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Sample records for alloimmune thrombocytopenic purpura

  1. Genotype and Phenotype Correlation in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)

    ClinicalTrials.gov

    2016-09-01

    Thrombotic Thrombocytopenic Purpura; Congenital Thrombotic Thrombocytopenic Purpura; Familial Thrombotic Thrombocytopenic Purpura; Thrombotic Thrombocytopenic Purpura, Congenital; Upshaw-Schulman Syndrome

  2. Thrombotic thrombocytopenic purpura preceding systemic lupus erythematosus.

    PubMed Central

    Simeon-Aznar, C P; Cuenca-Luque, R; Fonollosa-Pla, V; Bosch-Gil, J A

    1992-01-01

    The case of a patient admitted with thrombotic thrombocytopenic purpura nine years after developing systemic lupus erythematosus (SLE) is reported. Thrombotic thrombocytopenic purpura associated with SLE has been described on other occasions, but in most patients the diagnosis of SLE precedes that of thrombotic thrombocytopenic purpura. The unusual sequence and the chronological separation of the two diseases is emphasised. PMID:1575591

  3. Hodgkin's disease presenting as idiopathic thrombocytopenic purpura.

    PubMed Central

    Murphy, W. G.; Allan, N. C.; Perry, D. J.; Stockdill, G.

    1984-01-01

    A case of Hodgkin's disease presenting as idiopathic thrombocytopenic purpura in a 23-year-old male is reported. This is a rare presentation of Hodgkin's disease having been previously described in only two cases. PMID:6541338

  4. Autoimmune Hepatitis Associated with Immune Thrombocytopenic Purpura

    PubMed Central

    Ito, Akihiro; Yoshizawa, Kaname; Fujimori, Kazuya; Morita, Susumu; Shigeno, Takashi; Maejima, Toshitaka

    2017-01-01

    Although autoimmune hepatitis (AIH) is frequently complicated with chronic thyroiditis or other autoimmune disorders, reports on its association with immune thrombocytopenic purpura (ITP) are scarce. We herein describe a case of AIH associated with ITP. A 75-year-old Japanese woman was admitted to our hospital due to increased aminotransferase levels and severe thrombocytopenia. Elevated serum immunoglobulin G (IgG) was detected, and tests for platelet-associated IgG and anti-nuclear antibody were positive. Following the diagnosis of AIH-associated ITP, prednisolone treatment of 0.6 mg/kg/day resulted in a decrease in the aminotransferase levels and an increased platelet count. PMID:28090042

  5. A rare combination of thrombotic thrombocytopenic purpura and antiphospholipid syndrome.

    PubMed

    Viner, Maya; Murakhovskaya, Irina

    2016-11-24

    Thrombocytopenia, in the setting of microangiopathic hemolytic anemia and thrombotic events, is characteristic of both thrombotic thrombocytopenic purpura and primary antiphospholipid syndrome. Clinically, it is difficult to distinguish between these two syndromes. We present a 41-year-old woman with chronic, relapsing thrombotic thrombocytopenic purpura in the presence of antiphospholipid antibodies. She had clinical manifestations of antiphospholipid syndrome without meeting laboratory criteria of the Sydney classification system. In the literature, there have only been nine cases of thrombotic thrombocytopenic purpura associated with primary antiphospholipid syndrome. Seven of the nine cases suffered from one or multiple strokes, a common feature in antiphospholipid syndrome, but an uncommon finding in thrombotic thrombocytopenic purpura. We introduce the possibility of an association between thrombotic thrombocytopenic purpura and the presence of antiphospholipid antibodies. Systematic testing of ADAMTS13 activity and anti-ADAMTS13 antibodies in patients who present with neurological symptoms and thrombocytopenia, in the presence of antiphospholipid antibodies, may help with the diagnosis of the rare thrombotic thrombocytopenic purpura-antiphospholipid syndrome combination.

  6. [Pregnancy and labor in idiopathic thrombocytopenic purpura].

    PubMed

    Tampakoudis, P; Billi, H; Tantanassis, T; Kalachanis, I; Garipidou, B; Sinakos, Z; Mantalenakis, S

    1995-10-01

    Clinical data from eight pregnant women with idiopathic thrombocytopenic purpura (ITP) were retrospectively analyses. The mean age of the women was 28.2 years. Five women underwent splenectomy during childhood. The lowest maternal platelet count observed ranged from 8000 to 88000/mm3. Genital bleeding occurred in only one case. Treatment was based on administration of corticosteroids with or without human-pooled immunoglobulins. Caesarian section was performed in all cases. Six newborns were healthy and had a successful subsequent course. Two infants died, one in utero because of abruptio placentae and the other one 1 month post partum because of a cerebral haematoma. After a mean follow-up of eighteen months, thrombocytopenia is still present in two women, despite the continuous treatment. In conclusion, ITP rather rarely coincides with pregnancy. Treatment is usually successful for the mother but the risk for the fetus remains considerably high.

  7. Platelet antibodies in idiopathic thrombocytopenic purpura.

    PubMed Central

    Veenhoven, W A; Van der Schans, G S; Nieweg, H O

    1980-01-01

    An immunofluorescence (IF) technique for the detection of antibodies was applied to idiopathic thrombocytopenic purpura (ITP). Serum platelet antibodies were found in thirteen out of twenty-two patients (59 percent) with active disease, but in only four out of fifteen patients (27 percent) who had attained remission. Direct tests for platelet-associated IgG were positive in 36 and 44 percent of these patients respectively. In two cases IgM was observed on the patients' platelet membranes. C3 was not detedted on patients' platelets. Platelet-associated IgG was also found in several other disorders and its occurrence is not therefore diagnostic of ITP. In addition, serum platelet antibodies do not indicate specifically ITP as they may also be due to previous isoimmunization. Antibodies in the sera of patients with ITP generally did not fix Clq and in most cases bound to platelets only in the presence of EDTA. In contrast, isoantibodies often fixed Clq and they had equal affinity for platelets suspended in ACD or EDTA plasma. This was confirmed by quantitative data on IgG binding by platelets obtained by measuring 125-I-labelled protein A uptake. The simplicity of the IF technique permits its routine application and the technique may give useful information with respect to the nature of the antibodies. It must, however, be considered of limited value in the diagnosis of ITP. PMID:6991171

  8. How I treat refractory thrombotic thrombocytopenic purpura

    PubMed Central

    Sayani, Farzana A.

    2015-01-01

    Acquired thrombotic thrombocytopenic purpura (TTP) is characterized by thrombocytopenia and microangiopathic hemolytic anemia (MAHA) without an obvious cause, and may include fever, mild renal failure, and neurologic deficits. It is characterized by a deficiency of the von Willebrand factor (VWF) cleaving enzyme, ADAMTS13 (a disintegrin and metalloproteinase, with a thrombospondin type 1 motif, member 13), resulting in formation of microthrombi in the high sheer environment of the microvasculature. This causes microvascular occlusion, MAHA, and organ ischemia. Diagnosis is based on the presence of clinical symptoms, laboratory aberrations consistent with MAHA, decreased ADAMTS13 activity, and possibly presence of anti-ADAMTS13 autoantibodies. Upfront treatment of acute TTP includes plasma exchange and corticosteroids. A significant number of patients are refractory to this treatment and will require further interventions. There are limited data and consensus on the management of the refractory TTP patient. Management involves simultaneously ruling out other causes of thrombocytopenia and MAHA, while also considering other treatments. In this article, we describe our management of the patient with refractory TTP, and discuss use of rituximab, increased plasma exchange, splenectomy, and immunosuppressive options, including cyclophosphamide, vincristine, and cyclosporine. We also review recent evidence for the potential roles of bortezomib and N-acetylcysteine, and explore new therapeutic approaches, including recombinant ADAMTS13 and anti-VWF therapy. PMID:25784681

  9. Therapeutic splenectomy in immune thrombocytopenic purpura.

    PubMed

    Wani, N A; Parray, F Q

    2000-01-01

    The effects of splenectomy in 41 patients managed from 1982 to 1995 at Sher-i-Kashmir Institute of Medical Sciences, Srinagar (Jammu and Kashmir), India, were studied. Immune thrombocytopenic purpura (ITP) was the main indication for therapeutic splenectomy among all the hematologic disorders. The mean age was 30 years (range 7-64), and the male to female ratio was 1.05:1. The mean platelet count in the preoperative period was 31,751/mm(3) (range 4000-85,000). All patients presented with thrombocytopenia, i.e., platelet count of <100,000/mm(3). In addition, 5 patients presented with anemia, i.e., Hb <10 g%. Among the patients with thrombocytopenia, 30 patients presented with counts <50,000/mm(3) and 11 patients presented with counts between 50,000-100,000/mm(3). None of the patients presented with leukopenia. The morbidity observed was 15% and mortality was 2%. The response to splenectomy was complete for thrombocytopenia in 3 patients and partial in 5 patients; 4 patients failed to show any response. In anemic patients, 4 patients showed complete response and 1 patient showed no response. The prognosis was excellent in patients with platelet count >50,000/mm(3), age <50 years, no concomitant disease, and disease of shorter duration.

  10. Pulmonary Endarterectomy in a Patient with Immune Thrombocytopenic Purpura

    PubMed Central

    Yıldızeli, Bedrettin; Yanartaş, Mehmed; Keskin, Sibel; Atagündüz, Işık; Altınay, Ece

    2015-01-01

    Immune thrombocytopenic purpura (ITP) patients are at high risk for bleeding complications regarding surgeries involving cardiopulmonary bypass. We report an ITP patient with chronic thromboembolic pulmonary hypertension who underwent uncomplicated pulmonary endarterectomy with receiving postoperative intravenous immunoglobulin (IVIG) therapy. The positive outcome of this case may suggest that pulmonary endarterectomy surgery is performed safely for ITP patients. PMID:26090264

  11. Genetics Home Reference: thrombotic thrombocytopenic purpura

    MedlinePlus

    ... purpura also results from a reduction in ADAMTS13 enzyme activity; however, people with the acquired form do not ... activity of the enzyme. A lack of ADAMTS13 enzyme activity disrupts the usual balance between bleeding and clotting. ...

  12. Multivessel Coronary Thrombosis in a Patient with Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Yagmur, Julide; Cansel, Mehmet; Acikgoz, Nusret; Yagmur, Murat; Eyupkoca, Ferhat; Ermis, Necip; Akturk, Erdal

    2012-01-01

    A 49-year-old woman who had idiopathic thrombocytopenic purpura was admitted to our hospital with severe chest pain. Electrocardiography revealed inferolateral myocardial infarction. The patient underwent immediate coronary angiography, which revealed thrombi in the left coronary system. Percutaneous intervention was not indicated, because the thrombi had occluded the distal segments of multiple coronary arteries. Administration of tirofiban satisfactorily dissolved the thrombi. PMID:23304046

  13. Immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection.

    PubMed

    Lai, Shih-Wei; Lin, Hsien-Feng; Lin, Cheng-Li; Liao, Kuan-Fu

    2017-03-01

    Little research focuses on the association between immune thrombocytopenic purpura and human immunodeficiency virus infection in Taiwan. This study investigated whether immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection in Taiwan. We conducted a retrospective population-based cohort study using data of individuals enrolled in Taiwan National Health Insurance Program. There were 5472 subjects aged 1-84 years with a new diagnosis of immune thrombocytopenic purpura as the purpura group since 1998-2010 and 21,887 sex-matched and age-matched, randomly selected subjects without immune thrombocytopenic purpura as the non-purpura group. The incidence of human immunodeficiency virus infection at the end of 2011 was measured in both groups. We used the multivariable Cox proportional hazards regression model to measure the hazard ratio and 95 % confidence interval (CI) for the association between immune thrombocytopenic purpura and human immunodeficiency virus infection. The overall incidence of human immunodeficiency virus infection was 6.47-fold higher in the purpura group than that in the non-purpura group (3.78 vs. 0.58 per 10,000 person-years, 95 % CI 5.83-7.18). After controlling for potential confounding factors, the adjusted HR of human immunodeficiency virus infection was 6.3 (95 % CI 2.58-15.4) for the purpura group, as compared with the non-purpura group. We conclude that individuals with immune thrombocytopenic purpura are 6.47-fold more likely to have human immunodeficiency virus infection than those without immune thrombocytopenic purpura. We suggest not all patients, but only those who have risk factors for human immunodeficiency virus infection should receive testing for undiagnosed human immunodeficiency virus infection when they develop immune thrombocytopenic purpura.

  14. Helicobacter pylori-associated idiopathic thrombocytopenic purpura: a narrative review.

    PubMed

    Franchini, Massimo; Vescovi, Pier Paolo; Garofano, Massimo; Veneri, Dino

    2012-07-01

    The Gram-negative bacterium Helicobacter pylori has a well-demonstrated role in several gastroduodenal diseases, including peptic ulcer disease, chronic active gastritis, mucosa-associated lymphoid tissue lymphoma, and gastric adenocarcinoma. In addition, more recently, several studies have focused on the possible causal role of H. pylori in various extragastric disorders, such as cardiovascular, respiratory, neurological, skin, and autoimmune conditions. The current status of the research on the pathogenesis, clinical and therapeutic aspects of H. pylori-associated idiopathic thrombocytopenic purpura in adults and children will be addressed in this narrative review.

  15. Immunodeficiency-associated thrombocytopenic purpura (IDTP). Response to splenectomy.

    PubMed

    Schneider, P A; Abrams, D I; Rayner, A A; Hohn, D C

    1987-10-01

    Immunodeficiency-associated thrombocytopenic purpura (IDTP) is a feature of the acquired immunodeficiency syndrome--related complex. Current therapeutic modalities for IDTP include splenectomy and the administration of corticosteroids or other agents. Empiric treatment of IDTP has been analogous to that for immunologic thrombocytopenic purpura (ITP). The present report reviews 15 patients who underwent splenectomy for IDTP, demonstrates the successful use of surgical therapy, and defines our indications for splenectomy in the treatment of this disorder. Thirteen of 15 patients had initially failed to respond to steroid therapy. Fourteen patients (93%) initially responded to splenectomy, with platelet counts increasing to 150 X 10(9)/L (150,000/mm3) or greater. A continuing complete response was achieved in nine patients (60%) following splenectomy. After postsurgical adjunctive therapy, durable remission was achieved in 73% (11/15) of the patients. Complications occurred in three patients, and there were no deaths. The mean follow-up was 12.4 months. Splenectomy may be performed in the treatment of IDTP with acceptable morbidity and likelihood of response.

  16. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies.

    PubMed

    Scully, M; Cataland, S; Coppo, P; de la Rubia, J; Friedman, K D; Kremer Hovinga, J; Lämmle, B; Matsumoto, M; Pavenski, K; Sadler, E; Sarode, R; Wu, H

    2017-02-01

    Essentials An international collaboration provides a consensus for clinical definitions. This concerns thrombotic microangiopathies and thrombotic thrombocytopenic purpura (TTP). The consensus defines diagnosis, disease monitoring and response to treatment. Requirements for ADAMTS-13 are given.

  17. Rapid encephalopathy associated with anti-D immune globulin treatment for idiopathic thrombocytopenic purpura.

    PubMed

    Golla, Sunitha; Horkan, Clare; Dogaru, Grigore; Teske, Thomas E; Christopher, Kenneth

    2008-01-01

    Rho (D) immune globulin intravenous (IV RhIG, WinRho SDF) has been shown to be a safe treatment for idiopathic thrombocytopenic purpura. Common side effects of IV RhIG include mild hemolysis, febrile reaction and headache. Significant hemolysis with renal impairment is infrequently noted. A single case of irreversible encephalopathy following IV RhIG has been reported. We report a second case of encephalopathy following an infusion of IV RhIG for treatment of idiopathic thrombocytopenic purpura.

  18. A Case of Immune Thrombocytopenic Purpura Secondary to Pulmonary Tuberculosis

    PubMed Central

    Meher, Lalit Kumar; Dalai, Siba Prasad; Nayak, Sachidananda; Tripathy, Sujit Kumar

    2016-01-01

    The haematological abnormalities associated with active pulmonary tuberculosis were known to human beings since decades but Immune Thrombocytopenic Purpura (ITP) secondary to pulmonary tuberculosis have been reported only in a couple of instances. We report a 27 year-old male patient who was admitted to our hospital with fever, shortness of breath, haematuria, epistaxis and generalized petechiae. The sputum positivity for Acid Fast Bacilli (AFB) and chest X-ray reports were suggestive of active pulmonary tuberculosis in our patient. Clinical and laboratory parameters including bone marrow aspiration cytology diagnosed the case to be ITP. Patient was put on Directly Observed Treatment and Short course (DOTS) category-1 Anti-Tuberculosis Therapy (ATT) and prednisone following which thrombocytopenia was corrected and there was complete recovery of the patient without recurrence of thrombocytopenia. PMID:27891382

  19. Thrombotic thrombocytopenic purpura: three peripartum cases and diagnostic challenges.

    PubMed

    Ab Rahman, Wan Suriana Wan; Abdullah, Wan Zaidah; Mustaffa, Rapiaah; Ahmed, Suhair Abbas; Hassan, Mohd Nazri; Husin, Azlan

    2013-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a medical emergency characterized by occlusive microangiopathy due to intravascular platelet aggregation. This event results in damage to the red blood cells (RBCs) known as microangiopathic hemolytic anemia (MAHA). Schistocytes are circulating fragments of damaged RBCs that have different morphological features including keratocytes, helmet cells, and spherocytes. It is critical to report even a small number of these abnormal RBCs in the peripheral blood and to be alert for the possible diagnosis of TTP, especially in unexplained anemia and thrombocytopenia. The application of pentad criteria in the diagnosis has been reviewed, and the challenges still remained on the hematologic evidence of this disorder. In the 3 cases discussed here, the red cell morphological diagnosis gave an impact on TTP diagnosis, but overdiagnosis might be encountered in obstetrical patients due to nonspecific diagnostic criteria.

  20. Thrombotic thrombocytopenic purpura: a syndrome of intravascular platelet consumption.

    PubMed Central

    Neame, P. B.; Hirsh, J.; Browman, G.; Denburg, J.; D'Souza, T. J.; Gallus, A.; Brain, M. C.

    1976-01-01

    In four of five patients with thrombotic thrombocytopenic purpura (TTP) in whom serial tests of hemostatic function were performed, severe thrombocytopenia, normal plasma fibrinogen concentrations and mildly increased concentrations of fibrinogen/fibrin degradation products were observed. Widespread platelet thrombi were found in arterioles and capillaries. Fibrin could be seen around some of the platelet clumps and was the main component in a small number of the thrombi in two patients. The observations show that TTP is a disorder in which intravascular platelet consumption results in disseminated platelet thrombosis. The coagulation system is apparently activated secondarily to platelet aggregation and variable quantities of fibrin are incorporated into the thrombi. Clinical improvement resulted from combined therapy with corticosteroids, heparin and drugs that suppress platelet function. Images FIG. 3 FIG. 4 FIG. 5 FIG. 6 PMID:1084215

  1. Thrombotic Thrombocytopenic Purpura: Three Peripartum Cases and Diagnostic Challenges

    PubMed Central

    Ab Rahman, Wan Suriana Wan; Abdullah, Wan Zaidah; Mustaffa, Rapiaah; Ahmed, Suhair Abbas; Hassan, Mohd Nazri; Husin, Azlan

    2013-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a medical emergency characterized by occlusive microangiopathy due to intravascular platelet aggregation. This event results in damage to the red blood cells (RBCs) known as microangiopathic hemolytic anemia (MAHA). Schistocytes are circulating fragments of damaged RBCs that have different morphological features including keratocytes, helmet cells, and spherocytes. It is critical to report even a small number of these abnormal RBCs in the peripheral blood and to be alert for the possible diagnosis of TTP, especially in unexplained anemia and thrombocytopenia. The application of pentad criteria in the diagnosis has been reviewed, and the challenges still remained on the hematologic evidence of this disorder. In the 3 cases discussed here, the red cell morphological diagnosis gave an impact on TTP diagnosis, but overdiagnosis might be encountered in obstetrical patients due to nonspecific diagnostic criteria. PMID:24093001

  2. Thrombotic thrombocytopenic purpura: diagnosis, pathogenesis and modern therapy.

    PubMed

    Eldor, A

    1998-06-01

    Thrombotic thrombocytopenic purpura (TTP) is an uncommon multisystem disorder, sometimes associated with predisposing conditions such as pregnancy, cancer, exposure to certain drugs, bone marrow transplantation and HIV-1 infection. An abnormal interaction between the vascular endothelium and platelets which occurs in certain organs leads to thrombosis, endothelial proliferation, minimal inflammation and micro-angiopathic haemolysis. Recent studies suggest that endothelial cell perturbation and apoptosis caused by an as yet unknown plasma factor(s) may lead to the release of abnormal von Willebrand factor which facilitates the deposition of platelet microthrombi. Exchange transfusions of plasma or plasma-cryosupernatant remain the cornerstone of the treatment of TTP along with corticosteroids, platelet inhibitor drugs, vincristine and splenectomy. In most cases remissions can be attained, and cures are now common-although approximately one-half of the patients will relapse. While relapses are usually milder, they still carry a significant mortality and preventive therapies are not always effective.

  3. [Thrombotic Thrombocytopenic Purpura --Pathophysiology and Assays of ADAMTS13 Activity].

    PubMed

    Kato, Seiji; Fujimura, Yoshihiro

    2015-10-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder classified with a type of thrombotic microangiopathy (TMA). TTP is caused by a deficiency of von Willebrand factor-cleaving protease called ADAMTS13 (a disintegrin-like and metalloprotease with a thrombospondin type1 motif 13). Low ADAMTS13 levels result in increased ultra-large von Willebrand factor multimers (UL-VWFM), which induce platelet adhesion and thrombosis. Congenital TTP (Upshaw-Schulman syndrome: USS) is an inherited disorder of ADAMTS13, and the other more commonly is an acquired TTP caused by autoantibodies against ADAMTS13. This article reviews the progress of ADAMTS13 activity measurement and the resulting changes in the diagnosis and treatment of TTP.

  4. ADAMTS13 and von Willebrand factor in thrombotic thrombocytopenic purpura.

    PubMed

    Zheng, X Long

    2015-01-01

    Pathogenesis of thrombotic thrombocytopenic purpura (TTP) was a mystery for over half a century until the discovery of ADAMTS13. ADAMTS13 is primarily synthesized in the liver, and its main function is to cleave von Willebrand factor (VWF) anchored on the endothelial surface, in circulation, and at the sites of vascular injury. Deficiency of plasma ADAMTS13 activity (<10%) resulting from mutations of the ADAMTS13 gene or autoantibodies against ADAMTS13 causes hereditary or acquired (idiopathic) TTP. ADAMTS13 activity is usually normal or modestly reduced (>20%) in other forms of thrombotic microangiopathy secondary to hematopoietic progenitor cell transplantation, infection, and disseminated malignancy or in hemolytic uremic syndrome. Plasma infusion or exchange remains the initial treatment of choice to date, but novel therapeutics such as recombinant ADAMTS13 and gene therapy are under development. Moreover, ADAMTS13 deficiency has been shown to be a risk factor for the development of myocardial infarction, stroke, cerebral malaria, and preeclampsia.

  5. [A case of thrombotic thrombocytopenic purpura with systemic lupus erythematosus].

    PubMed

    Ogawa, Yayoi; Mukai, Masaya; Gotoh, Hideki; Tanaka, Satoshi; Takada, Akio; Takenouchi, Toshinao

    2006-10-01

    We described a case of thrombotic thrombocytopenic purpura (TTP) with systemic lupus erythematosus (SLE). A-60-year old woman was admitted to our hospital because of fever, disconsciousness, and general fatigue. 32 years ago, she was diagnosed as SLE with Raynaud's phenomenon, rash, photosensitivity, arthritis, lymphocytopenia, and ANA. Her SLE was well controlled with 10 mg predonisolone as a maintance dose until several weeks ago. On admission, severe thrombocytopenia (0.7x10(4)/microl) and other laboratory data revealed microangiopathic hemolytic anemia and renal dysfunction, Immediately after diagnosed as TTP, plasma exchange and corticosteroid therapy started. In spite of the treatment, disconsciousness progressed and systemic convulsion occurred and died 4 days after admission. Autopsied examination revealed diffuse microvascular hyalinized thrombi in heart, kidney, liver, spleen, and pancreas. Some microvascular thrombi were detected in lymph nodes, bone marrow, intestine. Pathological diagnosis of TTP was made on microvascular hyalinized platelet thrombi in organs. Von Willebrand factor-cleaving protease (VWF-CP) activity in plasma on set is less than 0.5 percent of normal and inhibitor for VWF-CP was detected. We here report a valuable case for analysis of pathogenesis in SLE-TTP.

  6. Changes in splenic microcirculatory pathways in chronic idiopathic thrombocytopenic purpura.

    PubMed

    Schmidt, E E; MacDonald, I C; Groom, A C

    1991-09-15

    The spleen plays a central role in the pathogenesis of chronic idiopathic thrombocytopenic purpura (ITP); it produces massive quantities of antiplatelet antibodies, leading to accelerated phagocytosis of platelets. Lymphoid hyperplasia typically occurs in the spleen, characterized by large numbers of lymphatic nodules with active germinal centers. Whether changes in splenic microcirculatory pathways also occur is not known. We have studied this question by scanning electron microscopy of corrosion casts, comparing spleens removed from patients with ITP with normal spleens obtained from organ transplant donors. The casts demonstrate two major changes in microcirculatory pathways in ITP. Firstly, a striking proliferation of arterioles and capillaries is found in the white pulp and marginal zone (MZ), seen as extensive vascularization in 92.3% of lymphatic nodules (n = 191) versus 0.6% (n = 224) in normal spleens. Secondly, the marginal sinus, a series of flattened, anastomosing vascular spaces between the white pulp and MZ, is absent in 89.4% of lymphatic nodules versus 4.9% in normal spleens. The cause of these microcirculatory changes, which may not be exclusive to ITP, is presently unknown. Absence of the marginal sinus may affect distribution of blood flow through the MZ such that platelets spend increased amounts of time in the proximity of macrophages. In the presence of antiplatelet antibodies found in ITP spleens, this delayed transit would lead to greatly increased platelet destruction.

  7. Thrombotic thrombocytopenic purpura: from platelet aggregates to plasma.

    PubMed

    Marques, Marisa B; Mayfield, Charles A; Blackall, Douglas P

    2004-06-01

    Thrombotic thrombocytopenic purpura (TTP) is a syndrome of severe thrombocytopenia and microangiopathic hemolytic anemia without an alternative explanation. Although some patients also have a combination of fever and neurologic and/or renal manifestations, these are not required for the diagnosis. Thus, plasmapheresis should start as soon as TTP is placed high in the differential diagnosis to prevent significant mortality. Histopathologically, TTP is characterized by widespread platelet thrombi in the microcirculation. Ultralarge von Willebrand factor (vWf) multimers found in the patient's plasma are the basis for the platelet thrombi. Recent evidence has linked the abnormal fragments of vWf with deficiency of a plasma enzyme named vWf-cleaving protease, or ADAMTS-13. While a small percentage of patients with TTP have a constitutional defect in this enzyme, many with the acute idiopathic form have an antibody to ADAMTS-13, affecting its ability to cleave vWf. The determination of the enzyme activity and the presence of its inhibitor have emerged as a potential tool in the diagnosis and prognosis of TTP. Furthermore, it helps to differentiate TTP from the hemolytic uremic syndrome, in which the level of ADAMTS-13 is expected to be normal or only slightly decreased.

  8. Platelet antibody in prolonged remission of childhood idiopathic thrombocytopenic purpura

    SciTech Connect

    Ware, R.; Kinney, T.R.; Rosse, W.

    1985-11-01

    Evaluations were performed in 20 patients with childhood idiopathic thrombocytopenic purpura (ITP) who remained in remission longer than 12 months. The mean duration of follow-up from diagnosis was 39 months (range 17 to 87 months). Eleven patients (four girls) in group 1 had an acute course of ITP, defined as platelet count greater than 150 X 10(9)/L within 6 months of diagnosis. Nine patients (five girls) in group 2 had a chronic course, defined as platelet count less than 150 X 10(9)/L for greater than or equal to 1 year or requiring splenectomy in an attempt to control hemorrhagic symptoms. Platelet count and serum (indirect) platelet-associated IgG (PAIgG) levels were normal in all 20 patients at follow-up. Both direct and indirect PAIgG levels were measured using a SVI-monoclonal anti-IgG antiglobulin assay. All had normal direct PAIgG levels, except for one patient in group 1 who had a borderline elevated value of 1209 molecules per platelet. These data suggest that the prevalence of elevated platelet antibodies is low during sustained remission without medication in patients with a history of childhood ITP. These data may be relevant for pregnant women with a history of childhood ITP, with regard to the risk of delivering an infant with thrombocytopenia secondary to transplacental passage of maternal platelet antibody.

  9. Platelet antibody in idiopathic thrombocytopenic purpura and other thrombocytopenias

    SciTech Connect

    Sugiura, K.; Steiner, M.; Baldini, M.G.

    1980-10-01

    Platelet-associated immunoglobulin was measured by the use of fluorescent anti-1gG antibody. The method is simple, rapid, and sensitive and provides a precise quantitive assay of bound (direct) and free (indirect) 1gG with platelet specificity. We have evaluated this test in 30 normal volunteers and in 50 patients with immune and nonimmune, treated and untreated thrombocytopenias. All patients with immune thrombocytopenias (acute and chronic idiopathic thrombocytopenic purpura and systemic lupus erythematosus) having platelet counts < 100,000/..mu..l had elevated levels of platelet-bound 1gG and 86% had also positive results in the indirect assay. All patients with nonimmunological thrombocytopenias showed normal results in the direct and indirect assay of platelet-associated immunoglobulin. In patients studied repeatedly during the course of their illness, an inverse relation was found between platelet count and level of platelet-bound 1gG. Patients with systemic lupus erythematosus presented clear exceptions to this rule. Investigations of the absorbability of platelet autoantibodies and alloantibodies showed that this assay can readily differentiate between these two antibody species and can also identify specificities of alloantibodies.

  10. Takotsubo cardiomyopathy and thrombotic thrombocytopenic purpura preceding a lupus diagnosis: a case report.

    PubMed

    Georgiades, F; Demosthenous, S; Braimi, M; Tsitskari, T; Psarelis, S

    2015-11-01

    Takotsubo cardiomyopathy, a rare stress-related cardiomyopathy, has been observed in a few cases secondary to systemic lupus erythematosus (SLE). Herein, we report an unusual case where a postmenopausal woman presented initially with Takotsubo syndrome, later developed thrombotic thrombocytopenic purpura and cerebrovascular events, initially without clinical or laboratory features of SLE. During the course of her illness, she was found to satisfy four of the Systemic Lupus International Collaborating Clinics classification criteria for a SLE diagnosis. This unique presentation of our patient, initially with Takotsubo cardiomyopathy, the development of thrombotic thrombocytopenic purpura and cerebrovascular events preceding the diagnosis of SLE illustrates the importance of clinical observation and follow-up.

  11. Risk Factors for Autoimmune Diseases Development After Thrombotic Thrombocytopenic Purpura.

    PubMed

    Roriz, Mélanie; Landais, Mickael; Desprez, Jonathan; Barbet, Christelle; Azoulay, Elie; Galicier, Lionel; Wynckel, Alain; Baudel, Jean-Luc; Provôt, François; Pène, Frédéric; Mira, Jean-Paul; Presne, Claire; Poullin, Pascale; Delmas, Yahsou; Kanouni, Tarik; Seguin, Amélie; Mousson, Christiane; Servais, Aude; Bordessoule, Dominique; Perez, Pierre; Chauveau, Dominique; Veyradier, Agnès; Halimi, Jean-Michel; Hamidou, Mohamed; Coppo, Paul

    2015-10-01

    Autoimmune thrombotic thrombocytopenic purpura (TTP) can be associated with other autoimmune disorders, but their prevalence following autoimmune TTP remains unknown. To assess the prevalence of autoimmune disorders associated with TTP and to determine risk factors for and the time course of the development of an autoimmune disorder after a TTP episode, we performed a cross sectional study. Two-hundred sixty-one cases of autoimmune TTP were included in the French Reference Center registry between October, 2000 and May, 2009. Clinical and laboratory data available at time of TTP diagnosis were recovered. Each center was contacted to collect the more recent data and diagnosis criteria for autoimmunity. Fifty-six patients presented an autoimmune disorder in association with TTP, 9 years before TTP (median; min: 2 yr, max: 32 yr) (26 cases), at the time of TTP diagnosis (17 cases) or during follow-up (17 cases), up to 12 years after TTP diagnosis (mean, 22 mo). The most frequent autoimmune disorder reported was systemic lupus erythematosus (SLE) (26 cases) and Sjögren syndrome (8 cases). The presence of additional autoimmune disorders had no impact on outcomes of an acute TTP or the occurrence of relapse. Two factors evaluated at TTP diagnosis were significantly associated with the development of an autoimmune disorder during follow-up: the presence of antidouble stranded (ds)DNA antibodies (hazard ratio (HR): 4.98; 95% confidence interval (CI) [1.64-15.14]) and anti-SSA antibodies (HR: 9.98; 95% CI [3.59-27.76]). A follow-up across many years is necessary after an acute TTP, especially when anti-SSA or anti-dsDNA antibodies are present on TTP diagnosis, to detect autoimmune disorders early before immunologic events spread to prevent disabling complications.

  12. Risk Factors for Autoimmune Diseases Development After Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Roriz, Mélanie; Landais, Mickael; Desprez, Jonathan; Barbet, Christelle; Azoulay, Elie; Galicier, Lionel; Wynckel, Alain; Baudel, Jean-Luc; Provôt, François; Pène, Frédéric; Mira, Jean-Paul; Presne, Claire; Poullin, Pascale; Delmas, Yahsou; Kanouni, Tarik; Seguin, Amélie; Mousson, Christiane; Servais, Aude; Bordessoule, Dominique; Perez, Pierre; Chauveau, Dominique; Veyradier, Agnès; Halimi, Jean-Michel; Hamidou, Mohamed; Coppo, Paul

    2015-01-01

    Abstract Autoimmune thrombotic thrombocytopenic purpura (TTP) can be associated with other autoimmune disorders, but their prevalence following autoimmune TTP remains unknown. To assess the prevalence of autoimmune disorders associated with TTP and to determine risk factors for and the time course of the development of an autoimmune disorder after a TTP episode, we performed a cross sectional study. Two-hundred sixty-one cases of autoimmune TTP were included in the French Reference Center registry between October, 2000 and May, 2009. Clinical and laboratory data available at time of TTP diagnosis were recovered. Each center was contacted to collect the more recent data and diagnosis criteria for autoimmunity. Fifty-six patients presented an autoimmune disorder in association with TTP, 9 years before TTP (median; min: 2 yr, max: 32 yr) (26 cases), at the time of TTP diagnosis (17 cases) or during follow-up (17 cases), up to 12 years after TTP diagnosis (mean, 22 mo). The most frequent autoimmune disorder reported was systemic lupus erythematosus (SLE) (26 cases) and Sjögren syndrome (8 cases). The presence of additional autoimmune disorders had no impact on outcomes of an acute TTP or the occurrence of relapse. Two factors evaluated at TTP diagnosis were significantly associated with the development of an autoimmune disorder during follow-up: the presence of antidouble stranded (ds)DNA antibodies (hazard ratio (HR): 4.98; 95% confidence interval (CI) [1.64–15.14]) and anti-SSA antibodies (HR: 9.98; 95% CI [3.59–27.76]). A follow-up across many years is necessary after an acute TTP, especially when anti-SSA or anti-dsDNA antibodies are present on TTP diagnosis, to detect autoimmune disorders early before immunologic events spread to prevent disabling complications. PMID:26496263

  13. Platelet-associated complement C3 in immune thrombocytopenic purpura

    SciTech Connect

    Myers, T.J.; Kim, B.K.; Steiner, M.; Baldini, M.G.

    1982-05-01

    Platelet-associated C3 (PA-C3) was measured with a quantitative immunofluorescence assay. With this assay, PA-C3 levels were determined for 78 normal volunteers, 30 patients with immune thrombocytopenic purpura (ITP), and 20 patients with nonimmune thrombocytopenias. Platelet-associatd IgG (PA-lgG) levels were also measured with our standard quantitative immunofluorescence assay. All patients with nonimmune thrombocytopenias and ITP in remission had normal PA-C3 levels. Twenty-four patients with active ITP wre classified into 3 groups: 9 (38%) with increased PA-IgG and normal PA-C3 levels, 10 (42%) with elevated PA-C3 and PA-IgG levels, and 5 (20%) with increased PA-C3 values only. A direct correlation was found between PA-C3 and PA-IgG levels. PA-IgG levels were higher in the group of patients with elevated PA-C3 levels than in those with normal values. Platelet survival studies showed reduced survival times of 1.5-2.5 days for the 5 patients with elevated PA-C3 levels only. Elevated PA-C3 levels returned to normal in 7 ITP patients whose platelet counts increased in response to corticosteriod therapy or to splenectomy. Therefore, PA-C3 and PA-IgG assays can be used to identify patients with ITP, to follow their response to therapy, and to classify them into immunologic subgroups similar to red cell classifiation by Coombs' testing in immune hemolytic anemia.

  14. Hand-assisted laparoscopic splenectomy for idiopathic thrombocytopenic purpura during pregnancy.

    PubMed

    Iwase, K; Higaki, J; Yoon, H E; Mikata, S; Tanaka, Y; Takahashi, T; Hatanaka, K; Tamaki, T; Hori, S; Mitsuda, N; Kamiike, W

    2001-02-01

    A successful case of a hand-assisted laparoscopic splenectomy with low-pressure pneumoperitoneum for autoimmune thrombocytopenic purpura in a patient at 23 weeks' gestation is reported. Preoperative splenic arterial embolization was performed on the same day as the operation using painless contour embolic material and super-absorbent polymer microspheres. The abdominal wall retraction method first was applied to avoid the effects of pneumoperitoneum on systemic hemodynamic alterations. However, a sufficient surgical view could not be obtained, as the intra-abdominal organs were elevated because of the enlarged uterus. A surgical view with 4 to 6-mm Hg pneumoperitoneum was available for the hand-assisted splenectomy. The postoperative course was uneventful, and the patient vaginally delivered a healthy infant. A hand-assisted laparoscopic splenectomy with low-pressure pneumoperitoneum after splenic arterial embolization would be feasible for patients with autoimmune thrombocytopenic purpura during a relatively advanced pregnancy.

  15. Cerebral venous thrombosis after immune thrombocytopenic purpura and anti-D immune globulin therapy.

    PubMed

    Kayyali, Husam R; Abdelmoity, Ahmed T; Morriss, M Craig; Graf, William D

    2008-03-01

    Cerebral venous thrombosis has multiple etiologies and a wide variety of clinical manifestations. This article reports on a young girl who developed cerebral venous thrombosis after intravenous anti-D immune globulin therapy for immune thrombocytopenic purpura. In this case, venous infarction was manifested by an unusual pattern of restricted diffusion limited to the corpus callosum. The cause of cerebral venous thrombosis in this patient may be related to both immune thrombocytopenia and immunoglobulin therapy.

  16. Thrombotic thrombocytopenic purpura and focal segmental glomerulosclerosis associated with the use of ecstasy

    PubMed Central

    Kayar, Yusuf; Kayar, Nuket Bayram; Gangarapu, Venkatanarayana

    2015-01-01

    Ecstasy is a drug, which causes serious side effects and sometimes it can be lethal. These effects are due to idiosyncratic reactions as a result of various stimulations in adrenergic receptors. Here we present a case of a 36-year-old male patient who was diagnosed with thrombotic thrombocytopenic purpura associated with the use of ecstasy. Plasmapheresis along with methylprednisolone treatment restores patient condition to normal. PMID:25878432

  17. Differentiation between severe HELLP syndrome and thrombotic microangiopathy, thrombotic thrombocytopenic purpura and other imitators.

    PubMed

    Pourrat, O; Coudroy, R; Pierre, F

    2015-06-01

    Pre-eclampsia complicated by severe HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome is a multi-organ disease, and can be difficult to differentiate from thrombotic microangiopathy (appearing as thrombotic thrombocytopenic purpura or hemolytic uremic syndrome), acute fatty liver, systemic erythematous lupus, antiphospholipid syndrome and severe sepsis. Many papers have highlighted the risks of misdiagnosis resulting in severe consequences for maternal health, and this can be fatal when thrombotic thrombocytopenic purpura is misdiagnosed as severe HELLP syndrome. The aim of this paper is to propose relevant markers to differentiate pre-eclampsia complicated by severe HELLP syndrome from its imitators, even in the worrying situation of apparently indistinguishable conditions, and thereby assist clinical decision-making regarding whether or not to commence plasma exchange. Relevant identifiers to establish the most accurate diagnosis include the frequency of each disease and anamnestic data. Frank hemolysis, need for dialysis, neurological involvement and absence of disseminated intravascular coagulation are indicative of thrombotic microangiopathy. The definitive marker for thrombotic thrombocytopenic purpura is undetectable ADAMTS 13 activity.

  18. Immune Thrombocytopenic Purpura and Gastritis by H. pylori Associated With Type 1 Diabetes Mellitus

    PubMed Central

    Correa, Ricardo; Flores-Guevara, Igor; Espinoza Morales, Frank; Mejia, Christian R

    2016-01-01

    We present the 15th case reported worldwide and 3rd case reported in Latin America of immune thrombocytopenic purpura associated with Type 1 diabetes mellitus in Scopus, MEDLINE, and SciELO. An 11-year-old male patient of mixed ethnicity with immune thrombocytopenic purpura, Type 1 diabetes mellitus, and gastritis due to H. pylori presented to the emergency room with petechiae, ecchymosis, and gingival and conjunctival bleeding that had been worsening for the past three months. The patient had a body mass index of 18.85 kg/m2 (P75). A biochemical analysis showed 1×109 platelets/L, increased prothrombin time, increased partial thromboplastin time, and an HbA1C of 7.84% on admission. He was prescribed a single dose of intravenous methylprednisolone 750 mg in 100 mL of NaCl and daily oral 50 mg prednisolone, with intravenous 250 mg tranexamic acid every eight hours. The patient’s glycemic control was continued with the administration of insulin glargine (30 units every 24 hours) and prandial insulin glulisine (five to eight units per meal). Before admission, the patient was on a prescribed treatment of sitagliptin 50 mg and metformin 850 mg, but this was suspended in the emergency room. For the eradication of H. pylori he was prescribed amoxicillin 500 mg every eight hours, oral clarithromycin 335 mg every 12 hours, and IV omeprazole 40 mg. After 15 days, he showed disease resolution and he was discharged to his home with orders to follow-up with pediatrics, hematology, and endocrinology services. The first-line treatment for immune thrombocytopenic purpura patients with active bleeding and a platelet count < 30,000 platelets/μl is the administration of corticosteroids and inmunoglobulin. PMID:27026836

  19. Immune Thrombocytopenic Purpura and Gastritis by H. pylori Associated With Type 1 Diabetes Mellitus.

    PubMed

    Culquichicón-Sánchez, Carlos; Correa, Ricardo; Flores-Guevara, Igor; Espinoza Morales, Frank; Mejia, Christian R

    2016-02-24

    We present the 15th case reported worldwide and 3rd case reported in Latin America of immune thrombocytopenic purpura associated with Type 1 diabetes mellitus in Scopus, MEDLINE, and SciELO. An 11-year-old male patient of mixed ethnicity with immune thrombocytopenic purpura, Type 1 diabetes mellitus, and gastritis due to H. pylori presented to the emergency room with petechiae, ecchymosis, and gingival and conjunctival bleeding that had been worsening for the past three months. The patient had a body mass index of 18.85 kg/m(2) (P75). A biochemical analysis showed 1×10(9) platelets/L, increased prothrombin time, increased partial thromboplastin time, and an HbA1C of 7.84% on admission. He was prescribed a single dose of intravenous methylprednisolone 750 mg in 100 mL of NaCl and daily oral 50 mg prednisolone, with intravenous 250 mg tranexamic acid every eight hours. The patient's glycemic control was continued with the administration of insulin glargine (30 units every 24 hours) and prandial insulin glulisine (five to eight units per meal). Before admission, the patient was on a prescribed treatment of sitagliptin 50 mg and metformin 850 mg, but this was suspended in the emergency room. For the eradication of H. pylori he was prescribed amoxicillin 500 mg every eight hours, oral clarithromycin 335 mg every 12 hours, and IV omeprazole 40 mg. After 15 days, he showed disease resolution and he was discharged to his home with orders to follow-up with pediatrics, hematology, and endocrinology services. The first-line treatment for immune thrombocytopenic purpura patients with active bleeding and a platelet count < 30,000 platelets/μl is the administration of corticosteroids and inmunoglobulin.

  20. Plateletpheresis for postsplenectomy rebound thrombocytosis in a patient with chronic immune thrombocytopenic purpura on romiplostim.

    PubMed

    Raval, Jay S; Redner, Robert L; Kiss, Joseph E

    2013-08-01

    Immune thrombocytopenic purpura (ITP) is an autoimmune disease in which IgG-coated platelets are removed from circulation by the spleen, and platelet production is impaired due to increased thrombopoietin (TPO) clearance. Romiplostim, a novel TPO-mimetic agent, is approved for patients with ITP that are unresponsive to traditional treatments. However, there is little experience when using this drug before splenectomy. We describe herein the case of a young female with chronic ITP who was treated with romiplostim, underwent splenectomy shortly thereafter, and required plateletpheresis for postoperative rebound thrombocytosis with concomitant neurologic symptoms.

  1. Severe Thrombocytopenic Purpura in a Child with Brucellosis: Case Presentation and Review of the Literature

    PubMed Central

    Perogiannaki, Aikaterini; Chaliasos, Nikolaos

    2017-01-01

    Brucellosis is still endemic and a significant public health problem in many Mediterranean countries, including Greece. It is a multisystemic disease with a broad spectrum of clinical manifestations including hematological disorders, such as anemia, pancytopenia, leucopenia, and thrombocytopenia. Thrombocytopenia is usually moderate and attributed to bone marrow suppression or hypersplenism. Rarely, autoimmune stimulation can cause severe thrombocytopenia with clinically significant hemorrhagic manifestations. We present the case of a girl with severe thrombocytopenic purpura as one of the presenting symptoms of Brucella melitensis infection. Treatment with intravenous immunoglobulin and the appropriate antimicrobial agents promptly resolved the thrombocyte counts. A review of similar published cases is also presented. PMID:28127481

  2. Thrombotic thrombocytopenic purpura associated with metastatic gastric adenocarcinoma: successful management with plasmapheresis.

    PubMed

    Carr, D J; Kramer, B S; Dragonetti, D E

    1986-04-01

    A patient with metastatic gastric adenocarcinoma had progressive microangiopathic red blood cell changes, thrombocytopenia with increased marrow megakaryocytes, bleeding, altered mentation, and seizure. Coagulation parameters were inconsistent with disseminated intravascular coagulation; a clinical diagnosis of thrombotic thrombocytopenic purpura (TTP) was made. Plasmapheresis resulted in improvement on two separate occasions. The diagnosis of tumor-associated TTP should be considered in cancer patients. Plasmapheresis may be more effective than plasma transfusion alone in this syndrome, perhaps via removal of tumor-induced immune complexes from the circulation. Aggressive management of this complication seems justified in cancer patients for whom effective chemotherapy exists.

  3. Stroke due to typical thrombotic thrombocytopenic purpura treated successfully with intravenous thrombolysis and therapeutic plasma exchange

    PubMed Central

    Boattini, Matteo; Procaccianti, Gaetano

    2013-01-01

    We report a case of a 39-year-old man with expressive aphasia due to occlusion of the temporal stem of the left middle cerebral artery. Laboratory tests showed microangiopathic haemolytic anaemia and thrombocytopenia. A thrombotic thrombocytopenic purpura (TTP) was diagnosed, and thrombolytic therapy (TT) with alteplase followed by therapeutic plasma exchange (TPE) were performed with complete resolution of symptoms. The gold standard TTP treatment is TPE, and its delay can be lethal. The use of TT in TTP is controversial and has potential risks. This case shows a successful TT in a patient with typical TTP presenting as a stroke due to a large cerebral artery occlusion. PMID:23362068

  4. Clopidogrel-Associated Thrombotic Thrombocytopenic Purpura following Endovascular Treatment of Spontaneous Carotid Artery Dissection

    PubMed Central

    Rubano, Jerry A.; Chen, Kwan; Sullivan, Brianne; Vosswinkel, James A.; Jawa, Randeep S.

    2015-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening multisystem disease secondary to platelet aggregation. We present a patient who developed profound thrombocytopenia and anemia 8 days following initiation of therapy with clopidogrel after stent placement for carotid artery dissection. She did not have a disintegrin and metalloproteinase with thrombospondin domain 13 (ADAMTS 13) deficiency. Management included steroids and therapeutic plasma exchange. Clopidogrel has rarely been associated with TTP. Unlike other causes of acquired TTP, the diagnosis of early clopidogrel-associated TTP is largely clinical given the infrequent reduction in ADAMTS 13 activity. PMID:26623244

  5. [Protocol for the study and treatment of immune thrombocytopenic purpura (ITP). ITP-2010].

    PubMed

    Monteagudo, E; Fernández-Delgado, R; Sastre, A; Toll, T; Llort, A; Molina, J; Astigarraga, I; Dasí, M A; Cervera, A

    2011-06-01

    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.

  6. Regulatory T Cells in Patients with Idiopathic Thrombocytopenic Purpura.

    PubMed

    Akyol Erikçi, Alev; Karagöz, Bülent; Bilgi, Oğuz

    2016-06-05

    Amaç: İmmün trombositopenik purpura (İTP) trombositlerin otoantikorlar tarafından opsonize edildiği ve retiküloendotelyal sistem tarafından Fc reseptör aracılı fagositoz ile dalakta yıkıldığı immün kaynaklı bir kanama bozukluğudur. Bu bozukluğun patogenezinde otoimmün süreçler de sorumlu tutulmaktadır. CD4+CD25+Foxp3+ regulatuvar T (Treg) hücreleri ve CD8+CD28- Treg hücreler otoimmün hastalıklarda rol oynamaktadır. Çalışmamızda İTP’li hastalarda bu regülatuvar hücreleri araştırdık. Gereç ve Yöntemler: İTP’li 22 hasta ile yaş uyumlu 16 sağlıklı birey dahil edildi. CD4+CD25+Foxp3+ Treg hücreler ve CD8+CD28- hücreler üç renkli akım sitometri ile çalışıldı. Bu hücre popülasyonunun tüm lenfositlere oranı hesaplanmıştır. İstatiktiksel değerlendirmede Mann-Whitney U testi kullanılmıştır. Bulgular: CD4+CD25+ Treg hücreler İTP’de ve kontrol grubunda %9,69±3,70 ve %12,99±5,58 saptandılar. CD4+CD25 yüksek FoxP3+ hücreler ise İTP’de ve kontrol grubunda %27,72±19,74 ve %27,55±23,9 olarak saptandı. Her iki hücre tipi de kontrol grubu ile karşılaştırıldığında istatiktiksel olarak anlamlı bulunmamıştır. Sonuç: Lenfositlerdeki CD4+CD25+Foxp3+ Treg hücreler ve CD8+CD28- T hücrelerdeki oranlarında fark bulamadık. Biz çalışmamızda İTP’de dolaşan regulatuvar hücrelerde fark bulamadık ama daha geniş kapsamlı çalışmalara ihtiyaç vardır.

  7. Rotavirus-associated immune thrombocytopenic purpura in children: A retrospective study.

    PubMed

    Ai, Qi; Yin, Jing; Chen, Sen; Qiao, Lijin; Luo, Na

    2016-10-01

    Certain studies have previously indicated that an association may exist between rotavirus infection and primary immune thrombocytopenic purpura (ITP). The present retrospective study aimed to investigate whether rotavirus may cause ITP in children. Firstly, the incidence of ITP in children with or without rotavirus diarrhea was compared. A 14.58% incident rate was observed in children with rotavirus diarrhea compared with a 7.22% incident rate in children without rotavirus diarrhea. Subsequently, the clinical features of ITP children with or without rotavirus infection were compared. The results indicated that ITP children with rotavirus infection were significantly younger, showed significantly decreased mean platelet volume (MPV) levels and presented a significantly higher frequency of bleeding score of 3 against ITP children without rotavirus infection. In conclusion, these findings suggest that rotavirus serves a causative role in ITP.

  8. [Treatment of a pregnant patient after multiple trauma: rare combination with thrombotic thrombocytopenic purpura].

    PubMed

    Haffner, E; Pietsch, U; Fösel, T; Lindemann, W

    2013-02-01

    Multiple trauma during pregnancy is a relatively rare situation which poses a great challenge for the team in charge of treatment. A concomitant disease, such as thrombotic thrombocytopenic purpura (TTP) with thrombocytic coagulopathy increases the complexity of the treatment problems. This article describes the case of a 36-year-old pregnant woman referred to this hospital suffering from multiple trauma with severe liver rupture. Stabilization was achieved after an emergency Caesarean section and packing of the liver. Recurrent massive bleeding from the liver occurred after depacking and was treated successfully with recombinant factor VIIa. The concomitant TTP was treated by transfusion of fresh frozen plasma and corticosteroids. Rapid initiation of therapy was the goal to achieve hemostasis and prevent aggravation of the coagulation disorder and an unfavourable outcome despite severe thrombocytopenia.

  9. Spontaneous bilateral peripapillary, subhyaloid and vitreous hemorrhage with only minor platelet deficit in idiopathic thrombocytopenic purpura.

    PubMed

    Wan-Wei, Loo; Tengku-Norina, Tuan-Jaffar; Azma-Azalina, Ahmad-Alwi; Zulkifli, Abdul-Ghani; Zunaina, Embong

    2014-01-01

    A 45-year-old female with underlying idiopathic thrombocytopenic purpura (ITP) complained of acute onset of reduced vision and floaters, in both eyes, for 3 weeks. Visual acuity was 6/36 and 6/60 in the right eye and left eye, respectively. Ophthalmoscopy showed bilateral peripapillary, subhyaloid and vitreous hemorrhage. Hematological evaluation revealed moderate anemia (hemoglobin: 93 g/L) and mild thrombocytopenia (platelets: 120×10(9)/L). She was co-managed by a hematologist and ophthalmologists; she was treated medically. Follow-up care during the next 6 weeks revealed spontaneous, partially resolving hemorrhage, with improvement of visual acuity. The purpose of this case report is to highlight ophthalmic involvement of ITP in this patient, despite her only-mild thrombocytopenia, and her spontaneous recovery, despite her receiving only medical treatment.

  10. Nocardia transvalensis Disseminated Infection in an Immunocompromised Patient with Idiopathic Thrombocytopenic Purpura.

    PubMed

    García-Méndez, Jorge; Carrillo-Casas, Erika M; Rangel-Cordero, Andrea; Leyva-Leyva, Margarita; Xicohtencatl-Cortes, Juan; Arenas, Roberto; Hernández-Castro, Rigoberto

    2016-01-01

    Nocardia transvalensis complex includes a wide range of microorganisms with specific antimicrobial resistance patterns. N. transvalensis is an unusual Nocardia species. However, it must be differentiated due to its natural resistance to aminoglycosides while other Nocardia species are susceptible. The present report describes a Nocardia species involved in an uncommon clinical case of a patient with idiopathic thrombocytopenic purpura and pulmonary nocardiosis. Microbiological and molecular techniques based on the sequencing of the 16S rRNA gene allowed diagnosis of Nocardia transvalensis sensu stricto. The successful treatment was based on trimethoprim-sulfamethoxazole and other drugs. We conclude that molecular identification of Nocardia species is a valuable technique to guide good treatment and prognosis and recommend its use for daily bases diagnosis.

  11. Clopidogrel-induced refractory thrombotic thrombocytopenic purpura successfully treated with rituximab.

    PubMed

    Khodor, Sara; Castro, Miguel; McNamara, Colin; Chaulagain, Chakra P

    2016-06-01

    Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by microvascular aggregation of platelets and fibrin strands causing thrombocytopenia, microangiopathic hemolytic anemia, and organ dysfunction. TTP can develop as a result of a deficiency in ADAMTS13 enzyme activity due to either a genetic defect or, more commonly, the development of anti-ADAMTS13 autoantibodies. TTP can also be associated with pregnancy, organ transplant, lupus, infections, and drugs. Here, we present a case of TTP that developed shortly after the start of clopidogrel treatment for acute ischemic stroke and acute myocardial infarction, and describe the clinical presentation, refractory course of the disease, and successful induction of remission through the use of rituximab in a setting of pre-existing autoimmune diseases.

  12. Eculizumab refractory thrombotic thrombocytopenic purpura secondary to post-endoscopic retrograde cholangiopancreatography pancreatitis in a patient

    PubMed Central

    Malik, Faizan; Ali, Naveed; Ahsan, Irfan; Ghani, Ali Raza; Fidler, Christian

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare multisystem microvascular disorder, which is characterized by pentad of thrombocytopenia, microangiopathic hemolytic anemia, and organ dysfunction due to occlusive thrombi. The proposed pathophysiology involves an imbalance between unusually large von Willebrand factor multimers and the cleaving protease ADAMTS13. Acute pancreatitis is a well-described consequence of TTP, but TTP secondary to acute pancreatitis is a rare phenomenon. We present a patient who developed TTP due to post-ERCP pancreatitis with hematologic, cardiovascular, pulmonary, and renal complications and is the first case of this kind. Despite early initiation of therapy, the patient did not recover making it among the 10% of cases of TTP that prove fatal despite appropriate therapy. PMID:27987277

  13. Thrombotic thrombocytopenic purpura as an initial presentation of systemic lupus erythematosus with acquired ADAMTS 13 antibody

    PubMed Central

    Changcharoen, Bhisit; Bolger, Dennis Thomas

    2015-01-01

    We report a female patient presenting with headache, fatigue, ecchymoses and recent, excessive vaginal bleeding. Prompt review of the peripheral blood smear showed evidence of microangiopathic haemolytic anaemia (MAHA) and thrombocytopenia. Thrombotic thrombocytopenic purpura (TTP) was suspected. Plasma exchange and corticosteroids were started urgently. The patient responded favourably to the treatment. Subsequently, positive serological markers returned and were compatible with systemic lupus erythematosus (SLE). A disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13 (ADAMTS 13) activity was remarkably low with a positive inhibitory ADAMTS 13 antibody. Mycophenolate and hydroxychloroquine were started along with a prolonged course and taper of corticosteroids. These medications have been maintained with an excellent response in 14 months of follow-up. PMID:25701834

  14. Acquired thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome successfully treated with eculizumab

    PubMed Central

    Cottler-Fox, Michele; Motwani, Pooja

    2017-01-01

    Acquired idiopathic thrombotic thrombocytopenic purpura is a life-threatening disease with a mortality of up to 90%, if not promptly recognized and treated. We report a 64-year-old woman with this condition who presented with left-sided weakness and seizure-like activity preceded by headache and easy bruising. She did not achieve optimal response to plasma exchange, corticosteroids, rituximab, and vincristine. We initiated treatment with eculizumab, following which she had durable remission that continued for 30 months after discontinuation of the drug. We later found that our patient has homozygous deletion in two closely related genes, complement factor H–related 1 and complement factor H–related 3.

  15. Serum thrombopoietin levels in relation to disease status in patients with immune thrombocytopenic purpura.

    PubMed

    Kappers-Klunne, M C; de Haan, M; Struijk, P C; van Vliet, H H

    2001-12-01

    Pre- and post-treatment serum thrombopoietin (TPO) concentration was measured in 35 patients with immune thrombocytopenic purpura (ITP). Mean post-treatment levels were significantly lower (P = 0.02) than pretreatment and not different for treatment modality. No significant correlation between pre- or post-treatment TPO and platelet counts was demonstrable (R = -0.325, P = 0.056 and R = -0.227, P = 0.190 respectively). In patients with very low platelet counts (< or =20 x 10(9)/l), pretreatment serum TPO was significantly higher than in patients with higher counts (P = 0.033). The logarithm of the platelet turnover rate, measured in 15 patients, correlated with pretreatment TPO levels (R = 0.64). These findings suggest a contributory role for TPO in the mechanism of ITP.

  16. High-dose intravenous therapy with immune globulin before delivery for idiopathic thrombocytopenic purpura.

    PubMed Central

    Adderley, R. J.; Rogers, P. C.; Shaw, D.; Wadsworth, L. D.

    1984-01-01

    A 15-year-old girl with a 9-year history of idiopathic thrombocytopenic purpura resistant to high-dose steroid therapy and to splenectomy was admitted to hospital at 35 weeks' gestation with a platelet count of 10 X 10(9)/L. The bleeding time was normal, and measures of platelet aggregation were nearly so. Treatment with high intravenous doses of polyvalent immune globulin led to a rise in the platelet count to more than 110 X 10(9)/L within 5 days. An elective cesarean section was performed through the lower uterine segment with good hemostasis. After delivery the platelet count fell to its former level, but no postpartum bleeding occurred. There was a brief episode of thrombocytopenia in the infant, with some petechiae but no other hemorrhagic manifestations. No untoward effects of the immune globulin infusion were observed in either mother or daughter. PMID:6423252

  17. Nocardia transvalensis Disseminated Infection in an Immunocompromised Patient with Idiopathic Thrombocytopenic Purpura

    PubMed Central

    García-Méndez, Jorge; Carrillo-Casas, Erika M.; Rangel-Cordero, Andrea; Leyva-Leyva, Margarita; Xicohtencatl-Cortes, Juan; Arenas, Roberto; Hernández-Castro, Rigoberto

    2016-01-01

    Nocardia transvalensis complex includes a wide range of microorganisms with specific antimicrobial resistance patterns. N. transvalensis is an unusual Nocardia species. However, it must be differentiated due to its natural resistance to aminoglycosides while other Nocardia species are susceptible. The present report describes a Nocardia species involved in an uncommon clinical case of a patient with idiopathic thrombocytopenic purpura and pulmonary nocardiosis. Microbiological and molecular techniques based on the sequencing of the 16S rRNA gene allowed diagnosis of Nocardia transvalensis sensu stricto. The successful treatment was based on trimethoprim-sulfamethoxazole and other drugs. We conclude that molecular identification of Nocardia species is a valuable technique to guide good treatment and prognosis and recommend its use for daily bases diagnosis. PMID:27313917

  18. Peliosis hepatis presenting with massive hepatomegaly in a patient with idiopathic thrombocytopenic purpura.

    PubMed

    Kim, Sun Bean; Kim, Do Kyung; Byun, Sun Jeong; Park, Ji Hye; Choi, Jin Young; Park, Young Nyun; Kim, Do Young

    2015-12-01

    Peliosis hepatis is a rare condition that can cause hepatic hemorrhage, rupture, and ultimately liver failure. Several authors have reported that peliosis hepatis develops in association with chronic wasting disease or prolonged use of anabolic steroids or oral contraceptives. In this report we describe a case in which discontinuation of steroid therapy improved the condition of a patient with peliosis hepatis. Our patient was a 64-year-old woman with a history of long-term steroid treatment for idiopathic thrombocytopenic purpura . Her symptoms included abdominal pain and weight loss; the only finding of a physical examination was hepatomegaly. We performed computed tomography (CT) and magnetic resonance imaging (MRI) of the liver and a liver biopsy. Based on these findings plus clinical observations, she was diagnosed with peliosis hepatis and her steroid treatment was terminated. The patient recovered completely 3 months after steroid discontinuation, and remained stable over the following 6 months.

  19. Role of Helicobacter pylori Eradication Therapy on Platelet Recovery in Chronic Immune Thrombocytopenic Purpura

    PubMed Central

    Sheema, Khan; Arshi, Naz; Farah, Naz; Imran, Sheikh

    2017-01-01

    Background. Idiopathic thrombocytopenic purpura (ITP) is a bleeding disorder in which the immune system destroys native platelets. In this condition an autoantibody is generated against a platelet antigen. ITP affects women more often than men and is more common in children than adults. Objective. To assess the effect of Helicobacter pylori eradication therapy (HPET) on platelet count in Helicobacter pylori associated chronic immune thrombocytopenic purpura (chronic ITP) in adult. Materials and Methods. It is an interventional prospective study conducted at Liaquat University of Medical and Health Sciences, Jamshoro, from 2014 to 2015. A set of 85 patients diagnosed with chronic ITP were included in the study via convenient sampling. Patients with platelets count < 100 × 109/L for >3 months were selected. They were posed to first-line investigations which comprised complete blood count (CBC) and peripheral blood smear examination followed by second-line tests including bone marrow examination and Helicobacter pylori stool specific antigen (HpSA-EIA). Standard H. pylori eradication therapy was offered and the patients were assessed at regular intervals for 6 months. Results. Of the 85 study patients, 32 (37.6%) were male and 53 (62.3%) were female. Mean ages of H. pylori positive and negative subjects were 43.89 ± 7.06 and 44.75 ± 7.91 years, respectively. Bone marrow examination confirmed the diagnosis and excluded other related BM disorders. H. pylori stool antigen (HpSA) was detected in 34 (40%) patients and hence regarded as H. pylori positive; the rest were negative. Treatment with eradication therapy significantly improved the mean platelet counts from 48.56 ± 21.7 × 109/l to 94.2 ± 26.8 × 109/l. Conclusion. We concluded that the anti-H. pylori eradication therapy improves blood platelet counts in chronic immune thrombocytopenia. PMID:28194178

  20. Importance of immature platelet fraction as predictor of immune thrombocytopenic purpura

    PubMed Central

    Naz, Arshi; Mukry, Samina Naz; Shaikh, Mahwish Rauf; Bukhari, Ali Raza; Shamsi, Tahir Sultan

    2016-01-01

    Background and Objective: Immune thrombocytopenic purpura (ITP) is a clinical syndrome in which a decreased number of circulating platelets (thrombocytopenia) manifests as a bleeding tendency, easy bruising (purpura) or extravasation of blood from capillaries into skin and mucous membranes (petechiae). The diagnosis of ITP can be made clinically on the basis of symptoms, we need to see if ITP can be confirmed in patients by quantification of residual RNA containing immature platelets (megakaryocytic mass) or immature platelets fraction (IPF) using automated hematology analyzers (Sysmex XE-2100). Methods: In order to check the efficacy of IPF% parameter of Sysmex XE-2100 a total of 231 patients of thrombocytopenia were included in this study. Complete blood count (CBC) was estimated. The data was statistically analyzed by SPSS version 17. Results: About 62 patients were diagnosed as ITP and 169 patients were diagnosed as non ITP on the basis of clinical history. The mean IPF % value of ITP patients was 16.39% and the IPF % value of Non ITP patients was ~7.69% respectively. There was no significant difference in IPF% values with respect to time between sampling and acquisition of complete blood count. The diagnostic sensitivity of IPF% as biomarker for ITP and non-ITP was 85.71% (95%CI: 84.04% to 85.96%) and 41.76% (95% CI: 39.87% to 43.65%). Conclusion: The mean IPF % value by Sysmex XE-2100 can be used to predict ITP. PMID:27375692

  1. Hemorrhagic Stroke in an Adolescent Female with HIV-Associated Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Rakhmanina, Natella; Wong, Edward CC; Davis, Jeremiah C; Ray, Patricio E

    2014-01-01

    HIV-1 infection can trigger acute episodes of Idiopathic Thrombocytoponic Purpura (ITP), and Thrombotic Thrombocytopenic Purpura (TTP), particularly in populations with advanced disease and poor adherence to antiretroviral therapy (ART). These diseases should be distinguished because they respond to different treatments. Previous studies done in adults with HIV-TTP have recommended the prompt initiation or re-initiation of ART in parallel with plasma exchange therapy to improve the clinical outcome of these patients. Here, we describe a case of HIV-TTP resulting in an acute hemorrhagic stroke in a 16 year old female with perinatally acquired HIV infection and non-adherence to ART, who presented with severe thrombocytopenia, microangiopathic hemolytic anemia, and a past medical history of HIV-ITP. Both differential diagnosis and treatments for HIV-ITP and HIV-TTP were considered simultaneously. A decrease in plasma ADAMTS13 activity (<5%) without detectable inhibitory antibodies confirmed the diagnosis of HIV-TTP. Re-initiation of ART and plasma exchange resulted in a marked decrease in the HIV-RNA viral load, recovery of the platelet count, and complete recovery was achieved with sustained virologic suppression. PMID:25429351

  2. Excessive naked megakaryocyte nuclei in myelodysplastic syndrome mimicking idiopathic thrombocytopenic purpura: a complicated pre- and post-transplantation course.

    PubMed

    Olcay, Lale; Tuncer, A Murat; Okur, Hamza; Erdemli, Esra; Uysal, Zumrut; Cetin, Mualla; Duru, Feride; Cetinkaya, Duygu Uckan

    2009-09-01

    A boy 3 years 7 months old with thrombocytopenia and history of intracranial hemorrhage who underwent bone marrow transplantation is presented. He was refractory to steroids, immunoglobulin G, vincristine, azathioprine, cyclosporine A, interleukin-11, chemotherapy, and splenectomy. Idiopathic thrombocytopenic purpura was excluded by light /electron microscopic and flow cytometric findings; the diagnosis of refractory cytopenia, a subgroup of pediatric myelodysplastic syndrome, was made. Naked megakaryocyte nuclei were 55.38 +/- 28.2% vs. 31.67 +/- 23.22% of all megakaryocytes in the patient and the control group of 9 patients with idiopathic thrombocytopenic purpura, respectively (p = .016). The posttransplatation course was complicated by delayed platelet engraftment, bronchiolitis obliterans associated with pneumocystis carinii pneumonia, which resolved completely.

  3. Vitamin B12 Deficiency and Hemoglobin H Disease Early Misdiagnosed as Thrombotic Thrombocytopenic Purpura: A Series of Unfortunate Events.

