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Amegakaryocytic thrombocytopenia is a rare hematologic disorder characterized by a profound reduction in platelet production due to the near absence of megakaryocytes, leading to severe thrombocytopenia. This case report elucidates the diagnostic and therapeutic challenges encountered in managing such rare hematological conditions alongside significant cardiovascular disease. We detail the case of a patient who presented with chest pain and was diagnosed with non-ST elevation myocardial infarction (NSTEMI). Subsequent investigations revealed severe thrombocytopenia and underlying triple vessel disease, complicating immediate surgical intervention. Initial management strategies aimed at treating presumed immune thrombocytopenia proved ineffective. A definitive diagnosis of amegakaryocytic thrombocytopenia was established following a bone marrow biopsy. Despite treatment adjustments, including the administration of thrombopoietin agonists and immunosuppression, platelet counts improved but did not reach levels safe for coronary artery bypass grafting (CABG). This case underscores the critical importance of achieving adequate hematologic stability prior to surgical procedures in patients with complex cardio-hematologic profiles to minimize perioperative risks and optimize patient outcomes, illustrating the ongoing challenges in managing severe thrombocytopenia in cardiac patients.

Carboplatin/pegylated liposomal doxorubicin/bevacizumab is an accepted standard anti-cancer treatment option for recurrent ovarian cancer. However, the occurrence of adverse events associated with this therapeutic regimen limits its continued clinical use. Among these adverse events, acquired amegakaryocytic thrombocytopenia is a rare but often potentially life-threatening adverse effect, and is intolerant to multiple treatment approaches. We report, for the first time, the successful treatment using avatrombopag combined with cyclosporine in one case of carboplatin/pegylated liposomal doxorubicin/bevacizumab-induced acquired amegakaryocytic thrombocytopenia, which was refractory or intolerant to glucocorticoids, intravenous immunoglobulin, recombinant human thrombopoietin, androgen, and even thrombopoietin receptor receptor agonist eltrombopag and herombopag. To date, this case manifests as normal platelet counts that are independent of transfusion. Our findings suggest that this combination is a potential and valuable alternative in acquired amegakaryocytic thrombocytopenia.

Background Acquired amegakaryocytic thrombocytopenia (AAMT) is a rare disorder characterized by thrombocytopenia, marked megakaryocytic hypoplasia, and preserved other-lineage hematopoiesis in the bone marrow. The etiology of AAMT remains poorly understood owing to its rarity. Case description We encountered a diagnostically challenging case involving a 66-year-old man who showed severe thrombocytopenic bleeding with isolated megakaryocytic hypoplasia, elevated serum thrombopoietin levels, glycoprotein IIb/IIIa antibody positivity, and prolonged platelet transfusion refractoriness following mantle cell lymphoma (MCL). Treatment with corticosteroids and intravenous immunoglobulin was ineffective, while a combination of multiagent chemotherapy, including rituximab, was beneficial for both thrombocytopenia and MCL. Ultimately, the patient was diagnosed with AMMT and immune thrombocytopenia (ITP)-like platelet destruction. Discussion This case suggests that AAMT and ITP are non-exclusive and sometimes overlap as components of a broad spectrum of platelet-related autoimmune diseases.

Acquired amegakaryocytic thrombocytopenia (AAMT) is a rare disorder of the bone marrow characterized by a lack of megakaryocytes and preservation of other cell lines. It can occur due to an intrinsic stem cell defect or secondary to viral infections, autoimmune disorders, lymphoproliferative disorders or environmental toxins. With time, it can progress to aplastic anaemia (AA) and can have a poor prognosis. No standard guidelines exist for the treatment of AAMT progressing to AA. Herein, we report a rare case of AAMT leading to AA and review the handful of cases previously published in the literature.

