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.

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 red cell aplasia in a patient with thymoma progressing to aplastic anemia successfully treated with allogenic stem cell transplantation.

Association of pure red-cell aplasia with thymoma is well documented. However, acquired amegakaryocytic thrombocytopenia (AAMT) has been rarely associated with thymoma with only five reported cases in literature. We report a patient with thymoma complicated by pure red cell aplasia (PRCA) and AAMT who progressed to develop aplastic anemia (AA). The patient was refractory to 10-months of immunosuppressive therapy with cyclosporine, prednisone, and antithymocyte globulin. She was eventually treated with allogeneic stem cell transplantation (allo-SCT). On Day +323 the patient continues to be transfusion-independent. This case illustrates how in patients with thymoma and AAMT may herald development of AA. This is also the first report of a patient with AAMT progressing to thymoma-associated AA being successfully treated with allo-SCT. The successful outcome suggests allo-SCT as a feasible option similar to other AA patients.

Diagnóstico y tratamiento de la púrpura trombocitopénica inmunológica / Diagnosis and treatment of Immune thrombocytopenic purpura

Desde siempre los episodios de sangrado muco-cutáneos, al ser tan evidentes, causan mucha preocupación y zozobra, más aún si ocurren sin causa aparente. La púrpura trombocitopénica suele ser la responsable de estos desagradables sucesos. Esta revisión tiene por objetivo actualizar los conocimientos acerca de la fisiopatología, el diagnóstico y el tratamiento de la púrpura trombocitopénica inmunológica (PTI), una patología hematológica que afecta tanto a niños como a adultos y que se ve con relativa frecuencia en la actividad diaria de un hospital general...

Thrombocytopenic purpura is mostly responsible for episodes of muco-cutaneous bleeding. This review updates topics on the pathophysiology, diagnosis and treatment of immunologic thrombocytopenic purpura (IPT), an hematologic condition that afects both childern and adults, which is seen relatively frequent in daily practice in a general hospital...

[Plasmapheresis in haematology]. / Plazmafereza lecznicza w hematologii.

Plasmapheresis also known as a therapeutic plasma exchange (TPE) is a procedure of plasma removal with it's ineligible plasma's component. Usually it is a supportive measure used simultaneously with the treatment, but in a few diseases, e.g. in trombotictrombocytopenic purpura (TTP), it is a first-choice treatment. During the plasmapheresis plasma is mostly replaced by 20% solution of albumin or combination of 20% solution of albumin and 0.9% solution of NaCl, however in some diseases fresh frozen plasma (FFP) is used. Plasmaphereses have found a wide application in different branches of medicine: hematology, neurology, nephrology, reumatology. Plasmapheresis is an invasive procedure, but when performed by qualified staff it is rather safe and serious complications are very rare.The most common complications of plasmapheresis are mild, usually caused by electrolyte disturbances (hypokalemia, hypokalcemia) or anticoagulation. More serious complication can be associated with FFP transfusion, extracorporeal circulation or presence of intravenous catheter. The latter one is usually necessary to perform the plasmapheresis. In haematology the most common indication for plasmapheresis is the supportive treatment of multiple myeloma. The procedure is performed in patients with high protein levels endangered with hyperviscosity syndrome. Less frequent indications to plasmapheresis in haematology are: Waldenström's macroblobulynaemia, idiopathic thrombocytopenic purpura (ITP), pure red cell aplasia (PRCA), polyneuropaties connected with haematological disorders. Supportive treatment of haemofagocytic syndrome (HLH--hemophagocytic lymphohistiocytosis) is one of the new indications. Plasmaphereses are used in treatment of about 150 different diseases and more and more new needs for this method are identified.

Las trombopoyetinas en el tratamiento de la púrpura trombocitopénica inmunitaria y otras trombocitopenias / Thrombopoietines in the treatment of the thrombocytopenic purpura and other thrombocytopenics

La purpura trombocitopénica inmunitaria y las trombocitopenias secundarias representan condiciones patológicas graves cuyo tratamiento plantea diversos grados de dificultad. La aproximación terapéutica convencional ha sido la administración de esteroides, la esplenectomía y el uso de inmunoglobulina intravenosa u otros tipos de anticuerpos (e.g., anti-D). La mejor comprensión de la fisiología y fisiopatología de la trombopoyesis aunado a los avances en biología molecular ha permitido el desarrollo de una nueva aproximación terapéutica, la aplicación de las trombopoyetinas sintéticas o no inmunogénicas. Dentro de este grupo resaltan dos compuestos: el romiplostin (una proteína de fusión) y el eltrombopag (un compuesto sintético de bajo peso molecular). Ambas se encuentran disponibles comercialmente. Los estudios clínicos indican que estos medicamentos tienen un efecto satisfactorio en el tratamiento de las trombocitopenias, particularmente en los casos refractarios a los tratamientos convencionales.