    PubMed

    Andreadis, Panagiotis; Theodoridou, Stamatia; Pasakiotou, Marily; Arapoglou, Stergios; Gigi, Eleni; Vetsiou, Evaggelia; Vlachaki, Efthymia

    2015-01-01

    We herein would like to report an interesting case of a patient who presented with anemia and thrombocytopenia combined with high serum Lactic Dehydrogenase where Thrombotic Thrombocytopenic Purpura was originally considered. As indicated a central venous catheter was inserted in his subclavian vein which led to mediastinal hematoma and finally intubation and Intensive Care Unit (ICU) hospitalization. After further examination patient was finally diagnosed with B12 deficiency in a setting of H hemoglobinopathy. There have been previous reports where pernicious anemia was originally diagnosed and treated as Thrombotic Thrombocytopenic Purpura but there has been none to our knowledge that was implicated with hemothorax and ICU hospitalization or correlated with thalassemia and we discuss the significance of accurate diagnosis in order to avoid adverse reactions and therapy implications.

  4. Vitamin B12 Deficiency and Hemoglobin H Disease Early Misdiagnosed as Thrombotic Thrombocytopenic Purpura: A Series of Unfortunate Events

    PubMed Central

    Andreadis, Panagiotis; Theodoridou, Stamatia; Pasakiotou, Marily; Arapoglou, Stergios; Gigi, Eleni; Vetsiou, Evaggelia; Vlachaki, Efthymia

    2015-01-01

    We herein would like to report an interesting case of a patient who presented with anemia and thrombocytopenia combined with high serum Lactic Dehydrogenase where Thrombotic Thrombocytopenic Purpura was originally considered. As indicated a central venous catheter was inserted in his subclavian vein which led to mediastinal hematoma and finally intubation and Intensive Care Unit (ICU) hospitalization. After further examination patient was finally diagnosed with B12 deficiency in a setting of H hemoglobinopathy. There have been previous reports where pernicious anemia was originally diagnosed and treated as Thrombotic Thrombocytopenic Purpura but there has been none to our knowledge that was implicated with hemothorax and ICU hospitalization or correlated with thalassemia and we discuss the significance of accurate diagnosis in order to avoid adverse reactions and therapy implications. PMID:26609455

  5. Two novel heterozygote missense mutations of the ADAMTS13 gene in a child with recurrent thrombotic thrombocytopenic purpura

    PubMed Central

    Rossio, Raffaella; Ferrari, Barbara; Cairo, Andrea; Mancini, Ilaria; Pisapia, Giovanni; Palazzo, Giulia; Peyvandi, Flora

    2013-01-01

    Background Thrombotic thrombocytopenic purpura is a rare, life-threatening disease characterised by microangiopathic haemolytic anaemia, thrombocytopenia and symptoms related to organ ischaemia, mainly involving the brain and the kidney. It is associated with a deficiency of ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor. The congenital form (Upshaw-Schulman syndrome) is rare and is associated with mutations of the ADAMTS13 gene on chromosome 9q34. The clinical symptoms of congenital thrombotic thrombocytopenic purpura are variable, with some patients developing their first episode during the neonatal period or childhood and others becoming symptomatic in adulthood. Materials and methods We describe a case of thrombotic thrombocytopenic purpura, who presented to our attention with a relapsing form of the disease: the first episode occurred at the age of 13 months. Phenotype and genotype tests were performed in the patient and his family. Results The undetectable level of ADAMTS13 in the patient was caused by two novel heterozygote missense mutations on the ADAMTS13 gene: one mutation is c.788C > T (p.Ser263Phe) on exon 7 and the second is c.3251G > A (p.Cys1084Tyr) on exon 25 of the ADAMTS13 gene. All the relatives who have been investigated were found to carry one of these missense mutations in a heterozygous state. Discussion Although Upshaw-Schulman syndrome is a rare disease, it should be considered in all children with thrombocytopenia and jaundice in the neonatal period. In fact, once a child is confirmed to carry mutations of the ADAMTS13 gene causing early thrombotic thrombocytopenic purpura, prophylactic treatment should be started to avoid recurrence of symptoms. Genotype tests of relatives would also be important for those women in the family who could be carriers of ADAMTS13 mutations, particularly during pregnancy. PMID:23058857

  6. Case of twin pregnancy complicated by idiopathic thrombocytopenic purpura treated with intravenous immunoglobulin: Review of the literature.

    PubMed

    Zhao, W X; Yang, X F; Lin, J H

    2017-01-01

    Idiopathic thrombocytopenic purpura (ITP) is an acquired thrombocytopenia without other clear cause of thrombocytopenia. It is not common in a singleton pregnancy and less common in twin pregnancy. We report a 33-year-old ITP pluripara whose first pregnancy was uneventful. She carried twin pregnancy, complicated by recurrent very low platelets, and gave birth to preterm twins. This patient received multiple courses of intravenous immunoglobulin (IVIG) and showed a significant platelet count improvement with IVIG therapy.

  7. Immune thrombocytopenic purpura (ITP) associated with vaccinations: a review of reported cases.

    PubMed

    Perricone, Carlo; Ceccarelli, Fulvia; Nesher, Gideon; Borella, Elisabetta; Odeh, Qasim; Conti, Fabrizio; Shoenfeld, Yehuda; Valesini, Guido

    2014-12-01

    Immune thrombocytopenic purpura (ITP) is an autoimmune condition characterized by low platelet count with mucocutaneous and other bleedings. Clinical manifestations may range from spontaneous formation of purpura and petechiae, especially on the extremities, to epistaxis, bleeding at the gums or menorrhagia, any of which occur usually if the platelet count is below 20,000 per μl. A very low count may result in the spontaneous formation of hematomas in the mouth or on other mucous membranes. Fatal complications, including subarachnoid or intracerebral, lower gastrointestinal or other internal bleeding can arise due to an extremely low count. Vaccines may induce ITP by several mechanisms. Vaccine-associated autoimmunity may stem not only from the antigen-mediated responses but also from other constituents of the vaccine, such as yeast proteins, adjuvants, and preservatives diluents. The most likely is through virally induced molecular mimicry. The binding of pathogenic autoantibodies to platelet and megakaryocytes may cause thrombocytopenia by different mechanisms, such as opsonization, direct activation of complement, or apoptotic pathways. The autoantibodies hypothesis is not sufficient to explain all ITP cases: In the anti-platelet antibody-negative cases, a complementary mechanism based on T cell immune-mediated mechanism has been suggested. In particular, T cell subsets seem dysregulated with an increased production of pro-inflammatory cytokines, as IFN-γ and TNF, and chemokines, as CXCL10. Vaccines are one of the most striking discoveries in human history that changed dramatically life expectancy. Nonetheless, the occurrence of adverse events and autoimmune phenomena has been described following vaccination, and ITP may represent one of this.

  8. Thrombotic Thrombocytopenic Purpura in Black People: Impact of Ethnicity on Survival and Genetic Risk Factors.

    PubMed

    Martino, Suella; Jamme, Mathieu; Deligny, Christophe; Busson, Marc; Loiseau, Pascale; Azoulay, Elie; Galicier, Lionel; Pène, Frédéric; Provôt, François; Dossier, Antoine; Saheb, Samir; Veyradier, Agnès; Coppo, Paul

    2016-01-01

    Black people are at increased risk of thrombotic thrombocytopenic purpura (TTP). Whether clinical presentation of TTP in Black patients has specific features is unknown. We assessed here differences in TTP presentation and outcome between Black and White patients. Clinical presentation was comparable between both ethnic groups. However, prognosis differed with a lower death rate in Black patients than in White patients (2.7% versus 11.6%, respectively, P = .04). Ethnicity, increasing age and neurologic involvement were retained as risk factors for death in a multivariable model (P < .05 all). Sixty-day overall survival estimated by the Kaplan-Meier curves and compared with the Log-Rank test confirmed that Black patients had a better survival than White patients (P = .03). Salvage therapies were similarly performed between both groups, suggesting that disease severity was comparable. The comparison of HLA-DRB1*11, -DRB1*04 and -DQB1*03 allele frequencies between Black patients and healthy Black individuals revealed no significant difference. However, the protective allele against TTP, HLA-DRB1*04, was dramatically decreased in Black individuals in comparison with White individuals. Black people with TTP may have a better survival than White patients despite a comparable disease severity. A low natural frequency of HLA-DRB1*04 in Black ethnicity may account for the greater risk of TTP in this population.

  9. DNMT3B promoter polymorphism and risk of immune thrombocytopenic purpura in pediatric Egyptians.

    PubMed

    Shaheen, Iman A; Abukhalil, Reham E; Ali, Dina K; Afifi, Rasha A

    2012-10-01

    Idiopathic (immune) thrombocytopenic purpura (ITP) is a heterogeneous clinical disorder characterized by immune-mediated platelet destruction. Epigenetic changes in gene expression, including DNA methylation and histone modifications, might contribute to autoimmunity. Polymorphisms of the DNA methyltransferase 3B (DNMT3B) gene may influence DNMT3B activity on DNA methylation and increase the susceptibility to several diseases. The current study investigated the association between a single nucleotide polymorphism (SNP) in the promoter of DNMT3B gene and the risk for ITP in pediatric Egyptians. DNMT3B SNP was genotyped by PCR-restriction fragment length polymorphism in 71 pediatric ITP patients and 82 healthy controls matched for age and sex. The C/C wild genotype was not detected in ITP patients or in the controls. The frequencies of the T/T and C/T genotypes were 93.9 and 6.1% in the controls and 91.5 and 6.1% in ITP patients, respectively. There was no significant difference in either genotypes or allelic distribution between ITP patients and the controls. In conclusion, this polymorphism was almost equally distributed between ITP patients and the controls. These results demonstrated that this SNP may not be used as a stratification marker to predict the susceptibility to childhood ITP in Egypt.

  10. Thrombotic thrombocytopenic purpura and other thrombotic microangiopathic hemolytic anemias: diagnosis and classification.

    PubMed

    Shenkman, Boris; Einav, Yulia

    2014-01-01

    Thrombotic microangiopathies (TMAs) include several diseases, most prominently are thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS). TMAs are characterized by profound thrombocytopenia, microangiopathic hemolytic anemia and organ ischemia. In most cases TTP results from deficiency of ADAMTS13, the von Willebrand factor-cleaving protease leading to increase of ultra-large von Willebrand factor (ULVWF) multimers. Congenital TTP is due to mutations in the gene of ADAMTS13 whereas acquired TTP is due to production of autoantibodies against ADAMTS13. In both cases severe deficiency of ADAMTS13 exists. However, the presence of ADAMTS13 activity does not rule out TTP. Diagnostic criteria of TTP are based on clinical features of neurologic and renal disfunction along with anemia and thrombocytopenia, low ADAMTS13 activity, and the presence of ULVWF. The standard treatment of TTP includes plasma exchange, protein A immunoabsobtion, immunosuppressive drugs, CD20 antibodies against B cells, and splenectomy. HUS is commonly caused by infection with Shiga-toxin produced by Escherichia coli. HUS is characterized by thrombocytopenia, anemia, renal impairment and diarrhea. Rarely, atypical HUS appears as a consequence of mutations related to the alternative pathway for the compliment system. Plasmapheresis in HUS is not efficient. Alternatively, plasma therapy and in some cases dialysis are used. TMA diseases may be associated with other infections, bone marrow transplantation, pregnancy, systemic vasculitis, and certain drugs.

  11. Long-term salvage therapy with cyclosporin A in refractory idiopathic thrombocytopenic purpura.

    PubMed

    Emilia, Giovanni; Morselli, Monica; Luppi, Mario; Longo, Giuseppe; Marasca, Roberto; Gandini, Giovanna; Ferrara, Leonardo; D'Apollo, Nicola; Potenza, Leonardo; Bertesi, Marcello; Torelli, Giuseppe

    2002-02-15

    Treatment of severe, chronic idiopathic thrombocytopenic purpura (ITP) refractory to most usual therapies is a difficult challenge. Little information exists on the clinical use of cyclosporin A (CyA) in the treatment of ITP. This report describes long-term treatment with CyA (median, 40 months) and follow-up (median, 36.8 months) in 12 adult patients with resistant ITP. CyA used in relatively low doses (2.5-3 mg/kg of body weight per day) led to a clinical improvement in 10 patients (83.3%). Five had a complete response (41.1%), 4 a complete response to maintenance therapy (33.3%), and one a partial response (8.3%). Two patients had no response. Most patients with a response (60%) had a long-term remission (mean, 28.6 months) after discontinuation of CyA. One patient had a relapse of ITP 4 years after CyA therapy was stopped. Side effects were moderate and transient, even in patients dependent on continued CyA treatment. CyA seems to represent reasonable salvage treatment in severe, potentially life-threatening, refractory ITP.

  12. Does Helicobacter pylori play a role in the pathogenesis of childhood chronic idiopathic thrombocytopenic purpura?

    PubMed

    Maghbool, Maryam; Maghbool, Masood; Shahriari, Mehdi; Karimi, Mehran

    2009-06-08

    Idiopathic thrombocytopenic purpura (ITP) is an acute self-limited bleeding disorder that can progress to chronic form in 10-15% of the cases. Helicobacter pylori (H. pylori) infection is a possible cause of chronic ITP. We studied 30 children with resistant chronic ITP for H. pylori infection based on the detection of H. pylori fecal antigen. This retrospective study was based on data obtained from medical records of 30 children aged between five and 17 years (median age at ITP diagnosis was ten years). A specially-designed data sheet was used to record information on age, sex, duration of disease, family history of bleeding disorders, previous treatments and median platelet count. In patients with H. pylori infection, antimicrobial treatment consisted of amoxicillin, metronidazol and omeprazol. Response was assessed every month for one year and defined as complete (platelet count >150×10(9)/L) or partial (platelet count between 50 and 150×10(9)/L). We detected H. pylori infection in 5 patients. In 4 of them increased platelet count was seen during one year of follow-up and in one patient the platelet count was acceptable during six months. Although the pathological mechanism of H. pylori-induced thrombocytopenia was unclear in our patient sample, the assessment of H. pylori infection and use of eradication therapy should be attempted in chronic and resistant ITP patients.

  13. Thrombotic Thrombocytopenic Purpura in Black People: Impact of Ethnicity on Survival and Genetic Risk Factors

    PubMed Central

    Martino, Suella; Jamme, Mathieu; Deligny, Christophe; Busson, Marc; Loiseau, Pascale; Azoulay, Elie; Galicier, Lionel; Pène, Frédéric; Provôt, François; Dossier, Antoine; Saheb, Samir; Veyradier, Agnès; Coppo, Paul

    2016-01-01

    Black people are at increased risk of thrombotic thrombocytopenic purpura (TTP). Whether clinical presentation of TTP in Black patients has specific features is unknown. We assessed here differences in TTP presentation and outcome between Black and White patients. Clinical presentation was comparable between both ethnic groups. However, prognosis differed with a lower death rate in Black patients than in White patients (2.7% versus 11.6%, respectively, P = .04). Ethnicity, increasing age and neurologic involvement were retained as risk factors for death in a multivariable model (P < .05 all). Sixty-day overall survival estimated by the Kaplan-Meier curves and compared with the Log-Rank test confirmed that Black patients had a better survival than White patients (P = .03). Salvage therapies were similarly performed between both groups, suggesting that disease severity was comparable. The comparison of HLA-DRB1*11, -DRB1*04 and -DQB1*03 allele frequencies between Black patients and healthy Black individuals revealed no significant difference. However, the protective allele against TTP, HLA-DRB1*04, was dramatically decreased in Black individuals in comparison with White individuals. Black people with TTP may have a better survival than White patients despite a comparable disease severity. A low natural frequency of HLA-DRB1*04 in Black ethnicity may account for the greater risk of TTP in this population. PMID:27383202

  14. [Treatment of immune thrombocytopenic purpura in Pediatrics. Therapeutic efficacy of a regional intravenous immunoglobulin G].

    PubMed

    Buteler, C; Colombo, H; Gabosi, G; Manfredi, M J; Montero, S; Pasquali, M A; Rougier, C; Sisti, A M

    2001-01-01

    Immune thrombocytopenic purpura (ITP) is a bleeding disorder characterized by accelerated splenic removal of platelets opsonized with autoantibodies. Several different treatments have been tried in acute ITP patients, including intravenous immunoglobulin (IVIG) therapy. The aim of this paper was to assess the therapeutic efficacy, clinical tolerance and viral safety of Inmunoglobulina G Endovenosa-UNC, manufactured by Laboratorio de Hemoderivados, Cordoba National University, in the treatment of acute ITP patients. A prospective longitudinal study was carried out on 8 children, who were admitted to the Hospital de Niños de Córdoba, from July 1998 to June 1999. A dose of 1 g/Kg/day of Inmunoglobulina G Endovenosa-UNC was administered to those children whose platelet values remained < or = 20,000/mm3, 21 days after the first IVIG cycle. The observed results led us to conclude that Inmunoglobulina G Endovenosa-UNC is well tolerated and therapeutically effective in the treatment of acute ITP in children, with platelet values recovery, similar to those obtained with other IVIG. Moreover, it proved to be virally safe since the 8 patients were non reactive for viral markers of hepatitis B, hepatitis C and human immunodeficiency, 12 months after ending the treatment.

  15. Bleeding tendency and platelet function during treatment with romiplostim in children with severe immune thrombocytopenic purpura.

    PubMed

    Suntsova, Elena V; Demina, Irina M; Ignatova, Anastasia A; Ershov, Nikolay M; Trubina, Natalia M; Dobrynina, Juliya; Serkova, Irina V; Supik, Zhanna S; Orekhova, Ekaterina V; Hachatryan, Lili A; Kotskaya, Natalia N; Pshonkin, Aleksey V; Maschan, Aleksey A; Novichkova, Galina A; Panteleev, Mikhail A

    2017-03-07

    It has been suggested that platelet function in chronic immune thrombocytopenic purpura (ITP) may be abnormal. Thrombopoietin mimetics used for treatment can affect it, but the data remain limited. We investigated platelet function of 20 children diagnosed with severe ITP (aged 1-16 years, 12 females and eight males). Platelet functional activity in whole blood was characterized by flow cytometry before and after stimulation with SFLLRN plus collagen-related peptide. Levels of CD42b, PAC1, and CD62P, but not CD61 or annexin V, were significantly increased (P < 0.05) in resting platelets of patients before treatment compared with healthy donors. On average, PAC1 and CD62P in patients after activation were also significantly elevated, although some patients failed to activate integrins. Romiplostim (1-15 μg/kg/week s.c.) was prescribed to seven patients, with clinical improvement in six. Interestingly, one patient had clinical improvement without platelet count increase. Eltrombopag (25-75 mg/day p.o.) was given to four patients, with positive response in one. Others switched to romiplostim, with one stable positive response, one unstable positive response, and one non-responding. Platelet quality improved with romiplostim treatment, and their parameters approached the normal values. Our results suggest that platelets in children with severe ITP are pre-activated and abnormal, but improve with treatment.

  16. Pregnancy-associated thrombotic thrombocytopenic purpura with anti-centromere antibody-positive Raynaud's syndrome.

    PubMed

    Watanabe, Ryu; Shirai, Tsuyoshi; Tajima, Yumi; Ohguchi, Hiroto; Onishi, Yasushi; Fujii, Hiroshi; Takasawa, Naruhiko; Ishii, Tomonori; Harigae, Hideo

    2010-01-01

    Thrombotic thrombocytopenic purpura (TTP), scleroderma renal crisis (SRC), and hemolysis, elevated liver enzyme levels, and a low platelet count (HELLP) syndrome display common symptoms that include microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. Therefore, it is important to distinguish between them because their treatments vary: however, the differential diagnosis is sometimes difficult. We report a 32-year-old woman who was referred to our department for further examination of microangiopathic hemolytic anemia, thrombocytopenia, and a slightly elevated serum creatinine level with anti-centromere antibody-positive Raynaud's syndrome in the early puerperal period. TTP, SRC, and HELLP syndrome were considered in the differential diagnosis, but the measurement of a disintegrin-like metalloprotease with thrombospondin type 1 motifs 13 (ADAMTS 13) activity and its inhibitor level led to the diagnosis of TTP. She was successfully treated by plasma exchange and high-dose prednisolone and angiotensin-converting enzyme inhibitor. If microangiopathic hemolytic anemia and thrombocytopenia are observed in perinatal women or patients with signs of systemic sclerosis, the measurement of ADAMTS13 activity and its inhibitor level are essential for diagnosis and therapeutic choice.

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

    PubMed

    Hashimoto, Akari; Fujimi, Akihito; Kanisawa, Yuji; Matsuno, Teppei; Okuda, Toshinori; Minami, Shinya; Doi, Tadashi; Ishikawa, Kazuma; Uemura, Naoki; Tomaru, Utano

    2013-06-01

    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.

  18. Diffuse alveolar hemorrhage associated with thrombotic thrombocytopenic purpura after allogeneic bone marrow transplantation.

    PubMed

    Kalayoğlu Beşışık, Sevgi; Yenerel, Mustafa; Diz Küçükkaya, Reyhan; Çalışkan, Yaşar; Sargın, Deniz

    2004-12-05

    Alveolar hemorrhage is an early complication after bone marrow transplantation (BMT) and often associated with inflammatory pulmonary processes. We present a case of diffuse alveolar hemorrhage associated with BMT associated thrombotic thrombocytopenic purpura (BMT-TTP). An 18-years-old man with acute myeloid leukaemia (FAB; M5) underwent ABO incompatible BMT from his HLA-identical sister. On the 37th day of BMT, BMT-TTP was diagnosed with the occurrence of red cell fragmentation and rise in serum lactic dehydrogenase (LDH) level with severe sudden decrease in hemoglobin and platelet levels. Cyclosporine A (CsA) was ceased and plasma infusion with plasma exchange was started. On the 42nd day of BMT, the diagnosis of diffuse alveolar hemorrhage was made by the clinical, bronchoscopic and bronchoalveolar lavage fluid findings. Alveolar hemorrhage among patients with BMT-TTP has been scarce reported. These two complications may be regarded as related, as small vessel injury is a central feature in both and they may share aetiological and pathogenetic factors.

  19. Refractory thrombotic thrombocytopenic purpura associated with primary Sjogren syndrome treated with rituximab: a case report.

    PubMed

    Toumeh, Anis; Josh, Navpreet; Narwal, Rawan; Assaly, Ragheb

    2014-01-01

    Thrombotic thrombocytopenic purpura (TTP) is an uncommon, serious disease that involves multiple organs and is rapidly fatal if left untreated. TTP is associated with multisystem symptoms, such as thrombocytopenia, microangiopathic hemolytic anemia, renal impairment, central nervous system involvement, and fever. TTP is idiopathic in about 37% of the cases and can be associated with autoimmune diseases in 13% of the cases. Autoimmune disease-associated TTP can be refractory to plasma exchange and requires immunosuppressive therapy. We report a case of a previously healthy 55-year-old African American female who presented with shortness of breath, hemolytic anemia, renal impairment, and thrombocytopenia. The diagnosis of TTP was made, and plasmapheresis was initiated. However, recurrence happened 48 hours after plasmapheresis was stopped. Autoimmune workup for refractory TTP revealed positive antinuclear antibodies, Anti-SSA, and Anti-SSB. Lip biopsy revealed findings consistent with Sjogren syndrome. Treatment with Rituximab was started, and significant clinical and laboratory response was achieved. The patient remained asymptomatic thereafter. A high clinical suspicion of autoimmune diseases is important as TTP tends to be refractory to plasma exchange in these cases, and immunosuppressive therapy is a key.

  20. Interactions of von Willebrand factor and ADAMTS13 in von Willebrand disease and thrombotic thrombocytopenic purpura.

    PubMed

    Budde, U; Schneppenheim, R

    2014-01-01

    The function of von Willebrand factor (VWF), a huge multimeric protein and a key factor in platelet dependent primary haemostasis, is regulated by its specific protease ADAMTS13. The ADAMTS13 dependent degradation of VWF to its proteolytic fragments can be visualized as a characteristic so-called triplet structure of individual VWF oligomers by multimer analysis. Lack of VWF high molecular weight multimers (VWF-HMWM) or their pathologically enhanced degradation underlies a particular type of von Willebrand disease, VWD type 2A with a significant bleeding tendency, and may also be observed in acquired von Willebrand syndrome due to cardiovascular disease. In these conditions multimer analysis is an obligatory and powerful tool for diagnosis of VWD. The opposite condition, the persistence of ultralarge VWF (UL-VWF) multimers may cause the microangiopathic life-threatening disorder thrombotic thrombocytopenic purpura (TTP). During the course of active TTP, UL-VWF is consumed in the hyaline thrombi formed in the microvasculature which will ultimately result in the loss of UL-VWF and VWF-HMWM. Therefore, VWF multimer analysis is not a valid tool to diagnose TTP in the active phase of disease but may be helpful for the diagnosis of TTP patients in remission.

  1. Life-Threatening Autoimmune Hemolytic Anemia and Idhiopatic Thrombocytopenic Purpura. Successful Selective Splenic Artery Embolization

    PubMed Central

    Molica, Matteo; Massaro, Fulvio; Annechini, Giorgia; Baldacci, Erminia; D’Elia, Gianna Maria; Rosati, Riccardo; Trisolini, Silvia Maria; Volpicelli, Paola; Foà, Robin; Capria, Saveria

    2016-01-01

    Selective splenic artery embolization (SSAE) is a nonsurgical intervention characterized by the transcatheter occlusion of the splenic artery and/or its branch vessels using metallic coils or other embolic devices. It has been applied for the management of splenic trauma, hypersplenism with portal hypertension, hereditary spherocytosis, thalassemia and splenic hemangioma. We hereby describe a case of a patient affected by idiopathic thrombocytopenic purpura (ITP) and warm auto-immune hemolytic anemia (AIHA) both resistant to immunosuppressive and biological therapies, not eligible for a surgical intervention because of her critical conditions. She underwent SSAE and achieved a hematologic complete response within a few days without complications. SSAE is a minimally invasive procedure to date not considered a standard option in the management of AIHA and ITP. However, following the progressive improvement of the techniques, its indications have been extended, with a reduction in morbidity and mortality compared to splenectomy in patients with critical clinical conditions. SSAE was a lifesaving therapeutic approach for our patient and it may represent a real alternative for the treatment of resistant AIHA and ITP patients not eligible for splenectomy. PMID:27158433

  2. Congenital thrombotic thrombocytopenic purpura caused by new compound heterozygous mutations of the ADAMTS13 gene.

    PubMed

    Rank, Cecilie Utke; Kremer Hovinga, Johanna; Taleghani, Magnus Mansouri; Lämmle, Bernhard; Gøtze, Jens Peter; Nielsen, Ove Juul

    2014-02-01

    Upshaw-Schulman syndrome (USS) is due to severe congenital deficiency of von Willebrand factor (VWF)-cleaving protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 domains, nr 13) activity resulting in the presence of unusually large forms of VWF in the circulation, causing intravascular platelet clumping and thrombotic microangiopathy. Our patient, a 26-year-old man, had attacks of thrombotic thrombocytopenic purpura (TTP) with thrombocytopenia and a urine dipstick positive for hemoglobin (4+), often as the only sign of hemolytic activity. He had ADAMTS13 activity of <1% of normal plasma without the presence of inhibitors of ADAMTS13. ADAMTS13 deficiency was caused by two new mutations of the ADAMTS13 gene: a deletion of a single nucleotide in exon17 (c. 2042 delA) leading to a frameshift (K681C fs X16), and a missense mutation in exon 25 (c.3368G>A) leading to p.R1123H. This case report confirms the importance of the analysis of the ADAMTS13 activity and its inhibitor in patients who have episodes of TTP, with a very low platelet count and sometimes without the classic biochemical signs of hemolysis.

  3. Platelet-delivered ADAMTS13 inhibits arterial thrombosis and prevents thrombotic thrombocytopenic purpura in murine models.

    PubMed

    Pickens, Brandy; Mao, Yingying; Li, Dengju; Siegel, Don L; Poncz, Mortimer; Cines, Douglas B; Zheng, X Long

    2015-05-21

    ADAMTS13 metalloprotease cleaves von Willebrand factor (VWF), thereby inhibiting platelet aggregation and arterial thrombosis. An inability to cleave ultralarge VWF resulting from hereditary or acquired deficiency of plasma ADAMTS13 activity leads to a potentially fatal syndrome, thrombotic thrombocytopenic purpura (TTP). Plasma exchange is the most effective initial therapy for TTP to date. Here, we report characterization of transgenic mice expressing recombinant human ADAMTS13 (rADAMTS13) in platelets and its efficacy in inhibiting arterial thrombosis and preventing hereditary and acquired antibody-mediated TTP in murine models. Western blotting and fluorescent resonance energy transfer assay detect full-length rADAMTS13 protein and its proteolytic activity, respectively, in transgenic (Adamts13(-/-)Plt(A13)), but not in wild-type and Adamts13(-/-), platelets. The expressed rADAMTS13 is released on stimulation with thrombin and collagen, but less with 2MesADP. Platelet-delivered rADAMTS13 is able to inhibit arterial thrombosis after vascular injury and prevent the onset and progression of Shigatoxin-2 or recombinant murine VWF-induced TTP syndrome in mice despite a lack of plasma ADAMTS13 activity resulting from the ADAMTS13 gene deletion or the antibody-mediated inhibition of plasma ADAMTS13 activity. These findings provide a proof of concept that platelet-delivered ADAMTS13 may be explored as a novel treatment of arterial thrombotic disorders, including hereditary and acquired TTP, in the presence of anti-ADAMTS13 autoantibodies.

  4. Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura

    PubMed Central

    Yu, Jin; Heck, Susanne; Patel, Vivek; Levan, Jared; Yu, Yu; Bussel, James B.

    2008-01-01

    Immune thrombocytopenic purpura (ITP) is characterized by the presence of antiplatelet autoantibodies as a result of loss of tolerance. CD4+CD25+ regulatory T cells (Tregs) are important for maintenance of peripheral tolerance. Decreased levels of peripheral Tregs in patients with ITP have been reported. To test whether inefficient production or reduced immunosuppressive activity of Tregs contributes to loss of tolerance in patients with chronic ITP, we investigated the frequency and function of their circulating CD4+CD25hi Tregs. We found a com-parable frequency of circulating CD4+CD25hiFoxp3+ Tregs in patients and controls (n = 16, P > .05). However, sorted CD4+CD25hi cells from patients with chronic ITP (n = 13) had a 2-fold reduction of in vitro immunosuppressive activity compared with controls (n = 10, P < .05). The impaired suppression was specific to Tregs as shown by cross-mixing experiments with T cells from controls. These data suggest that functional defects in Tregs contribute to breakdown of self-tolerance in patients with chronic ITP. PMID:18420827

  5. Platelet antibodies of the IgM class in immune thrombocytopenic purpura

    SciTech Connect

    Cines, D.B.; Wilson, S.B.; Tomaski, A.; Schreiber, A.D.

    1985-04-01

    The clinical course and response to therapy of patients with immune thrombocytopenic purpura (ITP) are not completely determined by the level of IgG present on the platelet surface. It is possible that antibodies of other immunoglobulin classes also play a role in platelet destruction in some of these patients. Therefore, the authors studied 175 patients with ITP for the presence of IgM anti-platelet antibodies using radiolabeled polyclonal or monoclonal anti-IgM. They observed that 57% of patients with clinical ITP had increased levels of IgM on their platelets, compared with normal controls and patients with thrombocytopenia who did not have ITP. They obtained similar results using either radiolabeled polyclonal or monoclonal anti-IgM, reagents whose integrity was first characterized using erythrocytes coated with defined amounts of IgM antibody. Among patients with increased platelet-IgM there was a significant correlation both with the presence of increased platelet-C3 as well as the amount of platelet-C3. The authors demonstrated the presence of warm-reacting IgM anti-platelet antibodies in the plasma of two of these patients who were further studied. These studies demonstrate the presence of warm-reacting IgM anti-platelet antibodies in some patients with ITP. They suggest that the binding of complement to platelets by IgM antibodies may initiate platelet clearance as well as enhance the effect of IgG antibodies in ITP.

  6. Balancing Therapy with Thrombopoietin Receptor Agonists and Splenectomy in Refractory Immune Thrombocytopenic Purpura: A Case of Postsplenectomy Thrombocytosis Requiring Plateletpheresis.

    PubMed

    Zimmerman, Jacquelyn; Norsworthy, Kelly J; Brodsky, Robert

    2016-01-01

    Immune thrombocytopenic purpura (ITP) causes thrombocytopenia through the autoimmune destruction of platelets. Corticosteroids remain the first line of therapy, and traditionally splenectomy has been the second. While the availability of thrombopoietin receptor agonists (TPO-RAs) has expanded treatment options, there is little data for the ideal management of these agents in preparation for splenectomy. Thrombocytosis has been reported after splenectomy in patients treated with TPO-RA preoperatively, with one prior case requiring plateletpheresis for symptomatic thrombocytosis. We present a case report and review of the literature pertaining to this complication and provide recommendations for preventing postsplenectomy thrombocytosis in ITP patients on TPO-RAs.

  7. Balancing Therapy with Thrombopoietin Receptor Agonists and Splenectomy in Refractory Immune Thrombocytopenic Purpura: A Case of Postsplenectomy Thrombocytosis Requiring Plateletpheresis

    PubMed Central

    Zimmerman, Jacquelyn; Norsworthy, Kelly J.

    2016-01-01

    Immune thrombocytopenic purpura (ITP) causes thrombocytopenia through the autoimmune destruction of platelets. Corticosteroids remain the first line of therapy, and traditionally splenectomy has been the second. While the availability of thrombopoietin receptor agonists (TPO-RAs) has expanded treatment options, there is little data for the ideal management of these agents in preparation for splenectomy. Thrombocytosis has been reported after splenectomy in patients treated with TPO-RA preoperatively, with one prior case requiring plateletpheresis for symptomatic thrombocytosis. We present a case report and review of the literature pertaining to this complication and provide recommendations for preventing postsplenectomy thrombocytosis in ITP patients on TPO-RAs. PMID:27812394

  8. Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome concomitant with immune hemolytic anemia and immune thrombocytopenic purpura (Evans syndrome).

    PubMed

    Korkmaz, Huseyin; Bugdaci, Mehmet Sait; Temel, Tuncer; Dagli, Mehmet; Karabagli, Pinar

    2013-04-01

    Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) associated with Evans syndrome; combination of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP) has rarely been reported. We report the case of a 53-year-old patient who presented with weakness, myalgia, arthralgia, shortness of breath and purpura. Initial laboratory investigations revealed liver dysfunction, anemia and thrombocytopenia. Anti-nuclear (ANA) and antimitochondrial M2 (AMA M2) antibodies were positive. Diagnose of PBC-AIH overlap was made by clinical, serological and histological investigations. AIHA and ITP was identified with clinical-laboratory findings and bone marrow puncture. She was treated with IVIG followed by prednisolone and ursodeoxycholic acid. Hemoglobin-thrombocytes increased rapidly and transaminases improved at day 8. We have reported the first case in the literature with AIH-PBC overlap syndrome concurrent by ITP and AIHA which suggest the presence of shared genetic susceptibility factors in multiple autoimmune conditions including AIH, PBC, ITP and AIHA.

  9. Detection of expression of IL-18 and its binding protein in Egyptian pediatric immune thrombocytopenic purpura.

    PubMed

    Shaheen, Iman A; Botros, Shahira K A; Morgan, Dalia S

    2014-01-01

    Immune thrombocytopenic purpura (ITP) is an autoimmune disorder, characterized by dysfunctional cellular immunity including the presence of activated platelet specific autoreactive T cells that recognize and respond to autologous platelet antigens. Autoreactive T cells drive the generation of platelet reactive autoantibodies by B cells as well as T-cytotoxic cell-mediated lysis of platelets. Interleukin-18 (IL-18) is a mediator of T helper type 1 cell responses synergistically with IL-12 that initiate and promote host defense and inflammation. IL-18 has a specific binding protein (IL-18BP) which belongs to the immunoglobulin superfamily. In the present study, serum level and messenger RNA( mRNA) expression of IL-18 as well as IL-18BP mRNA expression were measured in peripheral blood mononuclear cells (PBMNCs) of 100 Egyptian pediatric patients with ITP (70 acute and 30 chronic). In addition to this, we recruited 80 healthy volunteers in order to investigate the possible association between the imbalance of IL-18 and IL-18 BP expressions and the pathogenesis of ITP. IL-18 serum level and mRNA expression were not elevated in cases more than in the control group, but IL-18 mRNA was higher in chronic cases when compared to the acute ones (p=0.031) and there was a good negative correlation between the platelet count and serum IL-18. IL-18 BP m-RNA was slightly elevated in cases more than in the control group (95% Confidence interval=1.15-2.01). Our results were not supportive for previous findings of elevated IL18/BP mRNA ratio in ITP patients. This could be referred to the fact that autoimmune diseases are complex genetic disorders, therefore further studies on polymorphisms affecting IL-18 gene expression as well as kinetics of IL-18 expression are required to evaluate the role of interleukin 18 and its binding protein in the pathogenesis of ITP.

  10. Two Types of Renovascular Lesions in Lupus Nephritis with Clinical Thrombotic Thrombocytopenic Purpura.

    PubMed

    Sekine, Akinari; Hasegawa, Eiko; Hiramatsu, Rikako; Mise, Koki; Sumida, Keiichi; Ueno, Toshiharu; Yamanouchi, Masayuki; Hayami, Noriko; Suwabe, Tatsuya; Hoshino, Junichi; Sawa, Naoki; Takaichi, Kenmei; Ohashi, Kenichi; Fujii, Takeshi; Ubara, Yoshifumi

    2015-01-01

    Renovascular lesions of lupus nephritis (LN) were classified into five categories by D'Agati in Heptinstall's Pathology of the Kidney, with thrombotic microangiopathy (TMA) and clinical thrombotic thrombocytopenic purpura (TTP) being combined. We encountered 2 cases with histological LN (class III and lass V), and they presented with clinical features of TTP, such as acute renal failure, microangiopathic hemolytic anemia, thrombocytopenia, fever, and central neurologic symptoms. Immunosuppressive therapy with plasmapheresis was performed in both patients. Case 1 progressed to end-stage renal failure requiring dialysis and died, while case 2 responded to treatment. In case 1, small renal arteries showed positive mural staining for IgG and C3, while intraluminal material was negative for IgG and C3 [although it was positive for phosphotungstic acid-hematoxylin (PTAH), indicating fibrin deposition]. In case 2, small renal arteries showed mural staining for IgG, C1q, and C3, with the intraluminal material also being positive for these immunoglobulins, but negative for PTAH. These cases suggest that immunosuppressive therapy with plasmapheresis can control LN when intravascular thrombosis is related to immune complexes associated with activation of the early complement components C1q and C3. In contrast, immunosuppressive therapy with plasmapheresis may not be effective when intravascular thrombosis is unrelated to these factors and involves fibrin deposition. Accordingly, in LN patients with clinical features of TTP, we report two types of renovascular lesions, in addition to typical vascular change of TMA with no immune deposits seen in nonlupus patients.

  11. Ribosomal and immune transcripts associate with relapse in acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura.

    PubMed

    Edgar, Contessa E; Terrell, Deirdra R; Vesely, Sara K; Wren, Jonathan D; Dozmorov, Igor M; Niewold, Timothy B; Brown, Michael; Zhou, Fang; Frank, Mark Barton; Merrill, Joan T; Kremer Hovinga, Johanna A; Lämmle, Bernhard; James, Judith A; George, James N; Farris, A Darise

    2015-01-01

    Approximately 40% of patients who survive acute episodes of thrombotic thrombocytopenic purpura (TTP) associated with severe acquired ADAMTS13 deficiency experience one or more relapses. Risk factors for relapse other than severe ADAMTS13 deficiency and ADAMTS13 autoantibodies are unknown. ADAMTS13 autoantibodies, TTP episodes following infection or type I interferon treatment and reported ensuing systemic lupus erythematosus in some patients suggest immune dysregulation. This cross-sectional study asked whether autoantibodies against RNA-binding proteins or peripheral blood gene expression profiles measured during remission are associated with history of prior relapse in acquired ADAMTS13-deficient TTP. Peripheral blood from 38 well-characterized patients with autoimmune ADAMTS13-deficient TTP in remission was examined for autoantibodies and global gene expression. A subset of TTP patients (9 patients, 24%) exhibited a peripheral blood gene signature composed of elevated ribosomal transcripts that associated with prior relapse. A non-overlapping subset of TTP patients (9 patients, 24%) displayed a peripheral blood type I interferon gene signature that associated with autoantibodies to RNA-binding proteins but not with history of relapse. Patients who had relapsed bimodally expressed higher HLA transcript levels independently of ribosomal transcripts. Presence of any one potential risk factor (ribosomal gene signature, elevated HLA-DRB1, elevated HLA-DRB5) associated with relapse (OR = 38.4; p = 0.0002) more closely than any factor alone or all factors together. Levels of immune transcripts typical of natural killer (NK) and T lymphocytes positively correlated with ribosomal gene expression and number of prior episodes but not with time since the most recent episode. Flow cytometry confirmed elevated expression of cell surface markers encoded by these transcripts on T and/or NK cell subsets of patients who had relapsed. These data associate elevated ribosomal and

  12. Mycophenolate mofetil (MMF) for the treatment of steroid-resistant idiopathic thrombocytopenic purpura.

    PubMed

    Hou, Ming; Peng, Jun; Shi, Yan; Zhang, Chunqing; Qin, Ping; Zhao, Chuanli; Ji, Xuebin; Wang, Xueyong; Zhang, Maohong

    2003-06-01

    The treatment of chronic idiopathic thrombocytopenic purpura (ITP) is difficult in those unresponsive to corticosteroids and/or splenectomy. We attempted to induce durable response in 21 patients with refractory ITP by applying mycophenolate mofetil (MMF) (1.5-2.0 g/d), a novel immunosuppressive agent. Overall response rate was 62% (13 of 21), including 24% (five of 21) in complete response (CR), 29% (six of 21) in partial response (PR), and 10% (two of 21) in minor response (MR). The response rates for non-splenectomized and splenectomized ITP patients were 64% (nine of 14) and 57% (four of seven), respectively (P > 0.05). 39% (five of 13) responders relapsed as a result of dose reduction or withdraw of MMF, and 61% (eight of 13) responders maintained their effectiveness for a median of 24 wk. Sustained response was observed in three patients in whom MMF was withdrawn. MMF was well tolerated with only slight nausea and diarrhea recorded in 3 of 21 cases. No premature withdrawal was found in this study. CD3+ peripheral blood mononuclear cells (PBMC) and CD19+ PBMC were significantly reduced 12 wk after MMF administration in the responders. Platelet-associated antibodies against glycoproteins GPIIb/IIIa were detected in 13 of 21 (62%) patients before MMF treatment, and antibody levels were significantly decreased in responders 12 wk after MMF administration. This suggested that MMF might correct the immunologic abnormalities underlying the destruction of circulating platelets in ITP. We conclude that MMF could be used as a second-line agent for the treatment of steroid-resistant ITP before or after splenectomy and thereby is worth of further evaluation in randomized studies.

  13. Helicobacter pylori Eradication in Patients with Immune Thrombocytopenic Purpura: A Review and the Role of Biogeography.

    PubMed

    Frydman, Galit H; Davis, Nick; Beck, Paul L; Fox, James G

    2015-08-01

    Idiopathic thrombocytopenic purpura (ITP) is typically a diagnosis of exclusion, assigned by clinicians after ruling out other identifiable etiologies. Since a report by Gasbarrini et al. in 1998, an accumulating body of evidence has proposed a pathophysiological link between ITP and chronic Helicobacter pylori (H. pylori) infection. Clinical reports have described a spontaneous resolution of ITP symptoms in about 50% of chronic ITP patients following empirical treatment of H. pylori infection, but response appears to be geography dependent. Studies have also documented that ITP patients in East Asian countries are more likely to express positive antibody titers against H. pylori-specific cytotoxic-associated gene A (CagA), a virulence factor that is associated with an increased risk for gastric diseases including carcinoma. While a definitive mechanism by which H. pylori may induce thrombocytopenia remains elusive, proposed pathways include molecular mimicry of CagA by host autoantibodies against platelet surface glycoproteins, as well as perturbations in the phagocytic activity of monocytes. Traditional treatments of ITP have been largely empirical, involving the use of immunosuppressive agents and immunoglobulin therapy. However, based on the findings of clinical reports emerging over the past 20 years, health organizations around the world increasingly suggest the detection and eradication of H. pylori as a treatment for ITP. Elucidating the exact molecular mechanisms of platelet activation in H. pylori-positive ITP patients, while considering biogeographical differences in response rates, could offer insight into how best to use clinical H. pylori eradication to treat ITP, but will require well-designed studies to confirm the suggested causative relationship between bacterial infection and an autoimmune disease state.

  14. Splenectomy: Does it still play a role in the management of thrombotic thrombocytopenic purpura?

    PubMed Central

    Dubois, Luc; Gray, Daryl K.

    2010-01-01

    Background Plasma exchange is first-line therapy for patients with thrombotic thrombocytopenic purpura (TTP). Splenectomy is often indicated for patients with relapsing or refractory disease. Concerns exist about its efficacy and safety in these patients. We describe a series of patients whose TTP was treated with laparoscopic splenectomy. We also reviewed the literature in order to describe the use and safety of splenectomy for refractory or relapsing TTP. Methods We reviewed the charts of consecutive patients with TTP referred for splenectomy and searched MEDLINE for studies describing outcomes following splenectomy for relapsing or refractory TTP. Results In all, 5 patients were referred for relapsing TTP and underwent uneventful laparoscopic splenectomy. All 5 were in remission after more than 40 months of follow-up. We found 18 studies (87 patients) reporting the results of splenectomy for relapsing TTP and 15 studies (74 patients) involving patients who underwent splenectomy for refractory TTP. The aggregate complication (6% v. 10%) and mortality rates (1.2% v. 5%) were lower for patients who received treatment for relapsing versus refractory TTP. The rate of postsplenectomy relapse among patients with relapsing disease was 17%, whereas the nonresponse rate was 8% for patients with refractory TTP. There were no complications among the 22 laparoscopic cases reported. Conclusion Although the data supporting splenectomy for treatment of TTP are limited to case series with no control groups, they suggest that splenectomy is an option for patients with refractory or relapsing disease. When performed laparoscopically in patients with relapsing disease, splenectomy is associated with minimal morbidity and mortality. PMID:20858382

  15. Opana ER abuse and thrombotic thrombocytopenic purpura (TTP)-like illness: a rising risk factor in illicit drug users.

    PubMed

    Kapila, Aaysha; Chhabra, Lovely; Chaubey, Vinod K; Summers, Jeffery

    2014-03-03

    We report the case of a 22 year-old-woman who presented with upper extremity cellulitis secondary to an infiltration of illicit intravenous drug use. She confessed to the intravenous use of Opana ER (an extended release oral formulation of oxymorphone) which is an opioid drug approved only for oral use. She was found to have clinical evidence of profound thrombotic microangiopathy which resulted due to the intravenous use of Opana ER. She showed full clinical improvement after withholding drug and supportive clinical care. Recent report of Opana ER intravenous abuse was published from Tennessee county and has now been increasingly recognised as one of the causes of thrombocytopenia which mimicks clinically as thrombotic thrombocytopenic purpura. Physicians should be aware of this association as the lack of familiarity to this can pose serious management dilemmas for our patients (especially the polysubstance abusers).

  16. Multidrug resistance-1 in T lymphocytes and natural killer cells of adults with idiopathic thrombocytopenic purpura: effect of prednisone treatment.

    PubMed

    López-Karpovitch, Xavier; Graue, Gerardo; Crespo-Solís, Erick; Piedras, Josefa

    2008-07-01

    High P-glycoprotein-mediated multidrug resistance-1 (P-gp/MDR1) activity in lymphocytes from idiopathic thrombocytopenic purpura (ITP) patients may affect disease outcome. ITP treatment includes glucocorticoids that are substrates of P-gp; hence, P-gp functional activity and antigenic expression were assessed by flow cytometry in T and natural killer (NK) cells from ITP patients before and after prednisone therapy. Herein, patients' T and NK cells did not show increased MDR1 functional activity, whereas P-gp antigenic expression was significantly enhanced in both therapy-free and prednisone-treated patients. Prednisone treatment did not significantly modify the function and expression of MDR1 in T and NK cells of ITP patients.

  17. Thrombotic Thrombocytopenic Purpura with Reversible Neurological Features: Brain Diffusion MRI with ADC Map, Spect and EEG Findings. A Case Report.

    PubMed

    Yerdelen, D; Göksel, B K; Yıldırım, T; Karataş, M; Karaca, S; Reyhan, M; Ozdoğu, H

    2006-11-30

    Although nervous system involvement is common in thrombotic thrombocytopenic purpura (TTP), abnormalities on computerized tomography, magnetic resonance imaging and electroencephalography are not encountered so frequently and if present, these abnormalities are often reversible. We describe a 39-year-old woman with recurring transient focal neurological findings found to have laboratory findings consistent with TTP. In cerebral diffusion weighted images (DWI), diffuse cortical hyperintensity was noted in right frontal lobe, but the ADC (apparent diffusion coefficient) map was normal. Electroencephalography demonstrated lateralized slowing and repeated DWI showed diffuse cortical hyperintensity in the right hemisphere. SPECT showed luxury perfusion in the right hemisphere areas. The patient's condition resolved with plasmapheresis. Our patient illustrates that diffuse hemispheric involvement can be seen in DWI and EEG, and SPECT may show luxury perfusion after resolution of neurological findings in TTP cases. To our knowledge, this is the first TTP case in which the ADC map was normal.

  18. Low-dose vincristine in the treatment of corticosteroid-refractory idiopathic thrombocytopenic purpura (ITP) in non-splenectomized patients.

    PubMed Central

    Cervantes, F.; Montserrat, E.; Rozman, C.; Diumenjo, C.; Feliu, E.; Grañena, A.

    1980-01-01

    Eight non-splenectomized patients with corticosteroid-refractory idiopathic thrombocytopenic purpura (ITP) were treated with low-dose vincristine (1 mg/week up to a total dose of 4 mg). Complete remission was achieved in 2 cases and partial remission in 3. Bleeding stopped in one patient who failed to remit. No statistical relationship was found between the response to vincristine and the duration of the disease or the corticosteroid-therapy. Side effects were only observed in one patient. By comparing these results with those reported in the literature, it can be inferred that low-dose vincristine may be useful in the management of corticosteroid-refractory ITP. PMID:7194478

  19. Simultaneous reactivation of herpes simplex virus and varicella-zoster virus in a patient with idiopathic thrombocytopenic purpura.

    PubMed

    Nikkels, A F; Frère, P; Rakic, L; Fassotte, M; Evrard, B; De Mol, P; Piérard, G E

    1999-01-01

    Simultaneous reactivation of distinct Herpesviridae with development of clinical manifestations is exceptional. We report a 48-year-old woman suffering from idiopathic thrombocytopenic purpura. As the disease remained refractory to corticosteroids, immunoglobulins and splenectomy, a cure of vinblastine was administered. An atypical stomatitis developed few days later. Immunohistochemistry on a Tzanck smear and a biopsy evidenced a Herpes simplex virus type 1 (HSV-1) infection. The patient presented simultaneously a single necrotic lesion on the abdomen. Immunohistochemistry on a skin biopsy revealed the presence of the varicella-zoster virus (VZV) gE, gB and IE63 proteins. Intravenous aciclovir was initiated. The present case of simultaneous clinical infections by HSV-I and VZV underlines the importance of complementary viral identification testing in the event of unusual clinical presentations.

  20. ADAMTS13 and anti-ADAMTS13 autoantibodies in thrombotic thrombocytopenic purpura - current perspectives and new treatment strategies.

    PubMed

    Tersteeg, Claudia; Verhenne, Sebastien; Roose, Elien; Schelpe, An-Sofie; Deckmyn, Hans; De Meyer, Simon F; Vanhoorelbeke, Karen

    2016-01-01

    A deficiency in ADAMTS13 (A Disintegrin And Metalloprotease with ThromboSpondin type-1 repeats, member 13) is associated with thrombotic thrombocytopenic purpura (TTP). Congenital TTP is caused by a defect in the ADAMTS13 gene resulting in decreased or absent enzyme activity; acquired TTP results from autoantibodies that either inhibit the activity or increase the clearance of ADAMTS13. Despite major progress in recent years in our understanding of the disease, many aspects around the pathophysiology of TTP are still unclear. Newer studies expanded the TTP field from ADAMTS13 and inhibitory antibodies to immune complexes, cloned autoantibodies, and a possible involvement of other proteases. Additionally, several new treatment strategies supplementing plasma-exchange and infusion are under investigation for a better and more specific treatment of TTP patients. In this review, we discuss the recent insights in TTP pathophysiology and describe upcoming therapeutic opportunities.

  1. Adult-onset congenital thrombotic thrombocytopenic purpura caused by a novel compound heterozygous mutation of the ADAMTS13 gene.

    PubMed

    Krabbe, Johannes G; Kemna, Evelien W M; Strunk, Annuska L M; Jobse, Pieter A; Kramer, P A; Dikkeschei, L D; van den Heuvel, L P W J; Fijnheer, Rob; Verdonck, Leo F

    2015-10-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease, characterized by microangiopathic hemolytic anaemia and thrombocytopenia, resulting in neurologic and/or renal abnormalities. We report a 49-year-old patient with a history of thrombotic events, renal failure, and thrombocytopenia. Blood analysis demonstrated no ADAMTS13 activity in the absence of antibodies against ADAMTS13. The complete ADAMTS13 gene was sequenced, and two mutations were identified: one mutation on exon 24 (Arg1060Asp), which had previously been described, and a mutation on exon 27 (Met1260IlefsX34), which has not been reported. For these mutations, compound heterozygosity appears to be necessary to cause TTP, as family members of the patient display only one of the mutations and all displayed normal ADAMTS13 activity.

  2. Thrombotic thrombocytopenic purpura (TPP) successfully rescued by plasma exchange in the ICU: A report of two cases

    PubMed Central

    ZOU, XIULI; WU, TIEJUN; ZHANG, XIHONG; QU, AIJUN; TIAN, SUOCHEN

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disorder, which is characterized by thrombus formation in small blood vessels. The present study retrospectively analyzed the clinical data from two patients with severe TTP, who were treated successfully in the intensive care unit (ICU) at the Liaocheng People's Hospital in 2013. Comprehensive therapies were administered to the patients, including plasma exchange (PE), mechanical ventilation (case 1 only), steroid therapy, blood transfusion and anti-inflammatory treatment (case 2 only). The two patients returned to a stable state and were transferred back to the hematology department following PE. The positive outcome achieved for these patients suggests that early intervention involving bedside PE in the ICU may reduce the mortality rate of patients with severe TTP who have concurrent respiratory or circulatory failure and cannot be treated in the dialysis unit. PMID:27347058

  3. [Detection, diagnosis and analysis of the first case of neonatal alloimmune thrombocytopenia purpura associated with anti-HPA-5b in China].

    PubMed

    Zhou, Yan; Zhong, Zhou-Lin; Li, Li-Lan; Shen, Wei-Dong; Wu, Guo-Guang

    2014-04-01

    This study was aimed to investigate the detection and diagnosis of the neonatal alloimmune thrombocytopenia purpura (NAITP) caused by anti-HPA-5b antibody. The platelet count and clinical manifestation in the newborn were examined. The HPA-1-21bw genotypes of the newborn and her parents were detected by multiple-PCR and DNA sequencing. The HPA-specific antibody in the sera of newborn and her mother were detected and identified by flow cytometry (FCM) and monoclonal antibody-specific immobilization of platelet antigens (MAIPA). The results indicated that the clinical manifestations of the newborn were lighter. The HPA genotyping showed that the genotype of the newborn was HPA-5ab, while that of her mother and father were HPA-5aa and HPA-5ab, respectively. The antibody against the platelet of newborn's father existed in the newborn's mother sera. The HPA antibody of the mother was identified as anti-HPA-5b. It is concluded that the newborn with neonatal alloimmune thrombocytopenia purpura was caused by the antibody against HPA-5b.

  4. Treatment of plasmapheresis refractory thrombotic thrombocytopenic purpura with double-filtration membrane plasmapheresis.

    PubMed

    Karakus, Volkan; Deveci, Burak; Kurtoğlu, Erdal

    2013-06-01

    Thrombotic thrombocytic purpura (TTP) is a life-threatening disorder. Without plasma exchange treatment (PET) the mortality rate is quite high. Double-filtration plasmapheresis is an alternative opportunity for TTP patients refractory to PET. Here we report our experience in a refractory TTP patient who was successfully treated by means of double-filtration plasmapheresis therapy.

  5. DNMT3B 579G>T promoter polymorphism and the risk for idiopathic thrombocytopenic purpura in a Chinese population.

    PubMed

    Zhao, Haifeng; Du, Weiting; Gu, Dongsheng; Wang, Donghai; Xue, Feng; Ge, Jing; Sui, Tao; Yang, Renchi

    2009-01-01

    Epigenetics may influence the expression of numerous genes, which might contribute to autoimmune diseases. DNA methylation is mediated by DNA methyltransferases, especially DNA methyltransferase 3B (DNMT3B). Polymorphisms of the DNMT3B gene may influence DNMT3B activity on DNA methylation and increase the susceptibility to several diseases. The current study investigated the association between DNMT3B 579G>T and the risk for idiopathic thrombocytopenic purpura (ITP). The DNMT3B 579G>T polymorphisms were analyzed by PCR-RFLP. There was no significant difference in genotype and allele distribution between the ITP patient and the controls (p = 0.722 and 0.667, respectively). Similar results were observed between the 2 groups when stratified by age and disease course, including acute in childhood, chronic in childhood, acute in adult and chronic in adult. Importantly, this study showed a statistical difference in the distribution of SNP of DNMT3B between Chinese and Koreans or Americans. It is shown that the SNP of DNMT3B 579G>T may not be used on its own as a marker to predict the susceptibility to ITP in a Chinese population and that DNMT3B 579G>T promoter SNP varies from one ethnic population to another.

  6. Complement activation on platelets correlates with a decrease in circulating immature platelets in patients with immune thrombocytopenic purpura.

    PubMed

    Peerschke, Ellinor I B; Andemariam, Biree; Yin, Wei; Bussel, James B

    2010-02-01

    The role of the complement system in immune thrombocytopenic purpura (ITP) is not well defined. We examined plasma from 79 patients with ITP, 50 healthy volunteers, and 25 patients with non-immune mediated thrombocytopenia, to investigate their complement activation/fixation capacity (CAC) on immobilized heterologous platelets. Enhanced CAC was found in 46 plasma samples (59%) from patients with ITP, but no samples from patients with non-immune mediated thrombocytopenia. Plasma from healthy volunteers was used for comparison. In patients with ITP, an enhanced plasma CAC was associated with a decreased circulating absolute immature platelet fraction (A-IPF) (<15 x 10(9)/l) (P = 0.027) and thrombocytopenia (platelet count < 100 x 10(9)/l) (P = 0.024). The positive predictive value of an enhanced CAC for a low A-IPF was 93%, with a specificity of 77%. The specificity and positive predictive values increased to 100% when plasma CAC was defined strictly by enhanced C1q and/or C4d deposition on test platelets. Although no statistically significant correlation emerged between CAC and response to different pharmacological therapies, an enhanced response to splenectomy was noted (P < 0.063). Thus, complement fixation may contribute to the thrombocytopenia of ITP by enhancing clearance of opsonized platelets from the circulation, and/or directly damaging platelets and megakaryocytes.

  7. Thrombocytopenia in pregnancy: do the time of diagnosis and delivery route affect pregnancy outcome in parturients with idiopathic thrombocytopenic purpura?

    PubMed

    Yuce, T; Acar, D; Kalafat, E; Alkilic, A; Cetindag, E; Soylemez, F

    2014-12-01

    The objective of this study was to investigate the determining effects of diagnosis time on pregnancy outcomes in a population of pregnant women with idiopathic thrombocytopenic purpura (ITP). Records of all the pregnant women with thrombocytopenia were evaluated. Those with a confirmed diagnosis of ITP were included in the study. Main outcome measures were antenatal thrombocyte count, postpartum haemorrhage rate, and route of delivery. Foetal outcomes such as foetal thrombocyte count, haemorrhage, and birth weight were also reported as secondary outcome measures. Time of diagnosis either antenatal or preconception did not significantly alter the investigated parameters. Delivery route had no impact on complication rates. Time of diagnosis also did not affect treatment modality. ITP is rare disorder accounting for less than 5 % of all pregnant thrombocytopenias. Time of diagnosis does not affect maternal-foetal outcomes or treatment modality unless diagnosis is made during labour. Compared to gestational thrombocytopenia, treatment rates may differ but treatment modalities remain the same and the effort put into making the differential should be weighed against maternal stress factors for lengthy laboratory evaluation as long as the thrombocytopenia is of pure nature without any systemic involvement.

  8. Idiopathic Relapsing Thrombotic Thrombocytopenic Purpura with Persistent ADAMTS13 Inhibitor Activity Treated Sequentially with Plasmapheresis, Rituximab, Cyclophosphamide and Splenectomy.

    PubMed

    Musa, Faisal; Baidas, Said

    2015-01-01

    We here describe a patient with an idiopathic thrombotic thrombocytopenic purpura (TTP) secondary to an ADAMTS13 inhibitor that continued to be dependent on plasmapheresis until the patient was treated with rituximab. TTP manifestations subsided with rituximab treatment in spite of a persistently low ADAMTS13 activity and continued a detectable inhibitor activity until the patient developed an intolerance to rituximab due to an allergic reaction when cyclophosphamide was added; this resulted in a normalization of ADAMTS13 activity and the disappearance of the inhibitor. Later, the patient developed an intolerance to rituximab due to a severe allergic reaction. Soon after stopping rituximab, the ADAMTS13 activity level dipped below 5% in addition to the appearance of the ADAMTS13 inhibitor. The patient had a splenectomy after rituximab and cyclophosphamide treatment; the medication was stopped based on several case reports of a complete remission of TTP after splenectomy. We believe that the reason TTP went into remission in our patient was because of rituximab treatment, in spite of both persistently low ADAMTS13 activity and a detectable inhibitor activity due to reducing the release of von Willebrand factor large multimers from the endothelial cells. We found that ADAMTS13 activity normalized and the inhibitor activity became undetectable when cyclophosphamide was added to rituximab. We suggest adding cyclophosphamide to rituximab for the treatment of patients with persistent ADAMTS13 inhibitors in order to prolong the remission period and lower the rate of relapse.

  9. The splenic autoimmune response to ADAMTS13 in thrombotic thrombocytopenic purpura contains recurrent antigen-binding CDR3 motifs.

    PubMed

    Schaller, Monica; Vogel, Monique; Kentouche, Karim; Lämmle, Bernhard; Kremer Hovinga, Johanna A

    2014-11-27

    Acquired thrombotic thrombocytopenic purpura (TTP) is the consequence of a severe ADAMTS13 deficiency resulting from autoantibodies inhibiting ADAMTS13 or accelerating its clearance. Despite the success of plasma exchange the risk of relapse is high. From 2 patients (A and B), splenectomized for recurrent episodes of acquired TTP, the splenic B-cell response against ADAMTS13 was characterized through generation of human monoclonal anti-ADAMTS13 autoantibodies (mAbs) by cloning an immunoglobulin G (IgG)4κ- and IgG4λ-Fab library using phage display technology and by Epstein-Barr virus transformation of switched memory B cells (CD19+/CD27+/IgG+). Sequence analysis of the anti-ADAMTS13 IgGs of both patients revealed that the VH gene use was limited in our patients to VH1-3 (55%), VH1-69 (17%), VH3-30 (7%), and VH4-28 (21%) and contained 8 unique and thus far not reported heavy-chain complementarity determining region 3 motifs, of which 4 were shared by the 2 patients. The discovery of several highly similar anti-ADAMTS13 autoantibodies in 2 unrelated TTP patients suggests that the autoimmune response is antigen driven, because the probability that such similar immunoglobulin rearrangements happen by chance is very low (< 10(-9)).

  10. Clinical Features and Treatment Outcomes of Primary Immune Thrombocytopenic Purpura in Hospitalized Children Under 2-Years Old

    PubMed Central

    Farhangi, H; Ghasemi, A; Banihashem, A; Badiei, Z; Jarahi, L; Eslami, G; Langaee, T

    2016-01-01

    Background Immune thrombocytopenic purpura (ITP) is the most prevalent cause of thrombocytopenia in children. Despite the importance of ITP in children under 2-years old, only a few publications are available in the literature.ITP usually presents itself as isolated thrombocytopenia and mucocutaneous bleeding. Materials and Methods This study was conducted on 187 under 2-year-old children diagnosed with ITP and treated at Dr. Sheikh Hospital from 2004 to 2011.In this retrospective study, clinical symptoms, laboratory findings, history of viral infections, vaccination history, and treatment efficacy in children under 2-years old with ITP were investigated.Patients were followed for one year after being discharged from the hospital. Results The risk of the disease developing into chronic form was higher in older children (0.001). ITP in children under 3-months old was significantly associated with vaccination (p=0.007). There was no significant differences between male and female patients in regards to newly diagnosed ITP, persistent, and chronic disease status (p = 0.21). No significant difference in bleeding symptoms was observed between patients under 3-months old and 3 to 24-months old (p=0.18). Conclusion Infantile ITP respond favorably to treatment. The risk of the disease developing into chronic form is higher in 3-to-24-month-old children compared to under-three-month olds. PMID:27222699

  11. New developments in idiopathic thrombocytopenic purpura (ITP): cooperative, prospective studies by the Intercontinental Childhood ITP Study Group.

    PubMed

    Imbach, Paul; Kühne, Thomas; Zimmerman, Sherri

    2003-12-01

    Based on 6 years of experience with worldwide cooperation of investigators in the field of hematology, the International Childhood ITP Study Group (ICIS) has provided a long-term concept for prospective studies and new, evidence-based definitions of idiopathic thrombocytopenic purpura (ITP). Structured interactions between the cooperating investigators, the ICIS board, the writing committees, an expert panel, and the central operative office are summarized in the Rules of the ICIS. Preliminary experience shows high acceptance of the activities of the ICIS by participants from many countries. There is good cooperation, resulting in analyses and publication of results. New areas of focus for ICIS include the formation of an expert panel, regular meetings, and publication of results from current studies. Long-term financial resources must be found. ICIS is looking back on 6 constructive years of international cooperation resulting in new or confirmatory evidence regarding the demographics, diagnosis, natural history, and management of childhood ITP. New structures and cooperation must be identified to continue this productive endeavor.

  12. Dysplastic changes in idiopathic thrombocytopenic purpura and the effect of corticosteroids to increase dysplasia and cause hyperdiploid macropolycytes.

    PubMed

    Olcay, L; Yetgin, S; Okur, H; Erekul, S; Tuncer, M

    2000-10-01

    This study evaluates the dysplastic hematological changes in nine patients with idiopathic thrombocytopenic purpura (ITP) in 11 attacks, before and after corticosteroid treatment. The pretreatment blood smears of patients with ITP, displayed more neutrophils with bizarre nuclei (P < 0.001), Döhle or Döhle-like inclusions (P < 0. 01), irregular distribution of granules (P < 0.05), hypo-agranulation (P < 0.05), pseudo-Pelger-Huet-like cells (P < 0. 01), and nuclei with chromatine clumping (P < 0.01) than the normal children. The eosinophils of ITP patients were also dysplastic, before treatment. The pretreatment diameter of the neutrophils and the percentage of macropolycytes were greater than those of the patients with viral infections and normal group (P < 0.05 for all). The percentage of neutrophils with bizarre nuclei and nuclei with chromatine clumping and the diameter of neutrophils and macropolycyte percentage increased with corticosteroid therapy (P < 0.01, < 0.01, < 0.01, and < 0.05, respectively). The neutrophil diameter, percentage of macropolycytes, and number of neutrophils with bizarre nuclei decreased within 1-4 weeks after the therapy was stopped. In the neutrophils of two patients, diploidy and hyperdiploidy were established before and on the last day of therapy, respectively, and diploidy reversed after therapy was stopped. In conclusion, ITP patients display dysplastic findings in both neutrophils and eosinophils before treatment and corticosteroids cause transient significant increase in some of the dysplastic changes in neutrophils.

  13. Use of Recombinant Factor VIIa in a Pediatric Patient With Initial Presentation of Refractory Acute Immune Thrombocytopenic Purpura and Severe Bleeding

    PubMed Central

    Gurion, Reut; Siu, Anita; Weiss, Aaron R.; Masterson, Margaret

    2012-01-01

    Severe bleeding in acute immune thrombocytopenic purpura (ITP) is rare but can cause significant complications to the patient. Here we report the case of a pediatric patient with acute ITP and hematuria refractory to anti-D immune globulin, high dose intravenous immunoglobulin G, and high dose steroids. Her hematuria was successfully treated with recombinant factor VIIa (rFVIIa). While further investigation on the use of rFVIIa in ITP is warranted, this case report contributes to the pediatric literature for its use during the course of an initial presentation of ITP with hemorrhagic complications. PMID:23258971

  14. Level of IL-16 and Reticulated Platelets Percentage during the Clinical Course of Immune Thrombocytopenic Purpura in Children.

    PubMed

    Abd El-Glil, Reem R; Assar, Effat H

    2015-01-01

    Immune thrombocytopenic purpura (ITP) is an immune-mediated acquired disease with transient or persistent decrease of thrombocytes number in the blood. Cytokines play important roles in the immune regulation and are known to be deregulated in autoimmune diseases. This study aimed to investigate serum IL-16 levels in relation to reticulated platelets in children with ITP and platelet count. Twenty six children with ITP (11 with newly diagnosed ITP, 9 with persistent ITP and 6 with chronic ITP) and 12 age-matched healthy children controls were studied. Serum level of IL-16 and reticulated platelets count were assessed by Enzyme Linked Immunosorbent Assay (ELISA) and flow cytometry respectively. Serum IL-16 levels were significantly higher in patients as compared to controls (P < 0.001). Within patients, the levels were higher in newly diagnosed compared to persistent and chronic ITP (P < 0.01) and (P < 0.001) respectively. IL-16 levels were also significantly higher in persistent ITP compared to chronic ITP (P < 0.001). Reticulated platelets were also elevated in patients compared to controls and the increase was significant in newly diagnosed group (P < 0.05). Negative correlation was found between IL-16 level and reticulated platelets and platelets counts (r = -0.284, P = 0.028, r = 0.274 P = 0.25) respectively. It is concluded that IL-16 may be valuable in predicting the clinical course of pediatrics ITP. Measurement of reticulated platelets may provide significant information about thrombopoietic activity during the clinical course of ITP in children.