Background. Hereditary bone marrow failure syndromes are a category of biologically different syndromes that can cause cytopenia in at least one hematopoietic cell lineage. Case. We present a 29-week-old male infant who had a low Apgar Score, advanced delivery room resuscitation, widespread petechial rash, and ecchymoses at birth, without any dysmorphic features. Initial laboratory tests revealed bicytopenia (platelet count 7x10 3 /uL, hemoglobin of 3.9 g/dL, neutrophil 2.0x103 /uL) with findings of disseminated intravasculer coagulation (DIC). Imaging studies demonstrated accompanying left-sided congenital pulmonary airway malformation. On the second postnatal week pancytopenia occurred and the bone marrow findings were consistent with congenital amegakaryocytic thrombocytopenia. Further evaluations for differential diagnosis of pancitopenia were performed and the results of congenital viral infections, metabolic and immunologic tests were negative. While supportive treatments were in progress, haploidentical bone marrow transplantation (BMT) was performed from the father at 84th day due to unavailability of HLA-matched relative or nonrelative donor. Whole exome sequencing revealed a novel heterozygous frameshift variation (c.1242dupT [p. Thr538fs]) in exon 8 of the MECOM gene and validated by Sanger sequencing. No variation was detected in the parents genetic analysis. Conclusions. In this report, we present a patient with congenital bone marrow failure successfully treated with haploidentic BMT and describe a novel, de novo pathogenic variant in MECOM gene.

BackgroundCongenital amegakaryocytic thrombocytopenia (CAMT) is a rare platelet production disorder caused mainly by loss of function biallelic mutations in myeloproliferative leukemia virus oncogene (MPL), the gene encoding the thrombopoietin receptor (TPOR). Patients with MPL-mutant CAMT are not only at risk for life-threatening bleeding events, but many affected individuals will also ultimately develop bone marrow aplasia owing to the absence of thrombopoietin/TPOR signaling required for maintenance of hematopoietic stem cells. Curative allogeneic stem cell transplant for patients with CAMT has historically used myeloablative conditioning; however, given the inherent stem cell defect in MPL-mutant CAMT, a less intensive regimen may prove equally effective with reduced morbidity, particularly in patients with evolving aplasia.MethodsWe report the case of a 2-year-old boy with MPL-mutant CAMT and bone marrow hypocellularity who underwent matched sibling donor bone marrow transplant (MSD-BMT) using a non-myeloablative regimen consisting of fludarabine, cyclophosphamide, and antithymocyte globulin (ATG).ResultsThe patient achieved rapid trilinear engraftment and resolution of thrombocytopenia. While initial myeloid donor chimerism was mixed (88% donor), due to the competitive advantage of donor hematopoietic cells, myeloid chimerism increased to 100% by 4 months post-transplant. Donor chimerism and blood counts remained stable through 1-year post-transplant.ConclusionThis experience suggests that non-myeloablative conditioning is a suitable approach for patients with MPL-mutant CAMT undergoing MSD-BMT and is associated with reduced risks of conditioning-related toxicity compared to traditional myeloablative regimens.

Abstract Association between thymoma and pure red cell aplasia is already well‐documented in literature whereas acquired amegakaryocytic thrombocytopenia is rarely reported. In this case, even with the addition of eltrombopag to standard immunosuppression, the cytopenias did not improve, probably due to the lack of surgical resection of the tumor.

