Acquired Pure Red Cell Aplasia and Acquired Amegakaryocytic Thrombocytopenia Associated With Clonal Expansion of T-Cell Large Granular Lymphocytes in a Patient With Lipopolysaccharide-responsive Beige-like Anchor (LRBA) Protein Deficiency.

Acquired pure red cell aplasia and acquired amegakaryocytic thrombocytopenic purpura are rare in children. Similarly, clonal expansion of T-cell large granular lymphocytes is infrequently seen in pediatrics. Lipopolysaccharide-responsive beige-like anchor (LRBA) protein deficiency is a recently described immunodeficiency syndrome that has been associated with inflammatory bowel disease and autoimmune phenomena such as Evans syndrome. Here, we describe a patient with LRBA deficiency who developed acquired pure red cell aplasia and acquired amegakaryocytic thrombocytopenic purpura associated with expansion of clonal T-cell large granular lymphocytes. This has not been described in the literature previously and adds to the knowledge on the spectrum of manifestations of LRBA deficiency.

Bleeding After Endoscopic Procedures in Patients With Chronic Hematologic Thrombocytopenia.

BACKGROUND: Procedure-induced bleeding is a major complication after endoscopic intervention. AIMS: The aim of this study was to investigate the risk of endoscopy-related bleeding in patients with chronic hematologic thrombocytopenia. METHODS: We investigated endoscopy-related bleeding in 175 procedures performed on 108 patients with immune thrombocytopenic purpura or aplastic anemia. The outcomes were compared with those of 350 procedures on age-, sex-, and procedure-matched control subjects. Endoscopic interventions included low-risk procedures such as endoscopic biopsy and high-risk procedures including polypectomy, endoscopic resection, and endoscopic retrograde cholangiopancreatogram with sphincterotomy. RESULTS: Bleeding occurred in 17 (9.7%) procedures among the patients with thrombocytopenia. This rate was significantly higher than that in procedures on controls (3.1%, P = 0.003). About 60% of all bleeding events were observed within 24 h after the endoscopic procedure. Bleeding after endoscopic biopsy developed more frequently in the patient group than in the control group (7.1 vs. 0.7%; P < 0.001). Bleeding occurred after 20% of all high-risk procedures. The incidence of bleeding was significantly elevated in patients with a platelet count less than 50 × 103/µl. Multivariate analysis revealed that high-risk procedures and low platelet count (less than 50 × 103/µl) were significantly related to procedure-related bleeding. All bleeding events stopped spontaneously or were controlled with endoscopic hemostasis. CONCLUSIONS: Endoscopic procedure-related bleeding develops frequently in patients with chronic hematologic thrombocytopenia. Post-procedural bleeding should be observed carefully in these patients, especially when the platelet count is less than 50 × 103/µl or high-risk endoscopic procedures are planned.

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.

Thymoma complicated by acquired amegakaryocytic thrombocytopenia and pure red cell aplasia.

Although the association of pure red cell aplasia (PRCA) and aplastic anemia with thymoma is well-known, acquired amegakaryocytic thrombocytopenia (AAMT) is not a recognized paraneoplastic manifestation of thymoma. This report discusses a patient with recurrent thymoma complicated by myasthenia gravis, PRCA, and AAMT. Both PRCA and AAMT are diagnosed after a thymoma recurrence, 11 years after complete resection of the initial tumor and 9 months after chemotherapy for the relapsed disease. Both PRCA and AAMT responded to immunosuppression with cyclosporine, corticosteroid, and an abbreviated course of antithymocyte globulin, achieving a very good erythroid response and a complete remission for AAMT, suggesting that AAMT, although extremely rare, can be an immune-mediated paraneoplastic manifestation of thymoma.

[Successful rituximab treatment for acquired amegakaryocytic thrombocytopenic purpura complicated with Coombs-negative autoimmune hemolytic anemia].

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare disorder characterized by severe thrombocytopenia associated with total absence or a selective decrease in bone marrow megakaryocytes. A 67-year-old male presented with a 2-month bleeding tendency. He was referred to our hospital because of severe thrombocytopenia. Bone marrow biopsy showed complete absence of megakaryocytes without dysplasia in cells of the myeloid and erythroid lineages. AATP was diagnosed. In addition, mild normocytic normochromic anemia and reticulocytosis were also observed and haptoglobin was below the detectable level. Coombs-negative autoimmune hemolytic anemia (AIHA) was diagnosed based on the high titer of RBC-bound IgG and negative direct and indirect coombs test results. He was first treated with cyclosporine 200 mg per day and subsequently with prednisolone but only slight temporary improvement was achieved. Administration of eight doses of rituximab 375 mg/m(2) per week ameliorated both thrombocytopenia and anemia. AATP should be considered in the differential diagnosis of thrombocytopenia, and immunosuppressive therapy is a potential first-line treatment. This is the first case report of AATP accompanied by AIHA successfully treated with rituximab.