  15. Rituximab therapy for chonic and refractory immune thrombocytopenic purpura: a long-term follow-up analysis

    PubMed Central

    Garcia-Chavez, Jaime; Montiel-Cervantes, Laura; Esparza, Miriam García-Ruiz; Vela-Ojeda, Jorge

    2007-01-01

    The aim of this study was to evaluate the long-term response to rituximab in patients with chronic and refractory immune thrombocytopenic purpura (ITP). Adults with ITP fail to respond to conventional therapies in almost 30% of cases, developing a refractory disease. Rituximab has been successfully used in these patients. We used rituximab at 375 mg/m2, IV, weekly for a total of four doses in 18 adult patients. Complete remission (CR) was considered if the platelet count was >100 × 109/l, partial remission (PR) if platelets were >50 × 109/l, minimal response (MR) if the platelet count was >30 × 109/l and <50 × 109/l, and no response if platelet count remained unchanged. Response was classified as sustained (SR) when it was stable for a minimum of 6 months. Median age was 43.5 years (range, 17 to 70). Median platelet count at baseline was 12.5 × 109/l (range, 3.0 to 26.3). CR was achieved in five patients (28%), PR in five (28%), MR in four (22%), and two patients were classified as therapeutic failures (11%). Two additional patients were lost to follow-up. The median time between rituximab therapy and response was 14 weeks (range, 4 to 32). SR was achieved in 12 patients (67%). There were no severe adverse events during rituximab therapy. During follow-up (median, 26 months; range, 12 to 59), no other immunosuppressive drugs were used. In conclusion, rituximab therapy is effective and safe in adult patients with chronic and refractory ITP. Overall response rate achieved is high, long term, and with no risk of adverse events. PMID:17874322

  16. Association of interleukin-(IL)10 haplotypes and serum IL-10 levels in the progression of childhood immune thrombocytopenic purpura.

    PubMed

    Tesse, Riccardina; Del Vecchio, Giovanni Carlo; De Mattia, Domenico; Sangerardi, Maria; Valente, Federica; Giordano, Paola

    2012-08-15

    Derangement of genetic and immunological factors seems to have a pivotal role in the pathophysiology of immune thrombocytopenic purpura (ITP). We investigated interleukin(IL)-10 genetically determined expression in children with an acute progression of ITP (n=41) compared to young patients with chronic ITP (n=44) and healthy controls (n=60), and attempted to correlate IL-10 production with the course of the disease. We genotyped our study population for three single nucleotide polymorphisms at positions -1082 (A/G), -819 (C/T) and -592 (C/A) in the promoter region of the IL-10 gene. IL-10 levels were measured by enzyme-linked immunoassay. The IL-10 production in our study population was significantly higher in patients carrying the GCC haplotype than those bearing ACC and ATA haplotypes (6.9 ± 1.5 vs 3.6 ± 0.8 vs 3.3 ± 0.3, p=0.03). The serum concentration of IL-10 was significantly higher in patients with an acute course of their disease, who mainly carried the GCC haplotype (92%), compared to chronic subjects, bearing the non-GCC haplotypes, and controls [17 pg/mL (1.7-18) vs 3.5 pg/mL (0.6-11) vs 3 pg/mL (1-7), p<0.01)]. Our findings show that patients carrying the GCC-high producer IL-10 haplotype have an acute development of ITP and that IL-10 levels might represent a useful predictive biomarker of the disease course.

  17. FRETS-VWF73 rather than CBA assay reflects ADAMTS13 proteolytic activity in acquired thrombotic thrombocytopenic purpura patients.

    PubMed

    Mancini, I; Valsecchi, C; Lotta, L A; Deforche, L; Pontiggia, S; Bajetta, M; Palla, R; Vanhoorelbeke, K; Peyvandi, F

    2014-08-01

    Collagen-binding activity (CBA) and FRETS-VWF73 assays are widely adopted methods for the measurement of the plasmatic activity of ADAMTS13, the von Willebrand factor (VWF) cleaving-protease. Accurately assessing the severe deficiency of ADAMTS13 is important in the management of thrombotic thrombocytopenic purpura (TTP). However, non-concordant results between the two assays have been reported in a small but relevant percentage of TTP cases. We investigated whether CBA or FRETS-VWF73 assay reflects ADAMTS13 proteolytic activity in acquired TTP patients with non-concordant measurements. Twenty plasma samples with non-concordant ADAMTS13 activity results, <10% using FRETS-VWF73 and ≥20% using CBA, and 11 samples with concordant results, <10% using either FRETS-VWF73 and CBA assays, were analysed. FRETS-VWF73 was performed in the presence of 1.5 M urea. ADAMTS13 activities were also measured under flow conditions and the VWF multimer pattern was defined in order to verify the presence of ultra-large VWF due to ADAMTS13 deficiency. In FRETS-VWF73 assay with 1.5 M urea, ADAMTS13 activity significantly increased in roughly 50% of the samples with non-concordant results, whereas it remained undetectable in all samples with concordant measurements. Under flow conditions, all tested samples showed reduced ADAMTS13 activity. Finally, samples with non-concordant results showed a ratio of high molecular weight VWF multimers higher than normal. Our results support the use of FRETS-VWF73 over CBA assay for the assessment of ADAMTS13 severe deficiency and indicate urea as one cause of the observed differences.

  18. Analysis of clinical effects and mechanism of recombinant human interleukin-11 with glucocorticoids for treatment of idiopathic thrombocytopenic purpura

    PubMed Central

    Wu, Xifeng; Wang, Lijuan; Sun, Lin; Li, Tantan; Ran, Xuehong

    2017-01-01

    The aim of the present study was to evaluate the effectiveness and safety of recombinant human interleukin-11 (IL-11) with glucocorticoids for treatment of adult idiopathic thrombocytopenic purpura (ITP) and the regulatory effect on immune mechanisms. A total of 80 patients with initial diagnosis of ITP admitted to our hospital were selected. Patients were randomly divided into the control group and observation group, with 40 cases each. The control group received glucocorticoids treatment, and the observation group received IL-11 and glucocorticoids. The treatment effects were compared. The total effective rate and effective degree of the observation group was higher than in the control group and the difference was statistically significant (P<0.05); comparing the incidence of complications of the two groups, there was no statistical difference (P>0.05). In the observation group, onset time was reduced, platelet recovery level increased and platelet antibody positive rate decreased, and the differences were statistically significant (P<0.05). The total treatment course was shorter and recurrence rate was lower in the observation group compared with the control group, and the differences were statistically significant (P<0.05). The percentage of CD4+CD25+ regulatory T cells decreased in the two groups after treatment, and was more pronounced in the observation group. The difference was statistically significant (P<0.05). In conclusion, IL-11 with glucocorticoids for the treatment of adult ITP is safe and effective, and may be associated with decreased percentage of CD4+CD25+ regulatory T cells. PMID:28352325

  19. Role of ADAMTS13 in the management of thrombotic microangiopathies including thrombotic thrombocytopenic purpura (TTP).

    PubMed

    Shah, Neil; Rutherford, Cynthia; Matevosyan, Karen; Shen, Yu-Min; Sarode, Ravi

    2013-11-01

    The clinical presentation of thrombotic thrombocytopenia purpura (TTP) and other thrombotic microangiopathies (TMAs) can often be similar. The role of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) in diagnosing TTP is accepted by most researchers but continues to be debated in a few studies. We report the experience of our single-centre academic institution, where ADAMTS13 is used to diagnose TTP and guide plasma exchange (PLEX). Patients presenting to our institution with thrombotic microangiopathy (60 patients) between January 2006 and December 2012 were divided into two groups based on ADAMTS13 activity and clinical history. Patients with ADAMTS13 activity <10% were included in the TTP (n = 30) cohort while patients with activity >11% were classified as 'other microangiopathies' (TMA, n = 30). PLEX was only initiated in patients with a high likelihood of TTP and discontinued when the baseline ADAMTS13 activity was >11%. Patients with severe ADAMTS13 deficiency (TTP group) showed significant presenting differences: lower platelet counts, less renal dysfunction, higher presence of neurological abnormalities, and greater haemolysis markers as compared to non-deficient patients (TMA group). Most importantly, patients without severe ADAMTS13 deficiency were safely managed without increased mortality despite receiving no PLEX or discontinuing PLEX after a short course (upon availability of ADAMTS13 results). In conclusion, ADAMTS13 can be used to diagnose TTP and guide appropriate PLEX therapy.

  20. A single-institution, 20-year prospective experience with an affordable Fc-receptor blockade method to treat patients with chronic, refractory autoimmune thrombocytopenic purpura.

    PubMed

    Estrada-Gómez, Roberto; Vargas-Castro, Olga; Oropeza-Borges, Mabel; González-Carrillo, Martha L; Pérez-Romano, Beatriz; Ruiz-Argüelles, Guillermo J

    2007-01-01

    In a 20-year period in a single institution, 34 patients with chronic, refractory autoimmune thrombocytopenic purpura were prospectively treated with ex vivo anti-D opsonized autologous red blood cells. All patients had received previous treatment with steroids and/or immunosuppressive agents, and 11 had been splenectomized. Twenty one patients had an increase in the platelet count; in five cases, the increase was more than 50 x 10(9)/L platelets and in 16 the increase was more than 100 x 10(9)/L platelets. Early responses were observed in 20 patients and late responses in seven, whereas seven patients (20%) did not respond at all. Nine of the 20 individuals who achieved an ER had a subsequent drop in the platelet count; however, only three had a drop below 50 x 10(9)/L. When last censored, of the 34 patients, 24 (70%) had a platelet count above 50 x 10(9)/L. The 84-month thrombocytopenia-free (over 50 x 10(9)/L platelets) status of the whole group is 70%, whereas the 84-month complete remission (over 100 x 10(9)/L platelets) status of the whole group is 50%. It is concluded that the use of ex vivo anti-D opsonized red blood cells may represent another, substantially cheaper treatment of patients with chronic, refractory, autoimmune thrombocytopenic purpura.

  1. Posttransfusion purpura associated with alloantibody specific for the platelet antigen, Pen(a).

    PubMed

    Simon, T L; Collins, J; Kunicki, T J; Furihata, K; Smith, K J; Aster, R H

    1988-09-01

    Posttransfusion purpura (PTP) and severe thrombocytopenia occurred 9 days after transfusion of red blood cells to a 48-year-old, multiparous Navajo woman. The platelet count rose to hemostatic levels after treatment with prednisone and three plasma exchange transfusions. Serologic studies showed that the patient's serum contained the potent antibody reactive with platelets from nearly all normal subjects, but nonreactive with autologous platelets obtained after recovery. This antibody was found to be specific for a high-frequency, platelet-specific antigen, designated Pen(a),implicated previously as an immunogen in neonatal alloimmune thrombocytopenic purpura. An exchange of serum showed that Pena is identical with an alloantigen designated Yuk(b) by Japanese workers. We conclude that PTP can occur in association with alloimmunization against Pen(a) (Yuk(b).

  2. Generation of Anti-Murine ADAMTS13 Antibodies and Their Application in a Mouse Model for Acquired Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Deforche, Louis; Tersteeg, Claudia; Roose, Elien; Vandenbulcke, Aline; Vandeputte, Nele; Pareyn, Inge; De Cock, Elien; Rottensteiner, Hanspeter; Deckmyn, Hans; De Meyer, Simon F.; Vanhoorelbeke, Karen

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy linked to a deficiency in the metalloprotease ADAMTS13. In the current study, a novel mouse model for acquired TTP was generated to facilitate development and validation of new therapies for this disease. Therefore, a large panel (n = 19) of novel anti-mouse ADAMTS13 (mADAMTS13) monoclonal antibodies (mAbs) of mouse origin was generated. Inhibitory anti-mADAMTS13 mAbs were identified using the FRETS-VWF73 assay. Four mAbs strongly inhibited mADAMTS13 activity in vitro (∼68–90% inhibition). Injecting a combination of 2 inhibitory mAbs (13B4 and 14H7, 1.25 mg/kg each) in Adamts13+/+ mice resulted in full inhibition of plasma ADAMTS13 activity (96 ± 4% inhibition, day 1 post injection), leading to the appearance of ultra-large von Willebrand factor (UL-VWF) multimers. Interestingly, the inhibitory anti-mADAMTS13 mAbs 13B4 and 14H7 were ideally suited to induce long-term ADAMTS13 deficiency in Adamts13+/+ mice. A single bolus injection resulted in full ex vivo inhibition for more than 7 days. As expected, the mice with the acquired ADAMTS13 deficiency did not spontaneously develop TTP, despite the accumulation of UL-VWF multimers. In line with the Adamts13-/- mice, TTP-like symptoms could only be induced when an additional trigger (rVWF) was administered. On the other hand, the availability of our panel of anti-mADAMTS13 mAbs allowed us to further develop a sensitive ELISA to detect ADAMTS13 in mouse plasma. In conclusion, a novel acquired TTP mouse model was generated through the development of inhibitory anti-mADAMTS13 mAbs. Consequently, this model provides new opportunities for the development and validation of novel treatments for patients with TTP. In addition, these newly developed inhibitory anti-mADAMTS13 mAbs are of great value to specifically study the role of ADAMTS13 in mouse models of thrombo-inflammatory disease. PMID:27479501

  3. Generation of Anti-Murine ADAMTS13 Antibodies and Their Application in a Mouse Model for Acquired Thrombotic Thrombocytopenic Purpura.

    PubMed

    Deforche, Louis; Tersteeg, Claudia; Roose, Elien; Vandenbulcke, Aline; Vandeputte, Nele; Pareyn, Inge; De Cock, Elien; Rottensteiner, Hanspeter; Deckmyn, Hans; De Meyer, Simon F; Vanhoorelbeke, Karen

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy linked to a deficiency in the metalloprotease ADAMTS13. In the current study, a novel mouse model for acquired TTP was generated to facilitate development and validation of new therapies for this disease. Therefore, a large panel (n = 19) of novel anti-mouse ADAMTS13 (mADAMTS13) monoclonal antibodies (mAbs) of mouse origin was generated. Inhibitory anti-mADAMTS13 mAbs were identified using the FRETS-VWF73 assay. Four mAbs strongly inhibited mADAMTS13 activity in vitro (∼68-90% inhibition). Injecting a combination of 2 inhibitory mAbs (13B4 and 14H7, 1.25 mg/kg each) in Adamts13+/+ mice resulted in full inhibition of plasma ADAMTS13 activity (96 ± 4% inhibition, day 1 post injection), leading to the appearance of ultra-large von Willebrand factor (UL-VWF) multimers. Interestingly, the inhibitory anti-mADAMTS13 mAbs 13B4 and 14H7 were ideally suited to induce long-term ADAMTS13 deficiency in Adamts13+/+ mice. A single bolus injection resulted in full ex vivo inhibition for more than 7 days. As expected, the mice with the acquired ADAMTS13 deficiency did not spontaneously develop TTP, despite the accumulation of UL-VWF multimers. In line with the Adamts13-/- mice, TTP-like symptoms could only be induced when an additional trigger (rVWF) was administered. On the other hand, the availability of our panel of anti-mADAMTS13 mAbs allowed us to further develop a sensitive ELISA to detect ADAMTS13 in mouse plasma. In conclusion, a novel acquired TTP mouse model was generated through the development of inhibitory anti-mADAMTS13 mAbs. Consequently, this model provides new opportunities for the development and validation of novel treatments for patients with TTP. In addition, these newly developed inhibitory anti-mADAMTS13 mAbs are of great value to specifically study the role of ADAMTS13 in mouse models of thrombo-inflammatory disease.

  4. Systemic Lupus Erythematosus Presenting as Refractory Thrombotic Thrombocytopenic Purpura: A Diagnostic and Management Challenge. A Case Report and Concise Review of the Literature

    PubMed Central

    Abu-Hishmeh, Mohammad; Sattar, Alamgir; Zarlasht, Fnu; Ramadan, Mohamed; Abdel-Rahman, Aisha; Hinson, Shante; Hwang, Caroline

    2016-01-01

    Patient: Female, 34 Final Diagnosis: Refractory thrombotic thrombocytopenic purpura Symptoms: Fatigue Medication: — Clinical Procedure: Plasma exchange Specialty: Rheumatology • Hematology and Critical Care Objective: Rare co-existance of disease or pathology Background: Thrombotic thrombocytopenic purpura (TTP) is one of the thrombotic microangiopathic (TMA) syndromes, caused by severely reduced activity of the vWF-cleaving protease ADAMTS13. Systemic lupus erythematosus (SLE), on the other hand, is an autoimmune disease that affects various organs in the body, including the hematopoietic system. SLE can present with TMA, and differentiating between SLE and TTP in those cases can be very challenging, particularly in patients with no prior history of SLE. Furthermore, an association between these 2 diseases has been described in the literature, with most of the TTP cases occurring after the diagnosis of SLE. In rare cases, TTP may precede the diagnosis of SLE or occur concurrently. Case Report: We present a case of a previously healthy 34-year-old female who presented with dizziness and flu-like symptoms and was found to have thrombocytopenia, hemolytic anemia, and schistocytes in the peripheral smear. She was subsequently diagnosed with TTP and started on plasmapheresis and high-dose steroids, but without a sustained response. A diagnosis of refractory TTP was made, and she was transferred to our facility for further management. Initially, the patient was started on rituximab, but her condition continued to deteriorate, with worsening thrombocytopenia. Later, she also fulfilled the Systemic Lupus International Collaborating Clinics (SLICC) criteria for diagnosis of SLE. Treatment of TTP in SLE patients is generally similar to that in the general population, but in refractory cases there are few reports in the literature that show the efficacy of cyclophosphamide. We started our patient on cyclophosphamide and noticed a sustained improvement in the platelet

  5. The TITAN trial--assessing the efficacy and safety of an anti-von Willebrand factor Nanobody in patients with acquired thrombotic thrombocytopenic purpura.

    PubMed

    Holz, Josefin-Beate

    2012-06-01

    The Phase II TITAN trial is designed to assess the efficacy and safety of an anti-von Willebrand factor (vWF) Nanobody in patients with acquired thrombotic thrombocytopenic purpura (TTP). Nanobodies are a novel class of therapeutic proteins and are based on the smallest functional fragments of single-chain antibodies that occur naturally in the Camelidae family (Nanobody® and Nanobodies® are registered trademarks of Ablynx NV). With vWF implicated in the thrombotic process underlying TTP, an anti-vWF Nanobody may hold significant promise as adjunctive therapy to plasma exchange. Recruitment is currently ongoing, and aims to include a total of 110 patients from countries in Europe, the Middle East, Australia and Northern America.

  6. Renal thrombotic microangiopathies/thrombotic thrombocytopenic purpura in a patient with primary Sjögren's syndrome complicated with IgM monoclonal gammopathy of undetermined significance.

    PubMed

    Koga, Tomohiro; Yamasaki, Satoshi; Nakamura, Hideki; Kawakami, Atsushi; Furusu, Akira; Taguchi, Takashi; Eguchi, Katsumi

    2013-01-01

    Thrombotic microangiopathy (TMA)/thrombotic thrombocytopenic purpura (TTP) is a rare but potentially lethal condition requiring rapid recognition, diagnosis, and initiation of therapy. We experienced a case of a 61-year-old woman with primary Sjögren's syndrome (pSS) complicated with severe renal TMA/TTP following IgM monoclonal gammopathy of undetermined significance (MGUS). She was admitted to our hospital for further evaluation of hypergammaglobulinema, acute renal failure, and severe thrombocytopenia. She had been diagnosed with pSS 13 years prior to admission. Histological examination of her kidney revealed fibrin thrombi in the glomeruli and arterioles, a finding that is consistent with TMA/TTP. The patient was subsequently treated with plasma exchange, which resulted in a successful outcome without any complications. This rare case suggests that it is important to make a therapeutic decision based on appropriate and prompt pathological diagnosis.

  7. Acquired thrombotic thrombocytopenic purpura due to antibody-mediated ADAMTS13 deficiency precipitated by a localized Castleman's disease: a case report.

    PubMed

    Benevides, Thais Celi Lopes; Orsi, Fernanda Andrade; Colella, Marina Pereira; Percout, Priscila de Oliveira; Moura, Muriel Silva; Dias, Maria Almeida; Lins, Betina Diniz; Paula, Erich Vinicius de; Vassallo, Jose; Annichino-Bizzachi, Joyce

    2015-01-01

    Acquired ADAMTS13 inhibitor causing thrombotic thrombocytopenic purpura (TTP) may be precipitated by some infections, inflammatory diseases or neoplasia. We reported a case of refractory TTP precipitated by a newly diagnosed localized Castleman's disease (CD). TTP was initially treated with plasma exchange and immunosuppressive therapy with corticosteroids; however the treatment failed to promote sustained response. During hospitalization, an abdominal tumor was diagnosed and resected; the histological analysis revealed a CD of hyaline-vascular variant rich stroma. After tumor removal, the patient achieved a long-lasting clinical remission and normalized ADAMTS13 activity. This clinical case describes a novel association of acquired ADAMTS13 inhibitor and CD. The antibody to ADAMTS13 developed along with the systemic manifestation of CD and promptly disappeared after the resection of the tumor. There are reports of neoplasia-associated thrombotic microangiopathy however direct evidence of CD-dependent ADAMTS13 inhibitor had not yet been reported.

  8. Citrate anticoagulation during plasma exchange in a patient with thrombotic thrombocytopenic purpura: short heparin-free hemodialysis helps to attenuate citrate load.

    PubMed

    Buturović-Ponikvar, Jadranka; Pernat, Andreja Marn; Ponikvar, Rafael

    2005-06-01

    The treatment of thrombotic thrombocytopenic purpura requires plasma exchange using fresh frozen plasma as a replacement solution once or even twice daily. If citrate anticoagulation is needed, the citrate load (both from fresh frozen plasma and citrate as an anticoagulant) can be significant, causing metabolic complications. The aim of our report is to present our experience with citrate anticoagulation in a patient with thrombotic thrombocytopenic purpura treated with daily membrane plasma exchange. Twenty-six plasma exchange procedures were performed during 20 days of treatment in a 46-year-old female. The blood flow was 98 +/- 8 mL/min; 4% trisodium citrate was infused into the arterial line (134 +/- 11 mL/h) and 1 M CaCl2 into the venous line (11.4 +/- 1.8 mL/h). Fresh frozen plasma (first 7 procedures) or cryo-poor plasma (19 procedures) were used as a replacement solution, 3176 +/- 536 mL per procedure. A total of 88,930 mL of plasma was exchanged. No serious side-effects occurred. iCa before plasma exchange was significantly higher than afterwards (1.23 +/- 0.12 vs. 1.12 +/- 0.12, P = 0.0047). Significant alkalosis occurred after three plasma exchanges (pH 7.64, bicarbonate 36.2 mmol/L), and was corrected by 3-h heparin-free hemodialysis with dialysate as follows: K 4.0 mmol/L, calcium 1.5 mmol/L, and bicarbonate set to 24 mmol/L. After dialysis, pH was 7.45 and bicarbonate 29.4 mmol/L. Another (2-h) heparin-free hemodialysis procedure was repeated after six plasma exchanges. Citrate anticoagulation can be safely performed in patients treated with plasma exchange once or twice daily. Periodically performed short heparin-free hemodialysis can correct metabolic alkalosis and attenuate the citrate load.

  9. Treatment with liposome-encapsulated clodronate as a new strategic approach in the management of immune thrombocytopenic purpura in a mouse model.

    PubMed

    Alves-Rosa, F; Stanganelli, C; Cabrera, J; van Rooijen, N; Palermo, M S; Isturiz, M A

    2000-10-15

    Immune thrombocytopenic purpura (ITP) is an autoimmune disease related to the presence of elevated levels of platelet-associated immunoglobulin, or autoantibodies. In recent years the importance of macrophage Fc gamma receptors in the uptake of platelets in ITP has been confirmed. Although in patients with ITP the platelet destruction occurs in liver and spleen, in this present experimental mouse model the liver was the principal organ of sequestration of sensitized platelets. The uptake in the spleen, bone marrow, lung, and kidneys was negligible and not different from that in control animals. In addition, the trapped platelets did not return to circulation, and new cells derived from the platelet-storage pool or new thrombocytogenesis were necessary to restore the platelet count. The depletion of splenic and hepatic murine macrophages by liposome-encapsulated clodronate (lip-clod) was studied as a new strategy for ITP treatment. Lip-clod inhibits, in a dose-dependent manner, the antibody-induced thrombocytopenia. Moreover, lip-clod treatment rapidly restored (24 hours) the platelet count in thrombocytopenic animals to hematologic safe values, and despite additional antiplatelet antiserum treatment, mice were able to maintain this level of platelets at least up to 48 hours. The bleeding times in lip-clod-treated animals was not different from those in controls, demonstrating that the hemostasis was well controlled in these animals. The results presented in this study demonstrate that lip-clod treatment can be effective in the management of experimental ITP. (Blood. 2000;96:2834-2840)

  10. Comparison of intravenous immune globulin and high dose anti-D immune globulin as initial therapy for childhood immune thrombocytopenic purpura.

    PubMed

    Kane, Ian; Ragucci, Dominic; Shatat, Ibrahim F; Bussel, James; Kalpatthi, Ram

    2010-04-01

    This report documents our experience with intravenous immune globulin (IVIG) (1 g/kg, iv) and high-dose, anti-D immune globulin (anti-D) (75 microg/kg) as initial treatment for childhood immune thrombocytopenic purpura (ITP). The medical records of children diagnosed with ITP at a single institution between January 2003 and May 2008 were retrospectively reviewed. Participants received either IVIG or high-dose anti-D immune globulin as their initial treatment for ITP. For the 53 patients included for analysis, there was no statistical difference in efficacy between each group; however, patients who received anti-D experienced a higher rate of adverse drug reactions (ADRs), particularly chills and rigours, and 2 of 24 patients in the anti-D group developed severe anaemia requiring medical intervention. Patients who presented with mucosal bleeding had higher rates of treatment failure (32%) compared to those who presented with dry purpura (6%), regardless of treatment. Both IVIG and high-dose anti-D are effective first-line therapies for childhood ITP. However, we observed increased ADRs in the high-dose anti-D group in contrast to previously published reports. Further studies are needed to evaluate safety and premedications for high-dose anti-D and to determine the utility of using the presence of mucosal bleeding to predict treatment failure.

  11. Idiopathic thrombocytopenic purpura (ITP)

    MedlinePlus

    Blood tests will be done to check your platelet count . A bone marrow aspiration or biopsy may also be done. ... the disease usually goes away without treatment. Some children ... the platelet count in about half of people. However, other drug ...

  12. Thrombotic Thrombocytopenic Purpura

    MedlinePlus

    ... make a normal ADAMTS13 enzyme. As a result, enzyme activity is lacking or changed. Acquired TTP is the ... the body makes antibodies (proteins) that block the activity of the ADAMTS13 enzyme. It's not clear what triggers inherited and acquired ...

  13. Thrombotic thrombocytopenic purpura

    MedlinePlus

    ... level Mucus membrane biopsy Platelet count Urinalysis Von Willebrand factor assay Treatment You may have a treatment ... recover completely. But some people die of this disease, especially if it is not diagnosed right away. ...

  14. Association of CD4+CD25+FoxP3+ regulatory T cells with natural course of childhood chronic immune thrombocytopenic purpura

    PubMed Central

    Son, Bo Ra

    2015-01-01

    Purpose The purpose of this study was to determine the frequency of CD4+CD25+FoxP3+ regulatory T cells (Treg) in the peripheral blood of patients with childhood chronic immune thrombocytopenic purpura (ITP) exhibiting thrombocytopenia and spontaneous remission. The findings of this study indicate the possibility of predicting spontaneous recovery and pathogenesis of childhood chronic ITP. Methods Eleven children with chronic ITP (seven thrombocytopenic and four spontaneous remission cases; mean age, 8.8 years; range, 1.7-14.9 years) were enrolled in this study. Five healthy children and eight healthy adults were included as controls. The frequency of Treg was evaluated by flow cytometry in the peripheral blood. Results In this study, four patients (36%) achieved spontaneous remission within 2.8 years (mean year; range, 1.0-4.4 years). The frequency of Treg was significantly lower in patients with persisting thrombocytopenia (0.13%±0.09%, P<0.05), than that in the patients with spontaneous remission (0.30%±0.02%), healthy adults controls (0.55%±0.44%), and healthy children controls (0.46%±0.26%). A significantly positive correlation was found between the frequency of Treg and the platelet count in children. Conclusion These data suggest that a lower frequency of Treg contributes to the breakdown of self-tolerance, and may form the basis for future development of specific immunomodulatory therapies. Furthermore, Treg frequency has prognostic implication toward the natural course and long-term outcomes of childhood chronic ITP. PMID:26124848

  15. Systemic Lupus Erythematosus Presenting as Refractory Thrombotic Thrombocytopenic Purpura: A Diagnostic and Management Challenge. A Case Report and Concise Review of the Literature.

    PubMed

    Abu-Hishmeh, Mohammad; Sattar, Alamgir; Zarlasht, Fnu; Ramadan, Mohamed; Abdel-Rahman, Aisha; Hinson, Shante; Hwang, Caroline

    2016-10-25

    BACKGROUND Thrombotic thrombocytopenic purpura (TTP) is one of the thrombotic microangiopathic (TMA) syndromes, caused by severely reduced activity of the vWF-cleaving protease ADAMTS13. Systemic lupus erythematosus (SLE), on the other hand, is an autoimmune disease that affects various organs in the body, including the hematopoietic system. SLE can present with TMA, and differentiating between SLE and TTP in those cases can be very challenging, particularly in patients with no prior history of SLE. Furthermore, an association between these 2 diseases has been described in the literature, with most of the TTP cases occurring after the diagnosis of SLE. In rare cases, TTP may precede the diagnosis of SLE or occur concurrently. CASE REPORT We present a case of a previously healthy 34-year-old female who presented with dizziness and flu-like symptoms and was found to have thrombocytopenia, hemolytic anemia, and schistocytes in the peripheral smear. She was subsequently diagnosed with TTP and started on plasmapheresis and high-dose steroids, but without a sustained response. A diagnosis of refractory TTP was made, and she was transferred to our facility for further management. Initially, the patient was started on rituximab, but her condition continued to deteriorate, with worsening thrombocytopenia. Later, she also fulfilled the Systemic Lupus International Collaborating Clinics (SLICC) criteria for diagnosis of SLE. Treatment of TTP in SLE patients is generally similar to that in the general population, but in refractory cases there are few reports in the literature that show the efficacy of cyclophosphamide. We started our patient on cyclophosphamide and noticed a sustained improvement in the platelet count in the following weeks. CONCLUSIONS Thrombotic thrombocytopenic purpura is a life-threatening hematological emergency which must be diagnosed and treated in a timely manner. Refractory cases of TTP have been described in the literature, but without clear evidence

  16. Efficacy of a rituximab regimen based on B cell depletion in thrombotic thrombocytopenic purpura with suboptimal response to standard treatment: Results of a phase II, multicenter noncomparative study.

    PubMed

    Benhamou, Ygal; Paintaud, Gilles; Azoulay, Elie; Poullin, Pascale; Galicier, Lionel; Desvignes, Céline; Baudel, Jean-Luc; Peltier, Julie; Mira, Jean-Paul; Pène, Frédéric; Presne, Claire; Saheb, Samir; Deligny, Christophe; Rousseau, Alexandra; Féger, Frédéric; Veyradier, Agnès; Coppo, Paul

    2016-12-01

    The standard four-rituximab infusions treatment in acquired thrombotic thrombocytopenic purpura (TTP) remains empirical. Peripheral B cell depletion is correlated with the decrease in serum concentrations of anti-ADAMTS13 and associated with clinical response. To assess the efficacy of a rituximab regimen based on B cell depletion, 24 TTP patients were enrolled in this prospective multicentre single arm phase II study and then compared to patients from a previous study. Patients with a suboptimal response to a plasma exchange-based regimen received two infusions of rituximab 375 mg m(-2) within 4 days, and a third dose at day +15 of the first infusion if peripheral B cells were still detectable. Primary endpoint was the assessment of the time required to platelet count recovery from the first plasma exchange. Three patients died after the first rituximab administration. In the remaining patients, the B cell-driven treatment hastened remission and ADAMTS13 activity recovery as a result of rapid anti-ADAMTS13 depletion in a similar manner to the standard four-rituximab infusions schedule. The 1-year relapse-free survival was also comparable between both groups. A rituximab regimen based on B cell depletion is feasible and provides comparable results than with the four-rituximab infusions schedule. This regimen could represent a new standard in TTP. This trial was registered at www.clinicaltrials.gov (NCT00907751). Am. J. Hematol. 91:1246-1251, 2016. © 2016 Wiley Periodicals, Inc.

  17. Effect of immunoglobulin G (IgG) interchain disulfide bond cleavage on efficacy of intravenous immunoglobulin for immune thrombocytopenic purpura (ITP).

    PubMed

    Machino, Y; Ohta, H; Suzuki, E; Higurashi, S; Tezuka, T; Nagashima, H; Kohroki, J; Masuho, Y

    2010-12-01

    Intravenous immunoglobulin (IVIG) has been used widely to treat immune thrombocytopenic purpura (ITP), but the mechanisms of its action remain unclear. We investigated the affinity for Fcγ receptors (FcγRs) and the thrombocytopenia-ameliorating effect of S-sulfonated gammaglobulin (SGG) and S-alkylated gammaglobulin (AGG), in comparison with unmodified gammaglobulin (GG), in a mouse ITP model. Cleavage of immunoglobulin (Ig)G interchain disulfide bonds by either S-sulfonation or S-alkylation did not decrease the affinity for FcγRIIA (CD32A) and FcγRIIB (CD32B), but did decrease the affinity for FcγRIA (CD64A) and FcγRIIIA (CD16A), presumably because of changes in H-chain configuration. The interchain disulfide bond cleavage decreased the affinity much more for mouse FcγRIV than for mouse FcγRIIB. The ability of AGG to ameliorate ITP was greatly diminished, while SGG, whose disulfide bonds are reconstituted in vivo, was as effective as GG. These results suggest that the interchain disulfide bonds are important for therapeutic effect. It is also suggested that the interaction of IVIG with the inhibitory receptor FcγRIIB is insufficient for effective amelioration of ITP and that, at least in this model, direct binding of IVIG to FcγRIIIA is also required.

  18. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group.

    PubMed

    Rodeghiero, Francesco; Stasi, Roberto; Gernsheimer, Terry; Michel, Marc; Provan, Drew; Arnold, Donald M; Bussel, James B; Cines, Douglas B; Chong, Beng H; Cooper, Nichola; Godeau, Bertrand; Lechner, Klaus; Mazzucconi, Maria Gabriella; McMillan, Robert; Sanz, Miguel A; Imbach, Paul; Blanchette, Victor; Kühne, Thomas; Ruggeri, Marco; George, James N

    2009-03-12

    Diagnosis and management of immune thrombocytopenic purpura (ITP) remain largely dependent on clinical expertise and observations more than on evidence derived from clinical trials of high scientific quality. One major obstacle to the implementation of such studies and in producing reliable meta-analyses of existing data is a lack of consensus on standardized critical definitions, outcome criteria, and terminology. Moreover, the demand for comparative clinical trials has dramatically increased since the introduction of new classes of therapeutic agents, such as thrombopoietin receptor agonists, and innovative treatment modalities, such as anti-CD 20 antibodies. To overcome the present heterogeneity, an International Working Group of recognized expert clinicians convened a 2-day structured meeting (the Vicenza Consensus Conference) to define standard terminology and definitions for primary ITP and its different phases and criteria for the grading of severity, and clinically meaningful outcomes and response. These consensus criteria and definitions could be used by investigational clinical trials or cohort studies. Adoption of these recommendations would serve to improve communication among investigators, to enhance comparability among clinical trials, to facilitate meta-analyses and development of therapeutic guidelines, and to provide a standardized framework for regulatory agencies.

  19. Molecular mimicry by Helicobacter pylori CagA protein may be involved in the pathogenesis of H. pylori-associated chronic idiopathic thrombocytopenic purpura.

    PubMed

    Takahashi, Toru; Yujiri, Toshiaki; Shinohara, Kenji; Inoue, Yusuke; Sato, Yutaka; Fujii, Yasuhiko; Okubo, Masashi; Zaitsu, Yuzuru; Ariyoshi, Koichi; Nakamura, Yukinori; Nawata, Ryouhei; Oka, Yoshitomo; Shirai, Mutsunori; Tanizawa, Yukio

    2004-01-01

    The eradication of Helicobacter pylori often leads to platelet recovery in patients with chronic idiopathic thrombocytopenic purpura (cITP). Although this clinical observation suggests the involvement of H. pylori, little is known about the pathogenesis of cITP. We initially examined the effect of H. pylori eradication on platelet counts in 20 adult Japanese cITP patients. Then, using platelet eluates as the probe in immunoblot analyses, we examined the role of molecular mimicry in the pathogenesis of cITP. Helicobacter pylori infection was detected in 75% (15 of 20) of cITP patients. Eradication was achieved in 13 (87%) of the H. pylori-positive patients, seven (54%) of which showed increased platelet counts within the 4 months following treatment. Completely responsive patients also showed significant declines in platelet-associated immunoglobulin G (PAIgG) levels. Platelet eluates from 12 (nine H. pylori-positive and three H. pylori-negative) patients recognized H. pylori cytotoxin-associated gene A (CagA) protein, and in three completely responsive patients, levels of anti-CagA antibody in platelet eluates declined after eradication therapy. Cross-reactivity between PAIgG and H. pylori CagA protein suggests that molecular mimicry by CagA plays a key role in the pathogenesis of a subset of cITP patients.

  20. Micromegakaryocytes in a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and chronic thrombocytopenic purpura

    SciTech Connect

    Gangarossa, S.; Mattina, T.; Romano, V.; Milana, G.; Mollica, F.; Schiliro, G.

    1996-03-15

    Thrombocytopenia or pancytopenia is frequently reported in patients with partial 11q deletion but there are no reports on bone marrow morphology of these patients. We report on a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and its classical clinical manifestations including chronic thrombocytopenic purpura in whom micromegakaryocytes were found in the bone marrow aspirate. This is the first report of the presence of micromegakaryocytes in the bone marrow of a patient with 11q deletion. Accurate examination of the bone marrow of other patients with the 11q deletion may clarify whether the observation of micromegakaryocytes is common in these patients. Micromegakaryocytes may indicate a defect of development. Two genes for two DNA binding proteins that are likely to be involved in hematopoiesis map in the 11q region: Ets-1, that maps to 11q24, close to D11S912, and the nuclear-factor-related-kB gene that maps to 11q24-q25. It is possible that these genes, when present in only one copy, result in thrombocytopenia or pancytopenia as observed in this patient. 23 refs., 2 figs., 1 tab.

  1. Platelet turnover and kinetics in immune thrombocytopenic purpura: results with autologous 111In-labeled platelets and homologous 51Cr-labeled platelets differ

    SciTech Connect

    Heyns A du, P.; Badenhorst, P.N.; Loetter, M.G.P.; Pieters, H.; Wessels, P.; Kotze, H.F.

    1986-01-01

    Mean platelet survival and turnover were simultaneously determined with autologous 111In-labeled platelets (111In-AP) and homologous 51Cr-labeled platelets (51Cr-HP) in ten patients with chronic immune thrombocytopenic purpura (ITP). In vivo redistribution of the 111In-AP was quantitated with a scintillation camera and computer-assisted image analysis. The patients were divided into two groups: those with splenic platelet sequestration (spleen-liver 111In activity ratio greater than 1.4), and those with diffuse sequestration in the reticuloendothelial system. The latter patients had more severe ITP reflected by pronounced thrombocytopenia, decreased platelet turnover, and prominent early hepatic platelet sequestration. Mean platelet life span estimated with 51Cr-HP was consistently shorter than that of 111In-AP. Platelet turnover determined with 51Cr-HP was thus over-estimated. The difference in results with the two isotope labels was apparently due to greater in vivo elution of 51Cr. Although the limitations of the techniques should be taken into account, these findings indicate that platelet turnover is not always normal or increased in ITP, but is low in severe disease. We suggest that this may be ascribed to damage to megakaryocytes by antiplatelet antibody. The physical characteristics in 111In clearly make this radionuclide superior to 51Cr for the study of platelet kinetics in ITP.

  2. Thrombotic thrombocytopenic purpura - analysis of clinical features, laboratory characteristics and therapeutic outcome of 24 patients treated at a Tertiary Care Center in Saudi Arabia

    PubMed Central

    Iqbal, Shahid; Zaidi, Syed Z. A.; Motabi, Ibraheem H; Alshehry, Nawal Faiez; AlGhamdi, Mubarak S.; Tailor, Imran Khan

    2016-01-01

    Objective: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease. The primary aim was overall response rate (ORR) assessment in the treated patients Methods: This retrospective study included 24 patients treated during 2006-2015. TTP patients with microangiopathic hemolysis (MAHA) and thrombocytopenia were included. We analyzed clinical features, laboratory characteristics and treatment outcomes of 24 TTP patients treated at our tertiary care center (KFMC). Results: Twenty-four TTP patients (18 females; 6 males) had a mean age of 33.5±13.9 years; 22(91%) had neurologic features, 7(29%) fever, 10(42%) renal impairment; 4(20.83%) cardiac manifestations; 22(91.7%) had triad with additional neurologic abnormalities; only 2(8.2%) had pentad of TTP. Majority (54.16%) had idiopathic TTP. All patients received therapeutic plasma exchange (TPE); 23(95.8%) received adjunctive corticosteroids and 13(54.2%) received rituximab either due to refractoriness to TPE on ~day7, or earlier. Twenty-one out of 24 (87.5%) achieved complete remission (CR) without any subsequent relapse. At 22 months (median, range 1-113), 20 patients (83.3%) are alive at the time of report. Three patients died during acute episode because of sever disease or delayed treatment and one died in CR. Conclusion: TPE, steroids and or rituximab was very effective in preventing high risk of mortality and achieving durable CR in 87.5% of patients. More awareness is needed for early diagnosis and early referral to centers with appropriate tertiary care facilities.. PMID:28083052

  3. Thrombotic thrombocytopenic purpura misdiagnosed as autoimmune cytopenia: Causes of diagnostic errors and consequence on outcome. Experience of the French thrombotic microangiopathies reference centre.

    PubMed

    Grall, Maximilien; Azoulay, Elie; Galicier, Lionel; Provôt, François; Wynckel, Alain; Poullin, Pascale; Grange, Steven; Halimi, Jean-Michel; Lautrette, Alexandre; Delmas, Yahsou; Presne, Claire; Hamidou, Mohamed; Girault, Stéphane; Pène, Frédéric; Perez, Pierre; Kanouni, Tarik; Seguin, Amélie; Mousson, Christiane; Chauveau, Dominique; Ojeda-Uribe, Mario; Barbay, Virginie; Veyradier, Agnès; Coppo, Paul; Benhamou, Ygal

    2017-04-01

    Thrombotic thrombocytopenic purpura (TTP) has a devastating prognosis without adapted management. Sources of misdiagnosis need to be identified to avoid delayed treatment. We studied 84 patients with a final diagnosis of severe (<10%) acquired ADAMTS13 deficiency-associated TTP from our National database that included 423 patients, who had an initial misdiagnosis (20% of all TTP). Main diagnostic errors were attributed to autoimmune thrombocytopenia, associated (51%) or not (37%) with autoimmune hemolytic anemia. At admission, misdiagnosed patients were more frequently females (P = .034) with a history of autoimmune disorder (P = .017) and had organ involvement in 67% of cases; they had more frequently antinuclear antibodies (P = .035), a low/undetectable schistocyte count (P = .001), a less profound anemia (P = .008), and a positive direct antiglobulin test (DAT) (P = .008). In multivariate analysis, female gender (P = .022), hemoglobin level (P = .028), a positive DAT (P = .004), and a low schistocytes count on diagnosis (P < .001) were retained as risk factors of misdiagnosis. Platelet count recovery was significantly longer in the misdiagnosed group (P = .041) without consequence on mortality, exacerbation and relapse. However, patients in the misdiagnosed group had a less severe disease than those in the accurately diagnosed group, as evidenced by less organ involvement at TTP diagnosis (P = .006). TTP is frequently misdiagnosed with autoimmune cytopenias. A low schistocyte count and a positive DAT should not systematically rule out TTP, especially when associated with organ failure.

  4. The Relationship between Self-esteem and Quality of Life of Patients with Idiopathic Thrombocytopenic Purpura at Isfahan's Sayed Al-Shohada Hospital, Iran, in 2013

    PubMed Central

    Hemati, Zeinab; Kiani, Davood

    2016-01-01

    Background: Idiopathic thrombocytopenic purpura (ITP) is a chronic disease which is accompanied with hopelessness and loss of the sense of well-being due to its symptoms and treatment. It also affects patients' sense of social and spiritual well-being. This disorder decreases patients' self-esteem and their quality of life by changing their mental image and self-confidence. This study was performed to find the relationship between self-esteem and quality of life of patients with ITP. Subjects and Methods: This was a descriptive-analytical study on 64 patients with ITP who referred to Isfahan's Sayed Al-Shohada Hospital, Iran. In this study, patients with ITP were selected randomly using a random number chart. The data collection tools consisted of the World Health Organization Quality of Life (WHOQOL)-BREF and Coopersmith Self-esteem Inventory (CSEI). Data were analyzed using SPSS and chi-square and Mann-Whitney tests and the Pearson and Spearman’s rank correlation coefficients. Results: In total, 64 patients completed the questionnaires. Results showed that 32% of subjects were over 36 years of age and 59% were women. In addition, 29.7% of ITP patients had low self-esteem and quality of life. Chi-square test showed a significant relationship between self-esteem and quality of life of patients with ITP. Conclusions: The results of the present study showed that considerable attention must be paid to self-esteem, as one of the most important factors influencing the promotion of quality of life. Therefore, it is suggested that patient’s self-esteem be improved by the implementation of educational and psychological programs in order to decrease the consequences of poor quality of life. PMID:27252807

  5. The European Medicines Agency review of eltrombopag (Revolade) for the treatment of adult chronic immune (idiopathic) thrombocytopenic purpura: summary of the scientific assessment of the Committee for Medicinal Products for Human Use

    PubMed Central

    Nieto, Maria; Calvo, Gonzalo; Hudson, Ian; Feldschreiber, Peter; Brown, David; Lee, Ching Cheng; Lay, Geoffrey; Valeri, Anna; Abadie, Eric; Thomas, Angela; Pignatti, Francesco

    2011-01-01

    On 11th March 2010, the European Commission issued a marketing authorization valid throughout the European Union for Revolade for the treatment of adult chronic immune (idiopathic) thrombocytopenic purpura. Revolade is an orphan medicinal product indicated for splenectomized patients with immune (idiopathic) thrombocytopenic purpura who are refractory to other treatments (e.g. corticosteroids, immunoglobulins) and as second-line treatment for non-splenectomized patients where surgery is contraindicated. The active substance of Revolade is eltrombopag (ATC code B02BX05). Eltrombopag increases platelet production through activation of the thrombopoietin receptor. The recommended oral dose is 50 mg once daily to achieve and maintain a platelet count of the 50×109/L or more necessary to reduce or prevent the risk of bleeding. The benefit of Revolade is a durable response in maintaining platelet levels. The most common side effects include headache, nausea, hepatobiliary toxicity, diarrhea, fatigue, paresthesia, constipation, rash, pruritus, cataract, arthralgia and myalgia. The decision to grant the marketing authorization was based on the favorable recommendation of the Committee for Medicinal Products for Human Use of the European Medicines Agency. The objective of this paper is to describe the data submitted to the European Medicines Agency and to summarize the scientific review of the application. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the European Medicines Agency website (www.ema.europa.eu). PMID:21712542

  6. Length of stay, hospitalization cost, and in-hospital mortality in US adult inpatients with immune thrombocytopenic purpura, 2006–2012

    PubMed Central

    An, Ruopeng; Wang, Peizhong Peter

    2017-01-01

    Purpose In this study, we examined the length of stay, hospitalization cost, and risk of in-hospital mortality among US adult inpatients with immune thrombocytopenic purpura (ITP). Methods We analyzed nationally representative data obtained from Nationwide/National Inpatient Sample database of discharges from 2006 to 2012. Results In the US, there were an estimated 296,870 (95% confidence interval [CI]: 284,831–308,909) patient discharges recorded for ITP from 2006 to 2012, during which ITP-related hospitalizations had increased steadily by nearly 30%. The average length of stay for an ITP-related hospitalization was found to be 6.02 days (95% CI: 5.93–6.10), which is 28% higher than that of the overall US discharge population (4.70 days, 95% CI: 4.66–4.74). The average cost of ITP-related hospitalizations was found to be US$16,594 (95% CI: US$16,257–US$16,931), which is 48% higher than that of the overall US discharge population (US$11,200; 95% CI: US$11,033–US$11,368). Gender- and age-adjusted mortality risk in inpatients with ITP was 22% (95% CI: 19%–24%) higher than that of the overall US discharge population. Across diagnosis related groups, length of stay for ITP-related hospitalizations was longest for septicemia (7.97 days, 95% CI: 7.55–8.39) and splenectomy (7.40 days, 95% CI: 6.94–7.86). Splenectomy (US$25,262; 95% CI: US$24,044–US$26,481) and septicemia (US$18,430; 95% CI: US$17,353–US$19,507) were associated with the highest cost of hospitalization. The prevalence of mortality in ITP-related hospitalizations was highest for septicemia (11.11%, 95% CI: 9.60%–12.63%) and intracranial hemorrhage (9.71%, 95% CI: 7.65%–11.77%). Conclusion Inpatients with ITP had longer hospital stay, bore higher costs, and faced greater risk of mortality than the overall US discharge population. PMID:28176930

  7. Rituximab and intermediate-purity plasma-derived factor VIII concentrate (Koate®) as adjuncts to therapeutic plasma exchange for thrombotic thrombocytopenic purpura in patients with an ADAMTS13 inhibitor.

    PubMed

    Pandey, Soumya; Nakagawa, Mayumi; Rosenbaum, Eric R; Arnaoutakis, Konstantinos; Hutchins, Laura F; Makhoul, Issam; Milojkovic, Natasha; Cottler-Fox, Michele

    2015-02-01

    Thrombotic thrombocytopenic purpura (TTP) results from a congenital or acquired deficiency of the von Willebrand factor (vWF)-cleaving protease ADAMTS13. The disease can be fatal and hence treatment should be initiated promptly. Therapeutic plasma exchange (TPE) remains the standard treatment along with adjunct therapies including steroids and immunosuppressive drugs. Addition of rituximab to TPE has been shown to be beneficial in refractory/relapsing TTP; however, TPE results in removal of rituximab from the circulation requiring more frequent dosing of rituximab to achieve a favorable outcome. The intermediate-purity plasma-derived Factor VIII concentrate (FVIII) Koate® contains the highest amount of ADAMTS13 activity yet reported and has been used successfully in treating congenital TTP. Here we report our experience with addition of this FVIII concentrate to rituximab, corticosteroids and TPE in three TTP patients with an ADAMTS13 inhibitor to permit withholding TPE for 48 h after rituximab infusion.

  8. What Causes Thrombotic Thrombocytopenic Purpura?

    MedlinePlus

    ... is involved in blood clotting. Not having enough enzyme activity causes overactive blood clotting. In TTP, blood clots ... make a normal ADAMTS13 enzyme. As a result, enzyme activity is lacking or changed. "Inherited" means that the ...

  9. Octaploidy in idiopathic thrombocytopenic purpura

    PubMed Central

    Makroo, R. N.; Chowdhry, Mohit; Mishra, Manoj; Srivastava, Priyanka; Fauzdar, Ashish

    2011-01-01

    We report a case of an elderly 68-year-old male who presented in our hospital with chief complaints of petechial rashes and ecchymosis over extremities and bleeding from the oral cavity since 3–4 days prior to hospitalization. He saw a physician before coming to our hospital and received one dose of IV methylprednisolone and oral wysolone. He had come to our hospital for further management. Bone marrow karyotyping was done and chromosomal analysis revealed two cell lines. Eighty percent of the cells analyzed revealed apparently normal male karyotype. However, 20% cells analyzed revealed a total of 184 chromosomes, suggesting octaploidy. PMID:22346001

  10. Living with Thrombotic Thrombocytopenic Purpura

    MedlinePlus

    ... skin causes petechiae. Paleness or jaundice (a yellowish color of the skin or whites of the eyes). Fatigue (feeling very tired and weak). Fever. A fast heart rate or shortness of breath. Headache, speech changes, confusion, coma, stroke , or seizure. A low amount ...

  11. Expression of the 60 kDa and 71 kDa heat shock proteins and presence of antibodies against the 71 kDa heat shock protein in pediatric patients with immune thrombocytopenic purpura

    PubMed Central

    Xiao, Chengfeng; Chen, Sheng; Yuan, Mingchun; Ding, Fuyue; Yang, Dongliang; Wang, Ruibo; Li, Jianxin; Tanguay, Robert M; Wu, Tangchun

    2004-01-01

    Background Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by platelet destruction resulting from autoantibodies against platelet proteins, particularly platelet glycoprotein IIb/IIIa. Heat shock proteins (Hsp) have been shown to be major antigenic determinants in some autoimmune diseases. Antibodies to Hsps have also been reported to be associated with a number of pathological states. Methods Using western blot, we measured the levels of the 60 kDa heat shock protein (Hsp60) and of the inducible 71 kDa member of the Hsp70 family (Hsp71) in lymphocytes and the presence of antibodies against these hsps in plasma of 29 pediatric patients with ITP before the treatment and in 6 other patients before and after treatment. Results Interestingly only one out of 29 patients showed detectable Hsp60 in lymphocytes while this heat shock protein was detected in the 30 control children. Hsp71 levels were slightly lower in lymphocytes of patients with ITP than in controls (1567.8 ± 753.2 via 1763.2 ± 641.8 integrated optical density (IOD) units). There was a small increase of Hsp71 after recovery from ITP. The titers of plasma antibodies against Hsp60 and Hsp71 were also examined. Antibodies against Hsp71 were more common in ITP patients (15/29) than in control children (5/30). The titer of anti-Hsp71 was also higher in children patients with ITP. The prevalence of ITP children with antibodies against Hsp71 (51.7%) was as high as those with antibodies against platelet membrane glycoproteins (58.3%). Conclusions In summary, pediatric patients with ITP showed no detectable expression of Hsp60 in lymphocytes and a high prevalence of antibody against Hsp71 in plasma. These changes add to our understanding of the pathogenesis of ITP and may be important for the diagnosis, prognosis and treatment of ITP. PMID:15070425

  12. Negative regulation of human megakaryocytopoiesis by human platelet factor 4 and beta thromboglobulin: comparative analysis in bone marrow cultures from normal individuals and patients with essential thrombocythaemia and immune thrombocytopenic purpura.

    PubMed

    Han, Z C; Bellucci, S; Tenza, D; Caen, J P

    1990-04-01

    The effect of human platelet factor 4 (PF4) and beta-thromboglobulin (BTG) on megakaryocyte colony formation in normal subjects as well as in essential thrombocythaemia (ET) and in immune thrombocytopenic purpura (ITP) was studied. Both PF4 and BTG were found to be capable of inhibiting the development of isolated megakaryocytes and their colonies in normal marrow cultures in a dose-dependent fashion. A significant 50% inhibition was seen at a PF4 or BTG concentration of 1-2.5 micrograms/ml, and complete inhibition in the range of 5-10 micrograms PF4 or BTG/ml. The two platelet proteins had similar effects on megakaryocyte development. A combination of PF4 and BTG resulted in an additive effect. Antibodies against PF4 or BTG could effectively neutralize the inhibitory effect of PF4 or BTG respectively. In ET and ITP, in vitro megakaryocyte development was also inhibited by PF4 and BTG in a similar way to that seen in normal subjects, suggesting that the responsiveness of megakaryocyte progenitors to PF4 and BTG is normal in these two disorders. PF4 and BTG did not affect the growth of colony forming units granulocyte-macrophage (CFU-GM) except at very high concentration (greater than or equal to 10 micrograms/ml) but they did inhibit erythroid colony formation by normal and ET burst forming units erythroid (BFU-E). However, the inhibition of BFU-E by PF4 and BTG was dose-related, and a 50% inhibition required a PF4 or BTG dose ranging from 5 to 10 micrograms/ml. These results indicate that PF4 and BTG are involved in negative regulation of normal and pathologic megakaryocytopoiesis and that their inhibition acts predominantly on the megakaryocytic lineage.

  13. Investigation of whether the acute hemolysis associated with Rho(D) immune globulin intravenous (human) administration for treatment of immune thrombocytopenic purpura is consistent with the acute hemolytic transfusion reaction model

    PubMed Central

    Gaines, Ann Reed; Lee-Stroka, Hallie; Byrne, Karen; Scott, Dorothy E.; Uhl, Lynne; Lazarus, Ellen; Stroncek, David F.

    2012-01-01

    BACKGROUND Immune thrombocytopenic purpura and secondary thrombocytopenia patients treated with Rho(D) immune globulin intravenous (human; anti-D IGIV) have experienced acute hemolysis, which is inconsistent with the typical presentation of extravascular hemolysis—the presumed mechanism of action of anti-D IGIV. Although the mechanism of anti-D-IGIV–associated acute hemolysis has not been established, the onset, signs/symptoms, and complications appear consistent with the intravascular hemolysis of acute hemolytic transfusion reactions (AHTRs). In transfusion medicine, the red blood cell (RBC) antigen-antibody incompatibility(-ies) that precipitate AHTRs can be detected in vitro with compatibility testing. Under the premise that anti-D-IGIV–associated acute hemolysis results from RBC antigen-antibody–mediated complement activation, this study evaluated whether the incompatibility(-ies) could be detected in vitro with a hemolysin assay, which would support the AHTR model as the hemolytic mechanism. STUDY DESIGN AND METHODS Seven anti-D IGIV lots were tested to determine the RBC antibody identities in those lots, including four lots that had been implicated in acute hemolytic episodes. Hemolysin assays were performed that tested each of 73 RBC specimens against each lot, including the RBCs of one patient who had experienced acute hemolysis after anti-D IGIV administration. RESULTS Only two anti-D IGIV lots contained RBC antibodies beyond those expected. No hemolysis endpoint was observed in any of the hemolysin assays. CONCLUSION Although the findings did not support the AHTR model, the results are reported to contribute knowledge about the mechanism of anti-D-IGIV–associated acute hemolysis and to prompt continued investigation into cause(s), prediction, and prevention of this potentially serious adverse event. PMID:19220820

  14. Helicobacter pylori eradication shifts monocyte Fcγ receptor balance toward inhibitory FcγRIIB in immune thrombocytopenic purpura patients

    PubMed Central

    Asahi, Atsuko; Nishimoto, Tetsuya; Okazaki, Yuka; Suzuki, Hidekazu; Masaoka, Tatsuhiro; Kawakami, Yutaka; Ikeda, Yasuo; Kuwana, Masataka

    2008-01-01

    Immune thrombocytopenia purpura (ITP) is a bleeding disorder in which platelet-specific autoantibodies cause a loss of platelets. In a subset of patients with ITP and infected with Helicobacter pylori, the number of platelets recovers after eradication of H. pylori. To examine the role of H. pylori infection in the pathogenesis of ITP, the response of 34 ITP patients to treatment with a standard H. pylori eradication regimen, irrespective of whether they were infected with H. pylori, was evaluated. Eradication of H. pylori was achieved in all H. pylori–positive patients, and a significant increase in platelets was observed in 61% of these patients. By contrast, none of the H. pylori–negative patients showed increased platelets. At baseline, monocytes from the H. pylori–positive patients exhibited an enhanced phagocytic capacity and low levels of the inhibitory Fcγ receptor IIB (FcγRIIB). One week after starting the H. pylori eradication regimen, this activated monocyte phenotype was suppressed and improvements in autoimmune and platelet kinetic parameters followed. Modulation of monocyte FcγR balance was also found in association with H. pylori infection in individuals who did not have ITP and in mice. Our findings strongly suggest that the recovery in platelet numbers observed in ITP patients after H. pylori eradication is mediated through a change in FcγR balance toward the inhibitory FcγRIIB. PMID:18654664

  15. Foetal and neonatal alloimmune thrombocytopaenia.

    PubMed

    Kaplan, Cecile

    2006-10-10

    Foetal/neonatal alloimmune thrombocytopaenia (NAIT) results from maternal alloimmunisation against foetal platelet antigens inherited from the father and different from those present in the mother, and usually presents as a severe isolated thrombocytopaenia in otherwise healthy newborns. The incidence has been estimated at 1/800 to 1/1000 live births. NAIT has been considered to be the platelet counterpart of Rh Haemolytic Disease of the Newborn (RHD). Unlike RHD, NAIT can occur during a first pregnancy. The spectrum of the disease may range from sub-clinical moderate thrombocytopaenia to life-threatening bleeding in the neonatal period. Mildly affected infants may be asymptomatic. In those with severe thrombocytopaenia, the most common presentations are petechiae, purpura or cephalohaematoma at birth, associated with major risk of intracranial haemorrhage (up to 20% of reported cases), which leads to death or neurological sequelae. Alloimmune thrombocytopaenia is more often unexpected and is usually diagnosed after birth. Once suspected, the diagnosis is confirmed by demonstration of maternal antiplatelet alloantibodies directed against a paternal antigen inherited by the foetus/neonate. Post-natal management involves transfusion of platelets devoid of this antigen, and should not be delayed by biological confirmation of the diagnosis (once the diagnosis is suspected), especially in case of severe thrombocytopaenia. Prompt diagnosis and treatment are essential to reduce the chances of death and disability due to haemorrhage. Due to the high rate of recurrence and increased severity of the foetal thrombocytopaenia in successive pregnancies, antenatal therapy should be offered. However, management of high-risk pregnancies is still a matter of discussion.

  16. How Is Thrombotic Thrombocytopenic Purpura Diagnosed?

    MedlinePlus

    ... specializes in diagnosing and treating blood disorders. Medical History Your doctor will ask about factors that may affect TTP. For example, he or she may ask whether you: Have certain diseases or conditions, such as cancer, HIV, lupus, or infections (or whether you're pregnant). Have ...

  17. How Is Thrombotic Thrombocytopenic Purpura Treated?

    MedlinePlus

    ... and surgery. Treatments are done in a hospital. Plasma Therapy Plasma is the liquid part of your blood. It ... nutrients to your body. TTP is treated with plasma therapy. This includes: Fresh frozen plasma for people ...

  18. Psychogenic purpura

    PubMed Central

    Sarkar, Sharmila; Ghosh, Sudip Kumar; Bandyopadhyay, Debabrata; Nath, Saswati

    2013-01-01

    Psychogenic purpura, also known as Gardner-Diamond syndrome, is a rare, distinctive, localized cutaneous reaction pattern mostly affecting psychologically disturbed adult women. Repeated crops of tender, ill-defined ecchymotic lesions on the extremities and external bleeding from other sites characterize the condition. We report here a case of psychogenic purpura because of the rarity of the condition and to emphasize the importance of consideration of this entity during evaluation of a patient with recurrent ecchymoses. Early diagnosis of this condition will not only minimize the cost of the medical evaluation but will also benefit the patient. PMID:23825859

  19. Acute ST Elevation Myocardial Infarction in Patients With Immune Thrombocytopenia Purpura: A Case Report

    PubMed Central

    Dhillon, Sandeep K; Lee, Edwin; Fox, John; Rachko, Maurice

    2011-01-01

    Acute myocardial infarction (AMI) in patients with immune thrombocytopenic purpura (ITP) is rare. We describe a case of AMI in patient with ITP. An 81-year-old woman presented with acute inferoposterior MI with low platelet count on admission (34,000/µl). Coronary angiography revealed significant mid right coronary artery (RCA) stenosis with thrombus, subsequently underwent successful percutaneous coronary intervention (PCI). In some patients with immune thrombocytopenia purpura and acute myocardial infarction, percutaneous coronary intervention is a therapeutic option.

  20. Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients

    ClinicalTrials.gov

    2017-02-07

    Idiopathic Thrombocytopenic Purpura; Thrombocytopenia; Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP); Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP); Thrombocytopenic Purpura; Immune Thrombocytopenia

  1. Thrombotic thrombocytopenic purpura--possibilities of treatment and results.

    PubMed

    Gasparović, V; Mejić, S; Pisl, Z; Radonić, R; Radman, I

    2001-01-01

    Results of treatment of 13 patients fulfilling the criteria for TTP are presented. Thrombocytopenia was present in all patients (100%). Eleven of 13 patients (84.6%) had conciousness disorder, and seven of 13 patients (53.8%) had renal impairment. Immunosuppressive therapy with plasmapheresis and replacement of removed volume with fresh frozen plasma in a dosage of 25 ml/kg body weight resulted in statistically significant increase of platelet count (p = 0.0033), and significant improvement of consciousness as defined by increased Glasgow Coma Score (GCS) (p = 0.0524). In two patients, renal function recovered and, in one patient, hemodialysis was no longer needed. This improvement in a small patient group has no statistical significance.

  2. [Clinical analysis of 200 cases of idiopathic thrombocytopenic purpura].

    PubMed

    García-Stivalet, Lilia Adela; Muñoz-Flores, Aarón; Montiel-Jarquín, Alvaro José; Barragán-Hervella, Rodolfo Gregorio; Bejarano-Huertas, Ruth; García-Carrasco, Mario; López-Colombo, Aurelio

    2014-01-01

    INTRODUCCIÓN: la púrpura trombocitopénica idiopática se caracteriza por la extravasación de sangre en el tejido subcutáneo, membranas, mucosas o piel, que puede generar manifestaciones clínicas de sangrado como lesiones equimóticas, petequias de aparición brusca, epistaxis, gingivorragia y complicaciones graves como hemorragia intracraneal, debido a destrucción plaquetaria mediada por anticuerpos dirigidos contra la superficie de las plaquetas. El objetivo de este informe es presentar las características clínicas de los pacientes con púrpura trombocitopénica idiopática en un hospital de tercer nivel de atención, con la finalidad de tener estadísticas para estudios analíticos posteriores. MÉTODOS: se realizó un estudio descriptivo de 200 pacientes atendidos en el servicio de hematología con diagnóstico de púrpura trombocitopénica idiopática. Se describen sus manifestaciones clínicas, el diagnóstico y el tratamiento médico y quirúrgico empleados.

  3. The clinical implications of adult-onset henoch-schonelin purpura

    PubMed Central

    2011-01-01

    Henoch-Schonlein Purpura (HSP) is a small vessel vasculitis mediated by IgA-immune complex deposition. It is characterized by the clinical tetrad of non-thrombocytopenic palpable purpura, abdominal pain, arthritis and renal involvement. Pathologically, it can be considered a form of immune complex-mediated leukocytoclastic vasculitis (LCV) involving the skin and other organs. Though it primarily affects children (over 90% of cases), the occurrence in adults has been rarely reported. Management often involves the use of immunomodulatory or immune-suppressive regimens. PMID:21619657

  4. Henoch Schonlein purpura associated with bee sting: case report.

    PubMed

    Gálvez-Olortegui, José; Álvarez-Vargas, Mayita; Durand-Vergara, Juan; Díaz-Lozano, Marisol; Gálvez-Olortegui, Tomas; Armas-Ramírez, Indira; Hilario-Vargas, Julio

    2015-10-30

    Henoch Schonlein purpura (HSP) is a common childhood vasculitis, characterized by a non-thrombocytopenic palpable purpura and systemic features. It can be triggered by conditions like infections and insect bites. We present the case of a six-year-old girl with palpable maculopapular lesions on the lower limbs, itching, mild pain, swelling of feet, limitation of limb mobility, and a history of bee sting. Thigh skin biopsy was performed, with a report of leucocytoclastic vasculitis, and was diagnosed as HSP. She was prescribed bed rest, and was given oral hydration. The patient outcome was favorable and was discharged after five days. This is the fifth report of a HSP case associated with a bee sting with an uncomplicated course, which is in contrast to previous case reports.

  5. Genotyping for human platelet alloantigen polymorphisms: applications in the diagnosis of alloimmune platelet disorders.

    PubMed

    Curtis, Brian R

    2008-09-01

    Molecular typing for platelet allelic polymorphisms was first made possible by discovery of the HPA-1a/1b single nucleotide polymorphism in 1989. Since then, six other biallelic human platelet antigen (HPA) systems have been determined and can be typed using genomic DNA. The introduction of polymerase chain reaction enabled development of several different assays including polymerase chain reaction-sequence-specific primer, melting curve analysis by LightCycler, and 5'-nuclease assays. More recently, multiplex polymerase chain reaction has allowed for the development of high-throughput assays for genotyping large numbers of patients and blood donors for not only platelet gene polymorphisms but also for those of other blood cell genes. Platelet genotyping is a valuable tool in confirming platelet antigen specificities of alloantibodies detected in patient sera to complement the clinical history in the diagnosis of alloimmune platelet disorders such as fetal and neonatal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura, and multiplatelet transfusion refractoriness. In addition, it has made possible prenatal platelet typing of the fetus in suspected cases of FNAIT and large-scale blood donor typing for provision of antigen-negative platelets to transfuse highly alloimmunized patients. Platelet genotyping may also someday prove important as an aid in determining the relative risk of patients for various thrombotic disorders.