Acquired amegakaryocytic thrombocytopenia (AATP) is a rare disorder in which severely low platelet levels occur due to reduced or complete absence of megakaryocytes in the bone marrow. The pathophysiology of this disease is not fully understood, although anti-thyroid peroxidase antibodies (anti-TPO) binding to cellular-myeloproliferative leukemia (c-mpl) receptors is a proposed mechanism. Currently, no standard published guideline for treatment exists, but immunosuppressive therapies have been used based on the proposed mechanism and associated conditions. We present a case of a 57-year-old male who presented to the hospital with a 3-day history of progressive weakness and dysphagia. He had recently been discharged from an outside health system after evaluation for suspected gastrointestinal bleeding, although esophagogastroduodenoscopy and colonoscopy did not uncover a source of bleeding. Fifteen days later, he was admitted to our hospital for septic shock and acute renal failure with suspected lower gastrointestinal bleeding (melena on presentation). He was found to have a rapidly declining platelet count with a nadir of 0. Due to severe thrombocytopenia, filgrastim was administered. A bone marrow biopsy revealed findings consistent with amegakaryocytosis with otherwise preserved cell lines. Hematologic labs improved with the initiation of appropriate treatment for severe sepsis. After performing an extensive workup, the likely etiology of transient AATP in this case was severe sepsis-induced immune dysregulation and bone marrow suppression., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Barker et al.)

Background: Anti-PD-1/PD-L1 immunotherapy has achieved impressive responses in multiple types of malignancies in recent years. However, immune-related adverse events (irAEs) occur and limit their continuous clinical use. Among these irAEs, acquired amegakaryocytic thrombocytopenia (AAT) is rare but often clinically serious, life-threatening and refractory to multiple treatment approaches.Case summary: We reported for the first time the successful treatment of avatrombopag in two cases of anti-PD1 antibody-induced AAT (in particular, one case had progressed to aplastic anemia), which was refractory or intolerant to glucocorticoids, ciclosporin, intravenous immunoglobulin (IVIG), recombinant human thrombopoietin (rh-TPO) and even TPO receptor agonist (TPO-RA) eltrombopag. To date, the two cases manifested as normal platelet counts and are independent of transfusion.Conclusion: Anti-PD1 antibody-induced AAT occurs with low frequency but is often serious and difficult to manage, for which this study proposed vatrombopag as a potential curative and safe approach.

Acquired amegakaryocytic thrombocytopenia (AAMT) is a rare hematological disorder characterized by prolonged, severe thrombocytopenia, and reduced megakaryocytes on otherwise normal bone marrow biopsy. We report three cases of which two ultimately responded to treatment with eltrombopag, and one who one succumbed to illness despite treatment with multiple agents. These cases emphasize the difficulty of diagnosis and treatment of this rare condition.

Acquired amegakaryocytic thrombocytopenia (AAMT) is a rare disorder characterized by severe thrombocytopenia resulting from a marked reduction or absence of bone marrow megakaryocytes, and preserved hematopoiesis in other cellular lineages. We report a unique case of AAMT associated with Hodgkin Lymphoma, with spontaneous recovery following multiple cycles of combination chemotherapy. Our case provides evidence that AAMT associated with an underlying lymphoproliferative disorder may spontaneously recover following chemotherapy for the primary disease, and conservative management of thrombocytopenia could be considered in this setting.

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.

Congenital amegakaryocytic thrombocytopenia (CAMT) is a recessive disorder characterized by severe reduction of megakaryocytes and platelets at birth, which evolves toward bone marrow aplasia in childhood. CAMT is mostly caused by mutations in MPL (CAMT-MPL), the gene encoding the receptor of thrombopoietin (THPO), a crucial cytokine regulating hematopoiesis. CAMT can be also due to mutations affecting the THPO coding region (CAMT-THPO). In a child with the clinical picture of CAMT, we identified the homozygous c.-323C>T substitution, affecting a potential regulatory region of THPO. Although mechanisms controlling THPO transcription are not characterized, bioinformatics and in vitro analysis showed that c.-323C>T prevents the binding of transcription factors ETS1 and STAT4 to the putative THPO promoter, impairing THPO expression. Accordingly, in the proband the serum THPO concentration indicates defective THPO production. Based on these findings, the patient was treated with the THPO-mimetic agent eltrombopag, which induced a significant increase in platelet count and stable remission of bleeding symptoms. Herein, we report a novel pathogenic variant responsible for CAMT and provide new insights into the mechanisms regulating transcription of the THPO gene.

