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.

A Case of Acquired Amegakaryocytic Thrombocytopenia with Anti-c-mpl Autoantibody: Comparison with Idiopathic Thrombocytopenic Purpura.

Acquired amegakaryocytic thrombocytopenia (AAMT) is a rare disease that causes severe bleeding. The pathogenesis and treatment of AAMT have not yet been defined. We report the case of a 60-year-old woman diagnosed with AAMT, who presented with severe thrombocytopenia, gastroin-testinal bleeding, and significantly reduced bone marrow megakaryocytes. The patient was treated with methylprednisolone, cyclosporin, and intravenous immunoglobulin. After 2 weeks of treatment, her platelet count started to increase, and her bone marrow megakaryocyte count had normalized 3 months after diagnosis. At the time of diagnosis, the patient was seropositive for anti-c-mpl antibody but was seen to be seronegative once the platelet count recovered. In contrast, anti-c-mpl antibodies were not detected in the serum of 3 patients with idiopathic thrombocytopenic purpura. This case study suggests that anti-c-mpl antibody plays an important role in the development of AAMT, and that intensive immunosuppressive treatment is required for autoantibody clearance and recovery of megakaryocyte count.

Acquired Amegakaryocytic Thrombocytopenic Purpura Progressing into Aplastic Anemia.

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare hematological disorder characterized by severe thrombocytopenia and a complete or near-to complete absence of megakaryocytes in the bone marrow, while granulopoiesis, as well as erythropoiesis are usually preserved. Although autoimmune mechanisms are believed to be causative, the exact underlying pathogenesis is not known. To date, only few cases have been reported and management of this disease remains controversial with immunosuppression being the treatment modality of choice in the majority of patients. In this article, we report a case of newly acquired AATP without an associated autoimmune disease, refractory to corticoids, intravenous immunoglobulin (IVIG) and second-generation TPO (thrombopoietin) agonists, which have recently been approved for the treatment of thrombocytopenia. Finally, in accordance with other reports, disease progression into aplastic anemia has occurred.

Rifampcin-induced Thrombocytopaenia Purpura.

We report the case of a 28-year-old resident doctor with no past history of having taken rifampicin, who presented with thrombocytoapaenic purpura occurring after the initiation of anti-tuberculosis therapy (isoniazid, rifampicin, pyrazinamide and ethambutol) for tubercular lymphadenopathy.

Sulfamethoxazole-induced thrombocytopenia masquerading as posttransfusion purpura: a case report.

BACKGROUND: Drug-induced immune thrombocytopenia (DITP) is a rare clinical disorder characterized by accelerated platelet (PLT) clearance in the presence of drug-dependent antibodies. Distinguishing DITP from other immune-mediated disorders such as posttransfusion purpura (PTP) and autoimmune thrombocytopenia can represent a clinical challenge. CASE REPORT: A 68-year-old male with no prior transfusion history presented to the emergency department (ED) with dyspnea, epistaxis, and severe thrombocytopenia (<10 × 10(9)/L) 12 days after discharge from a hospital admission for a coronary artery bypass graft. Evaluation of the degree of thrombocytopenia and the temporal association between the peri- and postoperative receipt of multiple transfusions and the acute decrease in PLT count indicated PTP as a possible cause of the severe thrombocytopenia. Treatment with 1 g/kg intravenous immunoglobulin (IVIG) was initiated and followed by a rapid 48-hour increase in the PLT count. PLT antibodies lacking serologic specificity were subsequently identified in a sample collected upon presentation. Two weeks later he again presented to the ED with epistaxis and severe thrombocytopenia (<10 × 10(9)/L). Clinical history now revealed that the patient had been treated with trimethoprim-sulfamethoxazole by his primary care physician after his first hospitalization for a "cellulitic-appearing" leg and again before his final presentation for surgical site erythema and edema. IVIG was administered again with a rapid return of PLT count to baseline. Sulfamethoxazole-dependent PLT antibodies were subsequently identified in the original patient sample. CONCLUSION: This case report documents a case of IVIG-responsive DITP initially misdiagnosed as PTP, highlighting the clinical overlap of these immunologic-mediated phenomena.

Drug-induced immune thrombocytopenia: incidence, clinical features, laboratory testing, and pathogenic mechanisms.