  6. Understanding red blood cell alloimmunization triggers.

    PubMed

    Hendrickson, Jeanne E; Tormey, Christopher A

    2016-12-02

    Blood group alloimmunization is "triggered" when a person lacking a particular antigen is exposed to this antigen during transfusion or pregnancy. Although exposure to an antigen is necessary for alloimmunization to occur, it is not alone sufficient. Blood group antigens are diverse in structure, function, and immunogenicity. In addition to red blood cells (RBCs), a recipient of an RBC transfusion is exposed to donor plasma, white blood cells, and platelets; the potential contribution of these elements to RBC alloimmunization remains unclear. Much attention in recent years has been placed on recipient factors that influence RBC alloantibody responses. Danger signals, identified in murine and human studies alike as being risk factors for alloimmunization, may be quite diverse in nature. In addition to exogenous or condition-associated inflammation, autoimmunity is also a risk factor for alloantibody formation. Triggers for alloimmunization in pregnancy are not well-understood beyond the presence of a fetal/maternal bleed. Studies using animal models of pregnancy-induced RBC alloimmunization may provide insight in this regard. A better understanding of alloimmunization triggers and signatures of "responders" and "nonresponders" is needed for prevention strategies to be optimized. A common goal of such strategies is increased transfusion safety and improved pregnancy outcomes.

  7. Alloimmune refractoriness to platelet transfusions.

    PubMed

    Sandler, S G

    1997-11-01

    Patients who are transfused on multiple occasions with red cells or platelets may develop platelet-reactive alloantibodies and experience decreased clinical responsiveness to platelet transfusion. This situation, conventionally described as "refractoriness to platelet transfusions," is defined by an unsatisfactory low post-transfusion platelet count increment. If antibodies to HLAs are detected, improved clinical outcomes may result from transfusions of HLA-matched or donor-recipient cross-matched platelets. Because refractoriness is an expected, frequently occurring phenomenon, prevention of HLA alloimmunization is an important management strategy. Prevention strategies include efforts to decrease the number of transfusions, filtration of cellular components to reduce the number of HLA-bearing leukocytes, or pretransfusion ultraviolet B irradiation of cellular components to decrease their immunogenicity. Other investigational approaches include reducing the expression of HLAs on transfused platelets, inducing a transient reticuloendothelial system blockade by infusions of specialized immunoglobulin products, or transfusing semisynthetic platelet substitutes (thromboerythrocytes, thrombospheres) or modified platelets (infusible platelet membranes, lyophilized platelets).

  8. Thrombocytopenic syndromes in pregnancy

    PubMed Central

    Yan, Matthew; Malinowski, Ann K

    2015-01-01

    The physiological changes in pregnancy result in platelet counts that are lower than in nonpregnant women. Consequently, thrombocytopenia is a common finding occurring in 7–12% of pregnant women. Gestational thrombocytopenia, the most common cause of low platelet counts, tends to be mild in most women and does not affect maternal, fetal or neonatal outcomes. Gestational thrombocytopenia needs to be distinguished from other less common causes of isolated thrombocytopenia, such as immune thrombocytopenia, which affects approximately 3% of thrombocytopenic pregnant women and can lead to neonatal thrombocytopenia. Hypertensive disorders of pregnancy and thrombotic microangiopathies are both associated with thrombocytopenia. They share a considerable number of similar characteristics and are associated with significant maternal and neonatal morbidity and rarely mortality. Accurate identification of the aetiology of thrombocytopenia and appropriate management are integral to optimizing the pregnancy, delivery and neonatal outcomes of this population. Clinical cases are described to illustrate the various aetiologies of thrombocytopenia in pregnancy and their treatment. PMID:27512485

  9. Henoch-Schonlein Purpura

    MedlinePlus

    ... microscopic hallmark of HSP is the deposition of IgA (an antibody found in blood, saliva, tears, etc.) ... skin biopsy and the consequent failure to detect IgA. Treatment and Course of Henoch-Schönlein Purpura NSAIDs ...

  10. Challenges of alloimmunization in patients with haemoglobinopathies.

    PubMed

    Chou, Stella T; Liem, Robert I; Thompson, Alexis A

    2012-11-01

    Red blood cell (RBC) transfusions can be life-sustaining in chronic inherited anaemias, such as thalassaemia, and the indications for blood transfusions in patients with sickle cell disease continue to expand. Complications of transfusions, such as allosensitization, can create significant medical challenges in the management of patients with haemoglobinopathies. This review summarizes key findings from the medical literature related to alloimmunization in haemoglobinopathies and examines potential measures to mitigate these risks. Areas where future studies are needed are also addressed.

  11. Systemic lupus erythematosus and thrombotic thrombocytopenia purpura: a refractory case without lupus activity.

    PubMed

    Garcia Boyero, Raimundo; Mas Esteve, Eva; Mas Esteve, Maria; Millá Perseguer, M Magdalena; Marco Buades, Josefa; Beltran Fabregat, Juan; Cañigral Ferrando, Guillermo; Belmonte Serrano, Miguel Angel

    2013-01-01

    The association between systemic lupus erythematosus (SLE) and thrombotic thrombocytopenic purpura (TTP) has been infrequently reported. Usually, patients with TTP have more SLE activity and frequent renal involvement. Here we present a case of TTP associated to low-activity SLE. The absence of renal and major organ involvement increased the difficulty in making the initial diagnosis. ADAMTS13 activity in plasma in this patient was very low, as seen in other similar cases. The evolution of the patient was poor, needing plasma exchanges and immunosuppressive therapy, including the use of rituximab.

  12. Safety and Efficacy Study of Romiplostim (AMG 531) to Treat ITP in Pediatric Subjects

    ClinicalTrials.gov

    2014-07-18

    Idiopathic Thrombocytopenic Purpura; Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP); Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)

  13. Maternal anti-HLA class I antibodies are associated with reduced birth weight in thrombocytopenic neonates.

    PubMed

    Dahl, J; Husebekk, A; Acharya, G; Flo, K; Stuge, T B; Skogen, B; Straume, B; Tiller, H

    2016-02-01

    In this comparative cross-sectional study, possible associations between maternal anti-HLA class I antibodies and birth weight in neonatal thrombocytopenia are explored. Although commonly detected in pregnancies and generally regarded as harmless, it has been suggested that such antibodies might be associated with fetal and neonatal alloimmune thrombocytopenia (FNAIT). As a link between FNAIT due to human platelet antigen 1a-specific antibodies and reduced birth weight in boys has previously been demonstrated, we wanted to explore whether maternal anti-HLA class I antibodies might also affect birth weight. To examine this, suspected cases of FNAIT referred to the Norwegian National Unit for Platelet Immunology during the period 1998-2009 were identified. Pregnancies where the only finding was maternal anti-HLA class I antibodies were included. An unselected group of pregnant women participating in a prospective study investigating maternal-fetal hemodynamics at the University Hospital North Norway during the years 2006-2010 served as controls. Twenty-nine percent of controls had anti-HLA class I antibodies. The thrombocytopenic neonates had a significantly lower adjusted birth weight (linear regression, P=0.036) and significantly higher odds of being small for gestational age (OR=6.72, P<0.001) compared with controls. Increasing anti-HLA class I antibody levels in the mother were significantly associated with lower birth weight and placental weight among thrombocytopenic neonates, but not among controls. These results indicate that maternal anti-HLA class I antibodies in thrombocytopenic neonates are associated with reduced fetal growth. Further studies are needed to test if placental function is affected.

  14. Powerlifter's purpura: a valsalva-associated phenomenon.

    PubMed

    Pierson, Joseph C; Suh, Philip S

    2002-08-01

    The causes of purpura can be classified into intravascular, vascular, and extravascular mechanisms. We describe a case of cervicofacial purpura in a powerlifter attributed to the accompanying Valsalva-associated increased arterial pressure. Powerlifting should be added to the list of activities that may cause purpura.

  15. Purpura-associated congenital lymphedema.

    PubMed

    Berti, Samantha; Pieri, Alessandro; Lotti, Torello; Duranti, Alberto; Panelos, John; De Martino, Maurizio; Moretti, Silvia

    2009-01-01

    An 8-year-old girl referred to our Department for a two-month worsening of congenital primary lymphedema of the lower limb and for the appearance of several purpuric lesions on the right thigh and knee. We diagnosed a lichenoid pigmented purpura of Gougerot and Blum in a patient with Milroy disease, complicated by an insufficiency of anterior saphena. We treated the patient with topical steroids and compression stockings, until surgical intervention of phlebectomy. We report this case for the rarity of the disease, for the even more rare association with lichenoid pigmented purpura and for cutaneous immunopathological findings.

  16. A rare manifestation of neonatal alloimmune thrombocytopaenia.

    PubMed

    Jerónimo, Monica; Azenha, Cátia; Mesquita, Joana; Pereira, Dolores Faria

    2014-06-02

    Neonatal alloimmune thrombocytopaenia (NAIT) results from a fetomaternal incompatibility with maternal sensitisation against a fetal human platelet antigen (HPA) and antibodies transfer to the fetal circulation, leading to platelet destruction. The clinical presentation is variable and isolated intraocular haemorrhage is rare. We present the case of a male newborn, with intrauterine growth restriction, born at 29 weeks due to pre-eclampsia. He presented proptosis of the left eye, hyphaema and elevated intraocular pressure, with no other signs of haemorrhage. Severe thrombocytopaenia was found (27×10(9)/L). Perinatal infection and maternal thrombocytopaenia were excluded. Positive anti-HPA-1a and antihuman leucocyte antigen class I alloantibodies were found in the mother. Platelet crossmatch between the father's platelets and mother's plasma was positive. Platelet transfusions and intravenous immunoglobulin were given with favourable response. This case highlights an unusual presentation of NAIT, which should be suspected in the presence of severe thrombocytopaenia in the first 24-72 h of life.

  17. Alloimmune thrombocytopenia: state of the art 2006.

    PubMed

    Berkowitz, Richard L; Bussel, James B; McFarland, Janice G

    2006-10-01

    In alloimmune thrombocytopenia maternal immunoglobulin G anti-platelet alloantibodies cross the placenta and cause fetal thrombocytopenia. The diagnosis requires laboratory demonstration of incompatibility between a maternal and paternal platelet alloantigen, and detection of maternal antibody to the discordant paternal alloantigen. This disorder should be treated in utero because of its propensity to cause fetal intracranial bleeding. Administration of intravenous immunoglobulin 1 gm/kg/wk to the mother is successful in substantially raising the platelet count in many fetuses, but this is most successful if the count is >20,000/mL3 at the time that the therapy is initiated. The addition of prednisone administered daily to the mother and/or increasing the dose of intravenous immunoglobulin has a therapeutic benefit in cases that have failed to respond to initial therapy with intravenous immunoglobulin alone. The only reliable noninvasive indicator of the potential for severe fetal thrombocytopenia is a history of an antenatal intracranial hemorrhage in a prior affected sibling. Because fetal blood sampling to determine the fetal platelet count may be associated with significant fetal morbidity, attempts are being made to derive a rational, non-invasive, stratified approach to patient-specific therapy of this disorder in affected pregnancies.

  18. [The new paradigm of neonatal hemochromatosis: fetal alloimmune hepatitis].

    PubMed

    Costaguta, Alejandro; Alvarez, Fernando

    2012-01-01

    The classical model of neonatal hemochromatosis was based on the analogy with hereditary hemochromatosis. Medical treatment consisted on the antioxidant-chelator cocktail. The new hypothesis of an alloimmune origin of the process by which the pregnant woman mounts an IgG-based destructive response against fetal hepatocytes offers a pathogenic explanation, allowing treatment to be focused on the immunological aspects, with excellent results, and opens the possibility of preventive treatment in future pregnancies. This new paradigm produces a deep impact in diagnosis, prognosis and treatment of the disease, that should be called "fetal alloimmune hepatitis".

  19. Altered heme-mediated modulation of dendritic cell function in sickle cell alloimmunization

    PubMed Central

    Godefroy, Emmanuelle; Liu, Yunfeng; Shi, Patricia; Mitchell, W. Beau; Cohen, Devin; Chou, Stella T.; Manwani, Deepa; Yazdanbakhsh, Karina

    2016-01-01

    Transfusions are the main treatment for patients with sickle cell disease. However, alloimmunization remains a major life-threatening complication for these patients, but the mechanism underlying pathogenesis of alloimmunization is not known. Given the chronic hemolytic state characteristic of sickle cell disease, resulting in release of free heme and activation of inflammatory cascades, we tested the hypothesis that anti-inflammatory response to heme is compromised in alloimmunized sickle patients, increasing their risk of alloimmunization. Heme-exposed monocyte-derived dendritic cells from both non-alloimmunized sickle patients and healthy donors inhibited priming of pro-inflammatory CD4+ type 1 T cells, and exhibited significantly reduced levels of the maturation marker CD83. In contrast, in alloimmunized patients, heme did not reverse priming of pro-inflammatory CD4+ cells by monocyte-derived dendritic cells or their maturation. Furthermore, heme dampened NF-κB activation in non-alloimmunized, but not in alloimmunized monocyte-derived dendritic cells. Heme-mediated CD83 inhibition depended on Toll-like receptor 4 but not heme oxygenase 1. These data suggest that extracellular heme limits CD83 expression on dendritic cells in non-alloimmunized sickle patients through a Toll-like receptor 4-mediated pathway, involving NF-κB, resulting in dampening of pro-inflammatory responses, but that in alloimmunized patients this pathway is defective. This opens up the possibility of developing new therapeutic strategies to prevent sickle cell alloimmunization. PMID:27229712

  20. Crystallographic structure of the human leukocyte antigen DRA, DRB3*0101: models of a directional alloimmune response and autoimmunity.

    PubMed

    Parry, Christian S; Gorski, Jack; Stern, Lawrence J

    2007-08-10

    We describe structural studies of the human leukocyte antigen DR52a, HLA-DRA/DRB3*0101, in complex with an N-terminal human platelet integrin alphaII(B)betaIII glycoprotein peptide which contains a Leu/Pro dimorphism. The 33:Leu dimorphism is the epitope for the T cell directed response in neonatal alloimmune thrombocytopenia and post-transfusion purpura in individuals with the alphaII(B)betaIII 33:Pro allele, and defines the unidirectional alloimmune response. This condition is always associated with DR52a. The crystallographic structure has been refined to 2.25 A. There are two alphabeta heterodimers to the asymmetric unit in space group P4(1)2(1)2. The molecule is characterized by two prominent hydrophobic pockets at either end of the peptide binding cleft and a deep, narrower and highly charged P4 opening underneath the beta 1 chain. Further, the peptide in the second molecule displays a sharp upward turn after pocket P9. The structure reveals the role of pockets and the distinctive basic P4 pocket, shared by DR52a and DR3, in selecting their respective binding peptide repertoire. We observe an interesting switch in a residue from the canonically assigned pocket 6 seen in prior class II structures to pocket 4. This occludes the P6 pocket helping to explain the distinctive "1-4-9" peptide binding motif. A beta57 Asp-->Val substitution abrogates the salt-bridge to alpha76 Arg and along with a hydrophobic beta37 is important in shaping the P9 pocket. DRB3*0101 and DRB1*0301 belong to an ancestral haplotype and are associated with many autoimmune diseases linked to antigen presentation, but whereas DR3 is susceptible to type 1 diabetes DR52a is not. This dichotomy is explored for clues to the disease.

  1. Crystallographic Structure of the Human Leukocyte Antigen DRA, DRB3*0101: Models of a Directional Alloimmune Respone and Autoimmunity

    SciTech Connect

    Parry,C.; Gorski, J.; Stern, L.

    2007-01-01

    We describe structural studies of the human leukocyte antigen DR52a, HLA-DRA/DRB3*0101, in complex with an N-terminal human platelet integrin {alpha}II{sub B}{beta}III glycoprotein peptide which contains a Leu/Pro dimorphism. The 33:Leu dimorphism is the epitope for the T cell directed response in neonatal alloimmune thrombocytopenia and post-transfusion purpura in individuals with the {alpha}II{sub B}{beta}III 33:Pro allele, and defines the unidirectional alloimmune response. This condition is always associated with DR52a. The crystallographic structure has been refined to 2.25 {angstrom}. There are two {alpha}{beta} heterodimers to the asymmetric unit in space group P4{sub 1}2{sub 1}2. The molecule is characterized by two prominent hydrophobic pockets at either end of the peptide binding cleft and a deep, narrower and highly charged P4 opening underneath the beta 1 chain. Further, the peptide in the second molecule displays a sharp upward turn after pocket P9. The structure reveals the role of pockets and the distinctive basic P4 pocket, shared by DR52a and DR3, in selecting their respective binding peptide repertoire. We observe an interesting switch in a residue from the canonically assigned pocket 6 seen in prior class II structures to pocket 4. This occludes the P6 pocket helping to explain the distinctive '1-4-9' peptide binding motif. A {beta}57 Asp {yields} Val substitution abrogates the salt-bridge to {alpha}76 Arg and along with a hydrophobic {beta}37 is important in shaping the P9 pocket. DRB3*0101 and DRB1*0301 belong to an ancestral haplotype and are associated with many autoimmune diseases linked to antigen presentation, but whereas DR3 is susceptible to type 1 diabetes DR52a is not. This dichotomy is explored for clues to the disease.

  2. Angioma serpiginosum: a simulator of purpura.

    PubMed Central

    Cox, N. H.; Paterson, W. D.

    1991-01-01

    We describe two patients with angioma serpiginosum who had both undergone a variety of haematological tests for investigation of purpura, but in whom careful examination of the skin demonstrated abnormal blood vessels rather than extravasated blood. Recognition of vascular disorders which simulate purpura may avoid unnecessary investigations. Images Figure 1 PMID:1800966

  3. Primary Splenic Angiosarcoma Presenting as Idiopathic Thrombocytopenic Purpura: A Case Report and Review of the Literature

    PubMed Central

    Goldenberg-Sandau, Anna; Roy, Darshan; Sandau, Roy

    2016-01-01

    Angiosarcoma of the spleen is a rare malignancy that arises from vascular endothelial origin. This neoplasm is highly malignant and diagnosis is often delayed due to the vague presentation of clinical symptoms. A case report and concise review of the current diagnostic criteria and surgical treatment are provided to aid in the detection and treatment of this malignancy. We present a case of a 56-year-old female who presented with massive splenomegaly secondary to angiosarcoma of the spleen. The patient suffered from longstanding symptomatic anemia and thrombocytopenia. Diagnosis of a splenic angiosarcoma can be difficult due to the vague presentation and lack of concrete risk factors. Early identification and splenectomy are paramount. However, it is an aggressive malignancy with poor prognosis. We reviewed the literature of the current diagnostic and surgical treatment of primary splenic angiosarcoma. PMID:27651973

  4. Scleroderma renal crisis or thrombotic thrombocytopenic purpura: seeing through the masquerade.

    PubMed

    Keeler, Emily; Fioravanti, Gloria; Samuel, Bensson; Longo, Santo

    2015-01-01

    SCLERODERMA: renal crisis (SRC), a somewhat rare but serious complication of systemic scleroderma, is one of only a few known rheumatologic emergencies; it presents in as many as 10% of patients with scleroderma. Before the use of angiotensin converting enzyme (ACE) inhibitors to treat SRC, the mortality rate for SRC was extremely high-as much as 90% after 1 year. However, the mortality rate has significantly improved with the early and aggressive use of ACE inhibitors. SRC typically includes acute renal failure and accelerated hypertension. Patients may report headache, changes in vision, fever, dyspnea, and encephalopathy. Laboratory study results can show elevated creatinine levels, thrombocytopenia, and microangiopathic hemolytic anemia (MAHA) with schistocytes on blood smear. Given this clinical and laboratory presentation, SRC can easily be mistaken for TTP in clinical practice, as we demonstrate in 2 presentations of similar cases of SRC, the first in a 36-year-old Caucasian woman and the second in a 54-year-old Caucasian woman. In both cases, SRC masqueraded as TTP, and both patients were almost mistakenly treated for TTP until the clinical picture changed and certain laboratory test and kidney biopsy results confirmed otherwise.

  5. Autoimmune thrombocytopenic purpura in partial DiGeorge syndrome: case presentation.

    PubMed

    Hernández-Nieto, Leticia; Yamazaki-Nakashimada, Marco Antonio; Lieberman-Hernández, Esther; Espinosa-Padilla, Sara Elva

    2011-08-01

    The absence of an appropriate central tolerance in primary immunodeficiencies favors proliferation of autoreactive lymphocyte clones, causing a greater incidence of autoimmunity. Del 22q11.2 syndrome presents an increased incidence of allergic and autoimmune diseases. One of the most relevant and frequent immune manifestations is autoimmune thrombocytopenia. We present the case of a pediatric patient with autoimmune thrombocytopenia due to the immunological dysregulation observed in partial DiGeorge syndrome.

  6. Idiopathic thromobocytopenic purpura in two mothers of children with DiGeorge sequence: A new component manifestation of deletion 22q11?

    SciTech Connect

    Levy, A.; Philip, N.; Michel, G.

    1997-04-14

    The phenotypic spectrum caused by the microdeletion of chromosome 22q11 region is known to be variable. Nearly all patients with DiGeorge sequence (DGS) and approximately 60% of patients with velocardiofacial syndrome exhibit the deletion. Recent papers have reported various congenital defects in patients with 22q11 deletions. Conversely, some patients have minimal clinical expression. Ten to 25% of parents of patients with DGS exhibit the deletion and are nearly asymptomatic. Two female patients carrying a 22q11 microdeletion and presenting with idiopathic thrombocytopenic purpura are reported. Both had children with typical manifestations of DGS. 12 refs., 4 figs., 1 tab.

  7. Zinc deficiency in senile purpura.

    PubMed Central

    Haboubi, N Y; Haboubi, N A; Gyde, O H; Small, N A; Barford, A V

    1985-01-01

    Fasting plasma zinc concentrations were lower in elderly people with senile purpura than in a control group matched for age. No significant difference was found in the mean serum concentration of albumin, which is the main binder of zinc. No other clinical or laboratory findings differentiated the two groups. As the cause of the low plasma zinc values has not been found it is suggested that further studies of the related factors including input, output, and binding should be made before a therapeutic trial is launched. PMID:4056071

  8. Henoch-Schönlein purpura

    MedlinePlus

    ... St. Geme J, Schor N, Behrman RE, eds. Nelson Textbook of Pediatrics . 19th ed. Philadelphia, PA: Elsevier ... Schöenlein purpura. In: Marcdante KJ, Kliegman RM, eds. Nelson Essentials of Pediatrics . 7th ed. Philadelphia, PA: Elsevier ...

  9. Prevention of HLA alloimmunization: Role of leukocyte depletion and UV-B irradiation

    SciTech Connect

    Snyder, E.L. )

    1990-09-01

    HLA alloimmunization is a major cause of the platelet refractory state. The stimulus for HLA alloimmunization is believed to derive from incompatibility between the recipient's lymphocytes and the passenger donor lymphocytes contained in transfused red cells or platelet concentrates. Two techniques to prevent post-transfusion HLA alloimmunization include filtration, which physically removes the donor lymphocytes, and UV-B irradiation, which renders the donor leukocytes biologically inactive. The role of these two techniques in the prevention of HLA alloimmunization is the focus of this review.42 references.

  10. Prevention of HLA alloimmunization: role of leukocyte depletion and UV-B irradiation.

    PubMed Central

    Snyder, E. L.

    1990-01-01

    HLA alloimmunization is a major cause of the platelet refractory state. The stimulus for HLA alloimmunization is believed to derive from incompatibility between the recipient's lymphocytes and the passenger donor lymphocytes contained in transfused red cells or platelet concentrates. Two techniques to prevent post-transfusion HLA alloimmunization include filtration, which physically removes the donor lymphocytes, and UV-B irradiation, which renders the donor leukocytes biologically inactive. The role of these two techniques in the prevention of HLA alloimmunization is the focus of this review. PMID:2293501

  11. An improbable and unusual case of thrombotic thrombocytopenia purpura

    PubMed Central

    Patel, Jaymon; Patel, Preeti; Ahmed, Zohair

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening medical emergency which may be difficult to recognize given the wide spectrum in which it presents. A delay in treatment may be catastrophic as untreated cases of TTP have a mortality rate exceeding 90%. Given the high fatality rate of untreated TTP and its range of presenting symptoms, we present our unusual case of TTP in a post-splenectomy patient with early treatment and positive outcome. This case describes a 54-year-old female who presented with hematuria and gingival bleeding, followed by the development of a bilateral lower extremity petechial rash. Her past medical history was significant for multiple episodes of TTP, the last of which resulted in a splenectomy and a 20-year history of remission thereafter. On exam, she was alert, well appearing, and neurologically intact. Her only significant finding was a bilateral lower extremity petechial rash. Laboratory studies revealed mild anemia and thrombocytopenia, an elevated lactate dehydrogenase, and a decreased haptoglobin. Peripheral smear showed poikilocytosis, helmet cells, and schistocytes. Corticosteroid therapy was promptly initiated, her platelets were monitored closely, and she underwent urgent therapeutic plasma exchange. Due to the risk of significant morbidity and mortality that may result from delayed treatment of TTP as well as the significant variations of presentation, TTP requires a consistently high index of suspicion. Our patient suffered multiple relapses of TTP within a 30-year span, underwent splenectomy in early adulthood, and presented with atypical symptoms during her most recent relapse illustrating how persistent TTP can be as well as how unusually it may present. Providers should be aware of the vast spectrum of presentation and remember that TTP may recur following splenectomy despite prolonged remission. PMID:27609730

  12. [Cellular mechanisms implicated in anti-erythrocyte alloimmunization].

    PubMed

    Ansart-Pirenne, H; Rouger, P; Noizat-Pirenne, F

    2005-06-01

    In many clinical situations patients are dependent on blood transfusions. Occurrence of alloimmunization to blood group antigens (BGA) complicates the transfusion strategy and may be involved in clinical transfusion stalemate situations. B cell differentiation into antibody-secreting plasma cells is triggered by antigen and requires helper T cells which produce cytokines. Although antibodies implicated in BGA alloimmunization have been studied for many years, little is known about helper T cell responses that drive their production. Few studies on BGA specific T cell responses have been published today. This review summarizes the new developments in the field of cellular mechanisms implicated into antibody production. The definition of immunodominant peptides derived from RhD and Jk(a) BGAs, the cytokine patterns induced and the HLA class II molecules implicated in their presentation are analyzed. A tolerogenic route for RhD immunodominant peptides is experimented. Identification of such immunodominant peptides, the cytokine patterns induced and the HLA class II molecules implicated in their presentation, would facilitate the design of new therapeutic strategies including the specific control of alloimmunization with peptide antigen tolerogens or the ex-vivo induction of regulatory T cells.

  13. Selection of donor platelets for alloimmunized patients using a platelet-associated IgG assay

    SciTech Connect

    Myers, T.J.; Kim, B.K.; Steiner, M.; Baldini, M.G.

    1981-09-01

    A quantitative immunofluorescence platelet-associated immunoglobulin-G (PA-IgG) assay was used to detect alloimmunity to platelets in 8/12 multitransfused patients and to perform platelet crossmatching in the 8 alloimmunized patients. The correct separation of multitransfused patients into alloimmune and nonalloimmune groups was substantiated with chromium-51-labeled platelet survival studies. For 5 alloimmunized patients, compatible and incompatible donor platelets were demonstrated by PA-IgG crossmatching and were confirmed by platelet survival studies. With the other 3 alloimmunized patients, only Pa-IgG incompatible donor platelets were found. Survival studies with 5 of these incompatible donor platelets showed markedly reduced survival times on 4 occasions. Pa-IgG compatible donor platelets survived 3.5 to 8.7 days, while Pa-IgG incompatible platelets showed survival times of 0.1 to 2.4 days.

  14. The natural history of fetomaternal alloimmunization to the platelet-specific antigen HPA-1a (PlA1, Zwa) as determined by antenatal screening.

    PubMed

    Williamson, L M; Hackett, G; Rennie, J; Palmer, C R; Maciver, C; Hadfield, R; Hughes, D; Jobson, S; Ouwehand, W H

    1998-10-01

    Immunization against the human platelet antigen (HPA)-1 alloantigen is the most common cause of severe fetal and neonatal thrombocytopenia. Fetal therapy has substantial risks and its indications need better definition. Of 24,417 consecutive pregnant women, 618 (2.5%) were HPA-1a negative of whom 385 entered an observational study. All were HLA-DRB3*0101 genotyped and screened for anti-HPA-1a. Their partners and neonates were HPA-1 genotyped and the latter were assessed by cord blood platelet counts and cerebral ultrasound scans. Anti-HPA-1a was detected in 46 of 387 pregnancies (12.0%; 95% CI 8.7%-15.2%). All but one were HLA-DRB3*0101 positive (odds ratio 140; 95% CI 19-1035; P< .00001). One baby died in utero, and of 26 HPA-1a-positive babies born to women with persistent antenatal antibodies, 9 were severely thrombocytopenic (8 with a count <10 x 10(9)/L, 1 with a large porencephalic cyst), 10 were mildly thrombocytopenic, whereas 7 had normal platelet counts. Severe thrombocytopenia was significantly associated with a third trimester anti-HPA-1a titer >/= 1:32 (P = . 004), but was not observed in babies of women with either transient or postnatal-only antibodies. HPA-1a alloimmunization complicates 1 in 350 unselected pregnancies, resulting in severe thrombocytopenia in 1:1,200. HPA-1a and HLA-DRB3*0101 typing combined with anti-HPA-1a titration allows selection of the majority of pregnancies at risk of severe thrombocytopenia.

  15. Factitious purpura in a 10-year-old girl.

    PubMed

    Yamada, Kayo; Sakurai, Yoshihiko; Shibata, Mari; Miyagawa, Sachiko; Yoshioka, Akira

    2009-01-01

    We describe a 10-year-old girl who presented with bizarre purpura. Both congenital and autoimmune hemorrhagic disorders were excluded based on her past medical history and physical and laboratory findings. Child abuse was also ruled out as purpura continued to develop after child-family separation. Histologic examination of the skin lesions revealed disruption of collagen fiber bundles. This finding indicated application of external force, leading to a definitive diagnosis of factitious purpura. Although it is very rare in school-age children, the diagnosis of factitious purpura should be included in the differential diagnosis of purpura in children. Histologic analysis of skin biopsies may aid in establishing the diagnosis.

  16. Psychogenic Purpura (Gardner-Diamond Syndrome)

    PubMed Central

    Bhattacharya, Gaurav

    2015-01-01

    Psychogenic purpura, also known as Gardner-Diamond syndrome or autoerythrocyte sensitization syndrome, is a rare condition characterized by spontaneous development of painful edematous skin lesions progressing to ecchymosis over the next 24 hours. Severe stress and emotional trauma always precede the skin lesions. The condition is most commonly seen in women, but isolated cases have been reported in adolescents and in males. Psychodermatologic evaluation and dermatology and psychiatry liaison have been successful in the treatment of these patients. This report provides an overview of psychogenic purpura and presents the case of a 15-year-old girl. PMID:26137346

  17. Alloimmunization prevents the migration of transfused indium-111-labeled granulocytes to sites of infection

    SciTech Connect

    Dutcher, J.P.; Schiffer, C.A.; Johnston, G.S.; Papenburg, D.; Daly, P.A.; Aisner, J.; Wiernik, P.H.

    1983-08-01

    111In-labeled granulocytes were used to study the effects of histocompatibility factors on the migration of transfused granulocytes to infected sites. Fourteen alloimmunized and 20 nonalloimmunized patients received approximately 10(8) 111In-labeled granulocytes from ABO-compatible, non-HLA-matched donors, and scans were performed over known infected sites. All 14 alloimmunized patients had lymphocytotoxic antibody (LCTAb) and required HLA-matched platelet transfusions. Of the nonalloimmunized patients, 20/20 had positive scans at sites of infection. None of the 20 had LCTAb, 0/17 had a positive lymphocytotoxic crossmatch (LCTXM) with the donor, and 3/18 had a positive leukoagglutinin crossmatch (LAXM). Thus, histocompatibility testing was not found to be important in nonalloimmunized patients. In contrast, only 3/14 alloimmunized patients had positive scans at sites of infection (p . 0.00001 compared to nonalloimmunized patients). One of 3 had a positive LCTXM and 2/3 had a positive LAXM. Of the alloimmunized patients, 10/11 with negative scans had a positive LCTXM and 8/11 had a positive LAXM. Labeled granulocytes failed to reach sites of infection in 11/14 (78%) alloimmunized patients, demonstrating that histocompatibility factors can be of major importance in affecting the outcome of granulocyte transfusions. Granulocytes from random donors are unlikely to be effective in alloimmunized patients. The lack of an adequate crossmatching technique is a major problem limiting the ability to provide granulocyte transfusions for alloimmunized patients.

  18. Fatal alloimmune thrombocytopenia due to anti-HLA alloimmunization in a twin pregnancy: A very infrequent complication of assisted reproduction.

    PubMed

    Meler, Eva; Porta, Roser; Canals, Carme; Serra, Bernat; Lozano, Miguel

    2016-11-02

    The most frequently involved antigen in severe fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the human platelet antigen 1a. Platelets express the HLA-A and B antigens on their membrane and some studies report that maternal anti-HLA class I antibody can also cause FNAIT. We report here a very unusual case of a first twin pregnancy produced in vitro by oocyte and semen donation where the mother developed markedly elevated HLA antibodies, in the absence of anti-platelet or anti-neutrophil antibodies, that provoked in one of the twins a profound thrombocytopenia and intracranial hemorrhage and a mild thrombocytopenia and neutropenia in the second twin lasting until the fourth month of life. In addition, anti-D alloimmunization provoked hemolytic disease of the newborn with intrauterus anemia detected in the first twin and post-natal anemia in the second twin that required red blood cell transfusion and phototherapy. We hypothesize that the complete HLA-incompatible twin pregnancy due to the oocyte donation might have contributed to the severity of the clinical manifestations.

  19. Blood transfusion and alloimmunization in patients with thalassemia: multicenter study.

    PubMed

    Azarkeivan, Azita; Ansari, Shahla; Ahmadi, Mohammad Hossein; Hajibeigy, Bashir; Maghsudlu, Mahtab; Nasizadeh, Soheila; Shaigan, Mojgan; Toolabi, Abdolmajid; Salahmand, Mitra

    2011-09-01

    One of transfusion's side effects is alloimmunization against red blood cell (RBC) antigens. Early diagnosis by antibody screening is an important step in the detection of these alloantibodies. The authors studied the frequency of alloimmunization in thalassemic patients of 4 centers (2 adult and 2 pediatric centers) and compared the rates in children (up to 15 years) and adults. Antibody screening tests were performed by gel method according to its standard pattern and respective program. In positive cases, antibody identification test by gel method was performed. Eight hundred thirty-five patients were studied; 548 (65.6%) were adults (mean age = 24.5), and 287 (34.4%) cases were pediatrics (mean age = 10.05). Of these patients, 74.1% had no history of transfusion reaction, whereas 21 (2.5%) had hemolytic complications. Seventy-eight (9.3%) exhibited allergic symptoms, and 117 (14%) cases experienced febrile reactions during transfusion. Antibody screening showed positive results in 22 pediatric cases (7.7%) and 79 adults (14.4%); 72 (71.3%), 19 (18.8%), 3 (3%), and 1 (1%) cases exhibited single, double, triple, and autoantibodies, respectively. Anti-Kell antibody was seen in 34 (33.7%) cases, anti-D was seen in 11 (10.9%) cases, and anti-E in was seen in 10 (9.9%) cases. The authors observed 8 anti-D+C (7.9%) cases, 1 anti-D+E (1%), 3 anti-Kell+E, 3 anti-Kell+Kpa (3%), and 1 anti-Kell+D double antibodies. These antibodies were also a combination of Rh subgroups or Rh and Kell subgroups. The authors observed meaningful relations between history of transfusion reactions and age with antibody screening results (P = .005). Based on alloantibodies types, more than two thirds of them were Rh subgroups and Kell groups. Phenotype determination of RBCs before beginning chronic blood transfusion and careful cross-matching with Kell and Rh subgroups in addition to ABO may help reduce alloimmunization in chronic transfusion patients.

  20. Fetal and neonatal alloimmune thrombocytopenia: progress and ongoing debates.

    PubMed

    Bussel, James B; Primiani, Andrea

    2008-01-01

    Fetal and neonatal alloimmune thrombocytopenia (AIT) is a result of a parental incompatibility of platelet-specific antigens and the transplacental passage of maternal alloantibodies against the platelet antigen shared by the father and the fetus. It occurs in approximately 1 in 1000 live births and is the most common cause of severe thrombocytopenia in fetuses and term neonates. As screening programs are not routinely performed, most affected fetuses are identified after birth when neonatal thrombocytopenia is recognized. In severe cases, the affected fetus is identified as a result of suffering from an in utero intracranial hemorrhage. Once diagnosed, AIT must be treated antenatally as the disease can be more severe in subsequent pregnancies. While there have been many advances regarding the diagnosis and treatment of AIT, it is still difficult to predict the severity of disease and which therapy will be effective.

  1. Detection of platelet alloimmunity with a platelet-associated IgG assay

    SciTech Connect

    Myers, T.J.; Kim, B.K.; Steiner, M.; Bishop, J.; Baldini, M.G.

    1981-06-01

    A quantitative immunofluorescence PA-IgG assay was used to detect alloimmunity to platelets. The assay identified serum alloantibodies in 10 out of 14 multitransfused patients and for two of three infants with neonatal thrombocytopenia. The correct separation of all multitransfused patients into alloimmune and nonalloimmune groups by the PA-IgG assay was substantiated with chromium-51-labeled platelet survival studies. The allogeneic nature of the serum antibodies was demonstrated by progressive absorption of the antibody with increasing numbers of allogeneic platelets but not with autologous platelets. The sensitivity of the PA-IgG assay for detection of serum alloantibodies was superior to that of platelet aggregation, platelet serotonin release, and lymphocytotoxicity testing. In dilution experiments with alloimmune serum, elevated levels of serum PA-IgG could still be detected on donor platelets when platelet aggregation and serotonin release tests became negative. Platelet survival studies with selected platelets performed in the 10 alloimmunized, multitransfused patients confirmed the results of the PA-IgG assays, predicting alloimmunity to the donor platelets. In contrast, platelet aggregation, platelet serotonin release, and lymphocytotoxicity testing indicated alloimmunity for 50% or less of the patients. Reduced platelet survival times were also seen with HLA A- and HLA B-matched donor platelets when donor-recipient incompatibility was demonstrated by the PA-IgG assay. Thus the PA-IgG assay provides a sensitive method to detect serum platelet alloantibodies and may offer a technique in platelet crossmatching.

  2. Idiopathic purpura fulminans in dengue hemorrhagic fever.

    PubMed

    Karunatilaka, D H; De Silva, J R S; Ranatunga, P K; Gunasekara, T Mr; Faizal, M Am; Malavige, G N

    2007-08-01

    Purpura fulminans is a rapidly progressive thrombotic disease that has been described during both severe bacterial and viral infections. Disseminated intravascular coagulation (DIC), antiphospholipid antibodies and acquired or congenital C and S protein deficiency are thought to play a role in its pathogenesis. Here we report the case of a 4-year-old girl who developed gangrene of all her fingers and toes following dengue shock syndrome complicated by DIC and also discuss its management.

  3. Red blood cell alloimmunization is influenced by recipient inflammatory state at time of transfusion in patients with sickle cell disease.

    PubMed

    Fasano, Ross M; Booth, Garrett S; Miles, Megan; Du, Liping; Koyama, Tatsuki; Meier, Emily Riehm; Luban, Naomi L C

    2015-01-01

    Sickle cell disease (SCD) patients are at increased risk of red blood cell (RBC) alloimmunization. Recipient inflammatory state at time of transfusion has been shown to regulate alloimmunization in murine models, but evidence is lacking in SCD patients. We retrospectively studied a cohort of alloimmunized SCD patients to determine the influence of pro-inflammatory SCD-related complications at time of transfusion on alloimmunization. For each transfusion, the presence of pro-inflammatory state, degree of RBC antigen matching, unit age, storage solution and alloantibody detection date were ascertained. Transfusion-associated pro-inflammatory events were compared between transfusions resulting and not resulting in new alloantibodies. Univariate analysis and multivariate logistic regression were performed. Fifty-two patients received 3166 pre-storage leuco-reduced transfusions of which 128 resulted in alloantibodies. Transfusions during inflammatory events were associated with increased alloantibody risk on univariate and multivariate analysis; acute chest syndrome and vaso-occlusive crisis showed strongest associations with alloimmunization. Increased antigen matching demonstrated a protective effect on alloimmunization (univariate and multivariate analysis). Although an association was seen between citrate-phosphate-dextrose (adenine) stored units and alloimmunization on univariate analysis, no effect was found on multivariate analysis. Identifying recipient pro-inflammatory states at time of transfusion that promote alloimmunization can impact RBC unit selection decisions for SCD patients at risk for alloimmunization.

  4. Predictors of Red Cell Alloimmunization in Kurdish Multi Transfused Patients with Hemoglobinopathies in Iraq.

    PubMed

    Al-Mousawi, Muqdad M N; Al-Allawi, Nasir A S; Alnaqshabandi, Rubad

    2015-01-01

    Hemoglobinopathies are significant health problems in Iraq, including its Northern Kurdistan region. One of the essential components of management of these disorders is regular lifelong blood transfusions. The latter is associated with several complications including red cell alloimmunization. No study has looked at the frequency of alloimmunization and its associations in the country. To address the latter issue, 401 multi transfused patients [311 with β-thalassemia (β-thal) syndrome and 90 with sickle cell disease], registered at a large thalassemia care center in Iraqi Kurdistan had their records reviewed, and their sera tested for atypical antibodies using screening and extended red cell panels. Red cell alloimmunization was detected in 18 patients (4.5%) with a total of 20 alloantibodies, while no autoantibodies were detected. The most frequent alloantibody was anti-E, followed by anti-D, anti-K, anti-C(w), anti-C, anti-c and anti-Le(a). Ethnicity was an important predictor of alloimmunization, while age at start of transfusion (>2 vs. ≤2 years) (p = 0.005), Rhesus D (RhD) negative status (p = 0.0017) and history of previous transfusion reactions (p = 0.007) showed a statistically significant higher rate of alloimmunization. However, patients' age, gender, number of units transfused, underlying diagnosis and splenectomy were not significantly associated with alloimmunization. Based on our observations, measures to reduce alloimmunization rates may include extended matching for Rhesus and Kell antigens and early initiation of blood transfusions.

  5. Low incidence of anti-D alloimmunization following D+ platelet transfusion: The Anti-D Alloimmunization after D-incompatible Platelet Transfusions (ADAPT) study

    PubMed Central

    Cid, Joan; Lozano, Miguel; Ziman, Alyssa; West, Kamille A.; O'Brien, Kerry L.; Murphy, Michael F.; Wendel, Silvano; Vázquez, Alejandro; Ortín, Xavier; Hervig, Tor A.; Delaney, Meghan; Flegel, Willy A.; Yazer, Mark H.

    2014-01-01

    Summary The reported frequency of D alloimmunization in D- recipients after transfusion of D+ platelets varies. This study was designed to determine the frequency of D alloimmunization, previously reported to be an average of 5%±2%. A primary anti-D immune response was defined as the detection of anti-D ≥28 days following the first D+ platelet transfusion. Data were collected on 485 D- recipients of D+ platelets in 11 centres between 2010-2012. Their median age was 60 (range 2-100) years. Diagnoses included: haematological (203/485, 42%), oncological (64/485, 13%) and other diseases (218/485, 45%). Only 7/485 (1.44%; 95%CI 0.58-2.97%) recipients had a primary anti-D response after a median serological follow-up of 77 days (range: 28-2111). There were no statistically significant differences between the primary anti-D formers and the other patients, in terms of gender, age, receipt of immunosuppressive therapy, proportion of patients with haematological/oncological diseases, transfusion of whole blood-derived or apheresis platelets or both, and total number of transfused platelet products. This is the largest study with the longest follow-up of D alloimmunization following D+ platelet transfusion. The low frequency of D alloimmunization should be considered when deciding whether to administer Rh Immune Globulin to D- males and D- females without childbearing potential after transfusion of D+ platelets. PMID:25283094

  6. Hyperglobulinemic purpura in the course of multiple myeloma.

    PubMed

    Shalit, M; Bar-Sela, S; Leviatan, A; Naparstek, Y

    1980-01-01

    Secondary hyperglobulinemic purpura of Waldenström is characterized by polyclonal gammopathy associated mainly with autoimmune diseases. Its occurrence with multiple myeloma is very rare. We described a patient who developed characteristic lesions of hyperglobulinemic purpura in the course of IgA myeloma. Skin biopsy revealed deposition of IgA in the blood vessels.

  7. Red cell alloimmunization in RhD positive pregnant women and neonatal outcome.

    PubMed

    Sankaralingam, Prabakaran; Jain, Ashish; Bagga, Rashmi; Kumar, Praveen; Marwaha, Neelam

    2016-08-01

    The frequency of red blood cell (RBC) alloimmunization in RhD positive pregnant women is not known in our population. We planned to determine its frequency and correlation with neonatal outcome. We included 1000 RhD positive pregnant women: 500 had 'normal pregnancy' (Group I) and another 500 had 'high risk pregnancy' (Group II). ABO and extended Rh phenotyping were done by tube technique, antibody screening and identification by gel technique. For alloimmunized women, the paternal and neonatal ABO and extended Rh typing were done. Neonatal direct antiglobulin test (DAT) was also done and their clinical outcome observed. The frequency of RBC alloimmunization was 0.7% (7/1000) and all these women were from group II (p = 0.015). The alloantibodies were anti-E (85.7%), anti-c (71.4%), anti-Cw (14.3%) and anti-S (14.3%). Also, 6 women had history of transfusion (p < 0.01). Of the 7 neonates born to alloimmunized mothers, 4 (57.14%) had a positive DAT. The mean duration of phototherapy was higher in the DAT positive neonates (p < 0.01) and 2 (50%) required exchange transfusion. Thus, the frequency of alloimmunization was 0.7% in RhD positive pregnant women. High risk pregnancies and antenatal patients having a history of blood transfusion should be considered for regular antibody screening.

  8. T-cell alloimmunity and chronic allograft dysfunction.

    PubMed

    Safinia, Niloufar; Afzali, Behdad; Atalar, Kerem; Lombardi, Giovanna; Lechler, Robert I

    2010-12-01

    Solid organ transplantation is the standard treatment to improve both the quality of life and survival in patients with various end-stage organ diseases. The primary barrier against successful transplantation is recipient alloimmunity and the need to be maintained on immunosuppressive therapies with associated side effects. Despite such treatments in renal transplantation, after death with a functioning graft, chronic allograft dysfunction (CAD) is the most common cause of late allograft loss. Recipient recognition of donor histocompatibility antigens, via direct, indirect, and semidirect pathways, is critically dependent on the antigen-presenting cell (APC) and elicits effector responses dominated by recipient T cells. In allograft rejection, the engagement of recipient and donor cells results in recruitment of T-helper (Th) cells of the Th1 and Th17 lineage to the graft. In cases in which the alloresponse is dominated by regulatory T cells (Tregs), rejection can be prevented and the allograft tolerated with minimum or no immunosuppression. Here, we review the pathways of allorecognition that underlie CAD and the T-cell effector phenotypes elicited as part of the alloresponse. Future therapies including depletion of donor-reactive lymphocytes, costimulation blockade, negative vaccination using dendritic cell subtypes, and Treg therapy are inferred from an understanding of these mechanisms of allograft rejection.

  9. [Duodenal complications of rheumatoid purpura. Endoscopic aspects].

    PubMed

    Chapoy, P; Guidon, M J; Louchet, E

    1984-01-01

    The aim of this work was to describe the endoscopic features and clinical outcome of the duodenal complications in anaphylactoid purpura. Over a 3-year period, 20 patients were hospitalized in our unit because of purpura rheumatica. Duodenal complications occurred in 5 cases warranting endoscopic assessment. All patients had bilious vomiting and epigastric pain, constantly associated with low-grade purpuric rash. Plasma factor XIII concentrations were always decreased. The duodenal complication was suspected radiologically in 2 cases when "thumbprint" impressions were seen. Petechiae, oedema and intramural hematoma with superficial erosions were present endoscopically in 3 cases. The lesions were severe and extensive, involving the entire duodenum in 3 cases and the jejunum in one case. In one patient, there was a stricture of the upper part of the second duodenum. Treatment consisted of parenteral nutrition (using a central catheter: 3 cases, or a peripheral vein: 2 cases) and cimetidine (30 mg/kg.bw). The clinical outcome was favorable in 4 patients; the symptoms vanished and the endoscopic lesions were reversible (including the stricture) with restitutio ad integrum after 10 days. The last patient died the 8th day of treatment, 3 days after digestive improvement; the cause of death was probably iatrogenic and related to accidental migration of the central catheter. These results suggest that endoscopic examination should be performed in all patients with anaphylactoid purpura presenting with bilious vomiting. Endoscopy seems to be of great value in deciding if parenteral nutrition is indicated--or not--and perhaps in order to contraindicate the use of steroid therapy in the case of ulcerated hematomas.

  10. Autoantibody formation in the alloimmunized red blood cell recipient: clinical and laboratory implications.

    PubMed

    Zumberg, M S; Procter, J L; Lottenberg, R; Kitchens, C S; Klein, H G

    2001-01-22

    Alloimmunization to erythrocyte antigens is a well-characterized complication in heavily transfused patients. Less well recognized, however, is the frequency of autoantibody formation in these previously alloimmunized patients. The autoantibodies are heterogeneous and of variable clinical significance. We describe the clinical history, laboratory evaluation, diagnosis, and treatment in 4 patients who developed autoantibodies in temporal association with alloantibody formation. In one case, the autoantibody found on routine screening had no clinical significance. In another case, the autoantibody made accurate blood typing and subsequent transfusion exceedingly difficult. Two patients experienced hemolysis as a consequence of the autoantibody. The management of both patients included supportive measures, while one patient required glucocorticosteroids and red blood cell transfusion. We review the published literature concerning autoimmunization in the transfused alloimmunized host. The spectrum of clinical consequences is important for the general practitioner to recognize, as these complications may occur during routine blood transfusions.

  11. Protective Effect of HLA-DQB1 Alleles Against Alloimmunization in Patients with Sickle Cell Disease

    PubMed Central

    Tatari-Calderone, Zohreh; Gordish-Dressman, Heather; Fasano, Ross; Riggs, Michael; Fortier, Catherine; Andrew; Campbell, D.; Charron, Dominique; Gordeuk, Victor R.; Luban, Naomi L.C.; Vukmanovic, Stanislav; Tamouza, Ryad

    2015-01-01

    Background Alloimmunization or the development of alloantibodies to Red Blood Cell (RBC) antigens is considered one of the major complications after RBC transfusions in patients with sickle cell disease (SCD) and can lead to both acute and delayed hemolytic reactions. It has been suggested that polymorphisms in HLA genes, may play a role in alloimmunization. We conducted a retrospective study analyzing the influence of HLA-DRB1 and DQB1 genetic diversity on RBC-alloimmunization. Study design Two-hundred four multi-transfused SCD patients with and without RBC-alloimmunization were typed at low/medium resolution by PCR-SSO, using IMGT-HLA Database. HLA-DRB1 and DQB1 allele frequencies were analyzed using logistic regression models, and global p-value was calculated using multiple logistic regression. Results While only trends towards associations between HLA-DR diversity and alloimmunization were observed, analysis of HLA-DQ showed that HLA-DQ2 (p=0.02), -DQ3 (p=0.02) and -DQ5 (p=0.01) alleles were significantly higher in non-alloimmunized patients, likely behaving as protective alleles. In addition, multiple logistic regression analysis showed both HLA-DQ2/6 (p=0.01) and HLA-DQ5/5 (p=0.03) combinations constitute additional predictor of protective status. Conclusion Our data suggest that particular HLA-DQ alleles influence the clinical course of RBC transfusion in patients with SCD, which could pave the way towards predictive strategies. PMID:26476208

  12. Study of alloimmunization and autoimmunization in Iranian β-thalassemia major patients

    PubMed Central

    Davari, Kambiz; Soltanpour, Mohammad Soleiman

    2016-01-01

    Background: Thalassemia is one of the most common monogenic disorders characterized by reduced production of globin chains. Although regular red blood cell (RBC) transfusion support is the main treatment for these patients, it may be associated with complications such as RBC alloimmunization. Aim: The study aimed to determine the incidence of alloimmunization and autoimmunization to RBC antigens in β-thalassemia major patients from Zanjan, Zanjan Province, Iran. Materials and Methods: A total of 49 β-thalassemia major patients comprising 24 females and 25 males (mean age: 18.59 ± 8.16 years; range: 2-40 years) from Northwest Iran were included in a cross-sectional study. Alloantibody screening and identification were done using 3-cell and 10-cell reagent red blood cells, respectively. Autoantibody detection was performed using direct Coomb's test. Results: The incidence of alloimmunization was 16.32% with 10 alloantibodies identified in 8 patients. The most common clinically significant alloantibody identified in alloimmunized patients was anti-Kell (K-antigen) (60%) followed by anti-Rhesus (Rh) (E, c-antigens). The rate of alloimmunization was significantly lower in patients transfused with leukoreduced RBCs compared with those transfused with nonleukoreduced RBCs (9.53% vs 57.14%, P = 0.001). There was no significant correlation between alloantibody formation and the age, gender, hemoglobin levels, number of transfused units, and splenectomy. Conclusion: Transfusion of leukoreduced and phenotypically matched red blood cells for Kell (K) and Rh (E, c) antigens may help reduce the alloimmunization rate in Iranian β-thalassemia major patients. Moreover, autoimmunization to RBC antigens was rare in our patients. PMID:27011679

  13. Alloimmunization and erythrocyte autoimmunization in transfusion-dependent thalassemia patients of predominantly asian descent.

    PubMed

    Singer, S T; Wu, V; Mignacca, R; Kuypers, F A; Morel, P; Vichinsky, E P

    2000-11-15

    The development of hemolytic alloantibodies and erythrocyte autoantibodies complicates transfusion therapy in thalassemia patients. The frequency, causes, and prevention of this phenomena among 64 transfused thalassemia patients (75% Asian) were evaluated. The effect of red blood cell (RBC) phenotypic differences between donors (mostly white) and Asian recipients on the frequency of alloimmunization was determined. Additional transfusion and patient immune factors were examined. 14 (22%) of 64 patients (75% Asian) became alloimmunized. A mismatched RBC phenotype between the white population, comprising the majority of the donor pool, and that of the Asian recipients, was found for K, c, S, and Fyb antigens, which accounts for 38% of the alloantibodies among Asian patients. Patients who had a splenectomy had a higher rate of alloimmunization than patients who did not have a splenectomy (36% vs 12.8%; P =.06). Erythrocyte autoantibodies, as determined by a positive Coombs test, developed in 25% or 16 of the 64 patients, thereby causing severe hemolytic anemia in 3 of 16 patients. Of these 16, 11 antibodies were typed immunoglobulin G [IgG], and 5 were typed IgM. Autoimmunization was associated with alloimmunization and with the absence of spleen (44% and 56%, respectively). Transfused RBCs had abnormal deformability profiles, more prominent in the patients without a spleen, which possibly stimulated antibody production. Transfusion of phenotypically matched blood for the Rh and Kell (leukodepleted in 92%) systems compared to blood phenotypically matched for the standard ABO-D system (leukodepleted in 60%) proved to be effective in preventing alloimmunization (2.8% vs 33%; P =.0005). Alloimmunization and autoimmunization are common, serious complications in Asian thalassemia patients, who are affected by donor-recipient RBC antigen mismatch and immunological factors.

  14. Red Blood Cell Alloimmunization in Sickle Cell Disease: Listen to Your Ancestors

    PubMed Central

    Campbell-Lee, Sally A.; Kittles, Rick A.

    2014-01-01

    Summary Red blood cell (RBC) alloimmunization occurs in approximately 30% of transfused sickle cell disease patients compared to 2–5% of all transfusion recipients. Because RBC transfusion is an important part of therapy in sickle cell disease, the need for additional antigen matching once alloimmunization occurs is problematic and leads to therapeutic limitations. Thus, identification of risk factors would benefit this patient population. Genome-wide analyses, in particular, methods which take into account genetic ancestry such as admixture mapping, could identify molecular markers which could be used to identify immune responders to transfusion. PMID:25670930

  15. Acute infectious purpura fulminans due to probable spotted fever.

    PubMed

    Kundavaram, A; Francis, N R; Jude, A P J; Varghese, G N

    2014-01-01

    Purpura fulminans (PF) is associated with several infections, most notably with meningococcus, staphylococcus, and streptococcus infections. However, there are few reports of association of this entity with spotted fever from India. We report the case of a 55-year-old man who presented with fever, headache, and myalgia. On the seventh day of fever he developed nonblanching purple hemorrhagic purpura on the trunk and most prominently on the extremities consistent with purpura fulminans. Immunofluorescent assay confirmed the diagnosis of spotted fever. PF though common with rocky mountain spotted fever (RMSF) is rarely seen in association with Indian tick typhus, the usual cause of spotted fever in India.

  16. [Schoenlein-Henoch purpura with intestinal involvement].

    PubMed

    Blöchinger, M; Schmitt, W; Beer, M; Seib, H J

    1997-11-01

    A 51-year-old male patient admitted to the hospital because of colic-like abdominal pain, paralytic ileus, anal bleeding and microhaematuria with proteinuria, developed an intestinal ischemia with a serum lactate level of 6.3 mmol/l. An occlusion of the large vessels was excluded angiographically. Perfusion disorders were detected both endoscopically and histologically in the upper gastrointestinal tract and in the terminal ileum. When after two days a palpable purpura appeared on the anterior of both feet, a vasculitis type Schoenlein-Henoch was suspected and treated with high doses of steroids, resulting in decreasing symptoms. From the point of admittance, a nephritic urinary sediment had been apparent, and the renal affliction developed into a nephrotic syndrome without notable reduction in the glomerular filtration rate. On the 13th day of treatment the patient-being on a reduced dose of steroids-suffered from a severe relapse; however, this responded favorably to an increase of the dosage. The kidneys required approximately one year for complete recovery. Based on this case, the Schoenlein-Henoch purpura syndrome and its differential diagnosis are presented, particularly with respect to gastrointestinal symptoms and in view of the pertinent literature.

  17. Endoscopy in neutropenic and/or thrombocytopenic patients

    PubMed Central

    Tong, Michelle C; Tadros, Micheal; Vaziri, Haleh

    2015-01-01

    AIM: To evaluate the safety of endoscopic procedures in neutropenic and/or thrombocytopenic cancer patients. METHODS: We performed a literature search for English language studies in which patients with neutropenia and/or thrombocytopenia underwent endoscopy. Studies were included if endoscopic procedures were used as part of the evaluation of neutropenic and/or thrombocytopenic patients, yielding 13 studies. Two studies in which endoscopy was not a primary evaluation tool were excluded. Eleven relevant studies were identified by two independent reviewers on PubMed, Scopus, and Ovid databases. RESULTS: Most of the studies had high diagnostic yield with relatively low complication rates. Therapeutic endoscopic interventions were performed in more than half the studies, including high-risk procedures, such as sclerotherapy. Platelet transfusion was given if counts were less than 50000/mm3 in four studies and less than 10000/mm3 in one study. Other thrombocytopenic precautions included withholding of biopsy if platelet count was less than 30000/mm3 in one study and less than 20000/mm3 in another study. Two of the ten studies which examined thrombocytopenic patient populations reported bleeding complications related to endoscopy, none of which caused major morbidity or mortality. All febrile neutropenic patients received prophylactic broad-spectrum antibiotics in the studies reviewed. Regarding afebrile neutropenic patients, prophylactic antibiotics were given if absolute neutrophil count was less than 1000/mm3 in one study, if the patient was undergoing colonoscopy and had a high inflammatory condition without clear definition of significance in another study, and if the patient was in an aplastic phase in a third study. Endoscopy was also withheld in one study for severe pancytopenia. CONCLUSION: Endoscopy can be safely performed in patients with thrombocytopenia/neutropenia. Prophylactic platelet transfusion and/or antibiotic administration prior to endoscopy may be

  18. DRESS syndrome and thrombotic thrombocytopaenic purpura: are they related?

    PubMed Central

    Sandouk, Zahrae; Alirhayim, Zaid; Khoulani, Dania; Hassan, Syed

    2012-01-01

    A middle-aged man diagnosed with a drug reaction with eosinophilia and systemic symptom (DRESS) syndrome, secondary to phenytoin use, subsequently developed thrombotic thrombocytopaenic purpura. The patient improved with steroids and plasmapheresis. Their diagnosis can be challenging, and an early recognition and treatment are critical owing to their high mortality rates. Both diseases are thought to be of an autoimmune origin, and a potential relationship between them led to the consideration of the DRESS syndrome as an aetiology for thrombotic thrombocytopaenic purpura in this case. We concluded that two possibilities exist: some type of antibody developed during the clinical presentation of DRESS syndrome and subsequently resulted in an inhibition of a disintegrin and metalloproteinase with a thrombospondin type-1 motif, member 13 (ADAMTS13) leading to thrombotic thrombocytopaenic purpura, or perhaps this patient's autoimmune predisposition to thrombotic thrombocytopaenic purpura contributed to the drug reaction. PMID:23152183

  19. Frequency and Specificity of Red Blood Cell Alloimmunization in Chilean Transfused Patients

    PubMed Central

    Caamaño, José; Musante, Evangelina; Contreras, Margarita; Ulloa, Hernán; Reyes, Carolina; Inaipil, Verónica; Saavedra, Nicolás; Guzmán, Neftalí

    2015-01-01

    Summary Background Alloimmunization is an adverse effect of blood transfusions. In Chile, alloimmunization frequency is not established, and for this reason the aim of this study was to investigate the prevalence and specificity of red blood cell (RBC) alloantibodies in Chilean transfused subjects. Methods Records from 4,716 multi-transfused patients were analyzed. In these patients, antibody screening was carried out prior to cross-matching with a commercially available two-cell panel by the microcolum gel test, and samples with a positive screen were analyzed for the specificity of the alloantibody with a 16-cell identification panel. Results The incidence of RBC alloimmunization in transfused patients was 1.02% (48/4,716) with a higher prevalence in women (40/48). We detected 52 antibodies, the most frequent specificities identified were anti-E (30.8%), anti-K (26.9%), anti-D (7.7%), and anti-Fya (5.8%). The highest incidence of alloantibodies was observed in cancer and gastroenterology patients. Conclusion The data demonstrated a low alloimmunization frequency in Chilean transfused patients, principally associated with antibodies anti-E, anti-K, anti-D, and anti-Fya. PMID:25960709

  20. Prenatal testing for hemolytic disease of the newborn and fetal neonatal alloimmune thrombocytopenia - current status.

    PubMed

    Avent, Neil D

    2014-12-01

    Incompatibility of red cell and platelet antigens can lead to maternal alloimmunization causing hemolytic disease of the fetus & newborn and fetal neonatal alloimmune thrombocytopenia respectively. As the molecular background of these polymorphisms emerged, prenatal testing using initially fetal DNA obtained from invasively obtained amniotic fluid or chorionic villus was implemented. This evolved into testing using maternal plasma as source of fetal DNA, and this is in routine use as a safe non-invasive diagnostic that has no risk to the fetus of alloimmunization or spontaneous miscarriage. These tests were initially applied to high risk pregnancies, but has been applied on a mass scale, to screen fetuses in D-negative pregnant populations as national screening programs. Fetal neonatal alloimmune thrombocytopenia management has had comparatively small take up in non-invasive testing for causative fetal platelet alleles (e.g., HPA-1A), but mass scale genotyping of mothers to identify at risk HPA-1b1b pregnancies and their treatment with prophylactic anti-HPA-1A is being considered in at least one country (Norway).

  1. Characterization of pneumococcal purpura-producing principle.

    PubMed

    Chetty, C; Kreger, A

    1980-07-01

    Purpura was grossly observable in albino mice 6 to 8 h after the intraperitoneal injection of sterile, deoxyribonuclease-treated, cell-free extracts prepared by sodium deoxycholate-induced lysis, sonic disruption, Parr bomb treatment, autolysis without sodium deoxycholate, or alternate freezing and thawing of washed suspensions of Streptococcus pneumoniae type I. Cell-free extracts obtained from sonically disrupted, heat-killed cells (100 degrees C for 20 min) did not contain purpurogenic activity. The reaction was maximal at approximately 24 h postinjection, started to fade slowly after 24 to 48 h, and usually was not grossly observable by 4 to 6 days postinjection. The purpura-producing principle (PPP) in the cell-free extract was purified by sequential ammonium sulfate precipitation, protamine sulfate precipitation, Sepharose 6B gel filtration, wheat germ lectin-Sepharose 6MB affinity chromatography, ribonuclease and trypsin treatment, and a second Sepharose 6B gel filtration step. The final preparation (i) contained glucosamine (5.6%), muramic acid (8.0%), neutral carbohydrate (12.8%), phosphate (8.0%), orcinol-reactive material (6.0%), and Lowry-reactive material (1.6%), and (ii) was free of detectable amounts of deoxyribonucleic acid, capsular polysaccharide, neuraminidase, cytolysin, and hyaluronidase. The isoelectric point and molecular size of the PPP were approximately pI 3.0 and several million daltons, respectively, and the activity remained in the supernatant fluid after centrifugation for 1 day at 105,000 x g. PPP activity was destroyed by incubation with egg white lysozyme and sodium metaperiodate but was resistant to trypsin, pronase, alpha-amylase, deoxyribonuclease, ribonuclease, alkaline phosphatase, pancreatic lipase, 7% trichloroacetic acid, 6 M urea, autoclaving (121 degrees C) for 30 min, and mild acid and alkali exposure. Our observations indicate that the PPP requires intact beta-1,4-glucosidic linkages for activity and support the working

  2. Can the Interval Between Antibody Identifications be Increased for Alloimmunized Patients?

    PubMed Central

    Goss, Cheryl; Avecilla, Scott T.; Garbaini, Jennifer; Degtyaryova, Diana; Lo, Dian; Chang, Dustin Y.M.; Cushing, Melissa

    2016-01-01

    Background New alloantibody formation is unpredictable in patients who have been previously alloimmunized. Pretransfusion testing is designed to detect these antibodies while antibody identification (ABI) techniques are designed to identify the specificity of the antibody. Pretransfusion testing intervals are prescribed by regulatory and accrediting agencies, intervals for ABI in alloimmunized patients are not. Our institution evaluated the safety of increasing the interval from every 72-hours to 14-days. The current 72-hour interval was chosen at our institution to align with AABB standard 5.14.3.2 which requires a pretransfusion specimen drawn within 3-days of the scheduled transfusion for potentially immunized patients. Study Design and Methods Over 2 years, all ABI entries in the laboratory information system were screened. All cases of alloimmunized patients with an additional antibody specificity that developed within 14-days of a previous ABI were reviewed and confirmed by four transfusion medicine physicians. Results Initially, 8948 entries were screened. Thirty patients were identified to have formed 33 newly identified clinically significant alloantibodies within 14-days. After further categorization, only 13 antibodies (0.15% of all ABI, 0.47% of alloimmunized patients examined) were deemed to be newly formed clinically significant antibodies that would have led to a change in transfusion practice. Discussion Retrospective analysis of ABI results over a 2-year period revealed that 0.47% of previously alloimmunized patients that have samples for pretransfusion testing develop a new clinically significant alloantibody in 14-days or less. While there would be significant resource advantages to increasing the duration between repeat ABI, it does not outweigh the risk of a potential hemolytic transfusion reaction. PMID:26456540

  3. Alloimmunization in Patients with Sickle Cell Disease and Thalassemia: Experience of a Single Centre in Oman

    PubMed Central

    Alkindi, Salam; AlMahrooqi, Saba; AlHinai, Sumaiya; AlMarhoobi, Ali; Al-Hosni, Saif; Daar, Shahina; Fawaz, Naglaa; Pathare, Anil

    2017-01-01

    Background Blood transfusion is an integral part of the supportive care for patients with sickle cell disease (SCD) and thalassaemia. The hazard of red cell alloimmunization, however, is one of the main complications of this therapy. Objectives The aim of this study was to evaluate the prevalence of red cell alloimmunization in Omani patients with sickle cell anaemia and thalassemia. Methods This study included 262 patients whose historical transfusion records were available. One hundred and twenty-nine patients with thalassaemia who were attending the day care unit for regular transfusions, and 133 SCD patients admitted at our hospital were included in this study. The Diamed® gel system was used for the screening and identification of atypical antibodies. Results The rate of alloimmunization in SCD patients was 31.6% (n=42, 95%CI, 24.87–40.66), whereas in patients with thalassaemia it was 20% (n=26; 95%CI, 13.9–27.6). Antibodies to E, e, C, c, D, K, S, Fyª, Kpª, Jkª and Cw were observed; 85% of the patients were also immunised with Rh and Kell antigens. Considering the two groups together, 8 developed nonspecific antibodies and 12 developed more than one antibody. Conclusions Red cell transfusions were associated with a significant risk of alloimmunization. It is, therefore, imperative to perform an initial extended red cell phenotyping for both donors and recipients, and carefully select ABO, Rh and Kell matched donors. The higher incidence of alloimmunization in SCD patients is related to the inherent SCD-specific inflammatory state. PMID:28293401

  4. Emerging science, emerging ethical issues: who should fund innate alloimmunity-suppressing drugs?

    PubMed

    Land, W G; Gutmann, Th; Daar, A S

    2008-01-01

    An emerging body of evidence suggests that the innate immune system plays a critical role in allograft rejection. Any injury to the donor organ, e.g. the reperfusion injury, induces an inflammatory milieu in the allograft which appears to be the initial event for activation of the innate immune system. Injury-induced intragraft damage- associated molecular patterns (DAMPs) are recognized by donor-derived and recipient-derived, TLR4/2-bearing immature dendritic cells (iDCs). After recognition, these cells mature and initiate allorecognition/alloactivation in the lymphoid system of the recipient. Indeed, the key "innate" event, leading to activation of the adaptive alloimmune response, is the injury-induced, TLR4-triggered, and NFkappaB-mediated maturation of DCs ("innate alloimmunity"). Time-restricted treatment of innate immune events would include 1) treatment of the donor during organ removal, 2) in-situ/ex-vivo treatment of the donor organs alone, and 3) treatment of the recipient during allograft reperfusion and immediately postoperatively. Treatment modalities would include 1) minimization of the oxidative allograft injury with the use of antioxidants; 2) prevention of the TLR4-triggered maturation of DCs with the use of TLR4-antagonists; 3) inhibition of complement activation with the use of complement inhibiting agents. According to data from clinical and experimental studies it can be assumed that successful suppression of innate alloimmune events results in either subsequent significant reduction in, or even complete avoidance of the currently applied adaptive alloimmunity-suppressing drugs. However, in view of the time-restricted period of treatment, and the fear to potentially destroy its own business with currently applied alloimmunity-suppressing drugs, the pharmaceutical industry is still, but quite legitimately, reluctant to invest in the high cost of clinical development of those drugs for transplant patients because there are no marketing interests

  5. Treatments for hematologic malignancies in contrast to those for solid cancers are associated with reduced red cell alloimmunization.