Background. Hereditary bone marrow failure syndromes are a category of biologically different syndromes that can cause cytopenia in at least one hematopoietic cell lineage. Case. We present a 29-week-old male infant who had a low Apgar Score, advanced delivery room resuscitation, widespread petechial rash, and ecchymoses at birth, without any dysmorphic features. Initial laboratory tests revealed bicytopenia (platelet count 7x10 3 /uL, hemoglobin of 3.9 g/dL, neutrophil 2.0x103 /uL) with findings of disseminated intravasculer coagulation (DIC). Imaging studies demonstrated accompanying left-sided congenital pulmonary airway malformation. On the second postnatal week pancytopenia occurred and the bone marrow findings were consistent with congenital amegakaryocytic thrombocytopenia. Further evaluations for differential diagnosis of pancitopenia were performed and the results of congenital viral infections, metabolic and immunologic tests were negative. While supportive treatments were in progress, haploidentical bone marrow transplantation (BMT) was performed from the father at 84th day due to unavailability of HLA-matched relative or nonrelative donor. Whole exome sequencing revealed a novel heterozygous frameshift variation (c.1242dupT [p. Thr538fs]) in exon 8 of the MECOM gene and validated by Sanger sequencing. No variation was detected in the parents genetic analysis. Conclusions. In this report, we present a patient with congenital bone marrow failure successfully treated with haploidentic BMT and describe a novel, de novo pathogenic variant in MECOM gene. [ABSTRACT FROM AUTHOR]

Acquired amegakaryocytic thrombocytopenia (AAMT) is a rare cause of thrombocytopenia seen in systemic lupus erythematosus (SLE) that is frequently misdiagnosed as immune thrombocytopenic purpura (ITP). Often patients do not respond to standard ITP treatment. Prompt bone marrow biopsy and further workup should ensue as it is a diagnosis of exclusion. While no standard guidelines exist, the mainstay of treatment is immunosuppressive therapy. Some cases are refractory and should have a follow-up biopsy, typically showing worsening disease. The exact pathogenesis is unclear; multiple mechanisms may be involved, suggesting AAMT may be a syndrome of various aetiologies rather than a distinct pathology. A common complication is aplastic anaemia, and the patient may need a haematopoietic stem cell transplant (HSCT). We present a young man with severe refractory AAMT in the setting of SLE that progressed to aplastic anaemia and required an HSCT. We then discuss and interpret the literature on AAMT., Competing Interests: None., (© 2023 The Mediterranean Journal of Rheumatology (MJR).)

Thymoma combined with pure red cell aplasia (PRCA) and acquired amegakaryocytic thrombocytopenia (AAMT) has been rarely reported, often occurring in the initial stage of treatment and after chemotherapy or thymectomy, while PRCA and AAMT occurring after radiotherapy for thymoma has not been reported. The present study describes the case of a 42-year-old female patient with thymoma complicated by radiation-induced PRCA and AAMT after a rapid response to radiotherapy, who was in complete remission without recurrence after adjustment of initial symptomatic therapy to cyclosporine combined with prednisone. After 1 month, the patient underwent complete resection of mediastinal tumor. Next-generation sequencing revealed that the DNA damage repair pathway-related gene MSH3 was mutated, with p.A57P in abundance of 9.21%. To the best of our knowledge, the present study is the first to report that PRCA and AAMT secondary to thymoma after radiotherapy may be associated with increased sensitivity to radiotherapy caused by a mutation in the MSH3 gene., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Xue et al.)

Congenital amegakaryocytic thrombocytopenia (CAMT) generally begins at birth with severe thrombocytopenia and progresses to pancytopenia. It is caused by mutations in the thrombopoietin receptor gene, the myeloproliferative leukemia virus oncogene (c-MPL). The association between CAMT and c-MPL mutation type has been reported in the literature. Patients with CAMT have been categorized according to their clinical symptoms caused by different mutations. Missense mutations of c-MPL have been classified as type II and these patients have delayed onset of bone marrow failure compared to type I patients. Here we present a girl with severe clinical course of CAMT II having a missense mutation in exon 4 of the c-MPL gene who was admitted to our hospital with intracranial hemorrhage during the newborn period.