Mycophenolate mofetil therapy for juvenile dermatomyositis with immune thrombocytopenic purpura.

A 6-year-old girl, who had received corticosteroid and cyclosporine on the diagnosis of interstitial pneumonitis related to juvenile dermatomyositis, developed severe thrombocytopenia. Her thrombocytopenia was resistant to repeated intravenous immunoglobulin administration and methylprednisolone pulse therapy. After additional treatment with mycophenolate mofetil (MMF), instead of cyclosporine, the thrombocytopenia improved, facilitating a reduction in the dose of corticosteroid without exacerbation of the interstitial pneumonitis. We propose MMF as effective option in the treatment of immune thrombocytopenic purpura with autoimmune disease.

Concomitant thrombotic thrombocytopenic purpura and ANCA-associated vasculitis in an adolescent.

Thrombotic thrombocytopenic purpura (TTP) rarely occurs with systemic vasculitis. A 17-year-old girl presented with non-bloody diarrhea, menorrhagia, and syncope. She had severe anemia (hemoglobin = 3.8 g/dl), thrombocytopenia (platelet = 7,000/mm(3)), and acute kidney injury (serum creatinine, Cr = 2.3 mg%). Peripheral smear examination confirmed the presence of microangiopathic hemolytic anemia. Additionally, she had a positive anti-nuclear antibody (1:1600) and normal complement levels. We considered the diagnosis of TTP, possibly associated with systemic lupus erythematosus, and promptly initiated pulse methylprednisolone and daily 3-4 l of plasma exchange therapy. Following resolution of her thrombocytopenia in 48 h, we performed a kidney biopsy that revealed diffuse proliferative, focal crescentic, and necrotizing glomerulonephritis with mild IgG immunofluorescence staining. Concomitantly, autoimmune work-up was significant for positive perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA = 1:640) and decreased von Willebrand factor cleaving protease activity (<5%). A final diagnosis of TTP with microscopic polyangiitis (p-ANCA-mediated) was made and treatment with daily oral cyclophosphamide and prednisone resolved her renal injury over 2 months (follow-up Cr = 1.0 mg%). Our case highlights the importance of identifying systemic disorders such as ANCA-associated vasculitis with TTP.

Reversible posterior leukoencephalopathy syndrome in a patient with thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is an autoimmune disorder characterised by fever, microangiopathic haemolytic anaemia, renal insufficiency, and thrombocytopenia. Neurological involvement, a prominent component of TTP, is characterised by a variety of brain lesions which include reversible cerebral oedema or magnetic resonance imaging (MRI) features of reversible posterior leukoencephalopathy syndrome (RPLS). TTP is frequently associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13.Here, we report a case of TTP with severe acute encephalopathy. Posterior leukoencephalopathy and brainstem oedema with triventricular hydrocephalus were observed on MRI. The low activity of ADAMTS13 was not observed and ADAMTS-13 antibodies were absent. Neurological symptoms and patient's condition were completely resolved by plasma exchange therapy in addition to high dose of methylprednisolone.

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.

Thrombotic microangiopathies: new insights and new challenges.

PURPOSE OF REVIEW: Thrombotic microangiopathies (TMAs) manifest as a spectrum of related disorders in the form of thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). New data on both diseases support more and more the relatedness of the disorders and reveal related pathomechanisms, which, however, manifest in different organs. TTP develops primarily at neurological sites, and also in the kidney, and HUS is a kidney disease. In TTP thrombi formation occurs subsequently to the release of multimers of von Willebrand factor (vWF), and in HUS endothelial cell damage is considered the reason for complement and platelet activation leading to thrombus formation. RECENT FINDINGS: Genetic mutations are associated with both disorders: in TTP the ADAMTS13 gene, the vWF cleaving protease, is affected, and in HUS several complement genes are mutated. In addition autoimmune forms, with acquired, de-novo generated inhibitors in the form of autoantibodies exist for both disorders, affecting ADAMTS13 in TTP or the central complement inhibitor factor H in HUS. In HUS autoantibodies can develop in the context of a specific mostly homozygous chromosomal deletion that represents a new subform of the disease, which is termed DEAP-HUS (deficient for CFHR proteins and autoantibody positive HUS). SUMMARY: As the underlying disease mechanisms of TMA are now being better understood new options for a more precise diagnosis, improved therapy and prognosis for kidney transplantation become available for the benefit of patients. Here we summarize the recent developments in this rapidly progressing field.

