scientific evidence related to the mean platelet volume and to insist on its evaluation and meaning in daily clinical practice(AU)

Successful treatment of acquired amegakaryocytic thrombocytopenia with eltrombopag and immunosuppressant.

Acquired amegakaryocytic thrombocypenia (AAMT) is an extremely rare hematologic disorder and standard treatment strategy has not been established. We described herein two cases of AAMT who were fully responded to eltrombopag and immunosuppressant. Patient 1 was refractory to steroid, IVIG and recombinant human thrombopoietin (rhTPO). Patient 2 did not respond to high dosage of steroid, IVIG, rhTPO and rituximab. Moreover, his AAMT progressed to aplastic anemia in 5 months. Both patients took eltrombopag and immunosuppressant, then they achieved long-term remission without obvious side effects. Our findings suggest that this combination can be a valuable alternative in AAMT.

[Development of thrombocytopenic purpura following BNT162b2 mRNA COVID-19 vaccination].

Because the coronavirus disease 2019 (COVID-19) pandemic is still rampant, vaccination is being promoted worldwide. However, the safety of various COVID-19 vaccines remains poorly understood. We herein report the case of a 37-year-old woman who experienced thrombocytopenia following BNT162b2 mRNA COVID-19 vaccination. The patient presented with purpura on the extremities 10 days after the first vaccination. She had marked thrombocytopenia and no thrombosis. Thrombocytopenia resolved spontaneously. Given the possibility of occurrence of post-vaccination thrombocytopenia, vaccinated persons should be instructed to consult a medical institution if they experience bleeding symptoms.

Manejo oportuno de púrpura trombocitopénica trombótica en paciente con lupus eritematoso sistémico: reporte de caso / Timely management of thrombotic thrombocytopenic purpura in a patient with systemic lupus erythematosus: case report

Introducción: La púrpura trombocitopénica trombótica puede presentarse en menos del 2 por ciento de los pacientes con lupus eritematoso sistémico. Esta asociación implica un aumento de la mortalidad y un periodo de remisión más prolongado. Objetivo: Se presenta el caso de paciente peruana que desarrolló esta asociación y presentó complicaciones relacionadas con shock séptico. Caso clínico: Paciente femenina, con antecedente de púrpura trombocitopénica inmunológica y lupus eritematoso sistémico, acudió a emergencia por presentar palidez cutánea generalizada, petequias en miembros inferiores y hematuria. Posteriormente, su estado de salud se complicó con un shock séptico y deterioro del nivel de conciencia. Por todo esto, es referida a un hospital de mayor complejidad y hace su ingreso a la unidad de cuidados intensivos. La clínica y los exámenes de laboratorio revelaron hallazgos compatibles con púrpura trombocitopénica trombótica (anemia grave, plaquetopenia, esquistositosis) y lupus eritematoso sistémico activo grave. Antes de ser referida, recibió pulsos de metilprednisona y prednisona. Ya en unidad de cuidados intensivos, se cambió a soporte ventilatorio y tratamiento antibiótico. Con el diagnóstico presuntivo de púrpura trombocitopénica trombótica, asociada a lupus eritematoso sistémico activo grave, se inició tratamiento oportuno con plasmaféresis, corticoterapia y ciclofosfamida. La paciente recuperó los niveles plaquetarios y el nivel óptimo de conciencia. Actualmente acude a controles. Conclusiones: La púrpura trombocitopénica trombótica es una emergencia hematológica con alta mortalidad en ausencia de tratamiento. Su reconocimiento oportuno, sin dosificación de la proteína ADAMTS13, en esta asociación poco frecuente con lupus eritematoso sistémico es importante en el buen pronóstico del paciente(AU)

Introduction: Thrombotic thrombocytopenic purpura may occur in less than 2 percent of patients with systemic lupus erythematosus. This association implies an increase in mortality and a longer remission period. Objective: We present the case of a Peruvian woman who developed this association, and complicating herself with septic shock. Clinical case: A female patient, with a history of immunological thrombocytopenic purpura and systemic lupus erythematosus, comes to the emergency room due to generalized skin pallor, lower limb petechiae and hematuria. Subsequently, her state of health gets complicated with a septic shock and deterioration of the level of consciousness. For all of this, she was referred to a hospital of greater complexity and makes admission to an intensive care unit. Clinical and laboratory tests revealed findings compatible with thrombotic thrombocytopenic purpura (severe anemia, platelet disease, schistositosis) and severe active systemic lupus erythematosus. Before being referred, she received pulses of methylprednisone and prednisone. When already in the intensive care unit, it was changed to ventilatory support andantibiotic treatment. With the presumptive diagnosis of thrombotic thrombocytopenic purpura, associated with severe active systemic lupus erythematosus, a timely treatment was initiated with plasmapheresis, corticosteroids and cyclophosphamide. The patient recovered platelet levels and optimal level of consciousness. She is currently going to controls. Conclusions: Thrombotic thrombocytopenic purpura is a hematological emergency with high mortality in the absence of treatment. Its timely recognition, without dosing of ADAMTS13 protein, in this rare association with systemic lupus erythematosus is important in the good prognosis of the patient(AU)

Acquired amegakaryocytic thrombocytopenia after durvalumab administration.

Immune checkpoint inhibitors (ICIs), despite their ability to potentiate antitumor T-cell responses, may cause various immune-related adverse events. Most cases of thrombocytopenia induced by ICIs have revealed a pathophysiologic mechanism of immune thrombocytopenia with increased platelet destruction and preserved megakaryocytes. Acquired amegakaryocytic thrombocytopenic purpura (AATP) is an unusual disorder characterized by thrombocytopenia with markedly diminished bone marrow megakaryocytes in the presence of otherwise normal hematopoiesis. AATP caused by ICIs has not been reported on. Herein, we present the case of a 79-year-old man diagnosed with squamous cell carcinoma of the lung who developed AATP after two courses of durvalumab, a drug targeting programmed death-ligand 1. Two weeks after the second cycle, his platelet count decreased to 2.1 × 104/µL. After the patient underwent platelet transfusion, his platelet count increased to 8.1 × 104/µL the next day but subsequently decreased repeatedly even after the ICI was discontinued. Six weeks after the second cycle, he developed interstitial pneumonia and was administered prednisolone (50 mg/day). However, thrombocytopenia did not improve. Bone marrow biopsy showed scarce megakaryocytes (< 1 megakaryocyte/10 high-power fields) with preservation of myeloid and erythroid series. Myelodysplasia, myelofibrosis, or metastatic lesions were not observed. Cytogenetic analysis showed a normal male karyotype of 46XY. Hence, the patient received eltrombopag, a thrombopoietin receptor agonist, and his platelet count subsequently improved. After recovery, bone marrow aspiration revealed a normal number of megakaryocytes. AATP is rarely the type of thrombocytopenia induced by ICIs and may be successfully treated with thrombopoietin receptor agonists.