Drug-induced immune thrombocytopenia (DIIT) is a relatively uncommon adverse reaction caused by drug-dependent antibodies (DDAbs) that react with platelet membrane glycoproteins only when the implicated drug is present. Although more than 100 drugs have been associated with causing DIIT, recent reviews of available data show that carbamazepine, eptifibatide, ibuprofen, quinidine, quinine, oxaliplatin, rifampin, sulfamethoxazole, trimethoprim, and vancomycin are probably the most frequently implicated. Patients with DIIT typically present with petechiae, bruising, and epistaxis caused by an acute, severe drop in platelet count (often to <20,000 platelets/pL). Diagnosis of DIIT is complicated by its similarity to other non-drug-induced immune thrombocytopenias, including autoimmune thrombocytopenia, posttransfusion purpura, and platelet transfusion refractoriness, and must be differentiated by temporal association of exposure to a candidate drug with an acute, severe drop in platelet count. Treatment consists of immediate withdrawal of the implicated drug. Criteria for strong evidence of DIIT include (1) exposure to candidate drug-preceded thrombocytopenia; (2) sustained normal platelet levels after discontinuing candidate drug; (3) candidate drug was only drug used before onset of thrombocytopenia or other drugs were continued or reintroduced after resolution of thrombocytopenia, and other causes for thrombocytopenia were excluded; and (4) reexposure to the candidate drug resulted in recurrent thrombocytopenia. Flow cytometry testing for DDAbs can be useful in confirmation of a clinical diagnosis, and monoclonal antibody enzyme-linked immunosorbent assay testing can be used to determine the platelet glycoprotein target(s), usually GPIIb/IIIa or GPIb/IX/V, but testing is not widely available. Several pathogenic mechanisms for DIIT have been proposed, including hapten, autoantibody, neoepitope, drug-specific, and quinine-type drug mechanisms. A recent proposal suggests weakly reactive platelet autoantibodies that develop greatly increased affinity for platelet glycoprotein epitopes through bridging interactions facilitated by the drug is a possible mechanism for the formation and reactivity of quinine- type drug antibodies.

[Thrombocytopenia]. / Thrombocytopeniák.

Thrombocytopenia means low platelet count. This is the most frequent cause of bleeding abnormalities. Petechias, purpuras, mucosal bleeding are typical clinical findings. Severe, even life threatening gastrointestinal or intracranial bleeding may also occur. Diagnostic laboratory finding is the prolonged bleeding time. There are several causes of thrombocytopenia. The major mechanisms for a reduced platelet count are decreased production and increased destruction of platelets, or both. The major task is to reveal the underlying cause. Examination of the bone marrow and the peripheral blood smear can be helpful as well as special diagnostics of the assumed disease. Therapy targets the underlying disease, and also involves platelet transfusion. However, in case of diseases with increased platelet activation and consumption, platelet transfusion is contraindicated because it may lead to aggravation of the pathologic process.

The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia.

Immune thrombocytopenia (ITP) is commonly encountered in clinical practice. In 1996 the American Society of Hematology published a landmark guidance paper designed to assist clinicians in the management of this disorder. Since 1996 there have been numerous advances in the management of both adult and pediatric ITP. These changes mandated an update in the guidelines. This guideline uses a rigorous, evidence-based approach to the location, interpretation, and presentation of the available evidence. We have endeavored to identify, abstract, and present all available methodologically rigorous data informing the treatment of ITP. We provide evidence-based treatment recommendations using the GRADE system in those areas in which such evidence exists. We do not provide evidence in those areas in which evidence is lacking, or is of lower quality--interested readers are referred to a number of recent, consensus-based recommendations for expert opinion in these clinical areas. Our review identified the need for additional studies in many key areas of the therapy of ITP such as comparative studies of "front-line" therapy for ITP, the management of serious bleeding in patients with ITP, and studies that will provide guidance about which therapy should be used as salvage therapy for patients after failure of a first-line intervention.

Approach of using established and new laboratory tests to more comprehensively investigate noninfectious and nonhemolytic transfusion reactions--along with the experience in Japan.