Immune thrombocytopenic purpura and the secondary thrombocytopenias are conditions potentially severe with diverse degrees of treatment difficulties. Steroids administration, splenectomy and the use of intravenous immunoglobulin and other antibodies (e.g., anti-D) had been the conventional therapy. The better understanding of the thrombopoiesis physiology and physiopathology togetter with the biology advances have permitted the development of a new terapheutic approach: the use of synthetic or nonimmunogenic thrombopoietines. Among this group highlights composites: romiplostim (a fusion protein) and eltrombopag (a synthetic composite with low molecular wheigt). Both are already available and produce a satisfactory effect particularly in nonrespondent cases to the conventional treatment.

Post-transfusion increment of platelet count in thrombocytopenic patients treated with platelet concentrates.

The Platelet (PLT) Transfusion Therapy plays an important role in the support of surgical, haematological, oncological and transplant patients. The present study was assigned to find out the post transfusion increment of platelet count among the thrombocytopenic patients in Bangladeshi population. This descriptive study was conducted at the Departments of Haematology and Transfusion Medicine, BSMMU, Dhaka. Total 42 thrmbocytopenic patients were randomly assigned to receive a transfusion when their platelet counts below 10000 per cubic millimeter or with active bleeding. Pre transfusion and post transfusion platelet count were measured in all patients. Out of 42 patients, 26(61.90%) were male and 16(38.10%) were female. Leukemia was the most common cause of thrombocytopenia (47.62%). Most of the patients (71.34%) required transfusion of multiple units of platelet and 12(28.57%) patients required double units. Before transfusion of platelet concentrate <30×108/L, 30-80×108/L and >80×108/L platelet count were found in 30(71.43%), 08(19.05%) and 04(09.52%) patients respectively. After transfusion of platelet concentrate <50×108/L, 50-100×108/L and >100×108/L platelet count were found in 30(71.43%), 08(19.05%) and 04(09.52%) patients respectively. In all patients post transfusion platelet count increases but 2 or multiple units of transfusion were needed.

Falciparum--the masquerader.

The case of a 23-year-old male presenting with a rash on the chest and lower limbs is presented. Work up revealed bicytopenia and plasmodium falciparum on bone marrow biopsy. Treatment with antimalarial drugs resulted in resolution of haematological abnormalities and rash.

Favorable response of chronic refractory immune thrombocytopenic purpura to mesenchymal stem cells.

Seven patients with chronic refractory immune thrombocytopenic purpura (ITP) received adipose tissue-derived mesenchymal stem cells (AMSC) from haplo-identical family donors. The AMSC dose was 2.0×10(6)/kg. No side effects were noted after the AMSC infusions. Overall responses were reached in all patients and sustained response rate was 57.1% (4/7). The serum levels of transforming growth factor ß1 (TGF-ß1), interleukin (IL)-4, and IL-10 were significantly elevated, whereas those of interferon-γ (IFN-γ) and IL-2 were significantly decreased after AMSC administration, compared with those in the patients with active ITP. During follow-up, the cytokine profiles in patients maintaining sustained response remained stable compared with the post-treatment level, but IFN-γ and IL-2 levels were significantly increased, and those of TGF-ß1, IL-4, and IL-10 were significantly reduced again in relapsed patients. AMSC therapy seems to represent reasonable salvage treatment in severe, chronic refractory ITP by causing a shift in the Th1/Th2 cytokine balance to the same levels as normal controls.

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.

[Protocol for the study and treatment of immune thrombocytopenic purpura (ITP). ITP-2010]. / Protocolo de estudio y tratamiento de la trombocitopenia inmune primaria (PTI-2010).

Primary immune thrombocytopenia (ITP), formerly known as immune thrombocytopenic purpura, is a disease in which clinical and therapeutic management has always been controversial. The ITP working group of the Spanish Society of Paediatric Haematology and Oncology has updated its guidelines for diagnosis and treatment of ITP in children based on current guidelines, literature review, clinical trials and member consensus. The primary objective was to lessen clinical variability in diagnostic and therapeutic procedures in order to obtain best clinical results with minimal adverse events and good quality of life.

[Thrombotic microangiopathy after extracorporeal circulation: important differential diagnosis]. / Thrombotische Mikroangiopathien nach extrakorporaler Zirkulation : Wichtige Differenzialdiagnose.