    PubMed

    Evers, Dorothea; Zwaginga, Jaap Jan; Tijmensen, Janneke; Middelburg, Rutger A; de Haas, Masja; de Vooght, Karen M K; van de Kerkhof, Daan; Visser, Otto; Péquériaux, Nathalie C V; Hudig, Francisca; van der Bom, Johanna G

    2017-01-01

    Red cell alloimmunization may induce severe hemolytic side effects. Identification of risk-modifying conditions will help tailor preventative strategies. This study aims to quantify the associations of hematologic malignancies and solid cancers with red cell alloimmunization in patients receiving red cell transfusions. We performed a nested multicenter case-control study in a source population of 24,063 patients receiving their first and subsequent red cell transfusions during an 8-year follow-up period. Cases (n=505), defined as patients developing a first transfusion-induced red cell alloantibody, were each compared with 2 non-alloimmunized controls (n=1010) who received a similar number of red cell units. Using multivariate logistic regression analyses, we evaluated the association of various malignancies and treatment regimens with alloimmunization during a delineated 5-week risk period. The incidence of alloimmunization among patients with acute (myeloid or lymphoid) leukemia and mature (B- or T-cell) lymphoma was significantly reduced compared to patients without these malignancies: adjusted relative risks (RR) with 95% confidence interval (CI) 0.36 (range 0.19-0.68) and 0.30 (range 0.12-0.81). Associations were primarily explained by immunosuppressive treatments [RR for (any type of) chemotherapy combined with immunotherapy 0.27 (95%CI: 0.09-0.83)]. Alloimmunization risks were similarly diminished in allogeneic or autologous stem cell transplanted patients (RR 0.34, 95%CI: 0.16-0.74), at least during the six months post transplant. Alloimmunization risks of patients with other hematologic diseases or solid cancers, and their associated treatment regimens were similar to risks in the general transfused population. Our findings suggest that, in contrast to malignancies in general, hemato-oncological patients treated with dose-intensive regimens have strongly diminished risk of red cell alloimmunization.

  6. Treatments for hematologic malignancies in contrast to those for solid cancers are associated with reduced red cell alloimmunization

    PubMed Central

    Evers, Dorothea; Zwaginga, Jaap Jan; Tijmensen, Janneke; Middelburg, Rutger A.; de Haas, Masja; de Vooght, Karen M.K.; van de Kerkhof, Daan; Visser, Otto; Péquériaux, Nathalie C.V.; Hudig, Francisca; van der Bom, Johanna G.

    2017-01-01

    Red cell alloimmunization may induce severe hemolytic side effects. Identification of risk-modifying conditions will help tailor preventative strategies. This study aims to quantify the associations of hematologic malignancies and solid cancers with red cell alloimmunization in patients receiving red cell transfusions. We performed a nested multicenter case-control study in a source population of 24,063 patients receiving their first and subsequent red cell transfusions during an 8-year follow-up period. Cases (n=505), defined as patients developing a first transfusion-induced red cell alloantibody, were each compared with 2 non-alloimmunized controls (n=1010) who received a similar number of red cell units. Using multivariate logistic regression analyses, we evaluated the association of various malignancies and treatment regimens with alloimmunization during a delineated 5-week risk period. The incidence of alloimmunization among patients with acute (myeloid or lymphoid) leukemia and mature (B- or T-cell) lymphoma was significantly reduced compared to patients without these malignancies: adjusted relative risks (RR) with 95% confidence interval (CI) 0.36 (range 0.19–0.68) and 0.30 (range 0.12–0.81). Associations were primarily explained by immunosuppressive treatments [RR for (any type of) chemotherapy combined with immunotherapy 0.27 (95%CI: 0.09–0.83)]. Alloimmunization risks were similarly diminished in allogeneic or autologous stem cell transplanted patients (RR 0.34, 95%CI: 0.16–0.74), at least during the six months post transplant. Alloimmunization risks of patients with other hematologic diseases or solid cancers, and their associated treatment regimens were similar to risks in the general transfused population. Our findings suggest that, in contrast to malignancies in general, hemato-oncological patients treated with dose-intensive regimens have strongly diminished risk of red cell alloimmunization. PMID:27634204

  7. Treatment of D alloimmunization in pregnancy with plasmapheresis and intravenous immune globulin: case report.

    PubMed

    Fernández Alba, Juan J; León, Raquel; González-Macías, Carmen; Paz, Antonio; Prado, Fabiana; Moreno, Luis J; Torrejón, Rafael

    2014-08-01

    The prevalence of D alloimmunization occurs between 0.15% and 0.4%. The anti-D can cross the placenta and cause hemolysis and fetal anemia. At present, a Doppler study of the middle cerebral artery allows the monitoring of the degree of fetal anemia. The treatment in cases of moderate to severe anemia in fetuses of less than 34-35 weeks of gestation is intrauterine transfusion via cordocentesis. However, with high titers of anti-D, in the absence of fetal anemia it is possible to modulate the maternal immune response by plasmapheresis and intravenous immunoglobulin administration. We present a case report of an Rh(D) alloimmunized pregnancy treated with plasmapheresis followed by intravenous immunoglobulin administration. We performed a caesarean section at 31 weeks, 5 days of gestation. The hemoglobin at birth was 13.8 g/dl and hematocrit 40.8%. Intrauterine transfusion was not necessary.

  8. Delayed cord clamping in red blood cell alloimmunization: safe, effective, and free?

    PubMed Central

    2016-01-01

    Hemolytic disease of the newborn (HDN), an alloimmune disorder due to maternal and fetal blood type incompatibility, is associated with fetal and neonatal complications related to red blood cell (RBC) hemolysis. After delivery, without placental clearance, neonatal hyperbilirubinemia may develop from ongoing maternal antibody-mediated RBC hemolysis. In cases refractory to intensive phototherapy treatment, exchange transfusions (ET) may be performed to prevent central nervous system damage by reducing circulating bilirubin levels and to replace antibody-coated red blood cells with antigen-negative RBCs. The risks and costs of treating HDN are significant, but appear to be decreased by delayed umbilical cord clamping at birth, a strategy that promotes placental transfusion to the newborn. Compared to immediate cord clamping (ICC), safe and beneficial short-term outcomes have been demonstrated in preterm and term neonates receiving delayed cord clamping (DCC), a practice that may potentially be effective in cases RBC alloimmunization. PMID:27186530

  9. Red blood cell and leukocyte alloimmunization in patients awaiting kidney transplantation

    PubMed Central

    da Silva, Silvia Fernandes Ribeiro; Ferreira, Gláucia Maria; da Silva, Sonia Leite; Alves, Tânia Maria de Oliveira; Ribeiro, Ilana Farias; Ribeiro, Thyciana Rodrigues; Cavalcante, Maria do Carmo Serpa

    2013-01-01

    Objective To determine the rates of red blood cell and leukocyte alloimmunization in patients with chronic kidney disease awaiting kidney transplantation. Methods In this cross-sectional and prospective study, the serum of 393 chronic kidney disease patients on a transplant waiting list in Ceará, Northeastern Brazil were tested for red cell and leukocyte antibodies. In addition, demographic, clinical and laboratory data were collected. Results The average age in the sample of 393 patients was 34.1 ± 14 years. Slightly more than half (208; 52.9%) were male. The average numbers of transfusions and gestations were 3.1 ± 3.3 and 1.6 ± 6, respectively. One third (33.6%) were alloimmunized: 78% with leukocyte antibodies, 9.1% with red cell antibodies and 12.9% with both. Red cell antibodies were detected in 29 cases (7.4%), 17 of whom were women, who had received more transfusions than the males (p-value < 0.0001). The most frequently detected red cell antibodies belonged to the Rh (24.1%) and Kell (13.8%) blood group systems. Leukocyte antibodies were detected in 30.5% of cases, 83 of whom were women, who had received more transfusions than the males (p-value < 0.0001) and were more reactive to panel reactive antibodies (p-value < 0.0001). The mean alloreactivity to panel reactive antibodies was 47.7 ± 31.2%. Conclusion Chronic kidney disease patients on the transplant waiting list in Ceará, Brazil, display high rates of red cell (7.4%) and leukocyte (30.5%) alloimmunization. In this sample, alloimmunization was significantly associated with the number of transfusions and gender. PMID:23904808

  10. Alloimmunization is associated with older age of transfused red blood cells in sickle cell disease.

    PubMed

    Desai, Payal C; Deal, Allison M; Pfaff, Emily R; Qaqish, Bahjat; Hebden, Leyna M; Park, Yara A; Ataga, Kenneth I

    2015-08-01

    Red blood cell (RBC) alloimmunization is a significant clinical complication of sickle cell disease (SCD). It can lead to difficulty with cross-matching for future transfusions and may sometimes trigger life-threatening delayed hemolytic transfusion reactions. We conducted a retrospective study to explore the association of clinical complications and age of RBC with alloimmunization in patients with SCD followed at a single institution from 2005 to 2012. One hundred and sixty six patients with a total of 488 RBC transfusions were evaluated. Nineteen patients (11%) developed new alloantibodies following blood transfusions during the period of review. The median age of RBC units was 20 days (interquartile range: 14-27 days). RBC antibody formation was significantly associated with the age of RBC units (P = 0.002), with a hazard ratio of 3.5 (95% CI: 1.71-7.11) for a RBC unit that was 7 days old and 9.8 (95% CI: 2.66-35.97) for a unit that was 35 days old, 28 days after the blood transfusion. No association was observed between RBC alloimmunization and acute vaso-occlusive complications. Although increased echocardiography-derived tricuspid regurgitant jet velocity (TRV) was associated with the presence of RBC alloantibodies (P = 0.02), TRV was not significantly associated with alloimmunization when adjusted for patient age and number of transfused RBC units. Our study suggests that RBC antibody formation is significantly associated with older age of RBCs at the time of transfusion. Prospective studies in patients with SCD are required to confirm this finding.

  11. Sepsis-induced purpura fulminans caused by Pasteurella multocida

    PubMed Central

    Borges, Lisa; Oliveira, Nelson; Cássio, Isabel; Costa, Humberto

    2014-01-01

    A 52-year-old man was admitted with a cutaneous rash associated with septic shock and multiorganic failure, 6 days after a dog bite. He was started on empiric antibiotherapy and supportive measures. The patient's condition aggravated, with need for invasive mechanical ventilation and intermittent haemodialysis, and evolution from a petechiae-like rash to purpura and gangrene, culminating in bilateral lower limb amputation. The blood cultures revealed only Pasteurella multocida, after 10 days of incubation. P multocida infection is a rare cause of soft tissue infection that subsides with oral antibiotherapy. Infections causing sepsis are rare and appear in immunocompromised patients. Purpura fulminans induced by sepsis is a rare, life-threatening disorder. This syndrome should be recognised promptly, so early treatment is instituted. We found no case reports of purpura fulminans caused by Pasteurella infections in our literature review. PMID:24554680

  12. [Henoch-Schonlein purpura involving the penis: a case report].

    PubMed

    Croche Santander, Borja; Campos, Elena; Sánchez, Adela; Marcos, Laura; Díaz, Isabel; Toro, Cristóbal

    2016-08-01

    Schonlein-Henoch purpura accounts for the majority of cases of systemic vasculitis in children. Classical presentation is characterized by palpable purpura, glomerulonephritis, arthralgias and abdominal pain. Although genitourinary manifestations, in form of testicular and scrotal involvement, have been widely described, penile involvement remains an extremely rare complication. We report a case of a 6-year-old boy who presented with purpuric rash on the glans, prepuce and penile shaft, with painful edema in the penile region. He also had a 3-days history of fever, palpable purpuric rash on the buttocks and lower extremities along with right wrist pain. He was admitted with the diagnosis of Schonlein-Henoch purpura with penile involvement. After 2 days on oral steroids therapy (prednisone) a marked improvement was observed.

  13. Danazol: An Effective Option in Acquired Amegakaryocytic Thrombocytopaenic Purpura

    PubMed Central

    Mulroy, E.; Gleeson, S.; Chiruka, S.

    2015-01-01

    Acquired amegakaryocytic thrombocytopaenic purpura (AATP) is a rare haematological condition characterised by isolated thrombocytopaenia with normal other cell lines. It is often initially misdiagnosed as immune thrombocytopaenic purpura but has characteristic bone marrow findings of reduced megakaryocyte numbers. The optimal treatment of AATP is not clearly defined but revolves around immunosuppressive therapies. We report a case of successful treatment of AATP with danazol, an antioestrogenic medication. We also review the aetiologies and pathogenesis of the disorder and suggest that danazol should be considered as an effective alternative to potent immunosuppression in AATP. PMID:25945269

  14. Brucellosis mimicking Henoch-Schönlein purpura.

    PubMed

    Massasso, David; Gibson, Kathryn

    2007-06-04

    A young male immigrant from Syria with a vasculitic-appearing leg rash, asymmetrical polyarthritis, microscopic haematuria, and raised inflammatory markers was provisionally diagnosed with Henoch-Schönlein purpura. Skin biopsy showed leukocytoclastic vasculitis. Low-grade fevers persisted despite non-steroidal anti-inflammatory therapy, and Brucella sp. was subsequently grown from both blood and synovial fluid aspirates. Further tests gave positive results for B. abortus, and triple antibiotic therapy produced a rapid clinical response. Cutaneous vasculitis has rarely been described in brucellosis, and this is the first report in the English medical literature of brucellosis mimicking Henoch-Schönlein purpura.

  15. Successful Corticosteroid Treatment for Purpura Fulminans Associated with Quinolone

    PubMed Central

    Okamura, Ikue; Nakamura, Yukitsugu; Katsurada, Yuka; Sato, Ken; Ikeda, Takashi; Kimura, Fumihiko

    2016-01-01

    Purpura fulminans (PF) is a life-threatening syndrome comprising progressive hemorrhagic necrosis due to disseminated intravascular coagulation and dermal vascular thrombosis that leads to purpura and tissue necrosis. Various therapies have been used to arrest the progression of this disease, however, there is no established treatment because of the variety of underlying causes. We herein present an adult case of PF associated with leukocytoclastic vasculitis triggered by antibiotic (levofloxacin) intake. As a result of our rapid and accurate identification of the underlying cause, corticosteroid therapy successfully repressed the inflammatory process. As far as we know, this is the first report of levofloxacin-associated PF. PMID:27746448

  16. Estimation of combat-related blood group alloimmunization and delayed serologic transfusion reactions in U.S. military veterans.

    PubMed

    Tormey, Christopher A; Stack, Gary

    2009-05-01

    The goals of this study were to estimate blood group alloimmunization arising from combat-related transfusion and the prevalence of delayed serologic transfusion reactions (DSTRs) in military veteran patients. Blood group alloantibodies documented in the transfusion records at a Veterans Affairs (VA) medical center were categorized according to whether they developed before ("pre-existing") or during ("hospital-acquired") VA care and whether they were associated with anamnestic immune responses. Combat-related alloantibodies were estimated by adding anamnestic to pre-existing antibodies, revealing that 256 veterans made 322 combat-related alloantibodies. The combat-related alloimmunization rate was 1.37% (256/18,750), and combat-related alloantibodies represented 55.8% (322/577) of total alloantibodies. The highest rate of combat-related alloimmunization was observed in World War II-era veterans. Approximately 11.2% (25/224) of veterans with hospital-acquired antibodies experienced a DSTR due to prior alloimmunization. In conclusion, combat-related alloimmunization accounted for more than half of antibodies in military veterans and was a predisposing factor for DSTRs.

  17. Severe Rh alloimmunization and hemolytic disease of the fetus managed with plasmapheresis, intravenous immunoglobulin and intrauterine transfusion: A case report.

    PubMed

    Houston, Brett L; Govia, Rachelle; Abou-Setta, Ahmed M; Reid, Gregory J; Hadfield, Marie; Menard, Chantalle; Noyd, Jocelyn; Main, Susan; Zarychanski, Ryan

    2015-12-01

    Rh alloimmunization remains a potentially devastating complication of pregnancy, with fetal anemia causing hydrops and intrauterine death. Intrauterine transfusion is the standard treatment, but is particularly dangerous before 20 weeks gestation. When the need for intrauterine transfusion is anticipated early in pregnancy, immune-modulating therapies such as plasmapheresis and IVIG have been used to delay transfusion to a later gestational age. We report a 35-year-old G5P1 Rh(D)-negative woman with severe Rh alloimmunization managed successfully with sequential plasmapheresis, intravenous immune globulin and intrauterine transfusion. The optimal plasmapheresis treatment protocol and incremental benefit of IVIG remains unknown.

  18. [Rh alloimmunization in pregnant women, a look to diagnosis and therapeutic approach].

    PubMed

    Lambertino, José R; Villegas, Silvia M

    2014-11-01

    Prior to the onset of immunoglobulin antiD, many of the fetuses of mothers negative for the antigen "D" developing severe disease, history of prenatal diagnosis of alloimmunization is the perfect example of constructive effort by a diagnosis in order to identify cases in need of therapy to decrease morbidity and increase survival with the least number of invasive procedures and reducing the risks associated with them. Today it is difficult to determine the true prevalence of the disease in our environment, but the understanding of the pathophysiology has helped the evolution of diagnostic tests and better treatment approach to positively impact the evolution of the disease.

  19. [Possible correlations of Berger's disease and Schonlein-Henoch purpura].

    PubMed

    Maffei, S; Stefanelli, M; Germini, G; Bragetti, P; Riommi, R; Cesarini, A R; Rufini, S; Castellucci, G

    1989-01-01

    A case of IgA nephropathy is described. The patient had only an attack of Henoch-Schonlein purpura without renal involvement when she was 7 years old. After 6 years of normal urinalysis she developed repeated bouts of gross hematuria and proteinuria. In renal biopsy typical features of Berger's disease were found. This particular case permits to debate whether the two diseases suffered by our patient were related or quite different.

  20. Purpura and dermal thinning associated with high dose inhaled corticosteroids.

    PubMed Central

    Capewell, S; Reynolds, S; Shuttleworth, D; Edwards, C; Finlay, A Y

    1990-01-01

    OBJECTIVE--To assess the effect of high dose inhaled corticosteroids on skin. DESIGN--Cross sectional study of patients receiving treatment for chest diseases. SETTING--Outpatient chest clinic in a teaching hospital. PATIENTS--68 Patients divided into four groups of similar age--namely, 15 receiving long term oral prednisolone, 21 receiving high dose inhaled corticosteroids, 15 receiving low dose inhaled corticosteroids, and 17 controls. MAIN OUTCOME MEASURES--Skin thickness at three sites measured by A scan ultrasound and clinical assessment of purpura. RESULTS--Compared with controls patients in both the oral prednisolone treated group and the high dose inhaled corticosteroid treated group had significantly thinner skin at all three sites (group median thicknesses: prednisolone treated group 28-33% less than controls; high dose inhaled corticosteroid treated group 15-19% less than controls). Differences in skin thicknesses between the low dose inhaled corticosteroid treated group and the controls were trivial. The prevalence of purpura was significantly greater in patients receiving oral prednisolone (12/15 patients) and high dose inhaled corticosteroids (10/21) than in controls (2/17). CONCLUSION--Skin thinning and purpura represent further evidence of systemic effects of high dose inhaled corticosteroids. PMID:2372620

  1. Extreme Elevation of Alkaline Phosphatase in a Pregnancy Complicated by Gestational Diabetes and Infant with Neonatal Alloimmune Thrombocytopenia

    PubMed Central

    Healey, Michael

    2016-01-01

    There have been few case reports of isolated elevation of alkaline phosphatase beyond the normal physiologic amount with subsequent return to baseline after delivery. Here we present a similar case of extreme elevation of alkaline phosphatase in a pregnancy complicated by gestational diabetes and subsequently by neonatal alloimmune thrombocytopenia (NAIT). PMID:27610256

  2. [Rheumatoid purpura and Berger's disease in the same patient. 2 cases].

    PubMed

    Cotton, J B; Parchoux, B; Vincent, C; Ladreyt, J P; Rekawek, J

    1991-01-01

    The two patients reported experienced initially typical Henoch Schönlein purpura, and Berger disease some years later. Same cases are described in the literature pleading for the relationship between the two entities; Berger disease may be considered as a symptomatic form of anaphylactoïd purpura.

  3. Prolonged thrombocytopenia in a child with severe neonatal alloimmune reaction and Noonan syndrome.

    PubMed

    Salva, Inês; Batalha, Sara; Maia, Raquel; Kjollerstrom, Paula

    2016-06-01

    Fetomaternal alloimmune thrombocytopenia (FMAIT) caused by maternal antibodies is the leading cause of severe neonatal thrombocytopenia. A 1-month-old Caucasian girl was referred to our Hematology Clinic for persistent thrombocytopenia diagnosed after a bleeding episode. Diagnostic tests suggested FMAIT. Mild thrombocytopenia persisted for 18 months, and subsequent findings of dysmorphic facies, short stature and mild pulmonary stenosis led to the hypothesis of Noonan syndrome (NS), which was confirmed by genetic test. Other hematological abnormalities were excluded and she had no further bleeding episodes. This case illustrates the possibility of different diagnoses with the same clinical manifestations. The persistence of thrombocytopenia longer than expected associated with typical physical features led to the diagnosis of NS.

  4. Mouse model of alloimmune-induced vascular rejection and transplant arteriosclerosis.

    PubMed

    Enns, Winnie; von Rossum, Anna; Choy, Jonathan

    2015-05-17

    Vascular rejection that leads to transplant arteriosclerosis (TA) is the leading representation of chronic heart transplant failure. In TA, the immune system of the recipient causes damage of the arterial wall and dysfunction of endothelial cells and smooth muscle cells. This triggers a pathological repair response that is characterized by intimal thickening and luminal occlusion. Understanding the mechanisms by which the immune system causes vasculature rejection and TA may inform the development of novel ways to manage graft failure. Here, we describe a mouse aortic interposition model that can be used to study the pathogenic mechanisms of vascular rejection and TA. The model involves grafting of an aortic segment from a donor animal into an allogeneic recipient. Rejection of the artery segment involves alloimmune reactions and results in arterial changes that resemble vascular rejection. The basic technical approach we describe can be used with different mouse strains and targeted interventions to answer specific questions related to vascular rejection and TA.

  5. Recent progress in understanding the pathogenesis of fetal and neonatal alloimmune thrombocytopenia.

    PubMed

    Curtis, Brian R

    2015-12-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) occurs in c. 1 in 1000 births and is caused by maternal antibodies against human platelet alloantigens that bind incompatible fetal platelets and promote their clearance from the circulation. Affected infants can experience bleeding, bruising and, in severe cases, intracranial haemorrhage and even death. As maternal screening is not routinely performed, and first pregnancies can be affected, most cases are diagnosed at delivery of a first affected pregnancy. Unlike its erythrocyte counterpart, Haemolytic Disease of the Fetus and Newborn, there is no prophylactic treatment for FNAIT. This report will review recent advances made in understanding the pathogenesis of FNAIT: the platelet alloantigens involved, maternal exposure and sensitization to fetal platelet antigens, properties of platelet Immunoglobulin G antibodies, maternal-fetal antibody transport mechanisms and efforts to develop an effective FNAIT prophylaxis.

  6. Alloimmunization screening after transfusion of red blood cells in a prospective study

    PubMed Central

    Alves, Vitor Mendonça; Martins, Paulo Roberto Juliano; Soares, Sheila; Araújo, Gislene; Schmidt, Luciana Cayres; Costa, Sidneia Sanches de Menezes; Langhi, Dante Mário; Moraes-Souza, Helio

    2012-01-01

    Background Several irregular red blood cell alloantibodies, produced by alloimmunization of antigens in transfusions or pregnancies, have clinical importance because they cause hemolysis in the fetus and newborn and in transfused patients. Objective a prospective analysis of patients treated by the surgical and clinical emergency services of Hospital de Clínicas of the Universidade Federal do Triângulo Mineiro (HC/UFTM), Brazil was performed to correlate alloimmunization to clinical and epidemiological data. Methods Blood samples of 143 patients with initial negative antibody screening were collected at intervals for up to 15 months after the transfusion of packed red blood cells. Samples were submitted to irregular antibody testing and, when positive, to the identification and serial titration of alloantibodies. The Fisher Exact test and Odds Ratio were employed to compare proportions. Results Fifteen (10.49%) patients produced antibodies within six months of transfusion. However, for 60% of these individuals, the titers decreased and disappeared by 15 months after transfusion. Anti-K antibodies and alloantibodies against antigens of the Rh system were the most common; the highest titer was 1:32 (anti-K). There was an evident correlation with the number of transfusions. Conclusions Given the high incidence of clinically important red blood cell alloantibodies in patients transfused in surgical and clinical emergency services, we suggest that phenotyping and pre-transfusion compatibilization for C, c, E, e (Rh system) and K (Kell system) antigens should be extended to all patients with programmed surgeries or acute clinical events that do not need emergency transfusions. PMID:23049421

  7. /sup 111/In-oxine platelet survivals in thrombocytopenic infants

    SciTech Connect

    Castle, V.; Coates, G.; Kelton, J.G.; Andrew, M.

    1987-09-01

    Thrombocytopenia is a common occurrence (20%) in sick neonates, but the causes have not been well studied. In this report we demonstrate that thrombocytopenia in the neonate is characterized by increased platelet destruction as shown by shortened homologous /sup 111/In-oxine-labeled platelet life spans. Thirty-one prospectively studied thrombocytopenic neonates were investigated by measuring the /sup 111/In-labeled platelet life span, platelet-associated IgG (PAIgG), and coagulation screening tests. In every infant, the thrombocytopenia was shown to have a destructive component since the mean platelet life span was significantly shortened to 65 +/- 6 (mean +/- SEM) hours with a range of one to 128 hours compared with adult values (212 +/- 8; range, 140 to 260; gamma function analysis). The platelet survival was directly related to the lowest platelet count and inversely related to both the highest mean platelet volume and duration of the thrombocytopenia. In 22 infants the percent recovery of the radiolabeled platelets was less than 50%, which suggested that increased sequestration also contributed to the thrombocytopenia. Infants with laboratory evidence of disseminated intravascular coagulation (n = 8) or immune platelet destruction evidenced by elevated levels of PAIgG (n = 13) had even shorter platelet survivals and a more severe thrombocytopenia compared with the ten infants in whom an underlying cause for the thrombocytopenia was not apparent. Full-body scintigraphic images obtained in 11 infants showed an increased uptake in the spleen and liver, with a spleen-to-liver ratio of 3:1. This study indicates that thrombocytopenia in sick neonates is primarily destructive, with a subgroup having evidence of increased platelet sequestration.

  8. Simultaneous Manifestation of Chronic Myelomonocytic Leukemia and Multiple Myeloma during Treatment by Prednisolone and Eltrombopag for Immune-Mediated Thrombocytopenic Purpura

    PubMed Central

    Inoue, Morihiro; Kodama, Kenichiro; Uchida, Tomoyuki; Hua, Jian

    2016-01-01

    An 80-year-old man was admitted to our hospital because of severe thrombocytopenia. He was diagnosed with idiopathic thrombocytopenia, and prednisolone together with eltrombopag was started, leading to significant improvement of platelet counts. Four years later, there was a prominent increase of peripheral blood monocytes, which was accompanied by recurrence of thrombocytopenia. Bone marrow aspirates and serum electrophoresis revealed coexistence of chronic myelomonocytic leukemia (CMML) and multiple myeloma (MM). The patient received lenalidomide plus dexamethasone therapy but died due to exacerbation of the disorder. It was supposed that thrombocytopenia was secondarily caused by CMML and MM developed at a later period. PMID:27597907

  9. Synchronous Occurrence of Diffuse Large B-cell Lymphoma of the Duodenum and Gastrointestinal Stromal Tumor of the Ileum in a Patient with Immune Thrombocytopenic Purpura

    PubMed Central

    Takahashi, Tohru; Maruyama, Yumiko; Saitoh, Mayuko; Itoh, Hideto; Yoshimoto, Mitsuru; Tsujisaki, Masayuki; Nakayama, Masato

    2016-01-01

    A 64 year-old woman with steroid-dependent immune thrombocytopenia developed anemia. Esophagogastroduodenoscopy revealed the presence of a tumor, which was diagnosed to be diffuse large B-cell lymphoma, in the second portion of the duodenum. 18F-fluorodeoxy glucose positron emission tomography showed an increased uptake mass in the pelvic cavity as well as in the duodenum. Though the duodenal tumor disappeared after 4 cycles of chemotherapy, the pelvic mass did not shrink in size. As a result, laparoscopic resection of the pelvic tumor was performed and the tumor was histologically diagnosed to be a gastrointestinal stromal tumor. Subsequently, the patient was treated with 2 more cycles of the chemotherapy. Eventually, thrombocytopenia completely resolved. PMID:27746431

  10. High dose Intravenous Anti-D Immune Globulin is More Effective and Safe in Indian Paediatric Patients of Immune Thrombocytopenic Purpura

    PubMed Central

    Jena, Rabindra Kumar; Swain, Kali Prasanna

    2016-01-01

    Introduction Immune Thrombocytopenia (ITP) is characterised by an autoimmune antibody-mediated destruction of platelets and impaired platelet production. Few controlled trials exist to guide management of patients with ITP in Indian scenario for which patients require an individualized approach. Anti-D (Rho (D) immune globulin) at a higher dose can prove to be a cost effective and safe alternative for Indian patients with ITP. Aim To compare the safety and efficacy of higher dose (75μg/kg) intravenous Anti-D immune globulin against the standard dose of 50μg/kg for the management of ITP in Indian patients. Materials and Methods One hundred and sixty four children with newly diagnosed ITP between 4-14 years were randomly selected for inclusion and were treated with 50μg/kg (standard dose) or 75μg /kg (higher dose) of Anti-D to compare the efficacy and safety of higher dose intravenous anti-D immune globulin. Efficacy of Anti-D was measured in terms of rate of response and median time to response for increase in platelet counts. Any adverse event was noted. A decrease in haemoglobin concentration suggested accompanying haemolysis. Results Seventy one out of 84 patients treated with Anti-D at 75μg/kg produced complete response (85%) with median time of response being 2.5 days. On the contrary, 45 patients (70%) patients treated with 50μg/kg had complete response. However, there was no significant increase in haemolysis with higher dose. A significant correlation was found between dose and peak increase in platelet count measured at 7th day following administration. However, there was no relationship between the decrease in haemoglobin and the dose given, or between the increase in platelet count and fall in haemoglobin. Conclusion A 75μg/kg dose of Anti-D is more effective with acceptable side effect in comparison to 50μg dose for treatment of newly diagnosed Indian patients of ITP. PMID:28208873

  11. Successful treatment of an elderly frail patient with acquired idiopathic thrombotic thrombocytopenic purpura under close monitoring of ADAMTS13 activity and anti-ADAMTS13 antibody titers.

    PubMed

    Sano, Keigo; Yagi, Hideo; Hanamoto, Hitoshi; Fujita, Mariko; Iizuka, Takashi; Yamazaki, Keiko; Tsubaki, Kazuo

    2014-04-01

    A 68-year-old woman was admitted to the regional hospital because of hemolytic anemia, thrombocytopenia, and neurological abnormalities including unconsciousness. One week before admission, she suffered from diarrhea and subsequently passed out and hit her face on the ground. She was suspected of having TTP and was transferred to our hospital. We performed the assays of ADAMTS13 activity and anti-ADAMTS13 antibody titers, and confirmed the diagnosis of acquired idiopathic TTP with total deficiency of ADAMTS13 activity with its inhibitor. She was initially treated with plasma exchange combined with corticosteroids, however, we were forced to substitute plasma exchange with fresh frozen plasma infusion due to procedure-associated complications. The infusion of fresh frozen plasma was known as less effective and more likely to boost inhibitor titers compared to plasma exchange. In this circumstance, we could successfully switch the plasma therapy under close monitoring of ADAMTS13 activity and anti-ADAMTS13 antibody titers which precisely revealed the disease status of TTP in our patient, and eventually she achieved complete remission with normal level of ADAMTS13 activity and no inhibitor. Our experience suggested that the measurement of ADAMTS13 activity and inhibitor titer might be valuable not only for making the diagnosis but also for guiding treatment decisions by precise evaluating of disease status in patients with the acquired form of TTP.

  12. Multiple myeloma developing during long-term clinical course of refractory immune thrombocytopenic purpura: a case report and review of literature.

    PubMed

    Yao, Han; Zhang, Xi; Liu, Jia; Zhu, Lidan; Chen, Guo; Wu, Sha; Gao, Lei

    2015-01-01

    Immune thrombocytopenia (ITP) is an acquired, immune-mediated disease that is characterized by increased destruction of platelets by autoantibodies. Although the onset of the disease and clinical course are highly variable, the disease typically has a benign course. ITP associated with multiple myeloma (MM) has been rarely reported; it is even rarer for MM to develop during a long-term ITP (almost 20 years). Here, we first report on a case with a 20-year long clinical course of refractory ITP followed by newly diagnosed MM.

  13. Purpura fulminans associated with Streptococcus pneumoniae septicemia in an asplenic pediatric patient.

    PubMed

    Konda, S; Zell, D; Milikowski, C; Alonso-Llamazares, J

    2013-09-01

    Purpura fulminans is a rapidly progressive syndrome of small-vessel thrombosis and hemorrhagic necrosis of the skin accompanied by disseminated intravascular coagulation. We describe a case of Streptococcus pneumoniae septicemia in an asplenic 5-year-old boy on oral tacrolimus, with a past medical history of multivisceral organ transplantation and subsequent development of purpura fulminans on his chest and distal extremities. The acute infectious form of purpura fulminans is usually caused by gram-negative bacteria. Cases secondary to gram-positive encapsulated bacteria usually occur when individuals are immuno-suppressed or have anatomic or functional asplenia. Our patient had both, which likely increased his susceptibility, and he responded well to antimicrobial therapy in addition to prophylactic coverage in the setting of his immunosuppression. We review the literature for similar cases due to S. pneumoniae in the pediatric population and discuss the etiology and treatment of purpura fulminans.

  14. Henoch-Schönlein purpura with c-ANCA antibody in an adult*

    PubMed Central

    Torraca, Pedro de Freitas Silva; de Castro, Bruna Corrêa; Hans Filho, Günter

    2016-01-01

    The Henoch-Schönlein purpura is the vasculitis associated with deposits of immunoglobulin A in small vessels. Its association with cytoplasmic antineutrophil cytoplasmic antibodies is possible, but rare. This vasculitis is uncommon in adults and the main clinic manifestations are purpuric lesions in lower limbs with gastrointestinal symptoms and renal involvement. The present work describes a rare case of Henoch-Schönlein purpura in an adult with cytoplasmic antineutrophil cytoplasmic antibodies. PMID:27828648

  15. Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review.

    PubMed

    Winkelhorst, Dian; Murphy, Michael F; Greinacher, Andreas; Shehata, Nadine; Bakchoul, Tamam; Massey, Edwin; Baker, Jillian; Lieberman, Lani; Tanael, Susano; Hume, Heather; Arnold, Donald M; Baidya, Shoma; Bertrand, Gerald; Bussel, James; Kjaer, Mette; Kaplan, Cécile; Kjeldsen-Kragh, Jens; Oepkes, Dick; Ryan, Greg

    2017-01-27

    Several strategies can be used to manage fetal or neonatal alloimmune thrombocytopenia (FNAIT) in subsequent pregnancies. Serial fetal blood sampling (FBS) and intrauterine platelet transfusions (IUPT), and weekly maternal intravenous immunoglobulin infusion (IVIG), with or without additional corticosteroid therapy are common options, but the optimal management has not been determined. The aim of this systematic review was to assess antenatal treatment strategies for FNAIT. Four randomized controlled trials and twenty-two non-randomized studies were included. Pooling of results was not possible due to considerable heterogeneity. Most studies found comparable outcomes regarding the occurrence of intracranial hemorrhage, regardless of antenatal management strategy applied; FBS, IUPT or IVIG with/without corticosteroids. There is no consistent evidence for the value of adding steroids to IVIG. Fetal blood sampling or intrauterine platelet transfusion resulted in a relatively high complication rate, consisting mainly of preterm emergency cesarean section, 11% per treated pregnancy in all studies combined. Overall, non-invasive management in pregnant mothers who have had a previous neonate with FNAIT is effective without the relatively high rate of adverse outcomes seen with invasive strategies. This systematic review suggests that first line antenatal management in FNAIT is weekly IVIG administration, with or without the addition of corticosteroids.

  16. [Management of chicken pox purpura fulminans: a pediatric case report].

    PubMed

    Domergue, S; Rodiere, M; Bigorre, M; Guye, E; Captier, G

    2006-06-01

    The authors report a case of a 4 years old girl who had presented a chicken-pox purpura fulminans. Lesions appeared 5 days after chicken-pox start and were quickly evoluted in cutaneous and sub-cutaneous necrosis on external side of thighs and behind side of right calf. A medical management was done with fresh plasma, blood, antithrombine 3, and fibrin. Specifics treatments were done: heparin and activated C protein. Surgical treatment was realised 5 weeks later. It consisted of clean necrosis areas and put a thin skin graft witch was took on the scalp. The evolution was fast good. The follow-up is 3 years without big esthetic and functional consequences. Some cases of this pathology were described in literature with serious lesions. The management should be multidisciplinary. Surgical treatment should be realised when lesions are stabilized. Scalp is a donor site for skin graft very interesting because of big quantity of skin and not esthetic consequence.

  17. Prognostic factors of severe infectious purpura in children.

    PubMed

    Leclerc, F; Beuscart, R; Guillois, B; Diependaele, J F; Krim, G; Devictor, D; Bompard, Y; van Albada, T

    1985-01-01

    The French Club of Pediatric Intensive Care has prospectively studied 90 cases of infectious purpura which were hospitalized in 1981; the purpose of this study was to determine prognostic factors. The statistical study (X2 test) of all these cases is in agreement with data in the literature and shows that the mortality is significantly higher when there is: shock (p less than 0.001), coma (p less than 0.05), ecchymotic or necrotic purpura (p less than 0.01), temperature less than 36 degrees C (p less than 0.05), no clinical meningism (p less than 0.001), white cell count less than 10,000/mm3 (p less than 0.05), thrombocytopenia less than 100,000 (p less than 0.01), fibrinogen less than 1.5 g/l (p less than 0.001), kalemia greater than 5 mEq/l (p less than 0.01), spinal fluid cell count less than 20/mm3 (p less than 0.01). Because shock is one of the main prognostic factors (23 deaths in 55 shocked patients, versus 2 in 35 non-shocked) we have performed another statistical study (with the Benzecri method) to determine a prognostic index for patients in shock. For its determination, five initial parameters are used: age, kalemia, white cell count, clinical meningism, platelet count. The predictive value for survival is 91%. The predictive value for death is 87%. The score was applied on the patients hospitalized in shock in 1982: the predictive value for survival is 75%, the predictive value for death is 61%.

  18. Use of 8-methoxypsoralen and ultraviolet-A pretreated platelet concentrates to prevent alloimmunization against class I major histocompatibility antigens

    SciTech Connect

    Grana, N.H.; Kao, K.J. )

    1991-06-01

    The use of 8-methoxypsoralen (8-MOP) and UV-A irradiation to inactivate contaminating donor leukocytes in platelet concentrates and to prevent primary alloimmunization against donor class I major histocompatibility (MHC) antigens in mice was investigated. CBA/CaH-T6J mice with the H2k haplotype and BALB/cByJ mice with the H2d haplotype were used as donors and recipients, respectively. The mixed leukocyte reaction between these two strains of mice showed that treatment of spleen cells with 500 ng/mL 8-MOP and 5J/cm2 UV-A inhibited 99% of responder and 92% of stimulator function. There was no measurable loss of platelet aggregating activity after the treatment. After two weekly transfusions of platelets without any treatment, 93% of control mice (n = 15) developed anti-H2k antibody. In contrast, only 33% of mice (n = 15) receiving platelets treated with 8-MOP and UV-A became alloimmunized. After six weekly platelet transfusions, all mice became alloimmunized. Nevertheless, the mean titers of anti-H2k antibody in sera of the treated groups were significantly lower than the control groups. One hour posttransfusion recoveries of 51Cr-labeled donor platelets were also higher in mice transfused with the treated platelets. Thus, the pretreatment of platelet concentrates with 8-MOP and UV-A irradiation effectively reduced the alloantigenicity of class I MHC molecules. The implication of this finding in relation to the mechanism by which donor leukocytes allosensitize recipients is discussed.

  19. Red blood cell alloimmunization is influenced by the delay between Toll-like receptor agonist injection and transfusion.

    PubMed

    Elayeb, Rahma; Tamagne, Marie; Bierling, Philippe; Noizat-Pirenne, France; Vingert, Benoît

    2016-02-01

    Murine models of red blood cell transfusion show that inflammation associated with viruses or methylated DNA promotes red blood cell alloimmunization. In vaccination studies, the intensity of antigen-specific responses depends on the delay between antigen and adjuvant administration, with a short delay limiting immune responses. In mouse models of alloimmunization, the delay between the injection of Toll-like receptor agonists and transfusion is usually short. In this study, we hypothesized that the timing of Toll-like receptor 3 agonist administration affects red blood cell alloimmunization. Poly(I:C), a Toll-like receptor 3 agonist, was administered to B10BR mice at various time points before the transfusion of HEL-expressing red blood cells. For each time point, we measured the activation of splenic HEL-presenting dendritic cells, HEL-specific CD4(+) T cells and anti-HEL antibodies in serum. The phenotype of activated immune cells depended on the delay between transfusion and Toll-like receptor-dependent inflammation. The production of anti-HEL antibodies was highest when transfusion occurred 7 days after agonist injection. The proportion of HEL-presenting CD8α(+) dendritic cells producing interleukin-12 was highest in mice injected with poly(I:C) 3 days before transfusion. Although the number of early-induced HEL-specific CD4(+) T cells was similar between groups, a high proportion of these cells expressed CD134, CD40 and CD44 in mice injected with poly(I:C) 7 days before transfusion. This study clearly shows that the delay between transfusion and Toll-like receptor-induced inflammation influences the immune response to transfused red blood cells.

  20. The novel costimulatory programmed death ligand 1/B7.1 pathway is functional in inhibiting alloimmune responses in vivo.

    PubMed

    Yang, Jun; Riella, Leonardo V; Chock, Susanne; Liu, Tao; Zhao, Xiaozhi; Yuan, Xueli; Paterson, Alison M; Watanabe, Toshihiko; Vanguri, Vijay; Yagita, Hideo; Azuma, Miyuki; Blazar, Bruce R; Freeman, Gordon J; Rodig, Scott J; Sharpe, Arlene H; Chandraker, Anil; Sayegh, Mohamed H

    2011-08-01

    The programmed death ligand 1 (PDL1)/programmed death 1 (PD1) costimulatory pathway plays an important role in the inhibition of alloimmune responses as well as in the induction and maintenance of peripheral tolerance. It has been demonstrated recently that PDL1 also can bind B7.1 to inhibit T cell responses in vitro. Using the bm12 into B6 heart transplant model, we investigated the functional significance of this interaction in alloimmune responses in vivo. PD1 blockade unlike PDL1 blockade failed to accelerate bm12 allograft rejection, suggesting a role for an additional binding partner for PDL1 other than PD1 in transplant rejection. PDL1 blockade was able to accelerate allograft rejection in B7.2-deficient recipients but not B7.1-deficient recipients, indicating that PDL1 interaction with B7.1 was important in inhibiting rejection. Administration of the novel 2H11 anti-PDL1 mAb, which only blocks the PDL1-B7.1 interaction, aggravated chronic injury of bm12 allografts in B6 recipients. Aggravated chronic injury was associated with an increased frequency of alloreactive IFN-γ-, IL-4-, and IL-6-producing splenocytes and a decreased percentage of regulatory T cells in the recipients. Using an in vitro cell culture assay, blockade of the interaction of PDL1 on dendritic cells with B7.1 on T cells increased IFN-γ production from alloreactive CD4(+) T cells, whereas blockade of dendritic cell B7.1 interaction with T cell PDL1 did not. These data indicate that PDL1 interaction with B7.1 plays an important role in the inhibition of alloimmune responses in vivo and suggests a dominant direction for PDL1 and B7.1 interaction.

  1. [Guideline for prevention of RhD alloimmunization in RhD negative women].

    PubMed

    Lubuský, Marek; Procházka, M; Simetka, O; Holusková, I

    2010-08-01

    Events following which anti-D immunoglobulin should be given to all RhD negative women with no anti-D antibodies: First trimester indications (50 microg)--termination of pregnancy, spontaneous abortion followed by instrumentation, ectopic pregnancy, chorionic villus sampling, partial molar pregnancy; Second and third trimester indications (100 microg)--amniocentesis, cordocentesis, other invasive prenatal diagnostic or therapeutic procedures, spontaneous or induced abortion, intrauterine fetal death, attempt at external cephalic version of a breech presentation, abdominal trauma, obstetric haemorrhage; Antenatal prophylaxis at 28th weeks of gestation (250 microg); Delivery of an RhD positive infant * (100 microg); Minimal dose: before 20 weeks gestation--50 microg (250 IU), after 20 weeks gestation **--100 microg (500 IU); Timing: as soon as possible, but no later than 72 hours after the event. In cases where prevention of RhD alloimmunization is not performed within 72 hours of a potentially sensitising event, it is still reasonable to administer anti-D immunoglobulin (IgG anti-D) within 13 days, and in special cases, administration is still recommended up to a maximum interval of 28 days postpartum.; FMH (fetomaternal haemorrhage)--If the amount of fetal erythrocytes which entered the maternal circulation is quantitatively determined, administration of 10 microg IgG anti-D per 0.5 ml of fetal erythrocytes or 1 ml of whole blood is indicated. *also if the RhD type of the infant has not been determined or is in doubt, **in conjunction with a test to assess the volume of any fetomaternal hemorrhage.

  2. Fas ligand enhances hematopoietic cell engraftment through abrogation of alloimmune responses and nonimmunogenic interactions.

    PubMed

    Pearl-Yafe, Michal; Yolcu, Esma S; Stein, Jerry; Kaplan, Ofer; Yaniv, Isaac; Shirwan, Haval; Askenasy, Nadir

    2007-06-01

    Early after transplantation, donor lineage-negative bone marrow cells (lin(-) BMC) constitutively upregulated their expression of Fas ligand (FasL), suggesting an involvement of the Fas/FasL axis in engraftment. Following the observation of impaired engraftment in the presence of a dysfunctional Fas/FasL axis in FasL-defective (gld) donors or Fas-defective (lpr) recipients, we expressed a noncleavable FasL chimeric protein on the surface of donor lin(-) BMC. Despite a short life span of the protein in vivo, expression of FasL on the surface of all the donor lin(-) BMC improved the efficiency of engraftment twofold. The FasL-coated donor cells efficiently blunted the host alloimmune responses in primary recipients and retained their hematopoietic reconstituting potential in secondary transplants. Surprisingly, FasL protein improved the efficiency of engraftment in syngeneic transplants. The deficient engraftment in lpr recipients was not reversed in chimeric mice with Fas(-) stroma and Fas(+) BMC, demonstrating that the host marrow stroma was also a target of donor cell FasL. Hematopoietic stem and progenitor cells are insensitive to Fas-mediated apoptosis and thus can exploit the constitutive expression of FasL to exert potent veto activities in the early stages of engraftment. Manipulation of the donor cells using ectopic FasL protein accentuated the immunogenic and nonimmunogenic interactions between the donor cells and the host, alleviating the requirement for a megadose of transplanted cells to achieve a potent veto effect. Disclosure of potential conflicts of interest is found at the end of this article.

  3. Relapses in patients with Henoch–Schönlein purpura

    PubMed Central

    Calvo-Río, Vanesa; Hernández, José Luis; Ortiz-Sanjuán, Francisco; Loricera, Javier; Palmou-Fontana, Natalia; González-Vela, Maria C.; González-Lamuño, Domingo; González-López, Marcos A.; Armesto, Susana; Blanco, Ricardo; González-Gay, Miguel A.

    2016-01-01

    Abstract To further investigate into the relapses of Henoch–Schönlein purpura (HSP), we analyzed the frequency, clinical features, and predictors of relapses in series of 417 unselected patients from a single center. After a median follow-up of 12 (interquartile range [IQR]: 2–38) years, almost one-third of the 417 patients (n = 133; 32%; 85 men/48 women) had experienced at least 1 relapse. At the time of disease diagnosis, patients who later experienced relapses had less commonly infections than those who never suffered flares (30.8% vs 41.9%; P = 0.03). In contrast, patients who experienced relapses had a longer duration of the first episode of palpable purpura than those without relapses (palpable purpura lasting >7 days; 80.0% vs 68.1%; P = 0.04). Abdominal pain (72.3% vs 62.3%; P = 0.03) and joint manifestations (27.8% vs 15.5%; P = 0.005) were also more common in patients who later developed relapses. In contrast, patients who never suffered relapses had a slightly higher frequency of fever at the time of disease diagnosis (9.3% vs 3.8%; P = 0.06). At the time of disease diagnosis, corticosteroids were more frequently given to patients who later had relapses of the disease (44% vs 32% in nonrelapsing patients; P = 0.03). Relapses generally occurred soon after the first episode of vasculitis. The median time from the diagnosis of HSP to the first relapse was 1 (IQR: 1–2) month. The median number of relapses was 1 (IQR 1–3). The main clinical features at the time of the relapse were cutaneous (88.7%), gastrointestinal (27.1%), renal (24.8%), and joint (16.5%) manifestations. After a mean ± standard deviation follow-up of 18.9 ± 9.8 years, complete recovery was observed in 110 (82.7%) of the 133 patients who had relapses. Renal sequelae (persistent renal involvement) was found in 11 (8.3%) of the patients with relapses. The best predictive factors for relapse were joint and gastrointestinal manifestations at HSP diagnosis (odds ratio [OR]: 2

  4. Platelets and platelet alloantigens: Lessons from human patients and animal models of fetal and neonatal alloimmune thrombocytopenia

    PubMed Central

    Vadasz, Brian; Chen, Pingguo; Yougbaré, Issaka; Zdravic, Darko; Li, June; Li, Conglei; Carrim, Naadiya; Ni, Heyu

    2017-01-01

    Platelets play critical roles in hemostasis and thrombosis. Emerging evidence indicates that they are versatile cells and also involved in many other physiological processes and disease states. Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life threatening bleeding disorder caused by fetal platelet destruction by maternal alloantibodies developed during pregnancy. Gene polymorphisms cause platelet surface protein incompatibilities between mother and fetus, and ultimately lead to maternal alloimmunization. FNAIT is the most common cause of intracranial hemorrhage in full-term infants and can also lead to intrauterine growth retardation and miscarriage. Proper diagnosis, prevention and treatment of FNAIT is challenging due to insufficient knowledge of the disease and a lack of routine screening as well as its frequent occurrence in first pregnancies. Given the ethical difficulties in performing basic research on human fetuses and neonates, animal models are essential to improve our understanding of the pathogenesis and treatment of FNAIT. The aim of this review is to provide an overview on platelets, hemostasis and thrombocytopenia with a focus on the advancements made in FNAIT by utilizing animal models.

  5. Pneumatosis intestinalis associated with Henoch-Schönlein purpura.

    PubMed

    Fatima, Ayesha; Gibson, Donald Paul

    2014-09-01

    Henoch-Schönlein purpura (HSP) is the most common vasculitis in children. It is a disorder of the inflammatory cascade leading to immunoglobulin A deposition and leukocytoclastic vasculitis of small vessels of skin, kidneys, joints, and gastrointestinal (GI) tract. A wide variety of GI manifestations are seen in ∼50% to 75% of patients with HSP. Diffuse colicky abdominal pain is the most common GI symptom. The small bowel is the most frequently involved GI site. Intussusception is rare but is the most common surgical complication. We report the case of a 2-year-old girl with a 5-day history of abdominal pain followed by a palpable purpuric rash. Her urinalysis, complete blood cell count, and tests of renal function were normal. An acute abdominal series was unremarkable initially, and abdominal ultrasound imaging showed ascites and thickened small bowel loops. She was diagnosed with HSP. The abdominal pain worsened, and an abdominal computed tomography scan demonstrated distal small bowel wall thickening and pneumatosis intestinalis in the descending colon. She was started on total parenteral nutrition and antibiotics and placed on bowel rest. She was given 2 mg/kg of intravenous immunoglobulin. Her abdominal pain gradually improved over the next week, and a repeat computed tomography scan showed significant improvement of the small bowel wall thickening and pneumatosis. The purpuric rash improved, and her abdominal pain resolved. We report a case of HSP and pneumatosis intestinalis, an association that has not been reported previously.

  6. IgA nephropathy: Henoch-Schönlein purpura and Berger's disease in one patient.

    PubMed

    Thorner, P S; Farine, M; Arbus, G S; Poucell, S; Baumal, R

    1986-01-01

    A patient is described who had an attack of Henoch-Schönlein purpura with no renal dysfunction at 4 years of age. She recovered with conservative management. There were no further episodes of Henoch-Schönlein purpura and her urinalysis remained normal for the next 11 years. At age 15, she developed repeated bouts of gross hematuria and proteinuria, and a renal biopsy was performed 3 years later. Light microscopy showed mesangial proliferative glomerulonephritis with granular, mesangial deposits of IgA by immunofluorescence and numerous, electron-dense deposits in mesangial regions by electron microscopy. These findings were consistent with a diagnosis of Berger's disease. The occurrence of Henoch-Schönlein purpura at 4 years and Berger's disease at 15 years in the same patient suggests that these two conditions are related.

  7. Acute Esophageal Necrosis Presenting With Henoch-Schönlein Purpura.

    PubMed

    Iorio, Natalya; Bernstein, Gregory R; Malik, Zubair; Schey, Ron

    2015-10-01

    A 63-year-old woman with abdominal pain and melena developed a palpable, purpuric rash and acute kidney injury. Skin and kidney biopsy confirmed Henoch-Schönlein purpura. Upper endoscopy revealed diffuse, circumferential, black-appearing mucosa of the esophagus consistent with acute esophageal necrosis (AEN), also known as black esophagus. AEN is a very rare cause of gastrointestinal hemorrhage with a high mortality risk. To our knowledge, there have been no prior reports of AEN associated with Henoch-Schonlein purpura or other vasculitis.

  8. Acute Esophageal Necrosis Presenting With Henoch-Schönlein Purpura

    PubMed Central

    Bernstein, Gregory R.; Malik, Zubair; Schey, Ron

    2015-01-01

    A 63-year-old woman with abdominal pain and melena developed a palpable, purpuric rash and acute kidney injury. Skin and kidney biopsy confirmed Henoch-Schönlein purpura. Upper endoscopy revealed diffuse, circumferential, black-appearing mucosa of the esophagus consistent with acute esophageal necrosis (AEN), also known as black esophagus. AEN is a very rare cause of gastrointestinal hemorrhage with a high mortality risk. To our knowledge, there have been no prior reports of AEN associated with Henoch-Schonlein purpura or other vasculitis. PMID:26504868

  9. Severe myalgia of the lower extremities as the first clinical feature of meningococcal purpura fulminans.

    PubMed

    de Souza, Alexandre Leite; Sztajnbok, Jaques; Salgado, Maristela Marques; Romano, Carla C; Alkmin, Maria das Graças Adelino; Duarte, Alberto J S; Seguro, Antonio Carlos

    2007-10-01

    In patients with meningococcal infection, devastating presentations, such as purpura fulminans, which can progress to extensive tissue necrosis of the limbs and digits, have a significant social impact. The case presented herein illustrates such a phenomenon in a patient who developed bilateral necrosis of the lower extremities as a result of infection with Neisseria meningitis. We emphasize that severe myalgia was the first clinical manifestation of meningococcal purpura fulminans in our case. However, myalgia has typically been overlooked and undervalued as an early clinical feature of meningococcal sepsis. Early recognition and prompt initial antibiotic therapy continue to be the cornerstones of the successful management of this dramatic disease, reducing morbidity and mortality.

  10. Gastrointestinal manifestations of Henoch-Schonlein purpura: A report of two cases

    PubMed Central

    Prathiba Rajalakshmi, Parameswaran; Srinivasan, Kalyanasundaram

    2015-01-01

    Henoch-Schonlein purpura (HSP) is a small vessel vasculitis mediated by type III hypersensitivity with deposition of IgA immune complex in the walls of vessels. It is a multi-system disorder characterized by palpable purpura, arthritis, glomerulonephritis and gastrointestinal manifestations and commonly occurs in children and young adults. The patients with gastrointestinal involvement usually present with colicky abdominal pain, vomiting and melena. The imaging findings include multifocal bowel thickening with mucosal hyperenhancement, presence of skip areas, mesenteric vascular engorgement, with involvement of unusual sites like stomach, duodenum and rectum. These imaging findings in a child or young adult with appropriate clinical findings could suggest HSP. PMID:25825636

  11. Banking of pluripotent adult stem cells as an unlimited source for red blood cell production: potential applications for alloimmunized patients and rare blood challenges.

    PubMed

    Peyrard, Thierry; Bardiaux, Laurent; Krause, Claire; Kobari, Ladan; Lapillonne, Hélène; Andreu, Georges; Douay, Luc

    2011-07-01

    The transfusion of red blood cells (RBCs) is now considered a well-settled and essential therapy. However, some difficulties and constraints still occur, such as long-term blood product shortage, blood donor population aging, known and yet unknown transfusion-transmitted infectious agents, growing cost of the transfusion supply chain management, and the inescapable blood group polymorphism barrier. Red blood cells can be now cultured in vitro from human hematopoietic, human embryonic, or human-induced pluripotent stem cells (hiPSCs). The highly promising hiPSC technology represents a potentially unlimited source of RBCs and opens the door to the revolutionary development of a new generation of allogeneic transfusion products. Assuming that in vitro large-scale cultured RBC production efficiently operates in the near future, we draw here some futuristic but realistic scenarios regarding potential applications for alloimmunized patients and those with a rare blood group. We retrospectively studied a cohort of 16,486 consecutive alloimmunized patients (10-year period), showing 1 to 7 alloantibodies with 361 different antibody combinations. We showed that only 3 hiPSC clones would be sufficient to match more than 99% of the 16,486 patients in need of RBC transfusions. The study of the French National Registry of People with a Rare Blood Phenotype/Genotype (10-year period) shows that 15 hiPSC clones would cover 100% of the needs in patients of white ancestry. In addition, one single hiPSC clone would meet 73% of the needs in alloimmunized patients with sickle cell disease for whom rare cryopreserved RBC units were required. As a result, we consider that a very limited number of RBC clones would be able to not only provide for the need for most alloimmunized patients and those with a rare blood group but also efficiently allow for a policy for alloimmunization prevention in multiply transfused patients.

  12. Aquaporin-4 positive neuromyelitis optica spectrum disorders secondary to thrombopenic purpura

    PubMed Central

    Wang, Ying; Gong, Qiaoyun; Zhu, Mingqin; Lu, Chao; Sun, Li; Feng, Jiachun; Zhang, Hongliang

    2017-01-01

    Abstract Rationale: Neuromyelitis optica spectrum disorders (NMOSD) is considered as an immune-mediated disorder in the central nervous system (CNS). Numerous autoimmune diseases are frequently complicated with NMOSD and distinct clinical characteristics are noted in NMOSD patients with other autoimmune diseases. However, to our best knowledge, co-occurrence of NMOSD and thrombopenic purpura is rarely identified. Patient concerns: We presented a rare case of a 72-year-old female with 6-year history of thrombopenic purpura, and 1-month history of blurred vision as well as chest zonethesia. Anti-aquaporin-4 (AQP4) antibodies was positive in the serum of the patient. Diagnoses: With the addition of laboratory findings, iconography findings and physical examination results, the diagnosis of NMOSD was established according to the most recent diagnostic criteria. Interventions and outcomes: With the treatment of intravenous immunoglobulin (IVIg), the patient felt better at discharge without changing of expanded disability status scale (EDSS) score. Lessons: The case indicates that NMOSD could co-occur with thrombopenic purpura. The disturbance of immune system balance may explain this overlap. Further studies are warranted to reveal the mechanism and to explore whether patients with NMOSD with and without thrombopenic purpura have distinct clinical feature, drug responsiveness or prognosis. PMID:28079804

  13. [Psychogenic purpura with hematuria and sexual pain disorder: a case report].

    PubMed

    Ozyildirim, Ilker; Yücel, Başak; Aktan, Melih

    2010-01-01

    Psychogenic purpura (Gardner-Diamond syndrome) is the occurrence and spontaneous recurrence of painful ecchymosis following emotional stress and minor trauma. Although the exact mechanism of this syndrome remains unknown, apart from skin lesions, different types of hemorrhaging have been reported, such as epistaxis, gastrointestinal bleeding, and bleeding from the ear canals and eyes. We report a psychogenic purpura case that presented with hematuria in addition to skin lesions. Based on the psychiatric evaluation she was diagnosed with major depressive disorder, generalized anxiety disorder, and obsessive-compulsive disorder. Additionally, sexual pain disorder accompanied these disorders. With the help of antidepressant and supportive psychotherapy, the patient's ecchymosis and bleeding disappeared. During 8 months of follow-up the symptoms did not return. Vaginismus has not been reported in patients with psychogenic purpura. The presence of vaginismus, which is seen more frequently in eastern cultures and is thought to be related to sociocultural determinants, suggests that some cultural factors may be common to both psychogenic purpura and vaginismus. The aim of this case report was to call attention to a syndrome that is rarely seen and diagnosed, and to discuss its relationship to psychosocial factors. This syndrome should be considered in the differential diagnosis of not only ecchymotic lesions, but also various types of bleeding, including hematuria. Despite the fact that its etiology and treatment are not clearly understood, it should be noted that psychological factors play a role in this disease and therefore, psychopharmacological and psychotherapeutic approaches can be effective.

  14. A Case of Fulminant Varicella Infection with Purpura Fulminans, Hepatitis, and Rhabdomyolysis

    PubMed Central

    Karadag, A S; Bilgili, S G; Calka, O; Çeçen, İ; Akbayram, S

    2012-01-01

    Varicella zoster virus causes varicella which is a common disease. Generally it is self-limiting, and treatment is often unnecessary, but severe or life-threatening complications are rarely seen. We report a case of fulminant varicella complicating with purpura fulminans, hepatitis, and probable rhabdomyolysis in a previously healthy child. PMID:23248376

  15. Ibuprofen-induced Henoch–Schönlein purpura nephritis: First reported case

    PubMed Central

    Seong, Christopher Lim Thiam; Shanmuganathan, Malini

    2016-01-01

    Ibuprofen is a nonsteroidal anti-inflammatory drug that is used widely in treating pain, fever, and inflammation. Its side effects are mainly due to acute renal impairment and gastric discomfort. We hereby report a rare case of Henoch–Schönlein purpura nephritis secondary to ibuprofen consumption which has not been reported in literature before. PMID:28066119

  16. Immunity to Polyomavirus BK Infection: Immune Monitoring to Regulate the Balance between Risk of BKV Nephropathy and Induction of Alloimmunity

    PubMed Central

    Cioni, Michela; Basso, Sabrina; Gagliardone, Chiara; Potenza, Leonardo; Verrina, Enrico; Luppi, Mario; Zecca, Marco; Ghiggeri, Gian Marco; Ginevri, Fabrizio

    2013-01-01

    Polyomavirus BK-associated nephropathy (PyVAN) is the main infectious cause of allograft damage after kidney transplantation. A number of studies revealed an association between the presence of BKV-specific cellular immunity and BK viral clearance, with patients failing to recover specific T cells progressing to PyVAN. Evolution to allograft dysfunction can be prevented by restoration of BKV-specific immunity through a stepwise reduction of maintenance immunosuppressive drugs. Prospective monitoring of BK viral load and specific immunity, together with B-cell alloimmune surveillance, may allow a targeted modification/reduction of immunosuppression, with the aim of obtaining viral clearance while preventing graft injury due to deposition of de novo donor-specific HLA antibodies and late/chronic antibody-mediated allograft injury. Innovative, immune-based therapies may further contribute to BKV infection prevention and control. PMID:24000288

  17. Recombinant HPA-1a antibody therapy for treatment of fetomaternal alloimmune thrombocytopenia: proof of principle in human volunteers.

    PubMed

    Ghevaert, Cedric; Herbert, Nina; Hawkins, Louise; Grehan, Nicola; Cookson, Philip; Garner, Steve F; Crisp-Hihn, Abigail; Lloyd-Evans, Paul; Evans, Amanda; Balan, Kottekkattu; Ouwehand, Willem H; Armour, Kathryn L; Clark, Mike R; Williamson, Lorna M

    2013-07-18

    Fetomaternal alloimmune thrombocytopenia, caused by the maternal generation of antibodies against fetal human platelet antigen-1a (HPA-1a), can result in intracranial hemorrhage and intrauterine death. We have developed a therapeutic human recombinant high-affinity HPA-1a antibody (B2G1Δnab) that competes for binding to the HPA-1a epitope but carries a modified constant region that does not bind to Fcγ receptors. In vitro studies with a range of clinical anti-HPA-1a sera have shown that B2G1Δnab blocks monocyte chemiluminescence by >75%. In this first-in-man study, we demonstrate that HPA-1a1b autologous platelets (matching fetal phenotype) sensitized with B2G1Δnab have the same intravascular survival as unsensitized platelets (190 hours), while platelets sensitized with a destructive immunoglobulin G1 version of the antibody (B2G1) are cleared from the circulation in 2 hours. Mimicking the situation in fetuses receiving B2G1Δnab as therapy, we show that platelets sensitized with a combination of B2G1 (representing destructive HPA-1a antibody) and B2G1Δnab survive 3 times as long in circulation compared with platelets sensitized with B2G1 alone. This confirms the therapeutic potential of B2G1Δnab. The efficient clearance of platelets sensitized with B2G1 also opens up the opportunity to carry out studies of prophylaxis to prevent alloimmunization in HPA-1a-negative mothers.

  18. [Purpura pigmentosa progressiva in type III cryoglobulinemia and tartrazine intolerance. A follow-up over 20 years].

    PubMed

    Kalinke, D U; Wüthrich, B

    1999-01-01

    A 58 year old patient with hepatitis virus C (HCV) infection had a secondary polyclonal IgG-IgM cryoglobulinemia with a benign 20 year course. Clinically the patient suffered from progressive pigmented purpura (PPP). Histologic evaluation revealed a lymphocytic vasculitis. Food containing tartrazine triggered flares of the PPP, as demonstrated with controlled oral provocation testing. In most of the previously described cases of HCV and type III cryoglobulinemia, the typical cutaneous finding was palpable purpura with leukocytoclastic vasculitis.

  19. Red blood cell alloimmunization in sickle cell disease and in thalassaemia: current status, future perspectives and potential role of molecular typing.

    PubMed

    Matteocci, A; Pierelli, L

    2014-04-01

    Red blood cell (RBC) transfusions are a milestone in the treatment for sickle cell anaemia (SSA) and for thalassaemia. RBC alloimmunization remains a major challenge of chronic transfusion therapy, and it can lead to adverse life-threatening events. The alloimmunization risk could depend on multiple factors such as the number of transfusions and, most of all, the genetic background. Different ethnic groups are predisposed to immunization because of a significant degree of RBC antigenic mismatch between donor and recipient. There is no universal agreement and standards for the most appropriate selection of RBC units in chronically transfused subjects. Current practice only deals with compatibility of ABO, Rh and K antigens. Molecular RBC antigenic matching extended to other blood group systems is an innovative strategy to ensure a better quality and effectiveness of transfusion therapy.

  20. TIGIT-positive circulating follicular helper T cells display robust B-cell help functions: potential role in sickle cell alloimmunization.

    PubMed

    Godefroy, Emmanuelle; Zhong, Hui; Pham, Petra; Friedman, David; Yazdanbakhsh, Karina

    2015-11-01

    T follicular helper cells are the main CD4(+) T cells specialized in supporting B-cell responses, but their role in driving transfusion-associated alloimmunization is not fully characterized. Reports of T follicular helper subsets displaying various markers and functional activities underscore the need for better characterization/identification of markers with defined functions. Here we show that a previously unidentified subset of human circulating T follicular helper cells expressing TIGIT, the T-cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory domains, exhibit strong B-cell help functions. Compared to the subset lacking the receptor, T follicular helper cells expressing this receptor up-regulated co-stimulatory molecules and produced higher levels of interleukins (IL-21 and IL-4) critical for promoting B-cell activation/differentiation. Furthermore, this subset was more efficient at inducing the differentiation of B cells into plasmablasts and promoting immunoglobulin G production. Blocking antibodies abrogated the B-cell help properties of receptor-expressing T follicular helper cells, consistent with the key role of this molecule in T follicular helper-associated responses. Importantly, in chronically transfused patients with sickle cell anemia, we identified functional differences of this subset between alloimmunized and non-alloimmunized patients. Altogether, these studies suggest that expression of the T-cell immunoreceptor with Ig and immunoreceptor tyro-sine-based inhibitory domains not only represents a novel circulating T follicular helper biomarker, but is also functional and promotes strong B-cell help and ensuing immunoglobulin G production. These findings open the way to defining new diagnostic and therapeutic strategies in modulating humoral responses in alloimmunization, and possibly vaccination, autoimmunity and immune deficiencies.