Recurrent hypersplenism caused by giant accessory spleen due to portal hypertension after splenectomia.

Splenectomy is one of the primary choices of treatment in immune thrombocytopenic purpura. However, the disease may relapse despite splenectomy. One of the leading causes of relapse is the presence of accessory spleen, which may become enlarged significantly with underlying pathologies such as presence of portal hypertension. The accessory spleen, which will inevitably enlarge in time, may grow significantly within a short period of time in the presence of portal hypertension and may thus be misdiagnosed as a tumoral mass. Presence of ectopic spleen should be borne in mind in patients diagnosed with immune thrombocytopenic purpura with relapsing hypersplenism following splenectomy. This article discusses a patient developing portal hypertension secondary to chronic liver disease and presenting with a significantly enlarged accessory spleen as well as hypersplenism findings.

Myocardial necrosis in patients with thrombotic thrombocytopenic purpura: pathophysiology and rationale for specific therapy.

Myocardial necrosis is now recognized as a common feature of thrombotic thrombocytopenic purpura (TTP), usually due to platelet plugging in the microvasculature. Despite reports that TTP patients with myocardial damage have higher morbidity and mortality, there are no established guidelines for managing these high-risk patients. The universal occurrence of thrombocytopenia and variable findings including renal dysfunction present unique challenges in this setting. Established therapies including plasma exchange and immunosuppression are the mainstay of therapy for all TTP patients. For the subset of patients with myocardial damage, therapy with more potent antiplatelet drugs, agents that enhance NO availability and alleviate vasospasm and drugs that suppress von Willebrand factor levels may have additional benefit. However, clinical trials are needed to optimize therapy for this subset of TTP patients.

Neuraxial techniques in obstetric and non-obstetric patients with common bleeding diatheses.

BACKGROUND: There are few data in the literature regarding the safety of neuraxial techniques in patients with the most common bleeding diatheses, including hemophilia, von Willebrand's disease (vWD), and idiopathic thrombocytopenic purpura (ITP). Neuraxial techniques are not widely used in these populations because of concerns of potential hemorrhagic and/or subsequent neurologic complications. In this article, we review the available literature describing neuraxial techniques in patients with hemophilia, vWD, or ITP with the aim to assist anesthesiologists considering neuraxial techniques in these populations. METHODS: After a systematic Pubmed, MEDLINE, and EMBASE search, we reviewed 30 articles published between January 1, 1975 and October 1, 2008 in which neuraxial techniques were performed in patients with hemophilia, vWD, or ITP to determine the perioperative management and evaluate the frequency of hemorrhagic complications. RESULTS: We identified 507 neuraxial techniques (482 patients) performed in patients with hemophilia (107 neuraxial techniques, 85 patients), vWD (74 neuraxial techniques, 72 patients), or ITP (326 neuraxial techniques, 325 patients). Among the 507 neuraxial techniques performed, there were 371 lumbar epidural anesthetics, 78 spinal anesthetics, 53 lumbar punctures, 2 combined spinal epidural analgesia, 2 paravertebral blocks, and 1 thoracic epidural anesthetic. Four hundred six neuraxial techniques were placed in the obstetric population, 53 were performed in the emergency room for diagnostic lumbar puncture, 46 were performed for lower limb orthopedic surgery, 1 was performed for postoperative analgesia, and 1 was performed for an obstetric patient undergoing non-obstetric surgery. Factor replacement to normal levels (>0.5 IU mL(-1)) was initiated before block performance, though treatment was not standardized, in 105 of 107 patients with hemophilia and 10 of 74 with vWD. Sixty-four of the 74 patients with vWD had spontaneous normalization of factor levels before block performance. No hemorrhagic complications were reported when the diagnosis of hemophilia or vWD was known before the neuraxial technique. A single case of spinal hematoma (resulting in permanent paraplegia) was identified when the presence of hemophilia was not known before needle insertion and factor replacement had not been given. In all 326 cases of ITP, with or without systemic treatment of platelet transfusion, there were no reports of hemorrhagic complications associated with neuraxial techniques. Among the 326 neuraxial techniques placed in the setting of ITP, 9 patients had platelet counts of <50 x 10(9) L(-1), 19 had a platelet counts of 50-75 x 10(9) L(-1), 204 had a platelet counts of 75-100 x 10(9) L(-1), and 94 had a platelet count more than 100 x 10(9) L(-1) before needle insertion. CONCLUSIONS: There is a paucity of published data regarding the provision and safety of neuraxial techniques in patients with common bleeding diatheses. The minimum "safe" factor levels and platelet count for neuraxial techniques remain undefined in both the obstetric and general populations, and evidence-based recommendations in the setting of hemophilia, vWD, or ITP cannot be offered.