Thrombotic microangiopathies are characterized by platelet activation, endothelial damage, hemolysis and microvascular occlusion. This group of diseases is primary represented by thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Patients present with microangiopathic hemolytic anemia and thrombocytopenia as well as occlusion-related organ ischemia to a variable degree. A deficiency of the metalloprotease ADAMTS-13 is a major risk for acute disease manifestation as this is a regulator of unusually large von Willebrand factor (vWF) multimers, which are extremely adhesive and secreted by endothelial cells. In classical TTP an ADAMTS-13 activity below 5% is specific, whereas in other forms of thrombotic microangiopathies activity of ADAMTS-13 ranges from very low to normal. Symptoms of different forms of thrombotic microangiopathy are frequently overlapping and a clear classification according to clinical criteria is often difficult. Due to a high mortality, particularly of TTP, immediate diagnosis and therapy are essential. In this article two cases of thombotic microangiopathy after cardiac surgery are reported. After exclusion of TTP and HUS as well as other etiologies of thrombotic microangiopathy a relationship between the use of extracorporeal circulation and the pathogenesis of thrombotic microangiopathy is assumed.

Tratamiento de la púrpura trombocitopénica inmune crónica: buscando algo mejor: revisión / Treatment of the chronic immune thrombocytopenic purpura: looking for something better: review

La Púrpura Trombocitopenica Inmune crónica (PTIc) se ha convertido en un campo de múltiples ensayos terapéuticos. Más de 20 tipos de tratamiento han sido utilizados para obtener una respuesta plaquetaria favorable y prolongada. El tratamiento de la PTIc está orientado a inhibir la producción de anticuerpos antiplaquetarios, mediante interferencia del macrófago del sistema retículo endotelial y bloqueo de la respuesta antigénica disminuyendo en consecuencia la amplificación del estimulo inmunológico. Los esteroides tipo glucocorticoides y la esplenectomía constituyen el tratamiento de primera línea, en caso de no obtener respuesta se emplean los inmunosupresores no esteroideos y las inmunoglobulinas tipo IgG o anti-D. Se han reportado también ensayos terapéuticos con medicamentos inmunomoduladores. Recientemente con el advenimiento de nuevos fármacos destinados a estimular la producción plaquetaria en médula ósea, se ha abierto una nueva vía en el tratamiento de la PTIc. No obstante, la esplenectomía permanece aún como el tratamiento más simple, seguro y eficaz en PTIc. El criterio que debe prevalecer para obtener el bienestar del paciente, es que ningún tratamiento en PTIc debe estar enfocado a obtener una cuenta plaquetaria normal, sino a alcanzar niveles hemostáticos seguros con ausencia de manifestaciones hemorrágicas por tiempo prolongado. Inclusive, a pesar de persistir la trombocitopenia, el médico puede optar por mantenerlo sin tratamiento con la sola observación clínica estricta. Finalmente, se debe tomar en cuenta el costo beneficio a la hora de tomar la decisión de tratar estos pacientes, el cual se inclinaría hacia aquellos que proporcionen bajo costo y mínimos efectos secundarios.

Chronic Immune Thrombocytopenic Purpura (cITP) has become a field of multiple therapeutic assays. More than 20 types of treatment have been developed to obtain a favorable and prolonged platelet response. The treatment of cITP is oriented to inhibit the antiplatelet antibodies production by interference with the macrophage of the reticulum endothelial system and a blockade of the antigenic response with a decrease in the amplification of the immunological response. Steroids of the glucocorticoids type and splenectomy constitute the first line of treatment. Failure of these treatments leads to the use of second line drugs such as non steroid immunosupressors and the immunoglobulins type IgG and anti-D. Therapeutic assays with others immunomodulators have been reported. The introduction of new drugs destined to increase the megakaryocytic bone marrow platelet production, has opened a new way to treat the cITP. However, the splenectomy remains as the simplest, safest and most effective treatment in cITP. The principal criteria does not have to be focused on obtaining a normal platelet count, but to reach safe hemostatic levels in absence of hemorrhage, for a prolonged time. On the other hand, despite the persistence of thrombocytopenia, the hematologist can choose to maintain the patient with no treatment and with only a strict clinical observation. It is obvious that the cost-benefit from the different treatments is inclined towards those of lower cost and minimal secondary effects.

Glomeruloid hemangioma.