  1. Allo-immunization elicits CCR5 antibodies, SDF-1 chemokines, and CD8-suppressor factors that inhibit transmission of R5 and X4 HIV-1 in women.

    PubMed

    Wang, Y; Underwood, J; Vaughan, R; Harmer, A; Doyle, C; Lehner, T

    2002-09-01

    Studies in humans suggest that allo-immunization induces CC-chemokines, CD8-suppressor factors (SF) and anti-HIV immunity. Here we report that allo-immunization with unmatched leucocytes from partners of women with recurrent spontaneous abortion elicits specific antibodies to the CCR5 receptor. Such antibodies inhibit replication of M-tropic HIV-1 (R5) and MIP-1beta-mediated chemotaxis. These CCR5 antibodies were also found in the sera of multiparous women that were naturally immunized by semi-allogeneic fetal antigens. The specificity of these antibodies was demonstrated by adsorption with CCR5 transfected HEK-293 cells, a baculovirus CCR5 preparation and a peptide of the 2nd extra-cellular loop of CCR5. Allo-immunization also stimulated increased concentrations of the CXC chemokine, SDF-1alpha and CD8-SF that inhibit T-tropic HIV-1 (X4) replication. We suggest that allo- immunization may elicit (a) CC chemokines, CCR5 antibodies and CD8-SF that inhibit M-tropic HIV-1 infection and (b) the CXC chemokine SDF-1alpha and CD8-SF that inhibit T-tropic HIV-1 infection.

  2. Anti-Human Platelet Antigen-1a Immunoglobulin G Preparation Intended to Prevent Fetal and Neonatal Alloimmune Thrombocytopenia

    PubMed Central

    Weng, Ying-Jan; Husebekk, Anne; Skogen, Björn; Kjaer, Mette; Lin, Liang-Tzung; Burnouf, Thierry

    2016-01-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a severe disease that is caused by maternal alloantibodies generated during pregnancy or at delivery as a result of incompatibility between maternal and fetal human platelet antigens (HPAs) inherited from the father. Antibody-mediated immune suppression using anti-HPA-1a immunoglobulins is thought to be able to prevent FNAIT caused by HPA-1a. A fractionation process to prepare anti-HPA-1a immunoglobulin (Ig) G (IgG) from human plasma was therefore developed. Anti-HPA-1a plasma was obtained from volunteer mothers who underwent alloimmunization against HPA-1a during a previous pregnancy. Plasma was cryoprecipitated and the supernatant treated with caprylic acid and solvent/detergent (S/D), purified by chromatography, nanofiltered, concentrated, and sterile-filtered. The anti-HPA-1a immunoglobulin fraction was characterized for purity and safety. PAK12 and quantitative monoclonal antibody immobilization of platelet antigen (MAIPA) assays were used to detect anti-HPA-1a IgG. Hepatitis C virus (HCV) removal during nanofiltration was assessed by spiking experiments, using cell culture-derived reporter HCV and luciferase analysis. The caprylic acid treatment precipitated non-Ig proteins yielding a 90% pure Ig supernatant. S-HyperCel chromatography of the S/D-treated supernatant followed by HyperCel STAR AX provided high IgG recovery (>80%) and purity (>99.5%), and efficient IgA and IgM removal. Concentrations of complement factors C3 and C4 were < 0.5 and < 0.4 mg/dL, respectively. The final IgG could be nanofiltered on Planova 20N under conditions removing more than 3 log HCV infectivity to baseline mock infection level, and concentrated to ca. 30 g/L. Proteolytic activity and thrombin generation were low in the final fraction. The Pak12 and MAIPA assays showed good recovery of anti-HPA-1a throughout the process. Clinical-grade HPA-1a IgG can be prepared using a process compliant with current quality requirements

  3. Combined diagnostic imaging of intestinal involvement in Henoch-Schönlein purpura.

    PubMed

    Maggi, Fabio; Minordi, Laura Maria; Macis, Giuseppe; Vecchioli, Amorino

    2003-01-01

    The case of a 39-year-old male patient with symptoms of persistent abdominal pain and melena, affected by Henoch-Schönlein purpura, is reported. Abdominal CT was requested. The examination was justified by the fact that symptoms could be correlated with other pathological conditions (volvulus, neoplasms, Chron's disease, etc.) which had to be excluded. For optimum study of the abdominal wall, correct preparation and the use of oral contrast agents were required. From the analysis of CT findings, in particular loop thickening with stratified density, the increased density of mesenteric fat and the presence of fluid among loops led to the radiological diagnosis of intestinal involvement in Henoch-Schönlein purpura. Other imaging procedures (double contrast enema, sonography, Doppler US, MRI) now used in the study of intestinal loops, are examined.

  4. Posterior reversible encephalopathy syndrome in a child with Henoch-Schönlein purpura

    PubMed Central

    Sivrioglu, Ali Kemal; Incedayi, Mehmet; Mutlu, Hakan; Meral, Cihan

    2013-01-01

    Henoch-Schönlein purpura (HSP) is a small vessel vasculitis that affects the gastrointestinal and central nervous systems and the kidneys. The disease primarily affects children, but may occur in elderly children with allergic purpura and also in adults. Central nervous system involvement may be the first sign; however, it is rarely encountered. Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome of encephalopathy, headache, visual disturbance and seizures. Its radiological signs can be observed in grey and white matter at the posterior region of the cerebral hemispheres. HSP should be considered in children with PRES in the presence of rash, joint and gastrointestinal symptoms. We reported a 5-year-old patient who developed acute renal failure and PRES by reason of HSP. PMID:23946524

  5. Petechiae and purpura: the ominous and the not-so-obvious?

    PubMed

    Block, Stan L

    2014-08-01

    Petechiae and purpura are among the most alarming findings a pediatrician will commonly observe in the office. Severity of illness can range from a temper tantrum, to common viral infections, to the most deadly infections and diseases. To avoid many of the pitfalls in diagnosis, practitioners will need to be thorough in history taking, assessing fever and immunization status, and physical examination. In addition, a few simple laboratory tests will usually be needed and possibly a manual differential.

  6. High multi-cytokine levels are not a predictive marker of alloimmunization in transfused sickle cell disease patients.

    PubMed

    Tatari-Calderone, Zohreh; Fasano, Ross M; Miles, Megan R; Pinto, Ligia A; Luban, Naomi L C; Vukmanovic, Stanislav

    2014-07-01

    Patients with sickle cell disease (SCD) receive multiple red blood cell (RBC) transfusions for both prevention of and therapy for disease-related complications. In some patients, transfusion results in development of both allo- and auto-antibodies to RBC antigens. What precipitates the antibody formation is currently unclear. It has been hypothesized that a pro-inflammatory state preceding the therapeutic transfusion may be a predisposing factor. Plasma levels of ten cytokines were evaluated upon recruitment to the study of 83 children with SCD undergoing therapeutic RBC transfusions. The levels of cytokines were correlated with development of anti-RBC antibodies prior, or during seven years post recruitment. Twelve subjects displayed significantly higher levels of all cytokines examined, with pro-, as well as anti-inflammatory properties. Surprisingly, the elevated levels of cytokines were preferentially found in patients without anti-RBC allo- and/or auto-antibodies. Further, presence of high cytokine levels was not predictive of anti-RBC antibody development during the subsequent seven year follow up. These data suggest that the increased concentration of multiple cytokines is not a biomarker of either the presence of or susceptibility to the development of RBC alloimmunization.

  7. Neonatal Liver Failure and Congenital Cirrhosis due to Gestational Alloimmune Liver Disease: A Case Report and Literature Review

    PubMed Central

    Rostirola Guedes, Renata; Kieling, Carlos Oscar; Rossato Adami, Marina; Cerski, Carlos Thadeu Schmidt

    2017-01-01

    Neonatal liver failure (NLF) is a major cause of neonatal morbidity and mortality, presenting as acute liver failure and/or congenital cirrhosis. Many affected patients show antenatal signs of fetal injury. There are several causes of NLF and early diagnosis is mandatory to elucidate the etiology and determine a specific treatment or the best management strategy. Gestational alloimmune liver disease associated with neonatal hemochromatosis (GALD-NH) is a rare but potentially treatable cause of NLF. It should be considered in any neonate with fetal signs of disease and postnatal signs of liver failure with no other identifiable causes. GALD-NH is often diagnosed late and patients are therefore referred late to specialized centers, delaying treatment. This case highlights the consequences of late diagnosis and treatment of GALD-NH and emphasizes the importance of a high grade of suspicion of this disease in order to refer the patient to a specialized center soon enough to perform the appropriate treatment. PMID:28251010

  8. Henoch-Schönlein purpura due to methicillin-sensitive Staphylococcus aureus bacteremia from central venous catheterization.

    PubMed

    Uggeri, Simona; Fabbian, Fabio; Catizone, Luigi

    2008-06-01

    A 69-year-old Caucasian man was admitted to our hospital because of myocardial infarction. A central venous catheter (CVC) for infusive therapy was inserted. After two weeks he developed fever, purpura, and knee arthralgia. Hemoculture yielded methicillin-sensitive Staphylococcus aureus. Subsequently, oliguric renal failure, hematuria, and nephrotic range proteinuria were recorded. Renal biopsy showed mesangial proliferation and crescent formation. In an immunofluorescence study, IgA, IgG, and C3 deposition in the mesangium and along arteriolar walls were observed. A diagnosis of Henoch-Schönlein purpura associated with infection caused by CVC was made. After administration of antibiotic and steroid therapy, proteinuria was markedly reduced, renal function improved, and purpura disappeared. The association of HSP with methicillin-resistant Staphylococcus aureus has frequently been reported in the literature. We present here a case of HSP in association with MSSA bacteremia from central venous catheterization, a finding not reported previously.

  9. Sirolimus for Autoimmune Disease of Blood Cells

    ClinicalTrials.gov

    2017-03-16

    Autoimmune Pancytopenia; Autoimmune Lymphoproliferative Syndrome (ALPS); Evans Syndrome; Idiopathic Thrombocytopenic Purpura; Anemia, Hemolytic, Autoimmune; Autoimmune Neutropenia; Lupus Erythematosus, Systemic; Inflammatory Bowel Disease; Rheumatoid Arthritis

  10. Detection of Antileukocytic Antibodies in Blood Serum using Lymphocytes and Latex Microspheres Carrying HLA-Antigens upon Alloimmunization of Women with Recurrent Pregnancy Loss.

    PubMed

    Stepanova, E O; Nikolaeva, M A; Golubeva, E L; Vtorushina, V V; Van'ko, L V; Khodzhaeva, Z S; Krechetova, L V

    2016-03-01

    Anti-HLA-antibodies were detected using cross-reaction of blood serum with allogenic T and B cells and latex microspheres coated with HLA-I and HLA-II antigens. HLA+ and HLA-sera obtained from women before and after allogeneic immunization were tested. The results obtained by these methods significantly differed. The test with latex microspheres detected antibodies to HLA-I and HLA-II antigens with high sensitivity and specificity and can be used for assessment of clinical significance of alloantibody detection when using alloimmunization in the therapy of gestation disorders.

  11. Empiric treatment of protracted idiopathic purpura fulminans in an infant: a case report and review of the literature

    PubMed Central

    2011-01-01

    Introduction Idiopathic purpura fulminans is a cutaneous thrombotic disorder usually caused by autoimmune-mediated protein C or S deficiency. This disorder typically presents with purpura and petechiae that eventually slowly or rapidly coalesce into extensive, necrotic eschars on the extremities. We present the first known case of idiopathic purpura fulminans consistent with prior clinical presentations in the setting of a prothrombotic genetic mutation, but without hallmark biochemical evidence of protein C or protein S deficiency. Another novel feature of our patient's presentation is that discontinuation of anti-coagulation has invariably led to recurrence and formation of new lesions, which is unexpected in idiopathic purpura fulminans because clearance of autoimmune factors should be followed by restoration of anti-coagulant function. Although this disease is rare, infants with suspected idiopathic purpura fulminans should be rapidly diagnosed and immediately anti-coagulated to prevent adverse catastrophic outcomes such as amputation and significant developmental delay. Case presentation A six-month-old Caucasian boy was brought to our pediatric hospital service with a low-grade fever and subacute, symmetric, serpiginous, stellate, necrotic eschars on his forearms, legs and feet that eventually spread non-contiguously to his toes, thighs and buttocks. In contrast to his impressive clinical presentation, his serologic evaluation was normal, and he was not responsive to corticosteroids and antibiotics. Full-thickness skin biopsies revealed dermal vessel thrombosis, leading to a diagnosis of idiopathic purpura fulminans and successful treatment with low-molecular-weight heparin, which was transitioned to warfarin. Long-term management has included chronic anti-coagulation because of recurrence of lesions with discontinuation of treatment. Conclusion In infants with necrotic eschars, it is important to first consider infectious, inflammatory and hematologic

  12. Rapid improvement of Henoch-Schonlein purpura associated with the treatment of Helicobacter pylori infection

    PubMed Central

    Ulas, Turgay; Tursun, Irfan; Dal, Mehmet Sinan; Eren, Mehmet Ali; Buyukhatipoglu, Hakan

    2012-01-01

    Helicobacter pylori (H. pylori) are one of the most common bacterial infections, seen in humans, worldwide and their possible relationships to different diseases are a focus of attention nowadays. H. pylori may cause some extra intestinal manifestations some of which are dermatological conditions, including Henoch-Schönlein purpura (HSP), chronic urticaria and atopic dermatitis. We describe a 49-year-old man who presented with HSP triggered by gastric H. pylori infection. Treatment of H. Pylori infection was accompanied by prompt resolution of the gastrointestinal manifestations and purpuric rashes. These findings suggest a causative role for H. pylori in the occurrence of HSP. PMID:23833587

  13. Posterior reversible encephalopathy syndrome as a complication of Henoch-Schönlein purpura in a seven-year-old girl.

    PubMed

    Dos Santos, Daiane; Langer, Felipe Welter; Dos Santos, Tatiane; Rafael Tronco Alves, Giordano; Feiten, Marisa; Teixeira de Paula Neto, Walter

    2017-02-01

    Introduction Henoch-Schönlein purpura is a multisystem small vessel vasculitis. Neurologic manifestations are uncommon. Posterior reversible encephalopathy syndrome is a rare complication of Henoch-Schönlein purpura with typical clinical and neuroimaging findings that occurs most commonly in the setting of severe hypertension and renal injury. Case presentation A seven-year-old girl was admitted to our institution presenting with clinical and laboratory findings suggestive of Henoch-Schönlein purpura. Glucocorticoid therapy was initiated, but five days following her admission, she developed altered consciousness, seizures, arterial hypertension, and cortical blindness. Brain MRI scan revealed areas of vasogenic oedema in parieto-occipital lobes, consistent with posterior reversible encephalopathy syndrome. She was immediately initiated on antihypertensives and antiepileptics, which successfully improved her neurologic symptoms. Further laboratory work-up disclosed a rapidly progressive glomerulonephritis secondary to Henoch-Schönlein purpura that was the likely cause of her sudden blood pressure elevation. Immunosuppressive therapy was undertaken, and at one-year follow-up, the patient exhibited complete renal and neurologic recovery. Conclusion Posterior reversible encephalopathy syndrome is a severe complication of Henoch-Schönlein purpura. If promptly diagnosed and treated, children with Henoch-Schönlein purpura presenting with posterior reversible encephalopathy syndrome usually have a good prognosis. Clinicians should be familiar with the characteristic presentation of posterior reversible encephalopathy syndrome and be aware that hypertension and renal injury may predispose Henoch-Schönlein purpura patients to developing this complication.

  14. Mothers at risk of alloimmunization to the Rh (D) antigen and availability of gamma-globulin at the Mexican Institute of Social Security.

    PubMed

    Zavala, C; Salamanca, F

    1996-01-01

    Hemolytic disease of the newborn develops mainly when an Rh negative (D-) mother becomes sensitized and produces anti-Rh positive (anti-D) antibodies capable of hemolysing D+ fetal erythrocytes. Maternal alloimmunization can be prevented by the administration of anti-D gamma-globulin immediately after the birth of each Rh positive child. In order to identify the frequency of prevention of alloimmunization at the Instituto Mexicano del Seguro Social (IMSS), the amount of mothers at risk of sensitization from 1985 to 1995 was estimated from Rh and ABO blood group frequencies and with the number of deliveries and abortions at the Medical Institutions. Also, information in regard to the dose of gamma-globulin units purchased by the Institute of Social Security from 1985 to 1993 was obtained. The number of mothers at risk steadily increased from 16,616 in 1985 to 21,071 in 1995, amounting to a total of 203,203 in the 10-year period, while only 120,800 gamma-globulin units were purchased in that same period. The findings in this study suggest the need to define reasonable policies for the acquisition of gamma-globulin lots to prevent alloisoimmunization of mothers at risk.

  15. T-cell responses associated with neonatal alloimmune thrombocytopenia: isolation of HPA-1a-specific, HLA-DRB3*0101-restricted CD4+ T cells.

    PubMed

    Ahlen, Maria Therese; Husebekk, Anne; Killie, Mette Kjaer; Skogen, Bjørn; Stuge, Tor B

    2009-04-16

    T-cell responses have been implicated in the development of HPA-1a-induced neonatal alloimmune thrombocytopenia (NAIT). However, HPA-1a-specific T cells have neither been isolated nor characterized. Here, we aimed to determine whether HPA-1a-specific T cells could be isolated from HPA-1a-immunized women. In the present study, peripheral blood mononuclear cells (PBMCs) from an HPA-1a-alloimmunized woman were cultured for weeks in the presence of HPA-1a peptide, labeled with CFSE, and assayed for antigen-specific proliferation. Individual proliferating cells were isolated by fluorescence-activated cell sorting and expanded in culture. Antigen specificity and HLA restriction were determined by cytokine secretion (enzyme-linked immunospot [ELISPOT]) and proliferation assays. Several CD3(+)CD4(+) T-cell clones were isolated that proliferated and secreted cytokines in response to HPA-1a peptide. Two of these clones have been established in long-term culture in our laboratory. Both of these recognize synthetic as well as naturally processed HPA-1a antigen, and the recognition is restricted by the MHC molecule HLA-DRB3*0101 that is strongly associated with NAIT. These HPA-1a-specific T-cell clones represent unambiguous evidence for the association of T-cell responses with NAIT, and they will serve as unique tools to elucidate the cellular immune response that may result in NAIT.

  16. Central Nervous System Involvement in Henoch-Schonlein Purpura in Children and Adolescents

    PubMed Central

    Ivanov, Ivan S.; Stefanova, Krastina; Chepisheva, Elena; Chochkova, Lyubov; Grozeva, Dafina; Stoyanova, Angelina; Milenkov, Stojan; Stefanova, Penka; Petrova, Anna

    2017-01-01

    Central nervous system (CNS) involvement in Henoch-Schonlein purpura (HSP) is rare but poses diagnostic difficulties. The aim of the study was to establish the frequency of CNS involvement in HSP, to analyze its clinical characteristics and do a literature review. Medical files of patients with HSP admitted at the Department of Pediatrics, Plovdiv, were studied retrospectively for a five-year period (2009–2013). Diagnosis was based on the American College of Rheumatology criteria. Out of 112 children with HSP 1 case (0.9%) had CNS involvement presenting as Posterior Reversible Encephalopathy Syndrome (PRES), which may be a result of CNS vasculitis or arterial hypertension. It was an 8-year-old girl with atypical HSP which started with abdominal pain requiring surgery. On the third day after the operation a transient macular rash and arterial hypertension appeared, followed by visual disturbances, hemiconvulsive epileptic seizures, postictal hemiparesis, and confusion. Head CT showed occipital hypodense lesions and MRT-T2 hyperintense lesion in the left occipital lobe. The patient experienced a second similar episode after 2 weeks when palpable purpura had also appeared. Neurological symptoms and MRI resolved completely. HSP can be an etiological factor for PRES in childhood. Although PRES is a rare complication of HSP, clinicians must be aware of it and avoid diagnostic and therapeutic delays. PMID:28316855

  17. Glomerular membranopathy in children with IgA nephropathy and Henoch Schönlein purpura.

    PubMed

    Vogler, C; Eliason, S C; Wood, E G

    1999-01-01

    We evaluated renal biopsies from 34 children with IgA nephropathy or Henoch Schönlein purpura to further characterize the ultrastructural features of the glomerular membranopathy that occurs in these disorders. Focal glomerular basement membrane damage was identified in 29 children and was severe in 4 of the children. Alterations included focal and segmental attenuation, splitting, duplications, and spike-like subepithelial protrusions of the lamina densa, along with saccular glomerular microaneurysms arising at the paramesangium. Those cases with extensive glomerular basement membrane lesions had either moderate or severe glomerular alterations apparent by light microscopy. Over half of the cases with glomerular membranopathy had immunohistological or ultrastructural evidence of focal peripheral glomerular capillary wall immune deposits and electron-dense deposits occurred at sites of glomerular basement membrane splitting. Despite the focal attenuation of the glomerular basement membrane, we did not identify any biopsy with findings of thin basement membrane disease. The glomerular basement membrane ultrastructural findings we describe are characteristic of IgA nephropathy and Henoch Schönlein purpura, are common in children with these disorders, and are similar to the ultrastructural alterations of the basement membrane that occur in other glomerulonephritides. These basement membrane injuries may be inflammatory cell or immune mediated but their pathogenesis requires further study.

  18. A rare presentation of Henoch–Schönlein purpura and myocardial infarction at the 5th decade of life

    PubMed Central

    Joseph, Peter K.; Govindan, Vijayaraghavan

    2013-01-01

    Henoch–Schönlein purpura is an IgA-mediated, autoimmune, hypersensitivity vasculitis of childhood that results in a triad of symptoms, including a purpuric rash occurring on the lower extremities, abdominal pain or renal involvement, and arthritis. However, any of the triad may be absent, which often leads to a confusion in diagnosing the condition. Although the cause is unknown, Henoch–Schönlein purpura (HSP) is often associated with infectious agents, such as group A streptococci and mycoplasma. It has also been associated with food reactions, exposure to cold, insect bites, and drug allergies. The treatment is supportive and needs close followup of renal status. This report describes a rare presentation of Henoch–Schönlein purpura with coronary vasculitis which leads to myocardial infarction at the age of 53. Henoch–Schönlein purpura was diagnosed on the basis of no infection, accelerated ESR (35 mm/h), normal platelet count, positive skin biopsy, proteinuria, and negative searches for rheumatoid factor (RF), antinuclear antibody (ANA), antineutrophil cytoplasmic antibodies (ANCA), and anti-dsDNA. PMID:24265897

  19. An Elevated Fetal IL-6 Concentration Can Be Observed In Fetuses with Anemia Due To Rh Alloimmunization: Implications for the Understanding of the Fetal Inflammatory Response Syndrome

    PubMed Central

    Vaisbuch, Edi; Romero, Roberto; Gomez, Ricardo; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.

    2010-01-01

    Objective The fetal inflammatory response syndrome (FIRS) has been described in the context of preterm labor and preterm PROM and is often associated with intra-amniotic infection/inflammation. This syndrome is characterized by systemic fetal inflammation and operationally-defined by an elevated fetal plasma interleukin (IL)-6. The objective of this study was to determine if FIRS can be found in fetuses with activation of their immune system, such as the one observed in Rh alloimmune-mediated fetal anemia. Methods Fetal blood sampling was performed in sensitized Rh-D negative women with suspected fetal anemia (n=16). Fetal anemia was diagnosed according to reference range nomograms established for the assessment of fetal hematologic parameters. An elevated fetal plasma IL-6 concentration was defined using a cutoff of >11 pg/mL. Concentrations of IL-6 were determined by immunoassay. Non-parametric statistics were used for analysis. Results 1) The prevalence of an elevated fetal plasma IL-6 was 25% (4/16); 2) there was an inverse relationship between the fetal hematocrit and IL-6 concentration - the lower the hematocrit, the higher the fetal IL-6 (r= −0.68, p=0.004); 3) fetuses with anemia had a significantly higher plasma IL-6 concentration than those without anemia (3.74 pg/ml, interquartile range (IQR) 1.18–2.63 vs. 1.46 pg/ml, IQR 1.76–14.7; p=0.02); 4) interestingly, all fetuses with an elevated plasma IL-6 concentration had anemia (prevalence 40%, 4/10), while in the group without anemia, none had an elevated fetal plasma IL-6. Conclusions An elevation in fetal plasma IL-6 can be observed in a subset of fetuses with anemia due to Rh alloimmunization. This observation suggests that the hallmark of FIRS can be caused by non-infection-related insults. Further studies are required to determine whether the prognosis of FIRS caused by intra-amniotic infection/inflammation is different from that induced by alloimmunization. PMID:20701435

  20. Modulation of alloimmune response by commensal gut microbiota and potential new avenues to influence the outcome of allogeneic transplantation by modification of the 'gut culture'.

    PubMed

    Kanangat, S

    2017-02-01

    Host defence response against microbial infections was the foundation for the Science of Immunology. Now, we know the mechanisms of such host defence which include innate immune responses that is generally nonspecific but effective in many cases and lead to more specific responses called adaptive immune response. The gene loci of class I, II and III of the major histocompatibility complex (MHC) play a major role in directing the adaptive immune responses by presenting processed antigens to T and B cells to induce appropriate antigen-specific cellular and or humoral immune responses. In humans, these are commonly referred to as human leucocyte antigens class I/II-HLA I/II). The class III region, the gamma region in the MHC complex, is mostly associated with regulation of immune responses along with genes associated with complement activation. The adaptive immune responses are orchestrated by T and B cells that are tuned to respond to antigens that are normally foreign to the body, because these cells are educated to avoid self-antigens by a process of thymic education and selection of the T cells that are mostly non-self-reactive which also helps the B cells in eliciting specific immune responses to non-self-antigens. A by-product of this is the ability of the T and B cells to elicit strong immune responses to foreign HLA/MHC (alloimmune response), which developed into the field of histocompatibility testing for allogeneic transplantation of stem cells and organs. Now, we are beginning to learn that such alloimmune responses can be influenced by the microbiota that symbiotically live in our body especially on the mucosal surfaces and on the skin. This review deals with new and emerging data on how the commensal mucosal and skin microbiota influence the immune homeostasis, and how manipulating the commensal microbiota of the mucosa and skin could influence the survival and long-term functions of the allografts. Also, alterations of the microbiota by the inevitable

  1. Anti-KEL7 (anti-Js(b)) alloimmunization diagnostic supported by molecular KEL*6,7 typing in a pregnant woman with previous intrauterine deaths.

    PubMed

    Boturão-Neto, Edmir; Chiba, Akemi Kuroda; Oliveira Barros, Melca Maria; Barretto de Mello, Adriana; Fabron, Antonio; Orlando Bordin, José

    2006-12-01

    Anti-KEL7 (anti-Js(b)) is a rare antibody that has been related to haemolytic transfusion reactions and HDN. We report a case of anti-KEL7 alloimmunization detected in a pregnant woman who had an obstetric previous history of four miscarriages and one stillborn. Employing classical immunohematological techniques, we studied the propositus and her available relatives. Due to the unavailability of commercial anti-KEL6 and anti-KEL7 reagents, we used a KEL*6,7 genotyping method as an alternative tool to contribute with the identification of the alloantibody origin. The results of KEL genotyping showed that the propositus was KEL*6/6 homozygous, while her second partner was KEL*7/7 homozygous.

  2. Henoch Schonlein Purpura as a Cause of Renal Failure in an Adult

    PubMed Central

    Vimalachandran, Pradeepa; Kunadharaju, Rajesh; Mehta, Vishisht; Colanta, Agnes

    2016-01-01

    Henoch Schonlein purpura (HSP) is an immune mediated disease associated Immunoglobulin A (IgA) deposition within the affected organs. While the disease is commonly seen in the pediatric age group, it is rarely seen in adults. We report the case of a 93-year-old Caucasian lady who presented with nonthrombocytopenic purpuric rash and acute kidney injury after an episode of bronchitis. Rapid and progressive deterioration of renal function prompted a kidney biopsy, which showed findings consistent with IgA nephropathy confirming the diagnosis of HSP. The patient was treated with high dose intravenous methylprednisolone followed by oral prednisone; however, her kidney disease progressed to end stage renal disease requiring hemodialysis. HSP is usually a self-limiting disease in children. However, adults are at an increased risk of severe renal involvement including end stage renal disease. Purpuric skin rash with renal involvement should raise suspicion for HSP. This is the oldest known patient with HSP. PMID:27672395

  3. Association of acquired thrombotic thrombocytopaenic purpura in a patient with pernicious anaemia.

    PubMed

    Podder, Sidhertha; Cervates, Jose; Dey, Bimalangshu R

    2015-10-13

    Pernicious anaemia is an autoimmune disease caused by intrinsic factor antibody; it leads to vitamin B12 deficiency and is marked by ineffective erythropoiesis. Haematological features reveal macrocytosis, hyperchromasia and hypersegmented neutrophils. Schistocytes are typically seen in microangiopathy, such as in thrombotic thrombocytopaenic purpura (TTP)/haemolytic uraemic syndrome or disseminated intravascular haemolysis (DIC). We report a case of a patient with severe anaemia who presented to the emergency room. Peripheral smear revealed macrocytosis, hypersegmented neutrophils and marked schistocytosis. The patient also had high reticulocyte count with high serum lactate dehydrogenase, elevated D-dimer, low fibrinogen and low haptoglobin. Vitamin B12 level came back low and the presence of intrinsic factor antibody confirmed pernicious anaemia. ADAMTS13 level was noted to be mildly reduced, which raised the suspicion of the association of acquired TTP with pernicious anaemia. Acquired TTP is another autoimmune disorder and its association with pernicious anaemia needs further evaluation.

  4. Plantar Purpura as the Initial Presentation of Viridians Streptococcal Shock Syndrome Secondary to Streptococcus gordonii Bacteremia

    PubMed Central

    Liao, Chen-Yi; Su, Kuan-Jen; Lin, Cheng-Hui; Huang, Shu-Fang; Chin, Hsien-Kuo; Chang, Chin-Wen; Kuo, Wu-Hsien; Ben, Ren-Jy; Yeh, Yen-Cheng

    2016-01-01

    Viridians streptococcal shock syndrome is a subtype of toxic shock syndrome. Frequently, the diagnosis is missed initially because the clinical features are nonspecific. However, it is a rapidly progressive disease, manifested by hypotension, rash, palmar desquamation, and acute respiratory distress syndrome within a short period. The disease course is generally fulminant and rarely presents initially as a purpura over the plantar region. We present a case of a 54-year-old female hospital worker diagnosed with viridians streptococcal shock syndrome caused by Streptococcus gordonii. Despite aggressive antibiotic treatment, fluid hydration, and use of inotropes and extracorporeal membrane oxygenation, the patient succumbed to the disease. Early diagnosis of the potentially fatal disease followed by a prompt antibiotic regimen and appropriate use of steroids are cornerstones in the management of this disease to reduce the risk of high morbidity and mortality. PMID:27366188

  5. An 11-year and 10-month-old girl with purpura and chest pain.

    PubMed

    Chen, Pei-Hsuan; Chiang, Bor-Luen; Lu, Meng-Yao; Yang, Yao-Hsu

    2014-10-01

    Mucosa-associated lymphoid tissue lymphoma (MALToma) is a type of B-cell lymphoma. Case reports of childhood thymic MALToma and its association with vasculitis are rarely found in the related literature. Herein, we present a report of an 11-year and 10-month-old girl who was initially diagnosed with cutaneous vasculitis characterized by nonthrombocytopenic palpable purpura, positive antinuclear antibody and anti-SSA (Ro) antibody. Eight months later, a thymic mediastinal mass was found. Surgical excision was performed and results of pathological analysis revealed an extranodal marginal zone CD20(+) B-cell MALToma. Benign response to the chemotherapeutic regimen of Berlin-Frankfurt-Münster group NHL-BFM 90 R2 without relapse was noted in 2 years of follow-up. For the first time, our case demonstrated some clinical evidence of the association between vasculitis and childhood MALToma.

  6. Genetic homogeneity but IgG subclass-dependent clinical variability of alloimmune membranous nephropathy with anti-neutral endopeptidase antibodies.

    PubMed

    Vivarelli, Marina; Emma, Francesco; Pellé, Thimothée; Gerken, Christopher; Pedicelli, Stefania; Diomedi-Camassei, Francesca; Klaus, Günter; Waldegger, Siegfried; Ronco, Pierre; Debiec, Hanna

    2015-03-01

    Alloimmune antenatal membranous nephropathy (MN) during pregnancy results from antibodies produced by a neutral endopeptidase (NEP)-deficient mother. Here we report two recent cases that provide clues to the severity of renal disease. Mothers of the two children had circulating antibodies against NEP showing the characteristic species-dependent pattern by immunofluorescence on kidney slices. A German mother produced predominantly anti-NEP IgG4 accompanied by a low amount of IgG1. Her child recovered renal function within a few weeks. In sharp contrast, an Italian mother mainly produced complement-fixing anti-NEP IgG1, which also inhibits NEP enzymatic activity, whereas anti-NEP IgG4 has a weak inhibitory potency. Her child was dialyzed for several weeks. A kidney biopsy performed at 12 days of age showed MN, ischemic glomeruli, and arteriolar and tubular lesions. A second biopsy performed at 12 weeks of age showed aggravation with an increased number of collapsed capillary tufts. Both mothers were homozygous for the truncating deletion mutation 466delC and were thus NEP deficient. The 466delC mutation, identified in three previously described families, suggests a founder effect. Because of the potential severity of alloimmune antenatal MN, it is essential to identify families at risk by the detection of anti-NEP antibodies and NEP antigen in urine. On the basis of the five families identified to date, we propose an algorithm for the diagnosis of the disease and the prevention of complications.

  7. Terminal Ileitis as a Feature of Henoch-Schönlein Purpura Masquerading as Crohn Disease in Adults.

    PubMed

    Sampat, Hemal N; McAllister, Brian P; Gaines, Darryl D; Ostrov, Barbara

    2016-03-01

    Henoch-Schönlein purpura (HSP), more recently termed immunoglobulin A (IgA) vasculitis, is a systemic small-vessel vasculitis characterized by perivascular IgA deposition. This disease manifests clinically as palpable purpura, arthralgia, gastrointestinal symptoms, and renal dysfunction. Although ileitis can be seen in HSP, terminal ileitis is virtually pathognomonic for Crohn disease. We present a comprehensive review of the literature on this association, including 2 cases of our own, to demonstrate the importance of considering HSP in the differential diagnosis of ileitis suggestive of Crohn disease. We review the growing body of literature suggesting a pathophysiologic link between the conditions, possibly through an IgA-mediated mechanism.

  8. Lifetime cost of meningococcal disease in France: Scenarios of severe meningitis and septicemia with purpura fulminans.

    PubMed

    Bénard, Stève; Wright, Claire; Voisine, Jimmy; Olivier, Catherine W; Gaudelus, Joël

    2016-01-01

    Invasive meningococcal disease (IMD) is life-threatening and can result in severe sequelae. In France, no data have been published on the costs of severe IMD cases. Two realistic scenarios were developed with national experts (clinicians and social workers): a 6-year-old child with purpura fulminans with amputation of both legs below the knee (case A) and a 3-year-old with meningitis and severe neurological sequelae (case B). Additional scenarios included other typical sequelae of IMD such as chronic kidney disease (CKD), profound deafness and epilepsy. Data on healthcare, disability, educational and other resource use were obtained from experts and families of patients with similar sequelae. Unit costs (2013) were mainly obtained from the literature and the National Health Insurance (NHI). Time horizon was based on life expectancies of patients (77 and 55 years, respectively). A 4% discount rate decreasing to 2% after 30 years was applied. Costs are presented from the perspective of the NHI, publicly funded organizations and patients' families or their private health insurances. purpura fulminans with amputations is associated with a lifelong discounted cost of €768,875. Adding CKD doubles the amount (€1,480,545). Meningitis with severe neuro-cognitive sequelae results in a lifelong discounted cost of €1,924,475. Adding profound deafness and epilepsy slightly increases the total cost (€2,267,251). The first year is the most expensive in both scenarios (€166,890 and €160,647 respectively). The main cost drivers for each scenario are prostheses and child/adult stays in healthcare facilities, respectively. Overall, patients' families or his private insurance had to pay around 13% of total cost (101,833€ and 258,817€, respectively). This study fills a gap in the body of knowledge on IMD sequelae care and lifetime costs in France. The potentially high economic burden of IMD, in addition to its physical, psychological and social burden, reinforces the

  9. A Lower Proportion of Regulatory B Cells in Patients with Henoch–Schoenlein Purpura Nephritis

    PubMed Central

    Qu, Zhihui; Zhao, Songchen; Zhang, Li; Li, Man; Sun, Xiguang; Jiang, Yanfang

    2016-01-01

    Background Henoch—Schoenlein purpura is the one of most common types of systemic vasculitis that involves impaired renal function and Henoch-Schoenlein purpura nephritis (HSPN). The diagnosis of this condition is largely based on immunohistologic detection of immunoglobulin A1-containing immune complex in the glomerular deposits of mesangium. Despite clinical advances, the etiopathogenesis of HSPN is still largely unknown. Methods In this study, we enrolled 25 newly diagnosed HSPN patients and 14 healthy controls. Then, fractions of B cell subtypes were determined in venous blood using flow cytometry. The serum interleukin (IL)-10 concentration was determined by enzyme-linked immunosorbent assay. Results Compared to those in healthy controls, the numbers of CD38+CD19+, CD86+CD19+, CD38+CD86+CD19+, and CD95+CD19+ B cells per microliter of blood were significantly higher in HSPN patients. In contrast, the numbers of CD5+CD19+, IL-10+CD19+, CD5+CD1d+CD19+, and IL-10+CD5+CD1d+CD19+ B cells per microliter of blood and the serum IL-10 concentration were significantly lower in HSPN patients. Following treatment, the numbers of CD38+CD19+ and CD86+CD19+ B cells per microliter of blood were significantly reduced in HSPN patients. However, the numbers of CD5+CD1d+CD19+, CD5+CD1d+IL-10+CD19+, and IL-10+CD19+ B cells per microliter of blood and the serum IL-10 concentration were significantly increased in HSPN patients following treatment. The estimated glomerular filtration rate (eGFR) was negatively correlated with the number of CD38+CD19+ B cells but positively correlated with the numbers of IL-10+CD19+, CD1d+CD5+CD19+, and IL-10+CD1d+CD5+CD19+B cells per microliter of blood and the serum IL-10 concentration. The 24-h urinary protein concentration was positively correlated with the number of CD38+CD19+B cells but negatively correlated with the numbers of IL-10+CD19+, CD1d+CD5+CD19+, and IL-10+CD1d+CD5+CD19+B cells per microliter of blood and the serum IL-10 concentration

  10. Immune thrombocytopaenic purpura: an autoimmune cross-link between infections and vaccines.

    PubMed

    Rinaldi, M; Perricone, C; Ortega-Hernandez, O-D; Perricone, R; Shoenfeld, Y

    2014-05-01

    Immune thrombocytopaenic purpura (ITP) is an autoimmune systemic disease detectable by the presence of low blood platelets count (<10(5)/µl) and the production of autoantibodies against glycoproteins expressed on the platelet surface. The clinical course is often acute, and life-threatening events may occur especially in children, with 52% of paediatric patients recovering either spontaneously or after treatment. A chronic ITP evolution is observed in 64% of adults, of whom 12% will develop an overlapping autoimmune disease. Several microbial agents such as CagA-positive Helicobacter pylori or Candida albicans and a number of viruses including CMV, EBV or HIV can potentially trigger ITP through molecular mimicry. Moreover, ITP improves after treatment of the underlying infection. Similarly, vaccines such as MMR may prompt ITP (IRR 5.48, 1.61-18.64, p < 0.006). Early recognition of the underlying microbial trigger and the removal of modifiable aetiopathogenetic factors should be integrated as a complementary treatment strategy in all patients who do not readily improve with standard ITP care.

  11. Self-organizing phenomena induced by LLLT in Henoch-Schoenlein purpura

    NASA Astrophysics Data System (ADS)

    Ailioaie, Laura; Ailioaie, C.

    2001-06-01

    Henoch-Schoenlein purpura is characterized by vasculitis of small vessels, particularly those of the skin, gastrointestinal tract, and kidney. Patients have characteristic purpuric skin rash plus all or some of the following: migratory polyarthralgias or polyarthritis, colicky abdominal pain, nephritis. Because until now there is no satisfactory treatment, we applied low level laser therapy (LLLT) in order to compare it with the classical therapy. Twenty-three children (2-15 years of age) have been treated at debut of the disease. They were randomly divided: group A (11 children) received LLLT; group B (12 children) was administrated classical therapy. Two GaAlAs diode lasers (670 nm and 830 nm) were used. The density of energy (4-8 J/cm2), irradiating frequency (2.4 Hz) was applied one session daily, using scanning technique under a special treatment protocol on cutaneous purpuric areas (20 sessions). The best results were obtained in laser group. Despite the complex medication, some patients from group B fell back into the former state after apparent improvement, and two children developed nephritis. The results could be explained by self-organization. LLLT is acting as a trigger factor causing certain systemic effects through circulating blood and a response of the entire immune system, by way of synergetic mechanisms.

  12. Posterior Reversible Encephalopathy Syndrome in Henoch-Schonlein Purpura and Hemolytic Uremic Syndrome

    PubMed Central

    Fidan, Kibriya; Kandur, Yasar; Ucar, Murat; Gucuyener, Kivilcim; Soylemezoglu, Oguz

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological syndrome, composed of symptoms such as headache, seizures, visual disturbances, lethargy, confusion, stupor, focal neurologic findings and radiological findings of bilateral gray and white matter abnormalities suggestive of edema in the posterior regions of the cerebral hemispheres. PRES is associated with significant morbidity and mortality if it is not expeditiously recognized. Magnetic resonance image (MRI) represents the most sensitive imaging technique for recognizing PRES. PRES has been seen in various clinical settings including renal disorders such as acute glomerulonephritis, lupus nephritis, nephrotic syndrome, and drug usage such as calcineurin inhibitors. We aimed to present two study cases for such clinical setting. In this report, we present two patients with PRES in whom the primary diagnosis was hemolytic uremic syndrome (HUS) and Henoch-Schonlein purpura (HSP). Both of them were treated with anticonvulsant and proper antihypertensive drugs. A repeated MRI scan of the head, an ophthalmologic assessment, and a follow-up electroencephalogram produced normal results with no sequelae. Early recognition of PRES as a complication during different diseases and therapies in childhood may facilitate the appropriate treatment, so that intensive treatment should be performed as soon as possible to avoid neurological sequelae. PMID:27298664

  13. Increased serum IgD concentrations in children with Henoch-Schönlein purpura.

    PubMed

    Saulsbury, F T

    1998-05-01

    Serum IgD concentrations were measured in 39 children with Henoch Schonlein purpura (HSP) and 40 control children by means of radial immunodiffusion. Serum IgG, IgA and IgM concentrations in the HSP patients were measured by nephelometry. The geometric mean IgD concentration in children with HSP (16.7 microg/ml) was significantly higher than in control children (9.1 microg/ml; P=0.03). Serial testing in 10 HSP patients revealed no significant change in IgD concentrations over periods ranging from 1 to 12 months. There was no relationship between IgD and IgA concentrations in the HSP patients. Nineteen of the 39 HSP patients (49%) had nephritis. The mean IgD concentration in patients with nephritis (10.7 microg/ml) did not differ from control values, but was significantly lower than the mean IgD level in the remaining 20 patients who did not have nephritis (25.4 microg/ml; P=0.02). These results indicate that serum IgD levels are increased in children with HSP who did not have nephritis. IgD concentrations in patients with nephritis were similar to levels in control children.

  14. Lumbar Swelling as the Unusual Presentation of Henoch-Schonlein Purpura in a Child

    PubMed Central

    Duman, Mehmet Ali; Duru, Nilgün Selçuk; Çalışkan, Bahar; Sandıkçı, Hale; Çengel, Ferhat

    2016-01-01

    Background: Henoch-Schönlein Purpura (HSP) is a systemic hypersensitivity disease of unknown cause that is characterized by a purpuric rash and systemic manifestations, such as colicky abdominal pain, polyarthralgia, and acute glomerulonephritis. Common complications of HSP that lead to surgical intervention include intussusception, perforation, necrosis, and massive gastrointestinal bleeding. Unusual clinical manifestations of HSP may include edema of the scrotum and eyes. Lumbar swelling is rarely seen as a complication of HSP. Case Report: A four-year-old boy was admitted to our emergency room with a 7 day history of increasing abdominal pain. Within 48 hours of admission, erythematous macules and palpable purpuric lesions developed on the lower extremities. On the third day of hospitalization, sudden onset of severe back pain, swelling on the lumbar region and refusal to walk were seen. On the fifth day, lumbosacral edema and pain resolved but facial edema developed. He was diagnosed clinically with HSP. Conclusion: To the best of our knowledge, only a few cases of HSP with lumbar edema have been reported so far. If the first clinical symptoms of HSP are atypical, clinical progress can be atypical, too. PMID:27308084

  15. Purpura fulminans as clinical manifestation of atypical SLE with antiphospholipid antibodies: a case report.

    PubMed

    Gamba, G; Montani, N; Montecucco, C M; Caporali, R; Ascari, E

    1991-01-01

    Purpura Fulminans and DIC were the main clinical manifestations of the antiphospholipid syndrome observed in a 62-year-old man. The patient was well until 44 years of age when he began to suffer from recurrent thrombophlebitis, without other symptoms suggestive of immune disease. At the time of hospital admission the pt. appeared acutely ill, showing high fever, severe anemia, massive urinary blood loss, multiple purpuric patches evolving to hemorrhagic bullae and gangrene rapidly spreading over about 30% of the total body area. No signs of neurological involvement or of visceral thrombotic occlusions were present. Clotting tests were consistent with a diagnosis of DIC, further confirmed by skin biopsy showing the presence of thrombi in dermal arterioles. The autoantibody research was positive as follows: Waaler-Rose 1:40, Anti-DNA 1:80; ANF 1:640, aCA IgG 100 GPL. LA was diagnosed according to standard criteria: prolonged KCT and RVVT not corrected by a mixture of normal plasma and abnormal TTI. Plasma exchange in association with heparin and prednisone was effective in arresting the progression of the skin lesion; nevertheless the patient died ten days after hospital admission for sepsi and acute renal failure.

  16. A perspective on the measurement of ADAMTS13 in thrombotic thrombocytopaenic purpura.

    PubMed

    Pimanda, John E; Chesterman, Colin N; Hogg, Philip J

    2003-04-01

    The recent discovery of the von Willebrand Factor (vWF) cleaving protease (ADAMTS13) and the association of its deficiency with thrombotic thrombocytopaenic purpura (TTP) has generated both enormous interest and considerable confusion. Ultra large von Willebrand Factor (UL vWF) multimers are present in the plasmas of patients with chronic relapsing TTP in remission but disappear during an attack. This observation led to the recognition that UL vWF multimers precipitate the thrombotic occlusion of arterioles, a feature that characterizes TTP. Multiple mutations in ADAMTS13 are associated with congenital TTP and neutralizing autoantibodies have been demonstrated in the acquired TTP syndrome. Although a number of functional assays for this enzyme have been described, the more rigorously evaluated assays are difficult to perform outside a research laboratory. There is also an enduring uncertainty about the specificity of ADAMTS13 deficiency for the diagnosis of acquired TTP and a perception that the result does not alter patient management. The cloning of the ADAMTS13 gene has also raised the prospect of recombinant enzyme therapy for the treatment of TTP, and this has heightened the need for a simple assay. In this review, we evaluate the value of measuring this enzyme in the management of TTP.

  17. Hyperhemolytic Syndrome Complicating a Delayed Hemolytic Transfusion Reaction due to anti-P1 Alloimmunization, in a Pregnant Woman with HbO-Arab/β-Thalassemia

    PubMed Central

    Bezirgiannidou, Zoe; Christoforidou, Anna; Kontekaki, Eftychia; Anastasiadis, Athanasios G; Papamichos, Spyros I.; Menexidou, Helen; Margaritis, Dimitrios; Martinis, Georges; Mantadakis, Elpis

    2016-01-01

    Background Hyperhemolytic Syndrome or Hyperhemolytic Transfusion Reaction (HHTR), a life-threatening subset of Delayed Hemolytic Transfusion Reaction (DHTR) is characterized by destruction of both transfused and autologous erythrocytes evidenced by a fall in post transfusion hemoglobin below the pre-transfusion level. Case report We describe a case of DHTR due to anti-P1 alloimmunization manifesting with hyperhemolysis in a 30-year-old Greek Pomak woman with thalassemia intermedia (HbO-Arab/β-thalassemia), during the11th week of her first gestation. She was successfully managed with avoidance of further transfusions and administration of IVIG and corticosteroids. Conclusion A high index of suspicion for HHTR is of vital importance among clinicians especially since optimal methods for its prevention and treatment remain yet to be defined. Early recognition of HHTR leading to prompt cessation of additional transfusions and initiation of immunosuppressive treatment can be life-saving, especially in clinical settings where limited therapeutic options are available, such as in pregnancy. PMID:27872733

  18. Henoch-Schönlein purpura associated with a neuroblastoma: Report of one case and a review of the literature

    PubMed Central

    Dong, Qiaoli; Cao, Shanshan; Zhang, Hongwen; Geng, Hui

    2012-01-01

    Summary Malignancies such as solid tumors and hematologic malignancies can often induce or be associated with Henoch-Schönlein purpura (HSP) in older males but not in children. Described here is the case of a 5-year-old boy who clinically presented with HSP. An imaging study of the abdomen revealed a right retroperitoneal neoplasm that histopathology postoperatively confirmed to be a neuroblastoma. Malignancies are sometimes associated with HSP mostly in older males, though children are affected, albeit rarely. Thus, all patients with HSP must be carefully examined to identify or exclude an underlying disease. PMID:25343092

  19. HLA-B35, a common genetic trait, in a familial case of Henoch-Schoenlein purpura and Berger's disease.

    PubMed

    Pellegrin, M C; Matarazzo, L; Neri, E; Pennesi, M; Crovella, S

    2014-04-08

    Nephritis characterized by IgA mesangial depositions has been described both in Henoch-Schoenlein purpura (HSP) and in Berger's disease (BD), but common genetic traits are still uncertain. We report here the case of two brothers, the first affected by HSP with persistent nephritis and the second by BD, accidentally discovered as silent microhematuria 1 year after HSP onset in the first brother. HLA genotyping demonstrated the presence of HLA-B35 in both patients. Our findings reinforce the need to screen for urinary abnormalities in family members of patients affected by HSP nephritis to identify a silent IgA nephropathy.

  20. The first case of Henoch-Schonlein purpura associated with rosuvastatin: colonic involvement coexisting with small intestine.

    PubMed

    Gonen, Korcan Aysun; Erfan, Gamze; Oznur, Meltem; Erdogan, Cuneyt

    2014-03-19

    Henoch-Schönlein purpura (HSP) is a systemic vasculitis affecting small vessels. It is the most common systemic vasculitis in children, and is rare in adults. Serious gastrointestinal complications are more common in childhood. Infections and drugs are the most prominent factors in the aetiology. Wall thickening in segments of the small intestine is commonly seen in imaging studies in gastrointestinal system (GIS) involvement. Simultaneous involvement of small intestine and colon is rare. An HSP case involving small intestine and colon in an adult patient due to the use of rosuvastatin, an antihyperlipidaemic agent, is presented, and is first of its kind reported in the literature.

  1. Cocaine/levamisole-induced systemic vasculitis with retiform purpura and pauci-immune glomerulonephritis

    PubMed Central

    Veronese, F.V.; Dode, R.S.O.; Friderichs, M.; Thomé, G.G.; da Silva, D.R.; Schaefer, P.G.; Sebben, V.C.; Nicolella, A.R.; Barros, E.J.G.

    2016-01-01

    Levamisole has been increasingly used as an adulterant of cocaine in recent years, emerging as a public health challenge worldwide. Levamisole-associated toxicity manifests clinically as a systemic vasculitis, consisting of cutaneous, hematological, and renal lesions, among others. Purpura retiform, cutaneous necrosis, intravascular thrombosis, neutropenia, and less commonly crescentic nephritis have been described in association with anti-neutrophil cytoplasmic antibodies (ANCAs) and other autoantibodies. Here we report the case of a 49-year-old male who was a chronic cocaine user, and who presented spontaneous weight loss, arthralgia, and 3 weeks before admission purpuric skin lesions in the earlobes and in the anterior thighs. His laboratory tests on admission showed serum creatinine of 4.56 mg/dL, white blood count 3,800/μL, hemoglobin 7.3 g/dL, urinalysis with 51 white blood cells/μL and 960 red blood cells/μL, and urine protein-to-creatinine ratio 1.20. Serum ANCA testing was positive (>1:320), as well as serum anti-myeloperoxidase and anti-proteinase 3 antibodies. Urine toxicology screen was positive for cocaine and levamisole, with 62.8% of cocaine, 32.2% of levamisole, and 5% of an unidentified substance. Skin and renal biopsies were diagnostic for leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis, respectively. The patient showed a good clinical response to cocaine abstinence, and use of corticosteroids and intravenous cyclophosphamide. Last serum creatinine was 1.97 mg/dL, white blood cell count 7,420/μL, and hemoglobin level 10.8 g/dL. In levamisole-induced systemic vasculitis, the early institution of cocaine abstinence, concomitant with the use of immunosuppressive drugs in severe cases, may prevent permanent end organ damage and associate with better clinical outcomes. PMID:27119429

  2. [Sickle cell anemia and transfusion safety in Bamako, Mali. Seroprevalence of HIV, HBV and HCV infections and alloimmunization belonged to Rh and Kell systems in sickle cell anemia patients].

    PubMed

    Diarra, A B; Guindo, A; Kouriba, B; Dorie, A; Diabaté, D T; Diawara, S I; Fané, B; Touré, B A; Traoré, A; Gulbis, B; Diallo, D A

    2013-12-01

    Red cell transfusion is one of the main treatments in sickle cell disease. However there are potential risks of blood transfusions. In order to propose strategies to improve blood safety in sickle cell disease in Mali, we conducted a prospective study of 133 patients with sickle cell anemia recruited at the sickle cell disease research and control center of Bamako, November 2010 to October 2011. The study aimed to determine the prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections by serum screening and the frequency of red cell alloimmunization before and after blood transfusion. The diagnosis of sickle cell syndrome was made by HPLC, the detection of markers of viral infection was performed by ELISA, and the diagnosis of alloimmunization was conducted by the Indirect Coombs test. Prevalence of viral infections observed at the time of enrolment of patients in the study was 1%, 3% and 1% respectively for HIV, HBV and HCV. Three cases of seroconversion after blood transfusion were detected, including one for HIV, one for HBV and one another for HCV in sickle cell anemia patients. All these patients had received blood from occasional donors. The red cell alloimmunization was observed in 4.4% of patients. All antibodies belonged to Rh system only. Blood transfusion safety in sickle cell anemia patients in Mali should be improved by the introduction of at least the technique for detecting the viral genome in the panel of screening tests and a policy of transfusions of blood units only from regular blood donors.

  3. Henoch-Schönlein purpura from vasculitis to intestinal perforation: A case report and literature review

    PubMed Central

    Lerkvaleekul, Butsabong; Treepongkaruna, Suporn; Saisawat, Pawaree; Thanachatchairattana, Pornsri; Angkathunyakul, Napat; Ruangwattanapaisarn, Nichanan; Vilaiyuk, Soamarat

    2016-01-01

    Henoch-Schönlein purpura (HSP) is generally a self-limited vasculitis disease and has a good prognosis. We report a 4-year-old Thai boy who presented with palpable purpura, abdominal colicky pain, seizure, and eventually developed intestinal ischemia and perforation despite adequate treatment, including corticosteroid and intravenous immunoglobulin therapy. Imaging modalities, including ultrasonography and contrast-enhanced computed tomography, could not detect intestinal ischemia prior to perforation. In this patient, we also postulated that vasculitis-induced mucosal ischemia was a cause of the ulcer, leading to intestinal perforation, and high-dose corticosteroid could have been a contributing factor since the histopathology revealed depletion of lymphoid follicles. Intestinal perforation in HSP is rare, but life-threatening. Close monitoring and thorough clinical evaluation are essential to detect bowel ischemia before perforation, particularly in HSP patients who have hematochezia, persistent localized abdominal tenderness and guarding. In highly suspicious cases, exploratory laparotomy may be needed for the definite diagnosis and prevention of further complications. PMID:27468201

  4. Multicentric Castleman's disease associated with IgA vasculitis (Henoch-Schönlein purpura) responding well to tocilizumab: a case report.

    PubMed

    Oshima, Yoichi; Hoshino, Junichi; Suwabe, Tatsuya; Hayami, Noriko; Yamanouchi, Masayuki; Sekine, Akinari; Ueno, Toshiharu; Mizuno, Hiroki; Yabuuchi, Junko; Imafuku, Aya; Kawada, Masahiro; Hiramatsu, Rikako; Hasegawa, Eiko; Sawa, Naoki; Takaichi, Kenmei; Hayashi, Nobukazu; Fujii, Takeshi; Ubara, Yoshifumi

    2017-03-01

    A 41-year-old man was referred to our hospital for the evaluation of hypergammaglobulinemia (IgG 2898 mg/dL and IgA 587 mg/dL), inflammation (CRP 6.7 mg/dL and serum interleukin-6 (IL-6) 15.1 ng/L), and anemia (Hb 10.9 mg/dL). Castleman's disease (CD) was diagnosed by axillary lymph node biopsy. Five months later, painful purpura (multiple palpable 5 mm lesions) developed on his legs, gradually spreading to the upper limbs, thighs, and trunk, accompanied by arthralgia of the wrists, ankles, and knees. Skin biopsy revealed leukocytoclastic vasculitis with IgA deposits in dermal vessels. Accordingly, IgA vasculitis (Henoch-Schönlein purpura) was diagnosed. Tocilizumab (an anti-IL-6 receptor antibody) was administered intravenously at 8 mg/kg and treatment was repeated at monthly intervals. His purpura and clinical findings specific to CD improved rapidly. CD is well known to cause various skin lesions. The findings in this case indicate that overproduction of IL-6 contributes to IgA vasculitis (Henoch-Schönlein purpura) as well as to the pathogenesis of CD.

  5. Risk Factors Associated with Renal Involvement in Childhood Henoch-Schönlein Purpura: A Meta-Analysis

    PubMed Central

    Chan, Han; Tang, Yan-Ling; Lv, Xiao-Hang; Zhang, Gao-Fu; Wang, Mo; Yang, Hai-Ping; Li, Qiu

    2016-01-01

    Background and objective Henoch-Schönlein purpura (HSP) is an important cause of chronic kidney disease in children. This meta-analysis identified risk factors associated with renal involvement in childhood HSP. Methods PubMed, Embase, and Web of Science were searched. The quality of all eligible studies was assessed using the Newcastle-Ottawa scale criteria. An analysis of possible risk factors was conducted to report the odds ratio (OR) and weighted mean difference (WMD). Results Thirteen studies (2398 children) revealed 20 possible and 13 significant risk factors associated with renal involvement in HSP, with the following meta-analysis estimates of OR and WMD, with 95% confidence intervals: older age (0.90, 0.61–1.19); age > 10 y (3.13, 1.39–7.07); male gender (1.36, 1.07–1.74); abdominal pain (1.94,1.24–3.04); gastrointestinal bleeding (1.86, 1.30–2.65); severe bowel angina (3.38, 1.17–9.80); persistent purpura (4.02, 1.22–13.25); relapse (4.70, 2.42–9.14); WBC > 15 × 109/L (2.42, 1.39–4.22); platelets > 500 × 109/L (2.98, 1.22–7.25); elevated antistreptolysin O (ASO) (2.17, 1.29–3.64); and decreased complement component 3 (C3) (3.13, 1.62–6.05). Factors not significantly associated with renal involvement were: blood pressure; orchitis; elevated C-reactive protein; elevated erythrocyte sedimentation rate (ESR); and elevated serum IgA/IgE or IgG. Arthritis/arthralgia may be a risk factor according to the criteria of the American College of Rheumatology (1.41, 1.01–1.96). Conclusion The following are associated with renal involvement in pediatric HSP: male gender; > 10 y old; severe gastrointestinal symptoms (abdominal pain, gastrointestinal bleeding, and severe bowel angina); arthritis/arthralgia; persistent purpura or relapse; WBC > 15 × 109/L; platelets > 500 × 109/L; elevated ASO; and low C3. Relevant clinical interventions for these risk factors may exert positive effects on the prevention of kidney disease during the early

  6. Thrombocytopenic coagulopathy (Kasabach-Merritt phenomenon) is associated with Kaposiform hemangioendothelioma and not with common infantile hemangioma.

    PubMed

    Sarkar, M; Mulliken, J B; Kozakewich, H P; Robertson, R L; Burrows, P E

    1997-11-01

    Children with a large vascular tumor and associated Kasabach-Merritt coagulopathy respond inconsistently to therapy and have a high mortality rate. For this reason, we undertook a retrospective study of 21 such patients, and focused on clinical, radiographic, and histopathologic features. The male to female ratio was 1:1.6. Tumor was noted at birth in 50 percent of patients; the remainder appeared throughout infancy. The location was cervicofacial (n = 2), shoulder/upper limb (n = 4), trunk including retroperitoneum (n = 11), and lower limb (n = 4). These tumors grew rapidly to large size and were characterized by cutaneous purpura, edema, and an advancing ecchymotic margin. In contrast to common hemangioma, magnetic resonance imaging showed diffuse enhancement with ill-defined margins, cutaneous thickening, stranding of subcutaneous fat, hemosiderin deposits, and small feeding and draining vessels. All tumors were Kaposiform hemangioendothelioma (KHE); none were infantile hemangioma. Light microscopy showed irregular lobules or sheets of poorly formed, small vascular channels infiltrating and entrapping normal tissues. Characteristic features included spindle-shaped endothelial cells, diminished pericytes and mast cells, microthrombi, and hemosiderin deposits. Wide endothelial intercellular gaps and incomplete basement membranes were seen by electron microscopy. Dilated, hyperplastic, lymphaticoid channels were prominent in one tumor. KHE in 14 infants was treated with interferon alpha-2a: 6 had accelerated regression; 2 had stabilization of growth; and 6 evidenced no response. The mortality rate was 24 percent (5 of 21); this included three infants with retroperitoneal KHE. Kasabach-Merritt phenomenon does not occur with common hemangioma. Rather it is associated with the more aggressive KHE and rarely with other vascular neoplasms. Variable response to current pharmacologic therapy underscores our inadequate knowledge of the pathogenesis of thrombocytopenia in

  7. Joint effusions and purpura in multiply-transfused adult beta-thalassemia- clinical pointers to diagnosis of scurvy.

    PubMed

    Prakash, A; Pandey, A K

    2013-01-01

    Periodic transfusions and effective chelation have ensured that thalassemics survive in to adulthood but their life is punctuated by peculiar problems in adulthood. Three cases of scurvy are being reported presenting uniquely as purpura, right hip joint effusion and right knee joint effusion with haemorrhage in prepatellar and retropatellar bursae, respectively over an 18 month period (2009-2010). The first two cases did give a history of gum bleed. None had any coagulation disturbance or transfusion-transmitted infections or connective tissue disorder. All the three cases responded dramatically to vitamin C supplementation. It is imperative to keep in mind that recurrent blood transfusions are associated with a state of subclinical vitamin C deficiency and overt scurvy may manifest as cumulative number of transfusions increase, as in adult thalassemics.

  8. Clinical features and outcomes of diffuse endocapillary proliferation Henoch-Schönlein purpura nephritis in children

    PubMed Central

    Fu, Haidong; Mao, Jianhua; Xu, Yanping; Gu, Weizhong; Zhu, Xiujuan; Liu, Aimin

    2016-01-01

    OBJECTIVE: To investigate the outcomes of childhood diffuse endocapillary proliferation Henoch-Schönlein purpura nephritis (DEP-HSPN) in response to early diagnosis and prompt treatment. METHODS: Eleven cases of DEP-HSPN in children were investigated in comparison to HSPN without diffuse endocapillary proliferation (non-DEP-HSPN). RESULTS: DEP-HSPN had a higher prevalence of nephrotic syndrome but a lower prevalence of hematuria compared to non-DEP-HSPN. IgA, IgG and IgM antibody deposition was found in DEP-HSPN by histopathological examination. Proteinuria cleared in all 11 cases through treatment with steroids and/or immunosuppressive drugs. However, half of the DEP-HSPN patients continuously had hematuria after treatment. CONCLUSION: The early diagnosis and prompt initiation of immunosuppressive treatment based on renal biopsy are important for achieving favorable outcomes. PMID:27652838

  9. A case of isotretinoin-induced purpura annularis telangiectodes of Majocchi and review of substance-induced pigmented purpuric dermatosis.

    PubMed

    Kaplan, Rachel; Meehan, Shane A; Leger, Marie

    2014-02-01

    IMPORTANCE Medications as well as chemical and food exposures have been causally linked to the development of pigmented purpuric dermatosis (PPD). We describe herein what is to our knowledge the first reported case of isotretinoin-induced PPD. OBSERVATIONS A woman in her 30s presented with purpura annularis telangiectodes of Majocchi on the lower extremities 2 months after initiating isotretinoin for the treatment of refractory nodulocystic acne. CONCLUSIONS AND RELEVANCE We believe isotretinoin was the most likely causative agent in this case because the lesions began after initiation of isotretinoin treatment and resolved shortly after its termination, and the pathologic findings were consistent with other described cases of drug-induced PPD. The lesions have continued to fade, and no new lesions have developed in a 3-month follow-up period. Drug-induced PPD is distinct from idiopathic PPD, and it is important to consider isotretinoin as a potential inciting agent.

  10. A novel mutation c.1048A>T at codon 350(Lys>Stop) in PROC gene causing neonatal purpura fulminans.

    PubMed

    Jain, Rakhi; T, Leenath; Chandran, Jolly; Jayandharan, Giridhara R; Palle, Arpana; Moses, Prabhakar D

    2013-12-01

    Purpura fulminans in the neonatal period due to severe congenital protein C deficiency (protein C activity <1 IU/dl) is a rare autosomal recessive disorder. If untreated, it is fatal. Early identification of such patients may be lifesaving. Acquired deficiency of protein C caused by increased consumption as overt disseminated intravascular coagulation (DIC) and severe infection creates a diagnostic dilemma. Mutation analysis plays a critical role in confirming the diagnosis of the disease and offering prenatal diagnosis. In this report, we describe a newborn who presented with purpura fulminans and DIC, molecular analysis showed a novel c.1048A>T transversion in a homozygous state at codon 350 (Lys>Stop) of protein C (PROC) gene. Prenatal diagnosis in subsequent pregnancy was done which revealed the affected fetus had the same mutation in homozygous form.

  11. Immunoreactions involving platelets. III. Quantitative aspects of platelet agglutination, inhibition of clot retraction, and other reactions caused by the antibody of quinidine purpura.

    PubMed

    SHULMAN, N R

    1958-05-01

    Quantitative aspects of platelet agglutination and inhibition of clot retraction by the antibody of quinidine purpura were described. The reactions appeared to depend on formation of types of antibody-quinidine-platelet complexes which could fix complement but complement was not necessary for these reactions. Complement fixation was at least 10 times more sensitive than platelet agglutination or inhibition of clot retraction for measurement and detection of antibody activity. Although it has been considered that antibodies of drug purpura act as platelet lysins in the presence of complement and that direct lysis of platelets accounts for development of thrombocytopenia in drug purpura, the present study suggests that attachment of antibody produces a change in platelets which is manifested in vitro only by increased susceptibility to non-specific factors which can alter the stability of platelets in the absence of antibody. The attachment of antibody to platelets in vivo may only indirectly affect platelet survival. In contrast to human platelets, dog, rabbit, and guinea pig platelets, and normal or trypsin-treated human red cells did not agglutinate, fix complement, or adsorb antibody; and intact human endothelial cells did not fix complement or adsorb antibody. Rhesus monkey platelets were not agglutinated by the antibody but did adsorb antibody and fix complement although their activity in these reactions differed quantitatively from that of human platelets. Cinchonine could be substituted for quinidine in agglutination and inhibition of clot retraction reactions but quinine and cinchonidine could not. Attempts to cause passive anaphylaxis in guinea pigs with the antibody of quinidine purpura were not successful.

  12. The accuracy of platelet counting in thrombocytopenic blood samples distributed by the UK National External Quality Assessment Scheme for General Haematology.

    PubMed

    De la Salle, Barbara J; McTaggart, Paul N; Briggs, Carol; Harrison, Paul; Doré, Caroline J; Longair, Ian; Machin, Samuel J; Hyde, Keith

    2012-01-01

    A knowledge of the limitations of automated platelet counting is essential for the effective care of thrombocytopenic patients and management of platelet stocks for transfusion. For this study, 29 external quality assessment specimen pools with platelet counts between 5 and 64 × 10(9)/L were distributed to more than 1,100 users of 23 different hematology analyzer models. The same specimen pools were analyzed by the international reference method (IRM) for platelet counting at 3 reference centers. The IRM values were on average lower than the all-methods median values returned by the automated analyzers. The majority (~67%) of the automated analyzer results overestimated the platelet count compared with the IRM, with significant differences in 16.5% of cases. Performance differed between analyzer models. The observed differences may depend in part on the nature of the survey material and analyzer technology, but the findings have implications for the interpretation of platelet counts at levels of clinical decision making.