Congenital amegakaryocytic thrombocytopenia caused by deleterious homozygous or compound heterozygous mutations in MPL (CAMT-MPL) is a rare inherited bone marrow failure syndrome presenting as an isolated thrombocytopenia at birth progressing to pancytopenia due to exhaustion of hematopoietic progenitors. The analysis of samples and clinical data from a large cohort of 56 patients with CAMT-MPL resulted in a detailed description of the clinical picture and reliable genotype-phenotype correlations for this rare disease. We extended the spectrum of CAMT causing MPL mutations regarding number (17 novel mutations) and impact. The clinical courses showed a great variability with respect to the severity of thrombocytopenia, the development of pancytopenia and the consequences from bleedings. The most severe clinical problems were (1) intracranial bleedings pre- and perinatally and the resulting long-term consequences, and (2) the development of aplastic anemia in the later course of the disease. An important and new finding was that thrombocytopenia was not detected at birth in a quarter of the patients. The rate of non-hematological abnormalities in CAMT-MPL was higher than described so far. Most of the anomalies were related to the head region (brain anomalies, ocular and orbital anomalies) and consequences of intracranial bleedings. The present study demonstrates a higher variability of clinical courses than described so far and has important implications on diagnosis and therapy. The diagnosis CAMT-MPL has to be considered even for those patients who are inconspicuous in the first months of life or show somatic anomalies typical for other inherited bone marrow failure syndromes.

We here describe a case involving a 67-yearold female patient who was referred to our hospital due to severe anemia (hemoglobin, 5.0 g/dL), thrombocytopenia (platelet count, 0.6×104/μL), and a mediastinal shadow with calcification noted on X-ray. On admission, an anterior mediastinal tumor was detected, and bone marrow biopsy revealed few megakaryocytes and severely reduced numbers of erythroid cells. The diagnosis was thymoma with pure red cell aplasia (PRCA) and acquired amegakaryocytic thrombocytopenia (AAMT). On Day 8 of admission, the patient received immunosuppressive therapy together with cyclosporine for the 2 severe hematologic diseases, which were stabilized within 2 months. Subsequently, total thymectomy was performed. The diagnosis of the tumor invading the left lung was invasive thymoma, Masaoka- Koga stage III. The histological diagnosis was World Health Organization type AB. Thymoma accompanied with PRCA and AAMT is very rare, and, based on our case, immunotherapeutic therapy for the hematologic disorders should precede surgical intervention.

Acquired amegakaryocytic thrombocytopenia (AATP) is a thrombocytopenic disorder characterized by a decrease in megakaryocytes in the bone marrow. AATP is effectively treated with immunosuppressive therapy. We report a case of a 68-years-old male referred to us due to purpuric lesions on the extremities and was noted to be thrombocytopenic. Bone marrow biopsy showed AATP with autoimmune hemolytic anemia (AIHA). Only two cases of AATP associated with AIHA have been reported. AATP should be differentiated carefully from other causes of peripheral destruction of platelets, such as immune thrombocytopenia (ITP)., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Ikeda et al.)

Amegakaryocytic thrombocytopenia (AMT) is a rare cause of acquired thrombocytopenia. The pathogenesis and treatment of AMT is not clearly known. Here we demonstrate a 50-year-old man presented with the clinical manifestations of severe thrombocytopenia (7000 platelets/µl) with a marked decrease to absent of megakaryocytes in the bone marrow. The patient did not respond to intravenous immunoglobulin, cyclosporine or high dose prednisone. After the treatment with anti-CD20 antibody (Rituximab), the patient's clinical symptoms and platelet counts improved.