A 64-year-old Japanese woman suffering from idiopathic thrombocytopenic purpura was treated with prednisolone. During the course of steroid withdrawal she developed parotid gland enlargement and cervical lymph node swelling with multiple dome-shaped red papules on her trunk and upper limbs. On admission the patient was found to have numbness of her lower limbs (polyneuropathy), lymph node swelling (organomegaly), high glucose level (endocrinopathy), Bence-Jones protein-kappa in the urine (M protein) and skin with hyperpigmentation, hypertrichosis and multiple glomeruloid hemangiomas (skin abnormalities), indicating polyneuropathy-organomegaly-endocrinopathy-M-protein-skin abnormality (POEMS) syndrome. The patient was also found to have peripheral edema, ascites, and pleural effusion. The glomeruloid hemangiomas had intravascular capillary growth, which was composed of conglomerates of capillaries resulting in structures resembling renal glomeruli. Cells within the capillary loops were lined by endothelial cells with scant cytoplasm (CD31(+)/CD34(+)/CD68(-)/CD105(+)/UEA-1(+)) while the outer surfaces of the loops were covered by either swollen endothelial cells containing PAS- and immunoglobulin-positive eosinophilic hyaline globules (CD31(+)/CD34(-)/CD68(-/+)/CD105(-)/UEA-1(-)) or cells without globules. These two phenotypically different endothelial cells were separated by alpha-smooth muscle actin-positive pericytes. Pericytes and endothelial cells covering the outer surface of the loops were bordered by basement membrane. Biopsy of parotid gland and lymph node indicated Sjögren's syndrome and Castleman's disease of a hyaline-vascular type, respectively. Resumed prednisolone therapy has been successful, and the patient was left with minimal residual symptoms. Glomeruloid hemangioma is a specific marker of POEMS syndrome and is related to Castleman's disease. Idiopathic thrombocytopenic purpura and Sjögren's syndrome may also be related.

Preoperative embolization of the splenic artery in patients that underwent splenectomy for immune thrombocytopenic purpura

Transfusion of platelets, red blood cells, or both is usually necessary immediately after splenic artery ligature in patients with immune thrombocytopenic purpura who undergo splenectomy. PURPOSE: To investigate whether preoperative embolization of the splenic artery reduced the need for transfusion of platelets, red blood cells, or both. METHODS: Twenty- seven consecutive patients that underwent splenectomy for purpura between October 1999 and March 2006 performed by the same surgical team were enrolled. The first 17 patients did not undergo embolization and were compared with the next 10 patients, who composed the embolization group. RESULTS: The platelet count in the embolization group rose from a mean 7000 u/µl before to 75000 u/µl after the procedure. There was no need for platelet or red blood cell transfusion in the embolization group; in the group without preoperative embolization, 11 patients (p=0.001) required platelet transfusion and 8 (p=0.01), red blood cell transfusion. CONCLUSION: Embolization of the splenic artery before splenectomy is a safe method to avoid blood transfusions in patients with ITP.

A transfusão de plaquetas e ou hemácias geralmente é realizada em pacientes submetidos a esplenectomia por Purpura Trombocitopênia Imune (PTI). OBJETIVO: Investigar se a embolização pré-operatória da artéria esplênica é eficaz na redução da necessidade de transfusão de hemácias ou plaquetas. MÉTODOS: Vinte e sete pacientes foram submetidos a esplenectomia por PTI de Outubro de 1999 a Março de 2006 pela mesma equipe cirúrgica. Os primeiros 17 pacientes não foram submetidos a embolização e foram comparados com os outros 10 individuos nos quais a embolização foi realizada. RESULTADOS: A contagem de plaquetas no grupo em que a embolização foi realizada subiu de uma média de 7000u/µl antes do procedimento, para 75000 u/µl após. Não foi necessário transfundir plaquetas ou glóbulos vermelhos no grupo submetido a embolização comparado com 11 pacientes com transfusão de plaquetas (p=0,001) e 8 pacientes com transfusão de hemácias (p=0,01) no grupo sem embolização pré-operatória. CONCLUSÃO: A embolização pré-operatória da artéria esplênica é um método seguro e eficaz para evitar o uso de transfusões em esplenectomias por PTI.

Pathology of thrombotic thrombocytopenic purpura in the placenta, with emphasis on the snowman sign.

Thrombotic thrombocytopenic purpura (TTP) commonly affects women of childbearing age. Although cases of TTP in pregnancy have been reported, the pathology of TTP in the placenta has not been described. In other organs, TTP has a distinctive pathology of arteriolar aneurysms with segmental intramural hyaline deposits. Published many decades ago, these classic papers antedate modern computerized literature searches, so this information has not been included in many modern reviews on TTP. We report 2 cases of TTP in pregnancy, both leading to fetal loss in the 2nd trimester. We noticed a distinctive pathology of TTP in the spiral arteries on the maternal surface of the placenta, particularly the "snowman sign," which differs somewhat from TTP in other organs due to the fact that TTP is superimposed on trophoblast-induced changes in these spiral arteries. In one of our cases, where the clinical diagnosis of TTP was difficult, the distinctive placental findings helped reinforce the clinical decision to perform potentially life-saving plasmapheresis.