  13. Targeting reservoirs to control human infections – a one health approach

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Shiga toxin producing Escherichia coli (STEC) cause hemorrhagic colitis and potentially fatal extraintestinal sequelae, such as the hemolytic uremic syndrome and thrombotic thrombocytopenic purpura, in humans. Currently, treatment of human STEC disease is only symptomatic and supportive. Antibioti...

  14. [Immune thrombocytopenia and HIV-1 infection. Response to splenectomy].

    PubMed

    Planells Roig, M V; Pallas Regueria, J A; Carbonell Tatay, F; Sancho Fornos, S

    1990-03-01

    We present a case of thrombocytopenic purpura associated to acquired immunodeficiency; this disease is very infrequently associated to AIDS; the clinical characteristics are similar to the classical Idiopathic Thrombocytopenic Purpura, including the response to splenectomy. We discuss the therapeutic approach of this condition and review the literature, adding this new case of a patient with AIDS, Walter and Reed's stage II, who responded to splenectomy.

  15. Adhesion of Neisseria meningitidis to Dermal Vessels Leads to Local Vascular Damage and Purpura in a Humanized Mouse Model

    PubMed Central

    Melican, Keira; Michea Veloso, Paula; Martin, Tiffany; Bruneval, Patrick; Duménil, Guillaume

    2013-01-01

    Septic shock caused by Neisseria meningitidis is typically rapidly evolving and often fatal despite antibiotic therapy. Further understanding of the mechanisms underlying the disease is necessary to reduce fatality rates. Postmortem samples from the characteristic purpuric rashes of the infection show bacterial aggregates in close association with microvessel endothelium but the species specificity of N. meningitidis has previously hindered the development of an in vivo model to study the role of adhesion on disease progression. Here we introduced human dermal microvessels into SCID/Beige mice by xenografting human skin. Bacteria injected intravenously exclusively associated with the human vessel endothelium in the skin graft. Infection was accompanied by a potent inflammatory response with the secretion of human inflammatory cytokines and recruitment of inflammatory cells. Importantly, infection also led to local vascular damage with hemostasis, thrombosis, vascular leakage and finally purpura in the grafted skin, replicating the clinical presentation for the first time in an animal model. The adhesive properties of the type IV pili of N. meningitidis were found to be the main mediator of association with the dermal microvessels in vivo. Bacterial mutants with altered type IV pili function also did not trigger inflammation or lead to vascular damage. This work demonstrates that local type IV pili mediated adhesion of N. meningitidis to the vascular wall, as opposed to circulating bacteria, determines vascular dysfunction in meningococcemia. PMID:23359320

  16. Antigenic complementarity in the origins of autoimmunity: a general theory illustrated with a case study of idiopathic thrombocytopenia purpura.

    PubMed

    Root-Bernstein, Robert; Couturier, Jacob

    2006-03-01

    We describe a novel, testable theory of autoimmunity, outline novel predictions made by the theory, and illustrate its application to unravelling the possible causes of idiopathic thrombocytopenia purpura (ITP). Pairs of stereochemically complementary antigens induce complementary immune responses (antibody or T-cell) that create loss of regulation and civil war within the immune system itself. Antibodies attack antibodies creating circulating immune complexes; T-cells attack T-cells creating perivascular cuffing. This immunological civil war abrogates the self-nonself distinction. If at least one of the complementary antigens mimics a self antigen, then this unregulated immune response will target host tissues as well. Data demonstrating that complementary antigens are found in some animal models of autoimmunity and may be present in various human diseases, especially ITP, are reviewed. Specific mechanisms for preventing autoimmunity or suppressing existing autoimmunity are derived from the theory, and critical tests proposed. Finally, we argue that Koch's postulates are inadequate for establishing disease causation for multiple-antigen diseases and discuss the possibility that current research has failed to elucidate the causes of human autoimmune diseases because we are using the wrong criteria.

  17. Autoimmune progesterone dermatitis: Case report with history of urticaria, petechiae and palpable pinpoint purpura triggered by medical abortion.

    PubMed

    Mbonile, Lumuli

    2016-03-17

    Autoimmune progesterone dermatitis (APD) is a rare autoimmune response to raised endogenous progesterone levels that occur during the luteal phase of the menstrual cycle. Cutaneous, mucosal lesions and other systemic manifestations develop cyclically during the luteal phase of the menstrual cycle when progesterone levels are elevated. APD symptoms usually start 3 - 10 days before menstruation and resolve 1 - 2 days after menstruation ceases. A 30-year-old woman presented with urticaria, petechiae and palpable pinpoint purpura lesions of the legs, forearms, neck and buttocks 1 week prior to her menses starting and 2 months after a medical abortion. She was diagnosed with allergic contact dermatitis and topical steroids were prescribed. Her skin conditions did not improve and were associated with her menstrual cycle. We performed an intradermal test using progesterone, which was positive. She was treated with oral contraceptive pills and the symptoms were resolved. This is a typical case of APD triggered by increased sensitivity to endogenous progesterone induced a few months after medical abortion.

  18. Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura

    PubMed Central

    Root-Bernstein, Robert; Couturier, Jacob

    2006-01-01

    We describe a novel, testable theory of autoimmunity, outline novel predictions made by the theory, and illustrate its application to unravelling the possible causes of idiopathic thrombocytopenia purpura (ITP). Pairs of stereochemically complementary antigens induce complementary immune responses (antibody or T-cell) that create loss of regulation and civil war within the immune system itself. Antibodies attack antibodies creating circulating immune complexes; T-cells attack T-cells creating perivascular cuffing. This immunological civil war abrogates the self-nonself distinction. If at least one of the complementary antigens mimics a self antigen, then this unregulated immune response will target host tissues as well. Data demonstrating that complementary antigens are found in some animal models of autoimmunity and may be present in various human diseases, especially ITP, are reviewed. Specific mechanisms for preventing autoimmunity or suppressing existing autoimmunity are derived from the theory, and critical tests proposed. Finally, we argue that Koch's postulates are inadequate for establishing disease causation for multiple-antigen diseases and discuss the possibility that current research has failed to elucidate the causes of human autoimmune diseases because we are using the wrong criteria. PMID:16603444

  19. Guidelines on the use of intravenous immune globulin for hematologic conditions.

    PubMed

    Anderson, David; Ali, Kaiser; Blanchette, Victor; Brouwers, Melissa; Couban, Stephen; Radmoor, Paula; Huebsch, Lothar; Hume, Heather; McLeod, Anne; Meyer, Ralph; Moltzan, Catherine; Nahirniak, Susan; Nantel, Stephen; Pineo, Graham; Rock, Gail

    2007-04-01

    Canada's per capita use of intravenous immune globulin (IVIG) grew by approximately 115% between 1998 and 2006, making Canada one of the world's highest per capita users of IVIG. It is believed that most of this growth is attributable to off-label usage. To help ensure IVIG use is in keeping with an evidence-based approach to the practice of medicine, the National Advisory Committee on Blood and Blood Products of Canada (NAC) and Canadian Blood Services convened a panel of national experts to develop an evidence-based practice guideline on the use of IVIG for hematologic conditions. The mandate of the expert panel was to review evidence regarding use of IVIG for 18 hematologic conditions and formulate recommendations on IVIG use for each. A panel of 13 clinical experts and 1 expert in practice guideline development met to review the evidence and reach consensus on the recommendations for the use of IVIG. The primary sources used by the panel were 3 recent evidence-based reviews. Recommendations were based on interpretation of the available evidence and where evidence was lacking, consensus of expert clinical opinion. A draft of the practice guideline was circulated to hematologists in Canada for feedback. The results of this process were reviewed by the expert panel, and modifications to the draft guideline were made where appropriate. This practice guideline will provide the NAC with a basis for making recommendations to provincial and territorial health ministries regarding IVIG use management. Specific recommendations for routine use of IVIG were made for 7 conditions including acquired red cell aplasia; acquired hypogammaglobulinemia (secondary to malignancy); fetal-neonatal alloimmune thrombocytopenia; hemolytic disease of the newborn; HIV-associated thrombocytopenia; idiopathic thrombocytopenic purpura; and posttransfusion purpura. Intravenous immune globulin was not recommended for use, except under certain life-threatening circumstances, for 8 conditions

  20. Using the Oxford classification of IgA nephropathy to predict long-term outcomes of Henoch-Schönlein purpura nephritis in adults.

    PubMed

    Kim, Chan Ho; Lim, Beom Jin; Bae, Yoon Sung; Kwon, Young Eun; Kim, Yung Ly; Nam, Ki Heon; Park, Kyoung Sook; An, Seong Yeong; Koo, Hyang Mo; Doh, Fa Mee; Lee, Mi Jung; Oh, Hyung Jung; Yoo, Tae-Hyun; Kang, Shin-Wook; Choi, Kyu Hun; Jeong, Hyun Joo; Han, Seung Hyeok

    2014-07-01

    Recently, there has been emerging concern that crescents, the main histologic feature of Henoch-Schönlein purpura nephritis, merely reflect active inflammation, and may not be useful in predicting long-term outcomes. We therefore conducted a single-center retrospective study to evaluate whether the new Oxford classification of immunoglobulin A nephropathy can be used to predict long-term outcome in patients with Henoch-Schönlein purpura nephritis. We included 61 biopsy-proven patients with Henoch-Schönlein purpura nephritis between January 1991 and August 2010. In addition to the International Study of Kidney Disease in Children classification, pathologic findings were also evaluated by the Oxford classification. Primary outcomes were defined as either the onset of estimated glomerular filtration rate <60 ml/min per 1.73 m(2) with ≥30% decrease in estimated glomerular filtration rate from baseline or end-stage renal disease. During a median follow-up of 49.3 months, 13 (21%) patients reached the primary end point. A Kaplan-Meier plot showed that renal event-free survival was significantly longer in patients with <50% crescents than in those with crescents in ≥50% of glomeruli (P=0.003). Among the components of the Oxford classification, patients with endocapillary hypercellularity (E1; P=0.016) and tubular atrophy/interstitial fibrosis (T1/T2; P=0.018) had lower renal survival rates than those with E0 and T0. In a multivariate Cox model adjusted for clinical and pathologic factors, E1 (hazard ratio=8.91; 95% confidence interval=1.47-53.88; P=0.017) and T1/T2 (hazard ratio=8.74; 95% confidence interval=1.40-54.38; P=0.020) were independently associated with reaching a primary outcome, whereas the extent of crescentic lesions was not. Our findings suggest that the Oxford classification can be used in predicting long-term outcomes of Henoch-Schönlein purpura nephritis.

  1. Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases

    ClinicalTrials.gov

    2005-06-23

    Purpura, Schoenlein-Henoch; Graft Versus Host Disease; Anemia, Hemolytic, Autoimmune; Rheumatoid Arthritis; Churg-Strauss Syndrome; Hypersensitivity Vasculitis; Wegener's Granulomatosis; Systemic Lupus Erythematosus; Giant Cell Arteritis; Pure Red Cell Aplasia; Juvenile Rheumatoid Arthritis; Polyarteritis Nodosa; Autoimmune Thrombocytopenic Purpura; Takayasu Arteritis

  2. Henoch-Schönlein Purpura Presenting as Severe Gastrointestinal and Renal Involvement with Mixed Outcomes in an Adult Patient

    PubMed Central

    Shah, Raj; Vollmar, Alexis; Harrell, Amanda; Van Trump, Richard; Masoud, Amgad

    2017-01-01

    Henoch-Schönlein purpura (HSP) is typically seen as a self-limiting disease in children, but can present more severely in adults, especially when there is renal involvement. Management of HSP in adults also remains a controversial topic with very few studies evaluating available therapies. In this case, HSP presenting as a combination of severe gastrointestinal involvement and a rapid decline in renal function in an adult patient directed our therapy. The patient was a 48-year-old Caucasian male with no known past medical history, who presented with a combination of purpuric rash over the lower extremities, severe abdominal pain with upper gastrointestinal bleeding and a rapidly increasing serum creatinine, with hematuria. He initially underwent a skin biopsy, along with investigation for other possible causes, including autoimmune and infectious etiologies, which were negative. He was started on therapy for presumed HSP with intravenous methylprednisolone. The skin biopsy, however, was not conclusive, and the patient had no improvement in his clinical status. He then underwent a kidney biopsy that was consistent with HSP nephritis (immunoglobulin A (IgA) predominant glomerulonephritis with crescents), and esophagogastroduodenoscopy (EGD) that showed mucosal inflammation, ulcerations, and stigmata of bleeding—findings that were consistent with ischemia. Cyclophosphamide was added to the regimen at this time. However, he had worsening abdominal pain, continued gastrointestinal bleeding, now with hematochezia, and also worsening renal function that required dialysis. Plasmapheresis was then initiated on days alternating with dialysis. This resulted in the improvement of his gastrointestinal symptoms, but no recovery was seen of his renal function, and the patient required outpatient dialysis. This case report exhibits the unique presentation of severe gastrointestinal (GI) manifestations and rapid progression to renal failure in an adult patient with partial

  3. Abnormal urinalysis on day 7 in patients with IgA vasculitis (Henoch–Schönlein purpura)

    PubMed Central

    Kawashima, Nozomu; Kawada, Jun-ichi; Nishikado, Yuichi; Kitase, Yuma; Ito, Sanae; Muramatsu, Hideki; Sato, Yoshiaki; Kato, Taichi; Natsume, Jun; Kojima, Seiji

    2016-01-01

    ABSTRACT Rare progression to renal failure imposes a burden on children with IgA vasculitis (Henoch–Schönlein purpura, HSP). An abnormal urinalysis on day 7 (7d-UA) may be a surrogate marker for persistent nephritis, but this has not been established. We retrospectively analyzed the risk factors for persistent nephritis in a cohort of 138 children. Of 35 children with abnormal 7d-UA, 24 (69%) had an abnormal urinalysis 6 months after the diagnosis of HSP, which was significantly more than 6 of 103 children (6%) with normal 7d-UA (P < 0.0001). The negative predictive values for normal urinalysis and negative proteinuria 6 months after diagnosis were 0.94 (95% confidence interval [CI], 0.90–0.97) and 0.98 (95% CI, 0.95–0.99), respectively. When children with abnormal urinalysis 6 months after diagnosis were compared with those without, the following factors were significantly associated: age at diagnosis, abnormal urinalysis at diagnosis, abnormal 7d-UA, complement C3, steroid treatment, and presence of abdominal pain. However, multivariate analysis revealed that abnormal 7d-UA was the only significant risk factor for abnormal urinalysis 6 months after diagnosis (odds ratio 54.3, 95% CI 15.3–275, P = 1.89 × 10−6). Abnormal 7d-UA may be an independent risk factor for persistent nephritis, but this should be confirmed in a prospective study. PMID:28008191

  4. Similar disturbances in B cell activity and regulatory T cell function in Henoch-Schonlein purpura and systemic lupus erythematosus

    SciTech Connect

    Beale, M.G.; Nash, G.S.; Bertovich, M.J.; MacDermott, R.P.

    1982-01-01

    The immunoglobulin synthesizing activities of peripheral mononuclear cells (MNC) from five patients with Henoch-Schonlein purpura (HSP) and eight patients with active systemic lupus erythematosus (SLE) were compared. Cumulative amounts of IgM, IgG, and IgA synthesized and secreted by unstimulated and PWM-stimulated patient cells over a 12-day period were determied in a solid-phase radioimmunoassay. In unstimulated control cultures mean rates of IgM, IgG, and IgA synthesis were less than 250 ng/ml. The synthetic activities of patient MNC were markedly increased. In HSP cultures IgA was the major immunoglobulin class produced (2810 x/divide 1.33 ng/ml) followed by IgG (1754 x/divide 1.32 ng/ml) and IgM (404 x/divide 1.16 ng/ml). In SLE cultures IgA and IgG syntheses were equally elevated (4427 x/divide 1.20 and 4438 x/divide 1.49 ng/ml, respectively) whereas IgM synthesis averaged 967 x/divide 1.66 ng/ml. PWM stimulation of pateient MNC caused a sharp decline in the synthesis of all three immunoglobulin classes. After T cell depletion B cell-enriched fractions from HSP and SLE patients maintained high levels of IgA and IgG synthesis that were inhibited by PWM and by normal allogeneic but not autologous T cells. In PWM-stimulted co-cultures, patient T cells nonspecifically suppressed the synthetic activities of autologous and control B cells. in contrast patient B cells achieved normal levels of immunoglobulin synthesis when cultured with control T cells plus PWM. In longitudinal studies patient B and T cell disturbances persisted despite clinical improvement.

  5. Hematologic Complications of Pregnancy

    PubMed Central

    Townsley, Danielle M.

    2013-01-01

    Pregnancy induces a number of physiologic changes that affect the hematologic indices, either directly or indirectly. Recognizing and treating hematologic disorders that occur during pregnancy is difficult owing to the paucity of evidence available to guide consultants. This paper specifically reviews the diagnosis and management of benign hematologic disorders occurring during pregnancy. Anemia secondary to iron deficiency is the most frequent hematologic complication and is easily treated with oral iron formulations,; however care must be taken not to miss other causes of anemia, such as sickle cell disease. Thrombocytopenia is also a common reason for consulting the hematologist and distinguishing gestational thrombocytopenia from immune thrombocytopenia (ITP), preeclampsia, HELLP syndrome, or thrombotic thrombocytopenic purpura (TTP) is essential since the treatment differs widely. Occasionally the management of mother and infant involves the expeditious recognition of neonatal alloimmune thrombocytopenia (NAIT), a condition that is responsible for severe life-threatening bleeding of the newborn. Additionally, inherited and acquired bleeding disorders affect pregnant women disproportionately and often require careful monitoring of coagulation parameters in order to prevent bleeding in the puerperium. Finally, venous thromboembolism (VTE) during pregnancy is still largely responsible for mortality during pregnancy and the diagnosis, treatment options and guidelines for prevention of VTE during pregnancy are explored. PMID:23953339

  6. Review of fetal and neonatal immune cytopenias.

    PubMed

    Lewin, Sharon; Bussel, James B

    2015-01-01

    The fetoplacental interface plays a unique role in pathologies of the fetus and neonate, and is increasingly being recognized for effects on fetal and neonatal development that resonate into adulthood. In this review, we will use several exemplary disorders involving each of the 3 types of blood cells to explore the effect of perinatal insults on subsequent development of the affected cell line. We will present new data regarding outcomes of infants treated prenatally for fetal and neonatal alloimmune thrombocytopenia (FNAIT) and contrast these with outcomes of infants affected by hemolytic disease of the fetus and newborn. We also will explore the differences between FNAIT and passively transferred antibodies, as seen in maternal idiopathic thrombocytopenic purpura. Neonatal hemochromatosis is an example of a disease that previously was largely fatal, but whose newly discovered etiology as an immune-mediated perinatal disorder has resulted in development of highly effective treatment. Finally, we will examine the interplay between lymphopoiesis and the placenta in an effort to further explore the phenomenon of neutropenia in preeclampsia, whose etiology remains unknown.

  7. A Case of Henoch-Schonlein Purpura Associated with Rotavirus Infection in an Elderly Asian Male and Review of the Literature

    PubMed Central

    Tang, Chen; Scaramangas-Plumley, Daphne; Nast, Cynthia C.; Mosenifar, Zab; Edelstein, Marc A.; Weisman, Michael

    2017-01-01

    Patient: Male, 73 Final Diagnosis: Henoch-Schönlein purpura (HSP) Symptoms: Abdominal pain • bloating • blood in stool • nausea • vomiting Medication: — Clinical Procedure: EGD • colonoscopy • kidney biopsy • skin biopsy • arthrocentesis Specialty: Rheumatology Objective: Unknown ethiology Background: Henoch-Schönlein purpura (HSP), a small vessel vasculitis mediated by deposition of immune-complexes containing IgA in the skin, gut, and glomeruli, often presents with abdominal pain, purpuric rash in the lower extremities and buttocks, joint pain, and hematuria. The disease most commonly targets children but can affect adults who tend to have a worse prognosis. Case Report: We discuss a case of HSP in an elderly Chinese male who presented with severe proximal bowel inflammation, vasculitic rash, and proteinuria; he was found to have positive stool rotavirus and giardia. He improved significantly with high dose steroids. We believe rotavirus may have been a triggering event in this patient. A brief review of the literature is also presented. Conclusions: This is the first case report describing a classic presentation of HSP in an adult following a rotavirus infection. HSP can cause significant morbidity and mortality in adult patients predominantly from progressive renal failure; therefore careful management and monitoring is important. GI infections seem to be a common trigger for HSP and this case report suggests that rotavirus may be part of the spectrum. PMID:28174414

  8. A case of neonatal alloimmune thrombocytopenia in the presence of both anti-HPA-4b and anti-HPA-5b antibody: clinical and serological analysis of the subsequent pregnancy.

    PubMed

    Kiyokawa, Tomoko; Koh, Yangsook; Mimura, Kazuya; Nakayama, Kotarosumitomo; Hosokawa, Mika; Sakuragi, Mikiko; Morikawa, Tamayo; Nakao, Mayumi; Aochi, Hiroshi; Fukumori, Yasuo; Kanagawa, Takeshi; Nagamine, Keisuke; Kimura, Tadashi; Tomiyama, Yoshiaki

    2014-10-01

    Neonatal alloimmune thrombocytopenia (NAIT) is induced by maternal alloantibodies raised against fetal platelet antigens inherited from the paternal parent. In contrast to Caucasians, in Asians, predominantly in Japanese, most frequently detected antibodies in NAIT are anti-HPA-4b and anti-HPA-5b. In some NAIT cases multiple alloantibodies are detected. In such cases it is very difficult to determine which antibody is the dominant antibody in NAIT. In this case report, we describe a NAIT case (first sibling) with severe thrombocytopenia and cephalhematoma in the presence of both anti-HPA-4b and anti-HPA-5b antibodies in the maternal serum. We carefully examined titers of anti-HPA antibodies during the subsequent pregnancy with HPA-4b-positive and HPA-5b-negative fetus determined by amniocentesis at gestational week 16. We administered IVIG (1 g/kg/w) to the mother from gestational week 32 to 35. The mother subsequently delivered a second sibling with normal platelet count by cesarean section. Although we could not completely rule out the involvement of anti-HPA-4b, our findings suggested that anti-HPA-5b was implicated in the NAIT in the first sibling.

  9. Evaluation of TGF-β1 and MCP-1 expression and tubulointerstitial fibrosis in children with Henoch-Schönlein purpura nephritis and IgA nephropathy: A clinical correlation

    PubMed Central

    Shuiai, Zhao; Huijun, Shen; Weizhong, Gu; Aimin, Liu; Jianhua, Mao

    2017-01-01

    OBJECTIVES: Henoch-Schönlein purpura nephritis and immunoglobulin A nephropathy are two diseases with similar clinical presentations but very different prognoses. Transforming growth factor β1 and monocyte chemoattractant protein-1 have been associated with the development of tissue fibrosis. We examined the development of tubulointerstitial fibrosis and its relationship with Transforming growth factor β1 and monocyte chemoattractant protein-1 expression in these patients. METHODS: Renal tissue samples were collected by renal biopsy from 50 children with Henoch-Schönlein purpura nephritis and 50 children with immunoglobulin A nephropathy. Hematoxylin and eosin and Masson's trichrome-stained tissues were examined using light microscopy. Tubulointerstitial fibrosis was graded using the method described by Bohle et al. 1. The immunohistochemical detection of Transforming growth factor β1 and monocyte chemoattractant protein-1 expression was correlated with the tubulointerstitial fibrosis grade. Clinical Trial registration number: ZJCH-2012-0105. RESULTS: Transforming growth factor β1 and monocyte chemoattractant protein-1 expression in the renal tissues was significantly greater in the patients with immunoglobulin A nephropathy than in the patients with Henoch-Schönlein purpura nephritis (both p<0.001). The immunoglobulin A nephropathy patients had a higher tubulointerstitial fibrosis grade than the Henoch-Schönlein purpura nephritis patients (p<0.001). The tubulointerstitial fibrosis grade was in accordance with the Transforming growth factor β1 and monocyte chemoattractant protein-1 expression levels in both diseases (both p<0.001). CONCLUSION: Transforming growth factor β1 and monocyte chemoattractant protein-1 expression was associated with the development of immunoglobulin A nephropathy and Henoch-Schönlein purpura nephritis. Further studies are needed to better evaluate this association. PMID:28273242

  10. Inhibition of HPA-1a alloantibody-mediated platelet destruction by a deglycosylated anti-HPA-1a monoclonal antibody in mice: toward targeted treatment of fetal-alloimmune thrombocytopenia.

    PubMed

    Bakchoul, Tamam; Greinacher, Andreas; Sachs, Ulrich J; Krautwurst, Annika; Renz, Harald; Harb, Habi; Bein, Gregor; Newman, Peter J; Santoso, Sentot

    2013-07-18

    Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is often caused by maternal alloantibodies against the human platelet antigen (HPA)-1a, which opsonizes fetal platelets (PLTs). Subsequent PLT destruction is mediated via the Fc part of the alloantibodies. The monoclonal antibody (mAb) SZ21 binds to the HPA-1a epitope and inhibits the binding of maternal alloantibodies. However, it also promotes complement activation and phagocytosis. Deglycosylation of antibodies abrogates the Fc-related effector functions. We modified the N-glycan of SZ21 by endoglycosidase F. The in vivo transplacental transport of N-glycan-modified (NGM)-SZ21 was not impaired. When injected into pregnant mice, both native-SZ21 and NGM-SZ21 were transported equally into fetal circulation (8.9% vs 8.7%, respectively, P = .58). Neither the binding properties of NGM-SZ21 to HPA-1a in surface plasmon resonance, nor the inhibition of anti-HPA-1a-induced PLT phagocytosis, were affected by N-glycan modification. NGM-SZ21 prevented PLT destruction induced by maternal anti-HPA-1a antibodies in vivo in a mouse model (PLT clearance after 5 hours; 18% vs 62%, in the presence or absence of NGM-SZ21, respectively, P = .013). Deglycosylation of SZ21 abrogates Fc-effector functions without interfering with placental transport or the ability to block anti-HPA-1a binding. Humanized, deglycosylated anti-HPA-1a mAbs may represent a novel treatment strategy to prevent anti-HPA-1a-mediated PLT destruction in FNAIT.

  11. [Treatment of thoracic and abdominal cavity perforation complicated by Henoch-Schonlein purpura nephritis in a patient with high-voltage electric burn].

    PubMed

    Zhang, Wei; Xie, Wei-guo; Min, Wei-xiong; Wang, De-yun; Zhang, Jia; Wan, Shi-yong

    2013-10-01

    A 55-year-old male patient suffered from severe high-voltage electric burn with an area of 20%TBSA full-thickness injury. The injury involved the distal end of left upper limb, right trunk, and whole abdominal wall. Fracture of the 7th-10th ribs was found in the right side of chest, with perforation of abdominal cavity, and bilateral pleural effusion was found. Part of the small intestine was necrotic and exposed. At the early stage, xeno-acellular dermal matrix was grafted after debridement of abdominal wound; peritoneal lavage was performed; negative pressure drainage was performed in orificium fistula of intestine for promoting the adhesion between perforated intestine and abdominal scar. Two orificium fistulas formed after closure of abdominal granulation wound by autologous skin grafting. Eschar of chest wall and denatured ribs were retained. The risk of infection of thoracic cavity was decreased by promoting the adhesion between lung tissue and chest wall. During the treatment, the patient was diagnosed with Henoch-Schonlein purpura nephritis by renal biopsy, with the symptoms of purpura in the lower limbs, heavy proteinuria, severe hypoalbuminemia, edema, etc. After control of kidney damage by immunosuppressive treatment instead of glucocorticoid, alleviation of the levels of proteinuria and blood albumin, free latissimus dorsi myocutaneous flap was excised to repair chest wall, and free skin graft was excised to repair intestinal fistula. After all the wounds were successfully covered, the patient was treated with glucocorticoid combined with immunosuppressants for more than 1 year. The patient was followed up for 3 years, and his renal function was completely recovered with satisfactory clinical outcome.

  12. Henoch-Schonlein Purpura in Children Hospitalized at a Tertiary Hospital during 2004-2015 in Korea: Epidemiology and Clinical Management

    PubMed Central

    Lee, Yong Hee; Kim, Yu Bin; Koo, Ja Wook

    2016-01-01

    Purpose To investigate the epidemiology, clinical manifestations, investigations and management, and prognosis of patients with Henoch-Schonlein purpura (HSP). Methods We performed a retrospective review of 212 HSP patients under the age of 18 years who were admitted to Inje University Sanggye Paik Hospital between 2004 and 2015. Results The mean age of the HSP patients was 6.93 years, and the ratio of boys to girls was 1.23:1. HSP occurred most frequently in the winter (33.0%) and least frequently in the summer (11.3%). Palpable purpura spots were found in 208 patients (98.1%), and gastrointestinal (GI) and joint symptoms were observed in 159 (75.0%) and 148 (69.8%) patients, respectively. There were 57 patients (26.9%) with renal involvement and 10 patients (4.7%) with nephrotic syndrome. The incidence of renal involvement and nephrotic syndrome was significantly higher in patients with severe GI symptoms and in those over 7 years old. The majority of patients (88.7%) were treated with steroids. There was no significant difference in the incidence of renal involvement or nephrotic syndrome among patients receiving different doses of steroids. Conclusion In this study, the epidemiologic features of HSP in children were similar to those described in previous studies, but GI and joint symptoms manifested more frequently. It is essential to carefully monitor renal involvement and progression to chronic renal disease in patients ≥7 years old and in patients affected by severe GI symptoms. It can be assumed that there is no direct association between early doses of steroids and prognosis. PMID:27738599

  13. Progressive Pigmentary Purpura

    MedlinePlus

    ... Sections of the JAOCD JAOCD Archive Published Members Online Dermatology Journals Edit This Favorite Name: Category: Share: Yes ... About Tanning 4/24/2013 Sun Safety IQ Online Surveys ... Osteopathic Association. The AOCD now oversees 32 dermatology residency programs that are currently training 163 residents ...

  14. Human protein C concentrate in the treatment of purpura fulminans: a retrospective analysis of safety and outcome in 94 pediatric patients

    PubMed Central

    2010-01-01

    Introduction Purpura fulminans (PF) is a devastating complication of uncontrolled systemic inflammation, associated with high incidence of amputations, skin grafts and death. In this study, we aimed to clarify the clinical profile of pediatric patients with PF who improved with protein C (PC) treatment, explore treatment effects and safety, and to refine the prognostic significance of protein C plasma levels. Methods In Germany, patients receiving protein C concentrate (Ceprotin®, Baxter AG, Vienna, Austria) are registered. The database was used to locate all pediatric patients with PF treated with PC from 2002 to 2005 for this national, retrospective, multi-centered study. Results Complete datasets were acquired in 94 patients, treated in 46 centers with human, non-activated protein C concentrate for purpura fulminans. PC was given for 2 days (median, range 1-24 days) with a median daily dose of 100 IU/kg. Plasma protein C levels increased from a median of 27% to a median of 71% under treatment. 22.3% of patients died, 77.7% survived to discharge. Skin grafts were required in 9.6%, amputations in 5.3%. PF recovered or improved in 79.8%, remained unchanged in 13.8% and deteriorated in 6.4%. Four adverse events occurred in 3 patients, none classified as severe. Non-survivors had lower protein C plasma levels (P < 0.05) and higher prevalence of coagulopathy at admission (P < 0.01). Time between admission and start of PC substitution was longer in patients who died compared to survivors (P = 0.03). Conclusions This retrospective dataset shows that, compared to historic controls, only few pediatric patients with PF under PC substitution needed dermatoplasty and/or amputations. Apart from epistaxis, no bleeding was observed. Although the data comes from a retrospective study, the evidence we present suggests that PC had a beneficial impact on the need for dermatoplasty and amputations, pointing to the potential value of carrying out a prospective randomised controlled

  15. Elevated levels of antibodies against phosphatidylserine/prothrombin complex and/or cardiolipin associated with infection and recurrent purpura in a child: a forme fruste of antiphospholipid syndrome?

    PubMed

    Kinoshita, Yuri; Mayumi, Nobuko; Inaba, Motoyuki; Igarashi, Touru; Katagiri, Ichigen; Kawana, Seiji

    2015-07-15

    Antiphospholipid syndrome is an autoimmune disorder characterized by the occurrence of venous and arterial thrombosis, as well as morbidity in pregnancy, in the presence of anti-phospholipid antibodies. The diagnosis of antiphospholipid syndrome is usually established based on clinical and laboratory findings by strictly following the 2006 Sapporo classification. However, the diagnosis remains challenging owing to the ongoing debates on the serological criteria. We report a case we describe as forme fruste antiphospholipid syndrome in which these criteria were not fulfilled. Purpura appeared repeatedly in a female infant starting from the age of 6 months and following episodes of upper respiratory infections and vaccinations. The levels of anti-cardiolipin IgG antibodies and anti-phosphatidylserine/prothrombin complex antibodies were elevated in accordance with these events. Histopathological evaluation revealed multiple small vessel thrombi in the dermis and adipose tissue. After 2 weeks of treatment with aspirin and heparin, the cutaneous symptoms subsided. Infection has long been associated with antiphospholipid syndrome, and anti-phosphatidylserine/prothrombin antibodies are considered a new marker for the diagnosis of antiphospholipid syndrome. Forme fruste antiphospholipid syndrome should be considered even if the antiphospholipid syndrome diagnostic criteria are not completely fulfilled, especially in the presence of elevated levels of anti-phosphatidylserine/prothrombin antibodies and known preceding infections.

  16. Characterization of the complications associated with plasma exchange for thrombotic thrombocytopaenic purpura and related thrombotic microangiopathic anaemias: a single institution experience

    PubMed Central

    McGuckin, S; Westwood, J-P; Webster, H; Collier, D; Leverett, D; Scully, M

    2014-01-01

    Background Plasma exchange (PEX) is a life-saving therapeutic procedure in patients with thrombotic thrombocytopaenic purpura (TTP) and other thrombotic microangiopathic anaemias (TMAs). However, it may be associated with significant complications, exacerbating the morbidity and mortality in this patient group. Study Design and Methods We reviewed all PEX procedures over a 72-month period, following the exclusive introduction of solvent–detergent double viral-inactivated plasma in high-volume users, such as TTP, in the United Kingdom (UK). We documented allergic reactions to plasma, citrate reactions, complications relating to central venous access insertion and venous thrombotic events (VTE) in 155 patient episodes and >2000 PEX procedures. Results The overall complication rate was low. Allergic plasma reactions occurred in 6·45% of the cohort with only one episode of acute anaphylaxis. Similarly, VTEs were 6·45%, not significantly greater than in medical patients receiving thromboprophylaxis, despite added potential risk factors in TTP. Citrate reactions were the most frequent complication documented, but toxicity was significantly reduced by administration of further calcium infusions during the PEX procedure. There were no serious central line infections and no catheter thrombosis. Conclusion Our data confirms that PEX continues to be a life-saving procedure in the acute TTP setting and, the procedure was not associated with an increased mortality and limited morbidity. PMID:24117855

  17. Bacterial Infections, Alloimmunity, and Transplantation Tolerance

    PubMed Central

    Ahmed, Emily B.; Daniels, Melvin; Alegre, Maria-Luisa; Chong, Anita S.

    2010-01-01

    Transplantation of solid organs across histocompatibility barriers in the absence of immunosuppression is invariably followed by acute allograft rejection. Although several immunosuppressive regimens have been developed to prevent allograft rejection, these global immunosuppressive agents effectively inhibit all T cells leaving the host vulnerable to infections. Thus a major goal in transplantation immunology is to induce donor-specific tolerance that results in the extended suppression of allograft-specific immune responses, while leaving the remainder of the immune system competent to fight infections and malignancies. Initial successes in identifying approaches that successfully induce transplantation tolerance in experimental models have led to a newer research focus of identifying potential barriers to the induction of such tolerance as well as events that may reverse established allograft tolerance. Both clinical and experimental studies have identified bacterial infections as a possible trigger of allograft rejection. Recently, experimental models of transplantation tolerance have identified that bacterial signals can promote acute allograft rejection either by preventing the induction of transplantation tolerance or by reversing tolerance after it has been stably established. This review summarizes experimental and clinical literature supporting the hypothesis that bacterial infections and innate immunity can qualitatively and quantitatively alter adaptive alloreactivity through effects on innate immune responses. PMID:21126661

  18. Total lymphoid irradiation in alloimmunity and autoimmunity

    SciTech Connect

    Strober, S.

    1987-12-01

    Total lymphoid irradiation has been used as an immunosuppressive regimen in autoimmune disease and organ transplantation. The rationale for its use originated from studies of patients with Hodgkin disease, in whom this radiotherapy regimen was noted to induce profound and long-lasting immune suppression and yet was well tolerated, with few long-term side effects. Total lymphoid irradiation is a unique immunosuppressive regimen that produces a selective (and long-lasting) reduction in the number and function of helper T cells and certain subsets of B cells. Conventional immunosuppressive drugs show little selectivity, and their effects are short-lived. The most important aspect of total lymphoid irradiation is the potential for achieving transplantation tolerance and permanent remissions in autoimmune disease in laboratory animals. Attempts are being made to achieve similar goals in humans given total lymphoid irradiation, so that immunosuppressive drugs can be ultimately withdrawn from transplant recipients and patients with lupus nephritis. 28 references.

  19. Childhood Henoch-Schönlein purpura nephritis and IgA nephropathy: one disease entity?--A clinico-pathologically comparative study.

    PubMed

    Zhou, Jianhua; Huang, Aixia; Liu, Tonglin; Kuang, Yujiu

    2005-01-01

    In order to characterize their relationship through clinicopathological comparison between IgA nephropathy and Henoch-Schönlein purpura nephritis (HSPN), 31 children with IgA nephropathy aged between 3 to 15 years and 120 children with HSPN aged between 4 to 15 years were compared with each other in clinical manifestation, blood biochemistry, serum immunology and follow-up study. Renal pathological findings under light microscope, immunofluorescence and electronic microscope were analyzed and also compared between 31 children with IgA nephropathy and 32 biopsied children with HSPN. The results showed that the onset age was over 12 years in 25.8% children with IgA nephropathy, but only 10% in HSPN (P < 0.05). The clinical patterns of IgA nephropathy and HSPN were similar, but extra-renal manifestations were more often in HSPN, all of them had skin purpura, 59% had gastrointestinal symptoms and 47% suffered from arthralgia, compared with only abdominal pain in 3.2% children with IgA nephropathy. The renal pathological investigation showed global sclerosis in 35.5% of IgA nephropathy and 3.1% of HSPN, mesangial sclerosis in 41.9% of IgA nephropathy and 6.3% of HSPN, but endothelial proliferation in 65.6% of HSPN and 29% of IgA nephropathy (all P < 0.01). Thin basement membrane nephropathy was only found in 6.5% children with IgA nephropathy, no in HSPN. The electronic dense deposits in HSPN were sparse, loose and wildly spread in glomerular mesangium, subendothelial area and even intra basement membrane, but it was dense, lumpy and mostly limited in mesangium and paramesangium in IgA nephropathy. Predominant IgA deposits were found in 81.2% of HSPN, and overwhelming IgG deposits in 12.5% of HSPN with relatively weak IgA deposits, moreover 6.3% of HSPN showed linear IgG deposits in glomerular capillary. Totally 71.9% of HSPN had IgG deposits in glomeruli and only 19.4% of IgA nephropathy showed glomerular IgG deposits (P < 0.01). No IgG deposit was observed in 81

  20. Purpura thrombopénique amégacaryocytaire acquis: penser au lupus érythémateux systémique

    PubMed Central

    Ernestho-ghoud, Indretsy Mahavivola; Rahamefy, Odilon; Ranaivo, Irina Mamisoa; Andrianarison, Malalaniaina; Ramarozatovo, Lala Soavina; Rabenja, Fahafahantsoa Rapelanoro

    2015-01-01

    L'amegacaryocytose acquise est exceptionnellement décrite au cours d'un Lupus Erythémateux Systémique (LES) à Madagascar. Nous rapportons la première observation d'un Purpura Thrombopénique Amegacaryocytaire Acquis (PTAA) simulant un Purpura Thrombopénique Idiopathique (PTI) révélateur d'un LES. Il s'agissait d'une femme de 24 ans, sans antécédents particuliers. Elle présentait un syndrome hémorragique avec une thrombopénie à 10 000/mm3. Le diagnostic de PTI était retenu avant l'hospitalisation. Elle avait reçu une corticothérapie mais ceci n’était pas suivi d'amélioration. A l'unité de Dermatologie, elle se plaignait d'une baisse de l'acuité visuelle. Elle était en bon état général. On retrouvait une tachycardie à 110 bpm, un érythème malaire en verspertilio typique et une pâleur cutanéo-muqueuse. Une hémorragie oculaire bilatérale était objectivée à l'examen ophtalmologique. Les examens paracliniques montraient une thrombopénie à 31000/mm3, une anémie microcytaire à 48g/dL. Les examens immunologiques étaient non réalisés. Un LES avec atteinte cutanée et hématologique était retenu. Un bolus de corticothérapie était administrée associée à une transfusion sanguine. L’évolution était marquée par l'apparition d'un signe d'engagement cérébral faisant suspecter un neurolupus. Le scanner cérébral révélait une hémorragie cérébrale avec une hydrocéphalie aigue traitée par un inhibiteur de l'anhydrase carbonique mais le neurolupus n’était pas écarté. L'anémie disparaissait par contre la thrombopénie s'aggravait à 16000/mm3. Le médullogramme montrait l'absence des mégacaryocytes. L’évolution était favorable à huit mois de suivi après un relais per os de la corticothérapie par la dose de 1 mg/kg/j à dose dégressive à huit mois de suivi. Les atteintes neurologiques, ophtalmologiques et hématologiques étaient compatible avec le diagnostic d'un LES. La persistance d'une thrombopénie doit

  1. Is Dosing of Therapeutic Immunoglobulins Optimal? A Review of a Three-Decade Long Debate in Europe

    PubMed Central

    Kerr, Jacqueline; Quinti, Isabella; Eibl, Martha; Chapel, Helen; Späth, Peter J.; Sewell, W. A. Carrock; Salama, Abdulgabar; van Schaik, Ivo N.; Kuijpers, Taco W.; Peter, Hans-Hartmut

    2014-01-01

    The consumption of immunoglobulins (Ig) is increasing due to better recognition of antibody deficiencies, an aging population, and new indications. This review aims to examine the various dosing regimens and research developments in the established and in some of the relevant off-label indications in Europe. The background to the current regulatory settings in Europe is provided as a backdrop for the latest developments in primary and secondary immunodeficiencies and in immunomodulatory indications. In these heterogeneous areas, clinical trials encompassing different routes of administration, varying intervals, and infusion rates are paving the way toward more individualized therapy regimens. In primary antibody deficiencies, adjustments in dosing and intervals will depend on the clinical presentation, effective IgG trough levels and IgG metabolism. Ideally, individual pharmacokinetic profiles in conjunction with the clinical phenotype could lead to highly tailored treatment. In practice, incremental dosage increases are necessary to titrate the optimal dose for more severely ill patients. Higher intravenous doses in these patients also have beneficial immunomodulatory effects beyond mere IgG replacement. Better understanding of the pharmacokinetics of Ig therapy is leading to a move away from simplistic “per kg” dosing. Defective antibody production is common in many secondary immunodeficiencies irrespective of whether the causative factor was lymphoid malignancies (established indications), certain autoimmune disorders, immunosuppressive agents, or biologics. This antibody failure, as shown by test immunization, may be amenable to treatment with replacement Ig therapy. In certain immunomodulatory settings [e.g., idiopathic thrombocytopenic purpura (ITP)], selection of patients for Ig therapy may be enhanced by relevant biomarkers in order to exclude non-responders and thus obtain higher response rates. In this review, the developments in dosing of therapeutic

  2. PT-VWD posing diagnostic and therapeutic challenges - small case series.

    PubMed

    Sánchez-Luceros, Analía; Woods, Adriana I; Bermejo, Emilse; Shukla, Shilpa; Acharya, Suchitra; Lavin, Michelle; Rydz, Natalia; Othman, Maha

    2016-11-07

    Despite the increased worldwide awareness, over the last decade, of the platelet-type von Willebrand Disease (PT-VWD), many uncertainties remain around this rare platelet bleeding disorder. This report aims to correctly identify and study the phenotype of new patients and highlights the diagnostic and therapeutic challenges this disease remains to pose. We describe four PT-VWD cases confirmed by genetic analysis in which either the diagnosis and/or the treatment posed challenge. We provide the details of the clinical presentation, laboratory analysis, and the treatment and the responses in each case. We show that in addition to type 2B VWD, PT-VWD can be misdiagnosed as idiopathic thrombocytopenic purpura, neonatal alloimmune thrombocytopenia, and unexplained gestational thrombocytopenia. The disease can be diagnosed as early as 1 year of age and with phenotypically normal parents. Bleeding in some patients can be managed successfully using Humate P and DDAVP combined with tranexamic acid with no significant thrombocytopenia. We provide for the first time an evidence of an efficient response to rFVIIa in PT-VWD. Anaphylactic reaction to VWF preparations may be related to PT-VWD and the development of HLA antibodies is not uncommon. Progressive thrombocytopenia with normal VWF levels can be seen with PT-VWD and the platelet count was normalized at 2.5 weeks postpartum in one case. We conclude that these studies represent a record of clinical observations/interventions that help improve diagnoses/management of PT-VWD, highlight the variations in age and clinical presentations, laboratory diagnostic approaches, the importance of genetic testing for accurate diagnosis and consideration of therapeutic alternatives.

  3. Association between HLA-A and -B polymorphisms and susceptibility to Henoch-Schönlein purpura in Han and Mongolian children from Inner Mongolia.

    PubMed

    Ren, S M; Yang, G L; Liu, C Z; Zhang, C X; Shou, Q H; Yu, S F; Li, W C; Su, X L

    2012-02-03

    We examined a possible association between HLA-A and -B polymorphisms and susceptibility to Henoch-Schönlein purpura (HSP) in Han and Mongolian children in Inner Mongolia, through a case-control study. Two hundred and sixty-eight unrelated children were enrolled, including 56 Mongolian and 50 Han children with HSP, 66 healthy Mongolian and 96 healthy Han children as a control group. HLA-A and -B alleles were indentified by PCR-sequence-specific oligonucleotide analysis and were further analyzed by PCR-sequencing-based typing (SBT). Frequencies of HLA-A*11, HLA-B*15 in Mongolian patients and HLA-A*26, HLA-B*35, HLA-B*52 in Han patients were higher than those in the corresponding control group (P < 0.05), while frequencies of HLA-B*07 and -B*40 in Mongolian HSP patients were lower than those in the control group (P < 0.05). Further analysis using PCR-SBT showed that all HLA-A*11 were HLA-A*1101, and most HLA-B*15 were HLA-B*1501 in Mongolian HSP patients. All HLA-A*26 were HLA-A*2601 and HLA-B*35 were mostly HLA-B*3503 in Han patients. There were more Han patients with severe manifestations than Mongolian patients (P < 0.05). Frequencies of HLA-A*26, HLA-B*35 and HLA-B*52 in Han patients were higher than in Mongolian patients (P < 0.05). We conclude that HLA-A*11(*1101) and -B*15(*1501) are associated with susceptibility to HSP in Mongolian children and HLA-A*26(*2601), HLA-B*35(*3503) and HLA-B*52 are associated with susceptibility to HSP in Han children. HLA-B*07 and -B*40 may be protective genes in Mongolian children. The different frequencies of HLA-A and -B in Mongolian and Han children may be responsible for the different manifestations in these two ethnic groups.

  4. Effect of CD40/CD40L signaling on IL-10-producing regulatory B cells in Chinese children with Henoch-Schönlein purpura nephritis.

    PubMed

    Yang, Baohui; Tan, Xiongjun; Xiong, Xiao; Wu, Daoqi; Zhang, Gaofu; Wang, Mo; Dong, Shifang; Liu, Wei; Yang, Haiping; Li, Qiu

    2016-11-11

    The aim of the present study was to examine the role and mechanism of interleukin-10 (IL-10)-producing regulatory B cells (B10 cells) in the pathogenesis of Henoch-Schönlein purpura nephritis (HSPN). We examined the percentage of B10 cells, CD19(+)CD24(hi)CD38(hi) B cells, CD19(+)CD24(hi)CD27(+) B cells, Th17 cells, and T regulatory (Treg) cells within the peripheral blood mononuclear cell (PBMC) population in healthy subjects and HSP/HSPN patients. The percentage of B10 cells and CD19(+)CD24(hi)CD38(hi) B cells was reduced in HSPN patients and that of CD19(+)CD24(hi)CD27(+) B cells was decreased only in HSPN patients with hematuria and proteinuria or massive proteinuria. The expression of IL-10 by B10 cells and their subsets was decreased in HSPN patients and returned to normal levels in HSP/HSPN patients in remission. B10 cells and their subsets negatively correlated with the Th17/Treg ratio. There was no difference in B10pro + B10 cells, Th17 cells, Treg cells, and the Th17/Treg ratio between children with HSP/HSPN and healthy controls after CD40L stimulation. On the other hand, the level of IL-10 expressed by CD19(+)CD40(+) B cells was decreased in HSPN, and the percentage of B10pro + B10 cells and Treg cells was reduced and that of Th17 cell was increased in the presence of anti-CD40L monoclonal antibody (mAb). Thus, decreased B10 cells and CD19(+)CD24(hi)CD38(hi) B cells may function as an early marker of renal impairment in HSPN. The dysfunction of B10 cells may play a role in the pathogenesis of HSPN by regulating the Th17/Treg balance. Moreover, the CD40/CD40L signaling pathway may play a role in B10 cell differentiation and functional maturation.

  5. The Interaction between Circulating Complement Proteins and Cutaneous Microvascular Endothelial Cells in the Development of Childhood Henoch-Schönlein Purpura

    PubMed Central

    Yang, Yao-Hsu; Tsai, I-Jung; Chang, Chun-Jung; Chuang, Ya-Hui; Hsu, Hui-Yao; Chiang, Bor-Luen

    2015-01-01

    Objective In addition to IgA, the deposition of complement (C)3 in dermal vessels is commonly found in Henoch-Schönlein purpura (HSP). The aim of this study is to elucidate the role of circulating complement proteins in the pathogenesis of childhood HSP. Methods Plasma levels of C3a, C4a, C5a, and Bb in 30 HSP patients and 30 healthy controls were detected by enzyme-linked immunosorbent assay (ELISA). The expression of C3a receptor (C3aR), C5a receptor (CD88), E-selectin, intercellular adhesion molecule 1 (ICAM-1), C3, C5, interleukin (IL)-8, monocyte chemotactic protein (MCP)-1, and RANTES by human dermal microvascular endothelial cells (HMVEC-d) was evaluated either by flow cytometry or by ELISA. Results At the acute stage, HSP patients had higher plasma levels of C3a (359.5 ± 115.3 vs. 183.3 ± 94.1 ng/ml, p < 0.0001), C5a (181.4 ± 86.1 vs. 33.7 ± 26.3 ng/ml, p < 0.0001), and Bb (3.7 ± 2.6 vs. 1.0 ± 0.6 μg/ml, p < 0.0001), but not C4a than healthy controls. Although HSP patient-derived acute phase plasma did not alter the presentation of C3aR and CD88 on HMVEC-d, it enhanced the production of endothelial C3 and C5. Moreover, C5a was shown in vitro to up-regulate the expression of IL-8, MCP-1, E-selectin, and ICAM-1 by HMVEC-d with a dose-dependent manner. Conclusion In HSP, the activation of the complement system in part through the alternative pathway may have resulted in increased plasma levels of C3a and C5a, which, especially C5a, may play a role in the disease pathogenesis by activating endothelium of cutaneous small vessels. PMID:25760949

  6. A higher frequency of CD4(+)CXCR5(+) T follicular helper cells in patients with newly diagnosed Henoch-Schönlein purpura nephritis.

    PubMed

    Zhang, Zhihui; Zhao, Songchen; Zhang, Li; Crew, Rebecca; Zhang, Nan; Sun, Xiguang; Jiang, Yanfang

    2016-03-01

    T follicular helper (TFH) cells play an important role in the humoral immune responses. The aim of this study was to examine the frequency of different subsets of CD4(+)CXCR5(+) TFH cells and B cells in patients with new-onset Henoch-Schönlein purpura nephritis (HSPN). The numbers of different subsets of CD4(+)CXCR5(+) TFH cells, B cells and the constituents of serum cytokines were detected in a total of 25 patients with newly diagnosed HSPN before and after treatment, and in 14 healthy controls (HC). The potential connection of these cells with the clinical characteristics in HSPN patients was analyzed. The numbers of circulating CD4(+)CXCR5(+), CD4(+)CXCR5(+)ICOS(+) and CD4(+)CXCR5(+)PD-1(+) TFH cells, CD86(+)CD19(+), CD38(+)CD19(+) B cells and serum IL-2, IL-4, IL-17A, IL-21 and IFN-γ were significantly higher in HSPN patients (p<0.05) than in HC. Before and after treatment the numbers of CD4(+)CXCR5(+) TFH cells were negatively correlated with the values of eGFR (r=-0.7162, p<0.05; r=-0.732, p<0.05, respectively). Similarly the numbers of CD4(+)CXCR5(+)PD-1(+) TFH cells were negatively correlated with 24-h urinary proteins (r=-0.4013, p<0.05; r=-0.7857, p<0.05, respectively), and the numbers of CD4(+)CXCR5(+)ICOS(+) TFH cells were positively correlated with the levels of serum IL-21 (r=0.5186, p<0.05; r=0.8503, p<0.05, respectively) and 24-h urinary protein (r=0.6045, p<0.05; r=0.833, p<0.05, respectively) in these patients, regardless of treatment. Following treatment the numbers of CD4(+)CXCR5(+), CD4(+)CXCR5(+)PD-1(+), and CD4(+)CXCR5(+)ICOS(+) TFH cells, as well as serum levels of IL-21 were significantly reduced, however IL-4 levels were noticeably increased (p<0.05). A higher frequency of circulating CD4(+)CXCR5(+) TFH cells existed in patients with HSPN and may be a viable therapeutic target.

  7. Platelets are versatile cells: New discoveries in hemostasis, thrombosis, immune responses, tumor metastasis and beyond.

    PubMed

    Xu, Xiaohong Ruby; Zhang, Dan; Oswald, Brigitta Elaine; Carrim, Naadiya; Wang, Xiaozhong; Hou, Yan; Zhang, Qing; Lavalle, Christopher; McKeown, Thomas; Marshall, Alexandra H; Ni, Heyu

    2016-12-01

    Platelets are small anucleate blood cells generated from megakaryocytes in the bone marrow and cleared in the reticuloendothelial system. At the site of vascular injury, platelet adhesion, activation and aggregation constitute the first wave of hemostasis. Blood coagulation, which is initiated by the intrinsic or extrinsic coagulation cascades, is the second wave of hemostasis. Activated platelets can also provide negatively-charged surfaces that harbor coagulation factors and markedly potentiate cell-based thrombin generation. Recently, deposition of plasma fibronectin, and likely other plasma proteins, onto the injured vessel wall has been identified as a new "protein wave of hemostasis" that may occur even earlier than the first wave of hemostasis, platelet accumulation. Although no experimental evidence currently exists, it is conceivable that platelets may also contribute to this protein wave of hemostasis by releasing their granule fibronectin and other proteins that may facilitate fibronectin self- and non-self-assembly on the vessel wall. Thus, platelets may contribute to all three waves of hemostasis and are central players in this critical physiological process to prevent bleeding. Low platelet counts in blood caused by enhanced platelet clearance and/or impaired platelet production are usually associated with hemorrhage. Auto- and allo-immune thrombocytopenias such as idiopathic thrombocytopenic purpura and fetal and neonatal alloimmune thrombocytopenia may cause life-threatening bleeding such as intracranial hemorrhage. When triggered under pathological conditions such as rupture of an atherosclerotic plaque, excessive platelet activation and aggregation may result in thrombosis and vessel occlusion. This may lead to myocardial infarction or ischemic stroke, the major causes of mortality and morbidity worldwide. Platelets are also involved in deep vein thrombosis and thromboembolism, another leading cause of mortality. Although fibrinogen has been

  8. Acute kidney injury in a patient with hemolytic anemia and thrombocytopenia.

    PubMed

    Breunig, Michael; Lalama, Miguel; Rivard, Gabrielle; Kashiwagi, Deanne; Cornell, Lynn

    2016-11-01

    Atypical hemolytic uremic syndrome (HUS) is clinically difficult to distinguish from HUS and thrombotic thrombocytopenic purpura. Atypical HUS results from dysregulation of complement activation causing thrombotic microangiopathy affecting multiple organ systems. Atypical HUS is associated with high morbidity and mortality, making early recognition and appropriate therapy necessary to improve patient outcomes.

  9. Thrombocytosis following thrombocytopenia in man

    PubMed Central

    Ogston, D.; Dawson, Audrey A.

    1969-01-01

    Observations are presented on the changes in the platelet count of patients during the treatment of Addisonian pernicious anaemia with vitamin B12, of thrombocytopenic purpura with prednisone, and of malignant disease with methotrexate. In each of these clinical situations, thrombocytopenia was succeeded, after a delay of a number of days, by a phase of thrombocytosis. PMID:5392350

  10. HUS AND TTP

    PubMed Central

    Trachtman, Howard

    2013-01-01

    SYNOPSIS This review will describe the epidemiology, pathophysiology, presentation, clinical causes, treatment, and long-term prognosis of pediatric patients who present with thrombotic microangiopathy (TMA). The focus will be on hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP), the most common phenotypes of TMA. PMID:24237985

  11. Clinical uses of radiolabeled platelets

    SciTech Connect

    Datz, F.L.; Christian, P.E.; Baker, W.J.

    1985-12-01

    Platelets were first successfully radiolabeled in 1953. At that time, investigators were primarily interested in developing a technique to accurately measure platelet life span in both normal and thrombocytopenic patients. Studies using platelets labeled with /sup 51/Cr have shown shortened platelet survival times in a number of diseases including idiopathic thrombocytopenic purpura, coronary artery disease, and diabetes mellitus. More recently, labels such as /sup 111/In have been developed that allow in vivo imaging of platelets. Indium-111 platelets are being used to better understand the pathophysiology of atherosclerosis, thrombophlebitis, pulmonary embolism and clotting disorders, and to improve the clinical diagnosis of these diseases.

  12. [Familial cases of Berger's disease or of Berger's disease and rheumatoid purpura. Cooperative study of the Société Française de Néphrologie].

    PubMed

    Levy, M

    1989-01-01

    Several instances of familial Berger's disease have been reported and suggested the possible role of genetic factors in the etiology of the disease. In order to show that familial cases are not a rare finding, a french cooperative study was initiated. It revealed 34 families with 2 or 3 relatives with biopsy-proven Berger's disease. The male predominance (77%) as well as the severity of the evolution (12 out of 69 patients in terminal renal failure) in this series of familial cases are similar to those found in isolated cases. However, the young age at onset (47% being 16 years old or less) deserves to be noted. The number of familial cases is perhaps higher since 90 other families with one patient with Berger's disease and relatives either having urinary abnormalities or terminal renal failure were collected. Although in many of these last patients, clinicians strongly suspected Berger's disease, this diagnosis could not be proven in the absence of immunofluorescent study. This cooperative study has shown that two different glomerular diseases could be encountered in the same family. The association of Henoch-Schönlein purpura and Berger's disease was noted in 4 of these 34 families as well in 11 other and may represent a supplementary argument in favor of a relationship between the two diseases. However, the multiple occurrence of cases in a family may be due to chance or may be the consequence of common environmental factors and does not demonstrate the presence of genetic factors. The use of genetic markers in the families would be helpful to prove the role of these factors in Berger's disease.

  13. Petechial rash in children: a clinical dilemma.

    PubMed

    Barnetson, Laura; Heaton, Paul Anthony; Palmer, Sarah; Paul, Siba Prosad

    2016-05-01

    Children with a petechial rash commonly present to emergency departments. The rash can be associated with serious illnesses, such as invasive meningococcal disease (IMD), but is usually associated with less severe conditions. This article discusses the common and important causes of petechial rash, including IMD, viral illnesses, trauma, Henoch-Schönlein purpura and idiopathic thrombocytopenic purpura. It also analyses the National Institute for Health and Care Excellence (NICE) ( 2014 ) pathway for management of petechial rash in children and examines treatment of the various causes. The article includes two relevant case studies and discusses the role of emergency nurses.

  14. Alloimmunization in autoimmune hemolytic anemia patient: The differential adsorption approach

    PubMed Central

    Dara, Ravi C.; Tiwari, Aseem Kumar; Arora, Dinesh; Mitra, Subhasis; Acharya, Devi Prasad; Aggarwal, Geet; Sharma, Jyoti

    2017-01-01

    Patients of β-thalassemia major are dependent on regular blood transfusions for their entire lifetime. Development of antibodies against red blood cell (RBC) antigen which may be alloantibody or autoantibody, several times as a result of frequent red cell component transfusions, further complicates the subsequent transfusion therapy. Among the autoantibodies, warm-reactive autoantibodies are commoner and interfere in the pretransfusion testing. These RBC autoantibodies present in patient's serum potentially react with all the cells of antibody identification panel giving “pan-reactive” picture and making alloantibody identification complex. In this report, we present our approach in a thalassemia patient who presented with warm-type autoimmune hemolytic anemia, low hemoglobin of 5.8 g/dl, and three significant alloantibodies (anti-D, anti-S, and anti-Jkb) which were masked by pan-reactive warm autoantibody(s). Differential adsorption was used to unmask underlying alloantibodies. We suggest that differential adsorption procedure is an effective and efficient method for autoantibody adsorption, detection, and identification of masked alloantibody(s), especially in patients with low hemoglobin and history of recent blood transfusion. PMID:28316442

  15. Further characterization of the thrombasthenia-related idiotype OG. Antiidiotype defines a novel epitope(s) shared by fibrinogen B beta chain, vitronectin, and von Willebrand factor and required for binding to beta 3

    PubMed Central

    1994-01-01

    A patient (OG) with Glanzmann thrombasthenia became refractory to platelet transfusion after the production of an immunoglobulin G (IgG) isoantibody (Ab1) specific for the integrin subunit beta 3. To determine the frequency at which the OG idiotype is found in the general population and in immune-mediated disease states, we developed a rabbit polyclonal antibody (Ab2) specific for affinity-purified OG anti-beta 3 Fab. The binding of Ab2 to Ab1 is inhibited by purified alpha IIb beta 3. Ab2 als binds to IgG specific for alpha IIb beta 3 obtained from one nonrelated Glanzmann thrombasthenia patient ES who has developed isoantibodies of similar specificity. On the other hand, Ab2 does not recognize alpha IIb beta 3-specific antibodies produced by two Glanzmann thrombasthenia patients, AF and LUC, who have developed isoantibodies with specificities distinct from that of the OG isoantibody. Moreover, Ab2 does not recognize alpha IIb beta 3-specific antibodies developed by three representative patients with (autoimmune) thrombocytopenic purpura or six representative patients with alloimmune thrombocytopenias, nor does it bind to IgG from any of 13 nonimmunized individuals. We have found that Ab2 also binds to selected protein ligands of alpha IIb beta 3 namely, fibrinogen, vitronectin, and von Willebrand factor, but not to other protein ligands or control proteins, such a fibronectin, type I collagen, and albumin. The epitope(s) recognized by Ab2 on each adhesive protein are either very similar or identical since each protein can inhibit the binding of Ab2 to any of the other proteins. The epitope on fibrinogen recognized by Ab2 resides in the B beta chain, and is likely contained within the first 42 amino acids from the NH2 terminus. Since OG IgG inhibits fibrinogen binding to alpha IIb beta 3, the specificity of the OG idiotype defines a novel binding motif for the integrin alpha IIb beta 3 that is shared by fibrinogen, vitronectin, and von Willebrand factor, but

  16. Validation of the absolute renal risk of dialysis/death in adults with IgA nephropathy secondary to Henoch-Schönlein purpura: a monocentric cohort study

    PubMed Central

    2013-01-01

    Background We established earlier the absolute renal risk (ARR) of dialysis/death (D/D) in primary IgA nephropathy (IgAN) which permitted accurate prospective prediction of final prognosis. This ARR was based on the potential presence at initial diagnosis of three major, independent, and equipotent risk factors such as hypertension, quantitative proteinuria ≥ 1 g per day, and severe pathological lesions appreciated by our local classification scoring ≥ 8 (range 0–20). We studied the validity of this ARR concept in secondary IgAN to predict future outcome and focused on Henoch-Schönlein purpura (HSP) nephritis. Methods Our cohort of adults IgAN concerned 1064 patients with 101 secondary IgAN and was focused on 74 HSP (59 men) with a mean age of 38.6 at initial diagnosis and a mean follow-up of 11.8 years. Three major risk factors: hypertension, proteinuria ≥1 g/d, and severe pathological lesions appreciated by our global optical score ≥8 (GOS integrated all elementary histological lesions), were studied at biopsy-proven diagnosis and their presence defined the ARR scoring: 0 for none present, 3 for all present, 1 or 2 for the presence of any 1 or 2 risk factors. The primary end-point was composite with occurrence of dialysis or death before (D/D). We used classical statistics and both time-dependent Cox regression and Kaplan-Meier survival curve methods. Results The cumulative rate of D/D at 10 and 20 years post-onset was respectively 0 and 14% for ARR = 0 (23 patients); 10 and 23% for ARR = 1 (N = 19); 27 and 33% for ARR = 2 (N = 24); and 81 and 100% (before 20 y) in the 8 patients with ARR = 3 (P = 0.0007). Prediction at time of diagnosis (time zero) of 10y cumulative rate of D/D event was 0% for ARR = 0, 10% for ARR = 1, 33% for ARR = 2, and 100% by 8.5y for ARR = 3 (P = 0.0003) in this adequately treated cohort. Conclusion This study clearly validates the Absolute Renal Risk of Dialysis

  17. Mitomycin-C-Induced TTP/HUS Treated Successfully with Rituximab: Case Report and Review of the Literature

    PubMed Central

    Yamin, Hanah; Smith, Hedy

    2013-01-01

    Microangiopathic hemolytic anemia (MAHA), thrombocytopenia, fever, renal failure, and neurologic symptoms comprise the cardinal features of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Etiologies can include medications, infections, cancers, or transplantation. We present a patient with a history of rectal cancer treated with mitomycin-C who developed MAHA, acute kidney injury, and thrombocytopenia 6 months after completing therapy and to did not respond the plasmapheresis or steroids. She was treated with four weekly doses of rituximab with full recovery. PMID:23762670

  18. Intermittent cyclophosphamide treatment of autoimmune thrombocytopenia

    PubMed Central

    Weinerman, Brian; Maxwell, Ian; Hryniuk, William

    1974-01-01

    Cyclophosphamide was given intermittently rather than daily to 14 patients with autoimmune thrombocytopenic purpura. Eight patients responded and six did not. In those who responded the rise in platelet count was rapid, and in all patients the lack of toxicity was striking. Intermittent cyclophosphamide seems effective in some cases of autoimmune thrombocytopenia and is safe, at least in the short term. Controlled trials would be required to prove that intermittent is better than daily administration. PMID:4473260

  19. Laboratory evaluation of a bleeding patient.

    PubMed Central

    Wallerstein, R O

    1989-01-01

    Most causes of abnormal bleeding can be determined from a complete blood count including platelet count and bleeding, prothrombin, activated partial thromboplastin, and thrombin times. Occasionally, further evaluation is necessary, such as tests of factor XIII function, fibrinolysis, and vascular integrity. Possible diagnoses include disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, vitamin K deficiency, von Willebrand's disease, heparin-induced thrombocytopenia, acquired inhibitors of factor VIII, lupus anticoagulants, and coagulation disorders related to the acquired immunodeficiency syndrome. PMID:2660407

  20. Catastrophic antiphospholipid antibody syndrome in systemic lupus erythematosus: an autopsy case report of a young woman.

    PubMed

    Mizuno, R; Fujimoto, S; Fujimoto, T; Nishino, T; Shiiki, H; Hashimoto, T; Nakamura, S; Dohi, K

    2000-10-01

    Catastrophic antiphospholipid syndrome (CAPS) is a severe variant of antiphospholipid syndrome (APS) characterized by disseminated microangiopathy that results in multiorgan failure. CAPS mainly occurs in association with systemic lupus erythematosus (SLE). Clinically, CAPS mimics disseminated SLE vasculitis, intravascular coagulation (DIC), and particularly thrombotic thrombocytopenic purpura (TTP). We describe an autopsy case of young woman with CAPS in SLE, which is difficult to differentiate from TTP secondary to SLE.

  1. Hospital-acquired pneumonia and bacteremia caused by Legionella pneumophila in an immunocompromised patient.

    PubMed

    Lai, C-C; Tan, C-K; Chou, C-H; Hsu, H-L; Huang, Y-T; Liao, C-H; Hsueh, P-R

    2010-04-01

    The Legionella species is an important cause of communityand hospital-acquired pneumonia. Bacteremic pneumonia caused by L. pneumophila is rarely reported. We describe the first reported case of hospital-acquired pneumonia and bacteremia caused by L. pneumophila from Taiwan in a patient with idiopathic thrombocytopenic purpura who received steroid treatment. The patient was successfully treated with ceftazidime and clindamycin initially, followed by ciprofloxacin for 14 days. The blood isolate was further confirmed by 16S rDNA sequence analysis.

  2. Correlation of TLR2 and TLR4 expressions in peripheral blood mononuclear cells to Th1- and Th2-type immune responses in children with henoch-schönlein purpura.