BACKGROUND AND OBJECTIVES: Noninfectious and nonhaemolytic transfusion reactions are the most common type of transfusion reactions. Several new tests have been made, helping diagnosis and understanding of their pathogenesis. This manuscript provides a review of the literature on currently available tests in association with the approach in Japan. MATERIALS & METHODS: Primarily by using key words, more than 100 pertinent articles in the Medline database were identified and reviewed. RESULTS: Numbers of laboratory tests are available including those for plasma protein levels, plasma protein antibodies, leucocyte and platelet antibodies, serum N-terminal-pro-brain natriuretic peptide levels, serum tryptase levels and genetic microchimerism. Cross-match tests, such as basophil activation test and neutrophil activation test, are also available to determine a causal relationship between the reaction and transfusion. CONCLUSIONS: Several tests should help to confirm diagnosis and determine causal relationship between adverse reactions and transfusion and to gain an insight into the mechanism of the reaction in some cases, although some of the recently developed tests have not been completely validated.

Laboratory testing for platelet antibodies.

Laboratory testing for immune-mediated thrombocytopenias involves identification and classification of antibodies present in patient sera or attached to patient platelets. This article summarizes the available types of platelet antibody testing and applications in disorders such as neonatal alloimmune thrombocytopenia, post-transfusion purpura, multiple platelet transfusion refractoriness, immune thrombocytopenia, and drug-induced thrombocytopenia.

Severe haematological complications during treatment with natalizumab.

The safety profile of natalizumab has been widely discussed due to several cases of progressive multifocal leukoencephalopathy, reported worldwide. Since the launch of natalizumab, 32 patients have been treated at our centre. In this context, we describe two cases (6.25%), one of immune-mediated acute haemolytic anaemia (IAHA) and another of immune thrombocytopenic purpura during treatment with natalizumab. The temporal relationship between drug administration and the nature of the haematological complications, confirmed with the serological findings in the case of the IAHA, suggests that natalizumab is the most probable cause for these adverse events. Although very uncommon, the haematological complications are severe enough to justify a close and careful monitoring for all patients with multiple sclerosis treated with an immunosuppressant treatment.

Rituximab-induced serum sickness in refractory immune thrombocytopenic purpura.

Serum sickness may occur in patients treated with chimeric monoclonal antibody. Rituximab, an anti-CD20 chimeric monoclonal antibody, is used with increasing frequency in chronic immune thrombocytopenic purpura (ITP). Rituximab is relatively safe; however, serum sickness is reported in 1-20% of patients, more commonly among those with autoimmune conditions. We describe a case of serum sickness in a patient with ITP and review the literature of rituximab-induced serum sickness.

Diabetic ketoacidosis preceding thrombocytopenia associated multiple organ failure in a child.

CONTEXT: Thrombocytopenia associated multiple organ failure is a rare but increasingly recognized condition in children. Diabetic ketoacidosis preceding thrombocytopenia associated multiple organ failure is previously unreported in pediatric patients. CASE REPORT: A 12-year-old female presented with diabetic ketoacidosis along with acute pancreatitis. She further developed thrombocytopenia and renal failure over the next two days. Although hemolytic uremic syndrome/thrombotic thrombocytopenic purpura spectrum was considered, the clinical picture seemed most consistent with thrombocytopenia associated multiple organ failure. The patient was treated with serial therapeutic plasma exchanges and made a complete recovery. CONCLUSION: A high index of suspicion of thrombocytopenia associated multiple organ failure is required in patients with diabetic ketoacidosis or pancreatitis who present with thrombocytopenia and renal failure. Plasma exchange is a life-saving intervention in such cases.

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.

Advances in the management and understanding of autoimmune lymphoproliferative syndrome (ALPS).

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of T cell dysregulation caused by defective Fas-mediated apoptosis. Patients with ALPS can develop a myriad of clinical manifestations including lymphadenopathy, hepatosplenomegaly, autoimmunity and increased rates of malignancy. ALPS may be more common that originally thought, and testing for ALPS should be considered in patients with unexplained lymphadenopathy, hepatosplenomegaly, and/or autoimmunity. As the pathophysiology of ALPS is better characterized, a number of targeted therapies are in preclinical development and clinical trials with promising early results. This review describes the clinical and laboratory manifestations found in ALPS patients, as well as the molecular basis for the disease and new advances in treatment.