A case of newly diagnosed metastatic pancreatic cancer presenting with associated immune thrombocytopenic purpura.

Metastatic pancreatic adenocarcinoma presenting with immune thrombocytopenic purpura is a very rare association. To date, only 1 case report found in the literature delineates such an association. We present a case of a patient with newly diagnosed, biopsy-proven metastatic pancreatic adenocarcinoma with new-onset immune thrombocytopenic purpura. The patient's platelet count returned to normal limits after being treated with oral corticosteroid therapy. In conclusion, immune thrombocytopenic purpura can be associated with metastatic pancreatic adenocarcinoma and responds well to corticosteroid therapy.

Acquired amegakaryocytic thrombocytopenia as a rare cause of thrombocytopenia during pregnancy.

A rare case of acquired amegakaryocytic thrombocytopenia (AATP) in a 35-year-old woman who presented with anaemia and thrombocytopenia at 22 weeks gestation. The first diagnostic impression was of an evolving aplastic anaemia; however, the patient was simultaneously diagnosed with severe vitamin B12 deficiency in the setting of vegetarianism. Once the cyanocobalamin deficiency was corrected, a repeat bone marrow biopsy revealed an isolated depletion of megakaryocytes, which suggested the diagnosis of AATP. Supportive care was provided for her anaemia and thrombocytopenia and she delivered a healthy baby girl with a normal platelet count. The patient was subsequently started on romiplostim with steady improvement in her platelet counts. This rare AATP case presentation highlights the importance of a well-structured diagnostic approach to thrombocytopenia during pregnancy and supports the successful use of thrombopoietin agonists for the management of AATP.

Acquired amegakaryocytic thrombocytopenia and pure red cell aplasia associated with an occult large granular lymphocyte leukemia.

Acquired amegakaryocytic thrombocytopenia and pure red cell aplasia rarely occur concurrently. We report a case in which these disorders were associated with an occult large granular lymphocyte leukemia. The peripheral blood cytopenias improved after glucocorticoids and intravenous immunoglobulin were administered, and response was maintained with cyclosporine. Large granular lymphocyte leukemia should be suspected in the setting of unexplained bone marrow failure.

Thrombotic thrombocytopenic purpura associated with multiple myeloma.

Thrombotic thrombocytopenic purpura is a thrombotic microangiopathic disease. Associations with collagen vascular diseases, pregnancy, some drugs, surgical intervention, and infections are documented (known). Malignancy is also one of the known factors associated with thrombotic thrombocytopenic purpura. These malignancies are usually the disseminated solid organ tumors. Hematological malignancies constitute a rare association. Here, we present a patient with thrombotic thrombocytopenic purpura associated with multiple myeloma and discuss the pathogenesis. To our knowledge, this is the first case report of thrombotic thrombocytopenic purpura associated with multiple myeloma.

Varicella pneumonia with immune thrombocytopenic purpura: a patient with multiple complications.

Viral syndromes can present with various cutaneous manifestations, from the morbilliform eruption of measles to the papular lesions of molluscum. The systemic manifestations of viral illness can be similarly varied, with different presentations in each individual. We describe a patient with recently diagnosed AIDS who presented to the emergency department with hemorrhagic papules and shortness of breath. She was found to be severely thrombocytopenic, and a Tzanck smear revealed multinucleate giant cells. She received a diagnosis of immune thrombocytopenic purpura (ITP) and primary varicella pneumonia. Acyclovir and intravenous immunoglobulin (IVIG) were initiated. Her respiratory status improved after 5 days of treatment and her cutaneous lesions healed, with some scarring. We believe the rapid resolution and benign outcome of this patient's varicella infection may have been attributed to the concomitant initiation of IVIG with antiviral therapy.