    PubMed

    Chang, Hong; Zhang, Qiu-Ye; Lin, Yi; Cheng, Na; Zhang, Shou-Qing

    2015-01-01

    We discussed the correlation of TLR2 (Toll-like receptor) and TLR4 expressions in peripheral blood mononuclear cells (PBMCs) to Th1- and Th2-type immune responses in children with Henoch-Schönlein Purpura (HSP). The role of TLR2 and TLR4 in the pathogenesis of HSP was analyzed. Sixty-four HSP children treated at our hospital from October 2011 to November 2012 were enrolled and divided into NHSPN group (complicated by renal impairment, 36 cases) and HSPN group (not complicated by renal impairment, 28 cases). In the meantime, 30 normal children receiving physical examination at our hospital were recruited as controls. Peripheral blood T cell subgroups and TLR2 and TLR4 expressions in PBMCs were detected by using flow cytometry; relative expression levels of TLR2 and TLR4 mRNA in PBMCs by real-time quantitative fluorescence PCR, and plasma levels of IFN-γ, IL-4 and IL-6 by ELISA method. Relative expression levels of TLR2 and TLR4 mRNAs in PBMCs and TLR2 and TLR4 protein expressions in children with HSP were significantly higher than those of the controls (P<0.01). The relative expression levels of TLR2 and TLR4 mRNAs in PBMCs and TLR2 and TLR4 protein expressions in HSPN group were obviously higher than those in NHSPN group (P<0.05; P<0.01; P<0.01; P<0.01); CD3(+) T cells and CD3(+)CD4(+) T cells in HSP group were significantly decreased, while CD3(+)CD8(+) T cells and CD3(+)HLADR(+) T activated cells were considerably increased (P<0.01); The plasma levels of IL-4 and IL-6 in HSP group were significantly higher than those of the normal controls (P<0.01, P<0.01); IFN-γ level in the former was much lower than in the control group (P<0.05); IFN-γ/IL-4 ratio in the former was also lower than that in the control (P<0.01); TLR2 and TLR4 expressions in HSP group showed significantly positive correlation with the plasma levels of IL-4 and IL-6 (P<0.01, P<0.05; P<0.01, P<0.01) and significantly negative correlation with IFN-γ/IL-4 ratio (P<0.01; P<0.01). TLR2 and TLR4

  3. Impaired activation of the fibrinolytic system in children with Henoch-Schönlein purpura: beneficial effect of hydrocortisone plus Sigma-aminocaproic acid therapy on disappearance rate of cutaneous vasculitis and fibrinolysis.

    PubMed

    Prandota, J; Pankow-Prandota, L; Kotecki, L

    2001-01-01

    Systemic vasculitis is a predominant clinical symptom in Henoch-Schönlein purpura (HSP), and some studies suggested that decreased blood fibrinolytic activity, as well as blood platelets, is of importance in the development of cutaneous vasculitis. Although patients with HSP have normal blood coagulation, little is known about the fibrinolytic system. On the other hand, it is known that the focus of Sigma-aminocaproic acid (EACA) activity in vivo is probably the blood platelet-vessel wall interaction or a vascular component alone. The aim of this study was, therefore, to investigate blood coagulation and fibrinolytic system as well as the effect of hydrocortisone (H) plus EACA therapy (Group I) on plasma antithrombin-III (AT-III), alpha1-proteinase inhibitor (alpha1-PI), alpha2-antiplasmin (alpha2-A), alpha2-macroglobulin (alpha2-M) activity, fibrinogen and plasminogen concentrations in plasma, euglobulin clot lysis time (ELT), and disappearance rate of cutaneous vasculitis in 14 children with HSP aged 7.6 +/- 3.1 (SD) years. Ten patients (8.6 +/- 2.5 years old) were treated with H alone (Group II), and 8 healthy, age-matched children served as controls. Plasma proteinase inhibitor activity was estimated with the kinetic method using Boehringer chromozyme tests before administration of H (9.2 +/- 3.3 mg/kg/d, i.v.) plus EACA (140 +/- 52 mg/kg/d, p.o.) for 5.93 +/- 2.05 days, and 24 hours after the last dose of EACA, as well as before and after treatment with H alone (8.25 +/- 1.74 mg/kg/24 h, i.v.) for 7.1 +/- 1.2 days. It was found that patients with HSP had the initial fibrinogen and plasminogen plasma concentrations significantly increased compared with the controls (Group I: 3.93 +/- 1.3 g/L and 124 +/- 38%; Group II: 4.24 +/- 0.89 g/L and 134 +/- 42% vs. 2.96 +/- 0.34 g/L, and 90 +/- 14%, respectively). Also, there was a marked decrease of the initial plasma alpha2-A activity in Group II compared with the controls (0.69 +/- 0.29 vs. 0.94 +/- 0.11 IU

  4. Henoch-Schönlein Purpura

    MedlinePlus

    ... Disease Chronic Kidney Disease (CKD) What Is Chronic Kidney Disease? Causes of CKD Tests & Diagnosis Managing CKD Eating Right Preventing CKD What If ... risk for high blood pressure and proteinuria during pregnancy. How is HSP diagnosed? A diagnosis of HSP is suspected when a person has ...

  5. VWF excess and ADAMTS13 deficiency: a unifying pathomechanism linking inflammation to thrombosis in DIC, malaria, and TTP.

    PubMed

    Schwameis, Michael; Schörgenhofer, Christian; Assinger, Alice; Steiner, Margarete M; Jilma, Bernd

    2015-04-01

    Absent or severely diminished activity of ADAMTS13 (A Disintegrin And Metalloprotease with a ThromboSpondin type 1 motif, member 13) resulting in the intravascular persistence and accumulation of highly thrombogenic ultra large von Willebrand factor (UL-VWF) multimers is the pathophysiological mechanism underlying thrombotic thrombocytopenic purpura. Reduced VWF-cleaving protease levels, however, are not uniquely restricted to primary thrombotic microangiopathy (TMA), e. g. thrombotic thrombocytopenic purpura, but also occur in other life-threatening thrombocytopenic conditions: severely decreased ADAMTS13 activity is seen in severe sepsis, disseminated intravascular coagulation (DIC) and complicated malarial infection. The clinical relevance of these secondary thrombotic microangiopathies is increasingly recognised, but its therapeutic implications have not yet been determined. The presence of a secondary TMA in certain diseases may define patient groups which possibly could benefit from ADAMTS13 replacement or a VWF-targeting therapy. This short-review focuses on the role of UL-VWF multimers in secondary TMA and discusses the potential of investigational therapies as candidates for the treatment of TTP. In conclusion, prospective clinical trials on the effectiveness of protease replacementin vivo seem reasonable. Carefully selected patients with secondary TMA may benefit from therapies primarily intended for the use in patients with TTP.

  6. Inflammatory abdominal aortic aneurysm followed by disseminated intravascular coagulation and immune thrombocytopenia.

    PubMed

    Machida, Hisanori; Kobayashi, Makoto; Taguchi, Hirokuni

    2002-11-01

    A 71-year-old man was diagnosed as having an abdominal aortic aneurysm when he was treated for idiopathic interstitial pneumonia (IIP). Three years later, he developed severe thrombocytopenia and had disseminated intravascular coagulation (DIC) that was associated with the inflammatory abdominal aortic aneurysm (IAAA). The coagulation abnormalities were corrected by low-molecular weight heparin, however the platelet count remained low. Bone marrow showed normocellularity with an increase of immature and mature forms of megakaryocytes. Platelet-associated IgG level was high. These findings suggested that the patient had severe thrombocytopenia caused by unusual complications of immune thrombocytopenic purpura and IAAA-associated DIC.

  7. Eltrombopag Use in Thrombocytopenia for Endoscopic Submucosal Dissection of a Gastric Carcinoid

    PubMed Central

    Kaltenbach, Tonya; Martin, Beth; Rouse, Robert V.; Soetikno, Roy

    2014-01-01

    Severe thrombocytopenia is a contraindication for therapeutic endoscopy due to the risk of bleeding. Platelet transfusions can temporarily increase platelet count, but are difficult to administer in the 2 weeks following endoscopic resection, during which the patient is at high risk for delayed bleeding. We present the use of a novel thrombopoietin receptor agonist, eltrombopag, to sustain platelet levels for the safe and complete endoscopic submucosal dissection of a gastric carcinoid in a patient with severe thrombocytopenia due to cirrhosis and idiopathic thrombocytopenic purpura. We performed complete and safe endoscopic removal of a gastric carcinoid after correcting the thrombocytopenia. PMID:26157896

  8. Thrombocytopenia-associated multiple organ failure or severe haemolysis, elevated liver enzymes, low platelet count in a postpartum case.

    PubMed

    Jagia, Manish; Taqi, Salah; Hanafi, Mahmoud; Aisha, Fakeir

    2013-01-01

    Thrombocytopenia-associated multiple organ failure (TAMOF) is a thrombotic microangiopathic syndrome that includes thrombotic thrombocytopenic purpura, secondary thrombotic microangiopathy, and disseminated intravascular coagulation. We report a case of postpartum female who presented with TAMOF or severe Haemolysis, elevated liver enzymes, low platelet count (HELLP) which was managed with plasma exchange. This case report is to make clinicians aware that TAMOF, severe HELLP, and other differential diagnosis in a postpartum case have a thin differentiating line and plasma exchange can be considered as one of the management options.

  9. Hypercoagulable states and strokes.

    PubMed

    Matijevic, Nena; Wu, Kenneth K

    2006-07-01

    Several hematologic disorders and hemostatic defects increase risk of ischemic stroke. A common feature of these disorders is the creation of a prothrombotic state, now commonly referred to as "hypercoagulable state." Hematologic diseases such as essential thrombocythemia, polycythemia vera, and thrombotic thrombocytopenic purpura clearly cause stroke. Effective treatment is now available for these disorders. Association of hemostatic defects with stroke risk is still at the investigational stage. Although a number of factors such as soluble thrombomodulin, fibrinogen, factor VIII, von Willebrand factor, and plasminogen activator inhibitor-1 are associated with stroke risk, their predictive values remain unknown. Furthermore, causal relationship has not been established.

  10. Thrombotic Microangiopathy Syndrome in a Basic Underwater Demolition/SEAL Student.

    PubMed

    Croom, Daniel; Tracy, Heather

    2016-01-01

    Thrombotic microangiopathy (TMA) syndromes represent a spectrum of illnesses that share common clinical and pathologic features of microangiopathic hemolytic anemia, thrombocytopenia, and organ injury from pathologic small-vessel thrombosis. At least nine primary TMA syndromes have been described and classified based on common probable etiologies, diagnostic criteria, and treatments. The most recognized of the TMA syndromes include thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS). Advanced laboratory techniques are required to distinguish between these syndromes; however, all patients should initially be treated with plasma exchange for presumed ADAMTS13 deficiency-mediated TMA. The authors present a case of a TMA syndrome in a Navy SEAL (Sea, Air, Land) candidate.

  11. Beginner's luck--the first in vivo demonstration of functioning platelets; William Duke, 1910.

    PubMed

    Boulton, F

    2012-04-01

    Blood platelets remained obscure until the early 20th century although from the 1880 s claims that low numbers were associated with certain types of 'purpura' began to gain favour. This article re-appraises critically, but with due consideration to the limited technology of the times, the first remarkable in vivo demonstration of the effects of platelets demonstrated by the serial 'Bleeding Times' reported by William Duke in 1910, when fresh blood was transfused to two thrombocytopenic people. It also speculates on the possible causes of the thrombocytopenia with which Duke's main patient presented.

  12. Breast Cancer Presenting as Paraneoplastic Erythroderma: An Extremely Rare Case

    PubMed Central

    Katsantonis, Ioannis; Roussos, Nikolaos; Manoludaki, Kassiani; Antonopoulos, Stavros

    2014-01-01

    The skin may exhibit the first clinical evidence of a systemic disease and may provide the first clues to a diagnosis in malignancies. Erythroderma is defined as generalized redness and scaling and it is a clinical manifestation of a variety of underlying diseases including, rarely, solid tumors. Breast cancer is associated with a variety of skin paraneoplastic manifestations like acanthosis nigricans, erythromelalgia, thrombotic thrombocytopenic purpura, acrokeratosis paraneoplastica, dermatomyositis, systemic sclerosis, and scleroderma. However, in the literature, the correlation of erythroderma with breast cancer is quite infrequent. Here, we describe a case of a 76-year-old woman who presented with a paraneoplastic manifestation of erythroderma due to breast cancer. PMID:25295062

  13. Thrombocytopenia and Cornelia de Lange syndrome: Still an enigma?

    PubMed

    Cavalleri, Valeria; Bettini, Laura R; Barboni, Chiara; Cereda, Anna; Mariani, Milena; Spinelli, Marco; Gervasini, Cristina; Russo, Silvia; Biondi, Andrea; Jankovic, Momcilo; Selicorni, Angelo

    2016-01-01

    Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder caused by mutations in the cohesion complex and its regulators. The syndrome is characterized by multiple organ system abnormalities, pre- and post-natal growth retardation and typical facial features. Thrombocytopenia is a reduction in platelet count to <150 × 10(9)  L. It can be caused by congenital or acquired decreased production, increased destruction, or sequestration of platelets. In recent years, several papers reported thrombocytopenia and immune thrombocytopenia in patients affected by CdLS. In 2011, Lambert et al. estimated the risk of idiopathic thrombocytopenia purpura in CdLS patients to be 31-633 times greater than in the general population. We describe the incidence of thrombocytopenia in 127 Italian CdLS patients, identifying patients with transient or persistent thrombocytopenia, but a lower incidence of true idiopathic thrombocytopenic purpura (ITP).

  14. The platelet-refractory bone marrow transplant patient: prophylaxis and treatment of bleeding.

    PubMed

    Benson, K; Fields, K; Hiemenz, J; Zorsky, P; Ballester, O; Perkins, J; Elfenbein, G

    1993-10-01

    Refractoriness to platelet transfusions remains a significant problem for oncology patients, occurring in 30% to 70% of multiply transfused recipients with bone marrow failure. Nonimmune causes are often present and include disseminated intravascular coagulation, concurrent use of amphotericin B, infection, presence of palpable spleen, use of antibacterial antibiotics, bleeding, veno-occlusive disease, and fever. Immune causes are also commonly responsible for refractoriness, with HLA alloimmunization dominating the list of immune factors. HLA antibodies can be identified in 25% to 30% of transfused leukemia patients and can be present in as many as 80% of aplastic anemia patients. Developing a consistent approach to managing these refractory patients is essential to preventing and treating bleeding manifestations. An HLA type should be obtained for all patients anticipated to have chronic transfusion requirements. Screening for lymphocytotoxic antibodies can confirm suspected HLA alloimmunization. Histocompatible platelets (cross-match compatible and HLA matched) should be provided for all patients with HLA antibodies. A number of other therapeutic modalities have been used in an effort to manage the alloimmunized patient; most of these methods have had little or no proven benefit. When bleeding develops in the alloimmunized patient, there are few therapeutic choices. If histocompatible platelets are unavailable or unsuccessful, massive platelet transfusions of pooled platelet concentrates are commonly used, although this practice is of no proven benefit. While antifibrinolytic agents have been available for over 30 years, they are only recently being applied to control bleeding in chronic thrombocytopenia. We have successfully managed bleeding episodes in thrombocytopenic bone marrow transplant recipients with the use of epsilon aminocaproic acid. A number of these patients were platelet refractory with demonstrable platelet antibodies. Platelet refractoriness

  15. Induction of antinuclear antibodies by de novo autoimmune hepatitis regulates alloimmune responses in rat liver transplantation.

    PubMed

    Nakano, Toshiaki; Goto, Shigeru; Lai, Chia-Yun; Hsu, Li-Wen; Tseng, Hui-Peng; Chen, Kuang-Den; Chiu, King-Wah; Wang, Chih-Chi; Cheng, Yu-Fan; Chen, Chao-Long

    2013-01-01

    Concanavalin A (Con A) is a lectin originating from the jack-bean and well known for its ability to stimulate T cells and induce autoimmune hepatitis. We previously demonstrated the induction of immunosuppressive antinuclear autoantibody in the course of Con A-induced transient autoimmune hepatitis. This study aimed to clarify the effects of Con A-induced hepatitis on liver allograft rejection and acceptance. In this study, we observed the unique phenomenon that the induction of transient de novo autoimmune hepatitis by Con A injection paradoxically overcomes the rejection without any immunosuppressive drug and exhibits significantly prolonged survival after orthotopic liver transplantation (OLT). Significantly increased titers of anti-nuclear Abs against histone H1 and high-mobility group box 1 (HMGB1) and reduced donor specific alloantibody response were observed in Con A-injected recipients. Induction of Foxp3 and IL-10 in OLT livers of Con A-injected recipients suggested the involvement of regulatory T cells in this unique phenomenon. Our present data suggest the significance of autoimmune responses against nuclear histone H1 and HMGB1 for competing allogeneic immune responses, resulting in the acceptance of liver allografts in experimental liver transplantation.

  16. Sera from dams of calves with bovine neonatal pancytopenia contain alloimmune antibodies directed against calf leukocytes.

    PubMed

    Pardon, Bart; Stuyven, Edith; Stuyvaert, Sabrina; Hostens, Miel; Dewulf, Jeroen; Goddeeris, Bruno Maria; Cox, Eric; Deprez, Piet

    2011-06-15

    Bovine neonatal pancytopenia (BNP) is a bleeding and pancytopenic syndrome in neonatal calves, which recently emerged all over Europe. The present study tested whether antibodies directed against calf leukocytes are present in sera from known BNP dams. Sera from BNP dams (n=11) were combined with leukocytes from 11 calves (5 BNP survivors and 6 controls). After adding a fluorescein conjugated F(ab')(2) fragment of rabbit anti-bovine IgG (H&L) the level of antibody binding was measured by flow cytometry. As control groups both sera from dams from BNP affected (n=48) as from unaffected (n=54) herds were combined with leukocytes from the same calves. With sera from BNP dams, antibody binding could be visualised by immunofluoresence in both peripheral blood as in bone marrow smears. Mean fluoresence intensity values of all leukocyte subpopulations were significantly higher for the BNP dams compared to both control groups (P<0.01). BNP dams showed significantly more antibody binding on multiple leukocyte subpopulations of both BNP survivors and control calves and this from cut off values of MFI 100 onwards (P<0.01). The BNP survivor calves reacted significantly more often with sera from the BNP dams than the control calves (P<0.01). In conclusion the present study supports the hypothesis that BNP is an immune-mediated disease.

  17. Neonatal alloimmune thrombocytopenia associated with maternal-fetal incompatibility for blood group B

    PubMed Central

    Curtis, Brian R.; Fick, Andrea; Lochowicz, Andrew J.; McFarland, Janice G.; Ball, Robert H.; Peterson, Julie; Aster, Richard H.

    2013-01-01

    BACKGROUND Blood group A and B antigens are expressed only weakly on platelets (PLTs) of most individuals but are very strongly expressed on PLTs from approximately 1 percent of normal subjects (Type II high expressers). The implications of this trait for transfusion medicine are undefined. STUDY DESIGN AND METHODS A family was studied in which two Group B infants were born with neonatal thrombocytopenia, whereas a third infant whose blood group was A2 had a normal PLT count at birth. RESULTS Serologic studies demonstrated a maternal antibody that reacted strongly with PLTs from the father and the two group B children in flow cytometry and with GPIIb/IIIa from their PLTs in solid-phase assays. No PLT-specific antibodies were detected in maternal serum sample, but it contained a high-titer immunoglobulin G antibody specific for blood group B. All PLT-reactive antibody in the mother’s serum was removed by absorption with pooled, washed group A and B red cells (RBCs). Studies with monoclonal anti-B and measurement of serum B-glycosyltransferase activity showed that the father and both group B children were Type II high expressers of blood group B. CONCLUSIONS The findings indicate that high-titer blood group antibodies acquired from the mother can cause thrombocytopenia in infants possessing the Type II high-expresser phenotype despite competition for antibody binding by blood group antigens expressed on RBCs and other tissues. PMID:18028270

  18. Red cell alloimmunization in a diverse population of transfused patients with thalassaemia.

    PubMed

    Thompson, Alexis A; Cunningham, Melody J; Singer, Sylvia T; Neufeld, Ellis J; Vichinsky, Elliott; Yamashita, Robert; Giardina, Patricia; Kim, Hae-Young; Trachtenberg, Felicia; Kwiatkowski, Janet L

    2011-04-01

    Red blood cell (RBC) transfusion is the primary treatment for severe forms of thalassaemia. Pre-storage screening has resulted in decreased transfusion-transmitted infections, but anti-RBC antibodies remain a major problem. We report on 697 participants who had ever received transfusions. Allo- and autoantibody rates were compared with respect to splenectomy status, ethnicity, diagnosis, duration of transfusions, treatment centre, and age at transfusion initiation, together with rates before and after 1990, when leucoreduction methods were routine at thalassaemia treatment centres. Allo- and autoantibodies were reported in 115 (16·5%) and 34 (4·9%) subjects, respectively. Splenectomized patients were more likely to have alloantibodies [odds ratio (OR) = 2·528, P ≤ 0·0001], or autoantibodies (OR = 2·590, P = 0·0133). Alloantibodies occurred in 19 of 91 (21%) splenectomized subjects who started transfusion after 1990, and only 18 of 233 (7·7%) nonsplenectomized subjects (P < 0·001). Data from this study demonstrate that RBC antibodies continue to develop in chronically transfused thalassaemia patients at a high rate. Splenectomy preceded the development of antibodies in most cases. Increased rates of RBC sensitization among splenectomized patients is concerning and deserves further study.

  19. Successful engraftment following unrelated donor transplant in an alloimmunized patient with Kostmann syndrome.

    PubMed

    Myers, Scott N; Zeevi, Adriana; Zorich, G Phil; Pillage, Gina; Martel, Joan; Goyal, Rakesh K

    2005-05-01

    Severe chronic neutropenia (SCN) is characterized by severe recurrent bacterial infections during infancy. Blood or marrow transplantation (BMT) is the only curative option for patients with refractory disease. This report describes the case of a 4-year-old girl with refractory SCN, who received a bone marrow transplant from a highly matched donor after becoming HLA sensitized to multiple granulocyte transfusions. She is clinically well with normal blood counts and stable mixed chimerism 3 years after BMT. She experienced no graft rejection or graft versus host disease.

  20. Bovine Neonatal Pancytopenia: is this alloimmune syndrome caused by vaccine-induced alloreactive antibodies?

    PubMed

    Bastian, Max; Holsteg, Mark; Hanke-Robinson, Heidrun; Duchow, Karin; Cussler, Klaus

    2011-07-18

    Bovine Neonatal Pancytopenia (BNP) is a new emerging disease observed since 2007 in Germany and neighbouring countries. The syndrome affects newborn calves and is characterized by pancytopenia, severe bleeding and high lethality. So far, a causative role of infectious or toxic agents has been ruled out. Instead, the syndrome is induced after ingestion of colostrum, the first milk that supplies the calf with maternal antibodies. In analogy to similar diseases in humans it has therefore been postulated that BNP is caused by alloreactive, maternal antibodies. There is a striking association between BNP and a previous vaccination of the respective dams with a particular vaccine against Bovine Virus Diarrhoea (BVD). This association has led to a suspension of the marketing authorisation for the vaccine, by the European Commission. The current study investigates the role of this vaccine in the pathogenesis of BNP. By flow cytometry we were able to demonstrate that sera of BNP dams (dams that gave birth to a BNP calf) harbour alloreactive antibodies binding to surface antigens on bovine leukocytes. A significantly weaker alloreactivity was observed with sera of non-BNP dams that have been vaccinated with the same vaccine but delivered healthy calves. No binding was seen with non-BVD-vaccinated control cows and animals that were vaccinated with other inactivated BVD vaccines so far not associated with BNP. The binding is functionally relevant, because opsonization of bovine leukocytes with alloantibodies led to an elevated cytophagocytosis by bovine macrophages. To test whether the vaccine induces alloreactive antibodies two strategies were employed: Guinea pigs were vaccinated with a panel of commercially available BVD-vaccines. Only the incriminated vaccine induced antibodies binding surface antigens on bovine leukocytes. Additionally, two calves were repeatedly vaccinated with the suspected vaccine and the development of alloreactivity was monitored. In dependence of the number of booster immunizations the induction of alloreactive antibodies could be observed. Finally, by affinity purification we were able to directly demonstrate that BNP associated alloantibodies cross react with the bovine kidney cell line used for vaccine production. Together this provides strong evidence that this particular BVD vaccine has the potential to induce BNP associated alloantibodies.

  1. Antigen and substrate withdrawal in the management of autoimmune thrombotic disorders

    PubMed Central

    McCrae, Keith R.; Zheng, X. Long; Sachais, Bruce S.; Luning Prak, Eline T.; Siegel, Don L.

    2012-01-01

    Prevailing approaches to manage autoimmune thrombotic disorders, such as heparin-induced thrombocytopenia, antiphospholipid syndrome and thrombotic thrombocytopenic purpura, include immunosuppression and systemic anticoagulation, though neither provides optimal outcome for many patients. A different approach is suggested by the concurrence of autoantibodies and their antigenic targets in the absence of clinical disease, such as platelet factor 4 in heparin-induced thrombocytopenia and β2-glycoprotein-I (β2GPI) in antiphospholipid syndrome. The presence of autoantibodies in the absence of disease suggests that conformational changes or other alterations in endogenous protein autoantigens are required for recognition by pathogenic autoantibodies. In thrombotic thrombocytopenic purpura, the clinical impact of ADAMTS13 deficiency caused by autoantibodies likely depends on the balance between residual antigen, that is, enzyme activity, and demand imposed by local genesis of ultralarge multimers of von Willebrand factor. A corollary of these concepts is that disrupting platelet factor 4 and β2GPI conformation (or ultralarge multimer of von Willebrand factor oligomerization or function) might provide a disease-targeted approach to prevent thrombosis without systemic anticoagulation or immunosuppression. Validation of this approach requires a deeper understanding of how seemingly normal host proteins become antigenic or undergo changes that increase antibody avidity, and how they can be altered to retain adaptive functions while shedding epitopes prone to elicit harmful autoimmunity. PMID:22966172

  2. Autoimmune diseases and HIV infection

    PubMed Central

    Virot, Emilie; Duclos, Antoine; Adelaide, Leopold; Miailhes, Patrick; Hot, Arnaud; Ferry, Tristan; Seve, Pascal

    2017-01-01

    Abstract To describe the clinical manifestations, treatments, prognosis, and prevalence of autoimmune diseases (ADs) in human immunodeficiency virus (HIV)-infected patients. All HIV-infected patients managed in the Infectious Diseases Department of the Lyon University Hospitals, France, between January 2003 and December 2013 and presenting an AD were retrospectively included. Thirty-six ADs were found among 5186 HIV-infected patients which represents a prevalence of 0.69% including immune thrombocytopenic purpura (n = 15), inflammatory myositis (IM) (n = 4), sarcoidosis (n = 4), Guillain–Barré syndrome (GBS) (n = 4), myasthenia gravis (n = 2), Graves’ disease (n = 2), and 1 case of each following conditions: systemic lupus erythematosus, rheumatoid arthritis, autoimmune hepatitis, Hashimoto thyroiditis and autoimmune hemolytic anemia. One patient presented 2 ADs. Thirty patients were known to be HIV-infected when they developed an AD. The AD preceded HIV infection in 2 patients. GBS and HIV infection were diagnosed simultaneously in 3 cases. At AD diagnosis, CD4 T lymphocytes count were higher than 350/mm3 in 63% of patients, between 200 and 350/mm3 in 19% and less than 200/mm3 in 19%. Twenty patients benefited from immunosuppressant treatments, with a good tolerance. ADs during HIV infection are uncommon in this large French cohort. Immune thrombocytopenic purpura, sarcoidosis, IM, and GBS appear to be more frequent than in the general population. Immunosuppressant treatments seem to be effective and well tolerated. PMID:28121924

  3. [Thrombocytopenia induced by rifampicin not previously sensitized: a case presentation].

    PubMed

    Neino Mourtala Mohamed, A; Tummino, C; Gouitaa, M; Chanez, P

    2013-11-01

    Thrombocytopenia induced by rifampicin in the absence of prior sensitization is exceptional, especially when it occurs in a patient without risk factors. We report the case of a patient aged 25 years with no past history of medical, surgical or knowledge of having taken rifampicin previously, who was hospitalized for treatment of thrombocytopenic purpura occurring after the initiation of fixed combination quadruple therapy (isoniazid, rifampicin, pyrazinamide and ethambutol) for pulmonary tuberculosis. The biological pretreatment and therapeutic education had not been made. The patient presented with thrombocytopenic purpura 30000/mm(3) on day 9 after the initiation of treatment. The platelet count returned to normal 10 days after discontinuation of treatment. We elected not to reintroduce rifampicin given the strong likelihood that it was responsible for this complication. We conducted a phased reintroduction of isoniazid, ethambutol and pyrazinamide. No recurrence of the thrombocytopenia occurred. Thus, the diagnosis of rifampicin-induced thrombocytopenia appears to have been confirmed and the patient tolerated the remainder of their treatment well.

  4. Coagulation parameters of ABO group-specific cryosupernatant.

    PubMed

    Gerhard, G S; Hoffman, S M; Williams, E C

    1998-04-01

    Patients with thrombotic thrombocytopenic purpura that is refractory to conventional fresh frozen plasma (FFP) exchange therapy are sometimes switched to cryosupernatant as the replacement fluid, although its hemostatic properties are not well defined. We performed several key coagulation assays on three pools of four units from each of three ABO groups of cryosupernatant and FFP. Fibrinogen, factor VIII activity, and von Willebrand factor antigen (vWF:Ag) levels were all significantly lower in cryosupernatant compared with FFP, although at levels usually not considered clinically significant. We confirmed that group O FFP contained significantly less factor VIII activity and vWF:Ag compared with groups AB and B. In contrast to FFP, group AB cryosupernatant contained lower levels of fibrinogen, factor V activity, factor VIII activity, and vWF:Ag than groups O or B. Group AB cryosupernatant, with the lowest levels of vWF:Ag and universal ABO compatibility, may be the product of choice for refractory thrombotic thrombocytopenic purpura.

  5. Autoimmune diseases and HIV infection: A cross-sectional study.

    PubMed

    Virot, Emilie; Duclos, Antoine; Adelaide, Leopold; Miailhes, Patrick; Hot, Arnaud; Ferry, Tristan; Seve, Pascal

    2017-01-01

    To describe the clinical manifestations, treatments, prognosis, and prevalence of autoimmune diseases (ADs) in human immunodeficiency virus (HIV)-infected patients.All HIV-infected patients managed in the Infectious Diseases Department of the Lyon University Hospitals, France, between January 2003 and December 2013 and presenting an AD were retrospectively included.Thirty-six ADs were found among 5186 HIV-infected patients which represents a prevalence of 0.69% including immune thrombocytopenic purpura (n = 15), inflammatory myositis (IM) (n = 4), sarcoidosis (n = 4), Guillain-Barré syndrome (GBS) (n = 4), myasthenia gravis (n = 2), Graves' disease (n = 2), and 1 case of each following conditions: systemic lupus erythematosus, rheumatoid arthritis, autoimmune hepatitis, Hashimoto thyroiditis and autoimmune hemolytic anemia. One patient presented 2 ADs. Thirty patients were known to be HIV-infected when they developed an AD. The AD preceded HIV infection in 2 patients. GBS and HIV infection were diagnosed simultaneously in 3 cases. At AD diagnosis, CD4 T lymphocytes count were higher than 350/mm in 63% of patients, between 200 and 350/mm in 19% and less than 200/mm in 19%. Twenty patients benefited from immunosuppressant treatments, with a good tolerance.ADs during HIV infection are uncommon in this large French cohort. Immune thrombocytopenic purpura, sarcoidosis, IM, and GBS appear to be more frequent than in the general population. Immunosuppressant treatments seem to be effective and well tolerated.

  6. Circulating DNA and myeloperoxidase indicate disease activity in patients with thrombotic microangiopathies.

    PubMed

    Fuchs, Tobias A; Kremer Hovinga, Johanna A; Schatzberg, Daphne; Wagner, Denisa D; Lämmle, Bernhard

    2012-08-09

    Thrombotic microangiopathies (TMAs) are a group of life-threatening disorders characterized by thrombocytopenia, fragmentation of erythrocytes, and ischemic organ damage. Genetic disorders, autoimmune disease, and cancer are risk factors for TMAs, but an additional, unknown trigger is needed to bring about acute disease. Recent studies suggest that DNA and histones are released during inflammation or infection and stimulate coagulation, thrombosis, thrombocytopenia, and organ damage in mice. We show that extracellular DNA and histones as well as markers of neutrophils are present in acute TMAs. Analysis of plasma from TMA patients of different clinical categories revealed elevated levels of DNA-histone complexes and myeloperoxidase (MPO) from neutrophil granules as well as S100A8/A9, a heterocomplex abundant in neutrophil cytosol. During therapy of thrombotic thrombocytopenic purpura, a subtype of TMAs often associated with severe ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13) deficiency, plasma DNA and MPO were inversely correlated with platelet counts, and their levels indicated amelioration or exacerbation of the disease. ADAMTS13 deficiency together with increased levels of plasma DNA and MPO were characteristic for acute thrombotic thrombocytopenic purpura. A minor infection often precedes acute TMA and extracellular DNA and histones released during the inflammatory response could provide the second hit, which precipitates acute TMA in patients with pre-existing risk factors.

  7. Severe Hemolysis and Pulmonary Hypertension in a Neonate With Upshaw-Schulman Syndrome.

    PubMed

    Tsujii, Nobuyuki; Shiraishi, Isao; Kokame, Koichi; Shima, Midori; Fujimura, Yoshihiro; Takahashi, Yukihiro; Matsumoto, Masanori

    2016-12-01

    Pulmonary involvement is extremely rare in thrombotic thrombocytopenic purpura. In this report, we present a girl patient with congenital thrombotic thrombocytopenic purpura, known as Upshaw-Schulman syndrome (USS), complicated with severe hemolysis and pulmonary hypertension (PH). The assay results of a disintegrin-like and metalloprotease with thrombospondin type 1 motifs 13 (ADAMTS13) activity measured by FRETS-VWF73 and ADAMTS13-act-ELISA were different. Hyperbilirubinemia (total bilirubin, 25.3 mg/dL) interfered strongly with the FRETS-VWF73 assay. Plasma levels of ADAMTS13 activity by act-ELISA were <0.5% of normal. The diagnosis of USS was confirmed by ADAMTS13 gene analysis, which showed compound heterozygous mutations of p.G139Vfs*17 and p.I673F. The p.G139Vfs*17 mutation was previously unreported, and its effect in splicing was confirmed by reverse transcription polymerase chain reaction. The patient received oxygen therapy for PH and exchange blood transfusion for severe hemolysis. The PH resolved without specific treatment. Based on these findings, the PH may have been caused by free hemoglobin that scavenged nitrogen oxide or platelet thrombi in the lungs caused by ADAMTS13 deficiency. Thus, severe PH can occur in neonatal patients with USS, and severe hemolysis might result in overestimation of ADAMTS 13 activity. Both possibilities are important for the diagnosis and management of USS.

  8. Moyamoya Syndrome Associated with Henoch-Schönlein Purpura

    PubMed Central

    SHIARI, Reza; TABATABAEI NODUSHAN, Seyed Mohamad Hossein; MOHEBBI, Mohamad Mahdi; KARIMZADEH, Parvaneh; JAVADZADEH, Mohsen

    2016-01-01

    Some reports have shown the association between Moyamoya syndrome and autoimmune diseases. Herewith, we present a 3.5 yr old girl with Henoch- Schönleinpurpura (HSP) who was treated with steroids because of sever colicky abdominal pain. However, central nervous system manifestations such as headache, ataxia and vision impairment developed during 6 months of her outpatient follow-up. More evaluation using MRA revealed intracranial stenosis of internal carotid artery and arterial collaterals that were in favor of Moyamoya syndrome. To our knowledge, this is the first report of Moyamoya syndrome following henoch-schönleinpurpura. PMID:27843469

  9. Hyperthyroidism and immune thrombocytopenia.

    PubMed Central

    Jacobs, P.; Majoos, F.; Perrotta, A.

    1984-01-01

    Hyperthyroidism and immune thrombocytopenia occurred concurrently in five patients; in a sixth, thyrotoxicosis developed after successful treatment of the thrombocytopenia. Correction of the hyperthyroidism was followed by a variable pattern of clinical response. In one case with mild asymptomatic thrombocytopenia spontaneous complete remission occurred. Two patients required adrenocorticosteroids to control severe thrombocytopenic purpura during the period of hyperthyroidism, after which complete remission occurred. Another patient with severe symptomatic thrombocytopenia remains with a partially compensated thrombocytolytic state but is without purpura and off all therapy. A fifth patient required splenectomy for drug-resistant thrombocytopenia and remains critically dependent on immunosuppressive therapy. The sixth patient had a relapse of immune thrombocytopenia with subsequent development of thyrotoxicosis but platelet count spontaneously returned to normal after correction of the hyperthyroidism. Pregnancy in two of these six patients was not associated with recurrence of either hyperthyroidism or thrombocytopenia. Management of symptomatic purpura in adults with co-existent hyperthyroidism may differ from that customarily employed since adrenocorticosteroid therapy may need to be extended until euthyroidism has been established before proceeding to splenectomy. When surgery is necessary, the risk of thyrotoxic storm should be anticipated, and the patient appropriately premedicated. PMID:6494085

  10. [Platelet antigens: immunology and immuno-allergology].

    PubMed

    de Sousa, J C; Palma-Carlos, A G

    1996-02-01

    Platelet immunology allows the understanding of clinical findings in a genetic and serologic basis. Blood platelets bear common antigens and same specific antigens, classified in five groups (HPA 1 to 5), that are localized on membrane glycoproteins Ia, Ib alpha, IIb and IIIa. Antiplatelet autoimmunization is generally due to IgG antibodies against membrane complexes IIb/IIIa or Ib/lX. Antiplatelet alloimmunization, clinically resulting in Posttransfusion Purpura and Neonatal Thrombocytopenia is more frequently associated with anti-IIb/IIIa antibodies, either anti-HPA-1a or HPA-1b. Finally, platelet participation in immunoallergic reactions is discussed, focusing both platelet activation by allergen itself and platelet recruitment by other inflammatory cells.

  11. [Novel uses of rituximab].

    PubMed

    Frenzel, Laurent

    2013-12-01

    Since its approved by HAS in 1998, the use of rituximab increases every year. Marketed in France under the name MabThera, rituximab is used primarily in the treatment of B-cell malignancies including follicular lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia and corresponding to the three main indications for treatment. However, given its action on B cells, rituximab also proves to be effective in rheumatoid arthritis. By extension as anti-B-cell, rituximab is actually used in other autoimmune diseases: in autoimmune cytopenias as idiopathic thrombocytopenic purpura and hemolytic anemia, in vasculitis, or multiple sclerosis, it is also used in organ transplantation as kidney in prophylaxy to rejection and treatment of EBV-mediated complications.

  12. [The revolution of monoclonal antibodies in the treatment of thrombotic microangiopathy].

    PubMed

    Sauvètre, G; Grange, S; Froissart, A; Veyradier, A; Coppo, P; Benhamou, Y

    2015-05-01

    Thrombotic microangiopathies (TMA) define a syndrome characterized by the association of microangiopathic haemolytic anaemia with schistocytes, peripheral thrombocytopenia, and organ injury of variable severity. Thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uremic syndrome (HUS) are the main forms of TMA. Recent advances in the pathophysiology of those two diseases, which include in HUS the identification of a deregulation of the alternative complement pathway, and in TTP a severe deficiency in ADAMTS-13, allowed to develop specific, pathophysiology-based therapies. Therefore, rituximab and eculizumab tends to be increasingly used, and there is an urgent need to define consensual modes of administration at the international level, as well as common definitions of response evaluation and follow-up explorations.

  13. [Dermatomiositis and evans syndrome associated with HTLV-1 infection].

    PubMed

    Loja-Oropeza, David; Zavala-Flores, Ernesto; Vilca-Vasquez, Maricela

    2016-03-01

    A 55-year-old female patient, born in Ayacucho, with a history of dermatomyositis for 3 years, who received irregular treatment with prednisone. Two months prior to admission, she presented with autoinmune hemolytic anemia and idiopathic thrombocytopenic purpura. The patient received methylprednisolone pulse therapy and packed red blood cells transfusions. Upon admission, she was drowsy, with a poor overall status, marked weight loss, dehydration, with presence of livedo reticularis in her lower extremities, and onychodystrophy and onycholysis on the toes of both feet. Western blot test was positive for human T-lymphotropic virus type 1 (HTLV-1). The patient evolved with recurrent hypoglycemia. Therefore, we report a case of dermatomyositis and Evans syndrome in the context of an HTLV-1 infection.

  14. Role of therapeutic apheresis and phlebotomy techniques in anaesthesia and critical care

    PubMed Central

    Bose, Neeta; Kanzariya, Hitendra

    2014-01-01

    Therapeutic transfusion techniques such as apheresis and phlebotomy are frequently used in intensive care units. Use of the apheresis technique for the treatment of various diseases in critically ill patients is growing day by day. There are increasing evidences for using apheresis as a primary therapy or as an adjunct to other therapies for various diseases such as thrombotic thrombocytopenic purpura, haemolytic uremic syndrome, drug toxicities, autoimmune disease, sepsis and fulminant hepatic failure. Apheresis is an invasive procedure. It has significant physiologic consequences, so the care of these patients requires continuous supervision. Phlebotomy is performed as an intervention for some disease management. Its use is nowadays restricted to conditions such as polycythaemia, haemochromatosis and porphyria cutanea tarda. In this review, we have looked at various indications, procedure and complications of apheresis and phlebotomy in critical care unit. PMID:25535434

  15. [Hemolytic anemias in adults].

    PubMed

    Müller, A; Zimmermann, R; Krause, S W

    2011-11-01

    The erythrocyte lifespan in haemolytic anemia is shortened while erythropoesis is increased. Important labaratory findings are increased reticulocytes, LDH, indirect bilirubin and a decreased haptoglobin level. The most important diagnostic tool for further work up of hemolytic anemia is the direct antiglobulin test (DAT, Coombs test) to differentiate autoimmune hemolytic anemia (AIHA) from other causes. Another important group are fragmentation syndroms (hemolytic uremic syndrome and thrombotic thrombocytopenic purpura). In these forms of haemolytic anemia fragmented red blood cells can be found in the blood smear together with thrombocytopenia. A severe problem in paroxysmal nocturnal hematuria is the incidence of thrombosis. The following review describes the most important forms of hemolytic anemia in the adult and the diagnostic and therapeutic strategies.

  16. Inherited Thrombocytopenia with a Different Type of Gene Mutation: A Brief Literature Review and Two Case Studies

    PubMed Central

    Arzanian, Mohammad Taghi

    2016-01-01

    Hereditary thrombocytopenias are rare bleeding disorders, which cause a deficiency of platelets in early infancy. This group of disorders is sometimes associated with abnormal phenotypes, like absence of radius. Diagnosis of this type of thrombocytopenia is usually difficult; other causes of thrombocytopenia, such as immune disorders and infections, must be ruled out. The symptoms of hereditary thrombocytopenia also vary from seldom and mild to severe bleeding and occasionally may first occur in late childhood. In this group of patients, we must differentiate heritable disorders from the acquired types of thrombocytopenia, like immune thrombocytopenic purpura. It is also important to watch for pitfalls to avoid unnecessary and potentially hazardous treatment. Herein, we briefly review the recent literature on hereditary thrombocytopenia and then present the cases of two referred patients. The first case had suffered from persistent thrombocytopenia since early infancy and was diagnosed with congenital amegakaryocytic thrombocytopenia, while the other patient presented with Wiskott - Aldrich syndrome. PMID:28203325

  17. Helicobacter pylori infection and extragastric disorders in children: a critical update.

    PubMed

    Pacifico, Lucia; Osborn, John F; Tromba, Valeria; Romaggioli, Sara; Bascetta, Stefano; Chiesa, Claudio

    2014-02-14

    Helicobacter pylori (H. pylori) is a highly prevalent, serious and chronic infection that has been associated causally with a diverse spectrum of extragastric disorders including iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, growth retardation, and diabetes mellitus. The inverse relation of H. pylori prevalence and the increase in allergies, as reported from epidemiological studies, has stimulated research for elucidating potential underlying pathophysiological mechanisms. Although H. pylori is most frequently acquired during childhood in both developed and developing countries, clinicians are less familiar with the pediatric literature in the field. A better understanding of the H. pylori disease spectrum in childhood should lead to clearer recommendations about testing for and treating H. pylori infection in children who are more likely to develop clinical sequelae. A further clinical challenge is whether the progressive decrease of H. pylori in the last decades, abetted by modern clinical practices, may have other health consequences.

  18. Neurocritical care complications of pregnancy and puerperum.

    PubMed

    Frontera, Jennifer A; Ahmed, Wamda

    2014-12-01

    Neurocritical care complications of pregnancy and puerperum such as preeclampsia/eclampsia, hemolysis, elevated liver enzymes, low platelets syndrome, thrombotic thrombocytopenic purpura, seizures, ischemic and hemorrhagic stroke, postpartum angiopathy, cerebral sinus thrombosis, amniotic fluid emboli, choriocarcinoma, and acute fatty liver of pregnancy are rare but can be devastating. These conditions can present a challenge to physicians because pregnancy is a unique physiologic state, most therapeutic options available in the intensive care unit were not studied in pregnant patients, and in many situations, physicians need to deliver care to both the mother and the fetus, simultaneously. Timely recognition and management of critical neurologic complications of pregnancy/puerperum can be life saving for both the mother and fetus.

  19. Helicobacter pylori infection and extragastric disorders in children: A critical update

    PubMed Central

    Pacifico, Lucia; Osborn, John F; Tromba, Valeria; Romaggioli, Sara; Bascetta, Stefano; Chiesa, Claudio

    2014-01-01

    Helicobacter pylori (H. pylori) is a highly prevalent, serious and chronic infection that has been associated causally with a diverse spectrum of extragastric disorders including iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, growth retardation, and diabetes mellitus. The inverse relation of H. pylori prevalence and the increase in allergies, as reported from epidemiological studies, has stimulated research for elucidating potential underlying pathophysiological mechanisms. Although H. pylori is most frequently acquired during childhood in both developed and developing countries, clinicians are less familiar with the pediatric literature in the field. A better understanding of the H. pylori disease spectrum in childhood should lead to clearer recommendations about testing for and treating H. pylori infection in children who are more likely to develop clinical sequelae. A further clinical challenge is whether the progressive decrease of H. pylori in the last decades, abetted by modern clinical practices, may have other health consequences. PMID:24587617

  20. Helicobacter pylori infection and thrombocytopenia: a single-institution experience in Mexico.

    PubMed

    Estrada-Gómez, Roberto A; Parra-Ortega, Israel; Martínez-Barreda, Carlos; Ruiz-Argüelles, Guillermo J

    2007-01-01

    The association between gastrointestinal H. pylori infection and thrombocytopenia was studied in a single institution in Mexico, over a 5-year period. In 99 individuals with H. pylori infection, the prevalence of thrombocytopenia was 14%, whereas in 23 consecutive patients with chronic refractory thrombocytopenic purpura, the prevalence of H. pylori infection was 60%, this figure being similar to that informed in the general population of Mexico (66%); the association between thrombocytopenia and H. pylori infection was not significant. In 14 patients who were found to have both thrombocytopenia and H. pylori infection, eradication treatment was given and the platelet count recovered in three. It is not still clear if detection of H. pylori infection should be routinely included in the initial workup of chronic thrombocytopenia.

  1. Miliary tuberculosis presenting with hyponatremia and thrombocytopenia.

    PubMed Central

    Cockcroft, D. W.; Donevan, R. E.; Copland, G. M.; Ibbott, J. W.

    1976-01-01

    A 74-year-old woman with miliary tuberculosis had moderately severe hyponatremia due to inappropriate secretion of antidiuretic hormone (SIADH) and very severe thrombocytopenia without other hematologic abnormalities. She was treated with isoniazid, rifampin, ethambutol, prednisone, vincristine and fluid restriction and recovered completely. The SIADH may have been a response by the posterior pituitary to a decrease in intravascular volume resulting from the extensive pulmonary disease or associated hypoxia, or the tuberculous lung may have released ADH or an ADH-like substance. The thrombocytopenia may have resulted from a direct or indirect toxic effect of infection or, less likely, the tuberculosis may have activated latent idiopathic thrombocytopenic purpura. Images FIG. 2 FIG. 3 PMID:991033

  2. Acute kidney injury in pregnancy: the thrombotic microangiopathies.

    PubMed

    Ganesan, Chitra; Maynard, Sharon E

    2011-01-01

    Acute kidney injury (AKI) is a rare but serious complication of pregnancy. Although prerenal and ischemic causes of AKI are most common, renal insufficiency can complicate several other pregnancy-specific conditions. In particular, severe preeclampsia/HELLP syndrome, acute fatty liver of pregnancy (AFLP) and thrombotic thrombocytopenic purpura (TTP) are all frequently complicated by AKI, and share several clinical features which pose diagnostic challenges to the clinician. In this article, we discuss the clinical and laboratory features, pathophysiology and treatment of these 3 conditions, with particular attention to renal manifestations. It is imperative to distinguish these conditions to make appropriate therapeutic decisions which can be lifesaving for the mother and fetus. Typically AFLP and HELLP improve after delivery of the fetus, whereas plasma exchange is the first-line treatment for TTP.

  3. Purification of glycocalicin from human plasma.

    PubMed

    HadjKacem, Basma; Mkaouar, Héla; Ben Amor, Ikram; Gargouri, Jalel; Gargouri, Ali

    2016-01-01

    Glycocalicin (GC) is a large extracellular proteolytic fragment of glycoprotein Ib, a membrane platelet component playing an essential role in the physiological processes of platelet adhesion and aggregation. GC contains the binding sites for thrombin and von Willebrand factor. GC circulates normally in vivo in significant concentrations and the plasma level of this protein reflects a complex function of factors including platelet count or platelet turnover. It can therefore serve as a good indicator for many diseases like hypoplastic thrombocytopenia and idiopathic thrombocytopenic purpura. For this reason, several purification assays have been previously described. In this work, we describe a novel analytical method for GC purification from human platelets based on preparative HPLC gel filtration followed by immuno-affinity chromatography on NHS activated column conjugated with specific antibody. Pure GC was obtained from tiny amount of starting material. Our protocol of GC purification is simple, fast and provides a pure end product.

  4. Developing therapeutic immunoglobulins: European regulatory perspectives and implications.

    PubMed

    Kurz, Manfred

    2008-01-01

    Prepared from pooled human blood/plasma, therapeutic immunoglobulins contain the natural antibody spectrum of the entire donor population and mediate a range of therapeutic effects when administered to patients. They are particularly indicated for the prevention of serious and life-threatening infections in patients with immune systems failing to produce functional antibodies. Other than treatment of such rare primary immunodeficiencies (primary antibody deficiencies), therapeutic immunoglobulins are also used in certain inflammatory and autoimmune disorders, including immune thrombocytopenic purpura, Guillain Barré syndrome, and Kawasaki disease. The conditions for licensure of therapeutic immunoglobulins in the EU and the associated regulatory issues and procedures are reviewed. Regulatory expectations about the manufacture and control of immunoglobulins are highlighted and safety and efficacy requirements described. Although the main focus is on European pharmaceutical legislation, other applicable public information is considered.

  5. Intracellular signaling as a potential target for antiplatelet therapy.

    PubMed

    Andre, Patrick

    2012-01-01

    Three classes of inhibitors of platelet aggregation have demonstrated substantial clinical benfits. Aspirin acts by irreversibly inhibiting COX-1 and therefore blocking the synthesis of proaggregatory thromboxane A (2) (TxA(2)). The indirect acting (ticlopidine, clopidogrel, prasugrel) and the direct acting (ticagrelor) antagonists of P2Y(12) block the thrombus stabilizing activity of ADP. Parenteral GP IIb-IIIa inhibitors directly block platelet-platelet interactions. Despite well-established benefits, all antiplatelet agents have important limitations: increased bleeding and gastrointestinal toxicities (aspirin), high incidence of thrombotic thrombocytopenic purpura (ticlopidine), potentially nonresponders (clopidogrel), severe bleeding (prasugrel, GP IIb-IIIa antagonists) and "complicated" relationships with aspirin ticagrelor). In this chapter, we present the genetic and pharmacological evidence that supports the development and expectations associated with novel antiplatelet strategies directed at intrasignaling pathways.

  6. Antiepileptic hypersensitivity syndrome: clinicians beware and be aware.

    PubMed

    Bessmertny, Olga; Pham, Trinh

    2002-01-01

    Antiepileptic hypersensitivity syndrome is a serious idiosyncratic, non-dose-related adverse reaction reported to occur with phenytoin, phenobarbital, carbamazepine, primidone, and lamotrigine. The reaction usually develops 1 to 12 weeks after initiation of therapy with one of the above agents and is recognized by the classic triad of fever, rash, and internal organ involvement. Immediate discontinuation of the suspected anticonvulsant is essential for good outcome. Patients usually are managed supportively with hydration, antihistamines, H(2)-receptor blockers, and topical corticosteroids. In severe cases, the use of systemic corticosteroids may be necessary. The use of intravenous immune globulin should be limited to severe cases where Kawasaki disease or idiopathic thrombocytopenic purpura cannot be ruled out. Education of health care professionals and patients is imperative to improving outcomes and prevention of this reaction in the future.

  7. Autoimmunity in Common Variable Immunodeficiency

    PubMed Central

    Agarwal, Shradha; Cunningham-Rundles, Charlotte

    2010-01-01

    Common variable immunodeficiency (CVID) is the most common clinically significant primary immune defect. Although the hallmark of CVID is hypogammaglobulinemia, the intrinsic dysregulation of the immune system leads to defective T-cell activation and proliferation, as well as dendritic cell and cytokine defects. Although 70% to 80% of patients have had recurrent sinopulmonary infections, auto-immunity and inflammatory complications are also common. The most common autoimmune conditions are immune thrombocytopenic purpura and hemolytic anemia, but other autoimmune complications arise, including rheumatoid arthritis, pernicious anemia, primary biliary cirrhosis, thyroiditis, sicca syndrome, systemic lupus, and inflammatory bowel disease. Treatment of autoimmunity includes high-dose immunoglobulins, corticosteroids, selected immunosuppressants, and other immune modulators. This review focuses on autoimmune conditions associated with CVID, potential mechanisms of immune dysregulation, and therapeutic strategies. PMID:19671377

  8. Myelodysplastic Syndrome Clinically Presenting with the “Classic TTP Pentad”

    PubMed Central

    Polanco Jácome, Evelyn Carolina; Guevara, Elizabeth; Mattoo, Vijay

    2017-01-01

    The clinical presentation of myelodysplastic syndrome (MDS) is not specific. Many patients can be asymptomatic and can be detected only due to an abnormal complete blood cell count (CBC) on routine exam or for other reasons while others can be symptomatic as a consequence of underlying cytopenias. Thrombotic thrombocytopenic purpura (TTP) usually is suspected under the evidence of microangiopathic hemolytic anemia (MAHA) and thrombocytopenia and because it is a life-threatening condition (medical emergency) immediate initiation of plasmapheresis could be life-saving. The following case illustrates an unusual presentation of MDS in a patient who came in to the emergency room with the classic TTP “pentad” of fever, renal involvement, MAHA, mental status changes, and thrombocytopenia. We will focus our discussion in the clinical presentation of this case. PMID:28255478

  9. Coronary artery aneurysm presenting as a large mass encroaching on the right atrium in an adult patient with untreated Kawasaki disease

    PubMed Central

    Wassef, Nancy

    2015-01-01

    A 26-year-old man presented with atypical chest pain and dyspnoea for several days before admission that was not related to exertion. The patient had no medical history other than a long duration of fever and rash as a child, which resolved after a few weeks. The initial blood investigations showed thrombocytopenia and raised inflammatory markers with a negative troponin level. The patient had positive antiplatelet antibodies and was diagnosed with immune thrombocytopenic purpura (ITP). Echocardiography showed a large cystic mass at the right atrium. Coronary multislice CT showed a huge aneurysm at the origin of the right coronary artery (RCA), which was confirmed by coronary angiography. The patient received intravenous immunoglobulin and platelet transfusion before coronary artery bypass surgery and he had a successful resection of the aneurysm with a saphenous vein graft to distal RCA. The patient had a good recovery and was discharged home. PMID:25819826

  10. Autoimmune diseases in a Nigerian woman--a case report.

    PubMed

    Talabi, O A; Owolabi, M O; Osotimehin, B O

    2003-12-01

    Autoimmune diseases (AD) are conditions in which there is the development of antibodies against self cells/ organs. AD could either be organ-specific or non-organ specific (systemic) in clinical presentation. Commonly reported ADs includes: Myasthenia gravis, Hashimoto thyroiditis, Guillian-Barre syndrome, vitiligo, type 1 diabetes mellitus, Graves diseases, Goodpastures syndrome, pemphigus, rheumatoid arthritis, systemic lupus erythematosis, Addisons disease, multiple sclerosis, pernicious anaemia, autoimmune haemolytic anaemia, chronic active hepatitis, idiopathic thrombocytopenic purpura. There is paucity of locally documented information on the occurrence of AD in same patient in our environment. We therefore report the case of a 66 year old woman who presented at the University College Hospital (UCH), Ibadan, with a spectrum of the AD, Vitiligo, rheumatoid arthritis, myasthenia gravis, impaired glucose tolerance.

  11. Cancer-associated thrombotic microangiopathy

    PubMed Central

    Govind Babu, K; Bhat, Gita R

    2016-01-01

    Cancer-associated thrombotic microangiopathy refers to a group of disorders characterised by microvascular thrombosis, thrombocytopenia, and ischaemic end-organ damage. Haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura are the two major subtypes. It can be a manifestation of the malignancy itself or a complication of its therapy. The addition of several new drugs to the therapeutic armamentarium of cancer has brought to light several novel causative factors of this hitherto uncommon complication. This review covers the aetiology, pathogenesis, clinical manifestations, complications, and the management of cancer-associated thrombotic microangiopathy. Careful review of the patient’s medical records coupled with the correlation of clinical findings and laboratory reports can help clinch the diagnosis and institute appropriate treatment on time. PMID:27433282

  12. Extraintestinal manifestations of Helicobacter pylori: A concise review

    PubMed Central

    Wong, Frank; Rayner-Hartley, Erin; Byrne, Michael F

    2014-01-01

    Helicobacter pylori (H. pylori) infection has been clearly linked to peptic ulcer disease and some gastrointestinal malignancies. Increasing evidence demonstrates possible associations to disease states in other organ systems, known as the extraintestinal manifestations of H. pylori. Different conditions associated with H. pylori infection include those from hematologic, cardiopulmonary, metabolic, neurologic, and dermatologic systems. The aim of this article is to provide a concise review of the evidence that supports or refutes the associations of H. pylori and its proposed extraintestinal manifestations. Based on data from the literature, PUD, mucosal associated lymphoid tumors lymphoma, and gastric adenocarcinoma has well-established links. Current evidence most supports extraintestinal manifestations with H. pylori in immune thrombocytopenic purpura, iron deficiency anemia, urticaria, Parkinson’s, migraines and rosacea; however, there is still plausible link with other diseases that requires further research. PMID:25232230

  13. [Acute renal failure secondary to hemolytic uremic syndrome in a pregnant woman with pre-eclampsia].

    PubMed

    García-Miguel, F J; Mirón Rodríguez, M F; Alsina Aser, M J

    2009-02-01

    Acute renal failure is a serious complication of pregnancy associated with a high rate of morbidity and mortality; the incidence is currently 1 per 10,000 pregnancies. The most common causes are gestational hypertension, bleeding, sepsis, and intrinsic renal disease. Other less common pregnancy-related syndromes, such as HELLP syndrome or thrombotic microangiopathy, may also lead to kidney failure. Hemolytic uremic syndrome and thrombotic thrombocytopenic purpura are forms of thrombotic microangiopathy and although neither is specific to pregnancy, the incidence of these entities rises during gestation. The classic symptoms are fever, hemolytic microangiopathic anemia, thrombopenia, neurologic dysfunction, and kidney abnormalities. When renal involvement is the predominant manifestation, the diagnosis is usually hemolytic uremic syndrome.

  14. Inherited ADAMTS13 deficiency (Upshaw-Schulman syndrome): a short review.

    PubMed

    Pérez-Rodríguez, Almudena; Lourés, Esther; Rodríguez-Trillo, Ángela; Costa-Pinto, Joana; García-Rivero, Aránzazu; Batlle-López, Ana; Batlle, Javier; López-Fernández, María Fernanda

    2014-12-01

    Congenital thrombotic thrombocytopenic purpura (TTP), also known as Upshaw-Schulman syndrome, is associated with an inherited deficiency of ADAMTS13, a von Willebrand factor-cleaving protease. It is a rare, life-threatening disorder characterized by thrombocytopenia, hemolytic anemia, neurological symptoms, renal dysfunction, and fever resulting from formation of platelet thrombi within the microvasculature. Patients have initial episodes mainly during infancy or early childhood, and are conventionally treated with fresh frozen plasma. However, a more appropriate approach based on recombinant ADAMTS13 is slated to begin shortly. Mutations throughout the ADAMTS13 have been identified in congenital TTP patients. The prevalence of this entity is probably underestimated because it is often not suspected, the clinical course is usually heterogeneous and most of the symptoms are common to other diseases. The present review summarizes our current knowledge about Upshaw-Schulman syndrome.

  15. Update on ADAMTS13 and VWF in cardiovascular and hematological disorders.

    PubMed

    Akyol, Omer; Akyol, Sumeyya; Chen, Chu-Huang

    2016-12-01

    Endothelial cells (EC) respond to injury by releasing numerous factors, including von Willebrand factor (VWF). High circulating levels of unusually large VWF multimers (UL-VWFM) have strong procoagulant activity and facilitate platelet adhesion and aggregation by interacting with platelets after an acute event superimposed on peripheral arterial disease and coronary artery disease. ADAMTS13-a disintegrin-like metalloproteinase with thrombospondin motif type 1 member 13-regulates a key physiological process of coagulation in the circulation by cleaving VWF multimers into small, inactive fragments. Low levels of ADAMTS13 in the blood may play a role in cardiovascular and hematological disorders, and clarifying its role may help improve disease management. The genetic, pharmacological, physiological, and pathological aspects related to ADAMTS13/VWF have been extensively investigated. Here, we provide an update on recent findings of the relationship between ADAMTS13 and hematological/cardiovascular disorders, including thrombotic thrombocytopenic purpura, arterial thrombosis, thrombotic microangiopathy, myocardial infarction, ischemic stroke, heart failure, and hypertension.

  16. Single incision laparoscopic splenectomy with double port.

    PubMed

    Vatansev, Celalettin; Ece, Ilhan

    2009-12-01

    In response to the increasing interest in minimally invasive surgery by both patients and surgeons, most abdominal surgery today is carried out laparoscopically. Laparoscopic splenectomy has become a gold standard in the treatment of spleen disorders related to hematologic diseases. Increasing laparoscopic surgery experience and improved new vessel sealing equipment have led to a decreasing number of ports in laparoscopic surgery and to operations from 1 incision. We carried out single-incision double-port laparoscopic splenectomy in a patient with immune thrombocytopenic purpura using only 2 trocars with a simple manipulation. Our review of the related literature revealed no earlier description of a single-incision double-port laparoscopic splenectomy. We therefore present herein this earlier unreported technique.

  17. Helicobacter pylori infection: New pathogenetic and clinical aspects

    PubMed Central

    Hagymási, Krisztina; Tulassay, Zsolt

    2014-01-01

    Helicobacter pylori (H. pylori) infects more than half of the world’s human population, but only 1% to 3% of infected people consequently develop gastric adenocarcinomas. The clinical outcome of the infection is determined by host genetic predisposition, bacterial virulence factors, and environmental factors. The association between H. pylori infection and chronic active gastritis, peptic ulcer disease, gastric cell carcinoma, and B cell mucosa-associated lymphoid tissue lymphoma has been well established. With the exception of unexplained iron deficiency anemia and idiopathic thrombocytopenic purpura, H. pylori infection has no proven role in extraintestinal diseases. On the other hand, there is data showing that H. pylori infection could be beneficial for some human diseases. The unpredictability of the long-term consequences of H. pylori infection and the economic challenge in eradicating it is why identification of high-risk individuals is crucial. PMID:24914360

  18. Thrombocytopenia associated with environmental exposure to polyurethane

    SciTech Connect

    Michelson, A.D. )

    1991-10-01

    Few chemicals in the environment have been implicated as causes of isolated thrombocytopenia, and the evidence is usually less than convincing because the patients were not rechallenged with the chemical in vivo. In the present paper, a child is reported with the onset of thrombocytopenia in temporal association with environmental exposure to polyurethane. Five years after the initial thrombocytopenia had resolved, an inadvertent in vivo rechallenge with environmental polyurethane resulted in recurrence of the thrombocytopenia. This recurrence, together with the fact that only 1-4% of cases of idiopathic thrombocytopenic purpura in children recur, provided strong evidence for a causal role for the polyurethane exposure in this patient's thrombocytopenia. In summary, environmental exposure to polyurethane should be considered in the differential diagnosis of acquired thrombocytopenia in childhood.

  19. Splenectomy for hematologic disease. The UCLA experience with 306 patients.

    PubMed

    Musser, G; Lazar, G; Hocking, W; Busuttil, R W

    1984-07-01

    Between 1956 and 1981, 306 splenectomies for hematologic diseases were performed at the UCLA Medical Center. Of these operations, more than 75% were performed for therapeutic reasons to control anemia, thrombocytopenia, neutropenia, or painful symptoms of splenomegaly. Of the 65 patients who had idiopathic thrombocytopenic purpura, 77% showed an excellent response, and of the 39 patients who had hereditary spherocytosis, 90% responded. Other diseases with predictably good response rates were autoimmune hemolytic anemias, Felty's syndrome, and hairy cell leukemia. Forty patients with Hodgkin's disease had splenectomies for diagnostic purposes the last 10 years. The overall morbidity and mortality were 24% and 6%, respectively, the most common complications being pneumonia, wound infections, and local postoperative bleeding, and the most common cause of death being sepsis. The review supports the thesis that in carefully selected patients, therapeutic splenectomy can have desirable palliative effects and that diagnostic splenectomy has a sufficiently low risk to warrant its consideration in patients with Hodgkin's disease.

  20. Abacavir induced T cell reactivity from drug naïve individuals shares features of allo-immune responses.

    PubMed

    Adam, Jacqueline; Wuillemin, Natascha; Watkins, Stephan; Jamin, Heidi; Eriksson, Klara K; Villiger, Peter; Fontana, Stefano; Pichler, Werner J; Yerly, Daniel

    2014-01-01

    Abacavir hypersensitivity is a severe hypersensitivity reaction which occurs exclusively in carriers of the HLA-B*57∶01 allele. In vitro culture of PBMC with abacavir results in the outgrowth of abacavir-reacting CD8+ T cells, which release IFNγ and are cytotoxic. How this immune response is induced and what is recognized by these T cells is still a matter of debate. We analyzed the conditions required to develop an abacavir-dependent T cell response in vitro. The abacavir reactivity was independent of co-stimulatory signals, as neither DC maturation nor release of inflammatory cytokines were observed upon abacavir exposure. Abacavir induced T cells arose in the absence of professional APC and stemmed from naïve and memory compartments. These features are reminiscent of allo-reactivity. Screening for allo-reactivity revealed that about 5% of generated T cell clones (n = 136) from three donors were allo-reactive exclusively to the related HLA-B*58∶01. The addition of peptides which can bind to the HLA-B*57∶01-abacavir complex and to HLA-B*58∶01 during the induction phase increased the proportion of HLA-B*58∶01 allo-reactive T cell clones from 5% to 42%. In conclusion, abacavir can alter the HLA-B*57∶01-peptide complex in a way that mimics an allo-allele ('altered self-allele') and create the potential for robust T cell responses.

  1. In vivo production of macrophage migration inhibition and stimulation factors during the inductive phase of the alloimmune response

    SciTech Connect

    Suslov, A.P.; Yazova, A.K.; Berkova, N.P.

    1986-12-01

    This paper offers a study of the production of macrophage migration inhibition factor (MIF), and also of the alternative macrophage migration stimulation factor (MSF), in vivo. Mice were injected with mouse spleen cells, irradiated with a dose of 1500 rads. The animals were divided into three groups, two of which were injected for a second time with irradiated mouse spleen cells. Samples of all fractions obtained by electrophoresis of sera of unimmunized mice had no significant effect of macrophage migration, while unfractionated sera of immunized mice obtained after a second injection of alloantigen as a rule stimulated macrophage migration. The results are evidence that T cells may function in vivo during the period before development of the antigen-specific proliferative response of T cells. The technique used to approach the problem, described in this study, can be used for preparative isolation of purified MIF and MSF without contamination by embryonic calf serum proteins which are usually present in culture in vitro.

  2. Is expertise in pediatric surgery necessary to perform laparoscopic splenectomy in children? An experience from a department of general surgery.

    PubMed

    Guaglio, Marcello; Romano, Fabrizio; Garancini, Mattia; Degrate, Luca; Luperto, Margherita; Uggeri, Fabio; Scotti, Mauro; Uggeri, Franco

    2012-06-01

    Splenectomy is frequently required in children for various hematologic pathologic findings. Because of progress in minimally invasive techniques, laparoscopic splenectomy (LS) has become feasible. The objective of this report is to present a monocentric experience and to evaluate the efficacy of and complications observed after laparoscopic splenic procedures in a department of general surgery. 57 consecutive LSs have been performed in a pediatric population between January 2000 and October 2010. There were 33 females and 24 males with a median age of 12 years (range 4-17). Indications were: hereditary spherocytosis 38 cases, idiopathic thrombocytopenic purpura 10, sickle cell disease (SCD) 6, thrombocytopenic thrombotic purpura 2 and non-hodgkin lymphoma 1 case. Patients were operated on using right semilateral position, employing Atlas Ligasure vessel sealing system in 49 cases (86%) and Harmonic Scalpel + EndoGIA in 8. In 24 patients (42.1%), a cholecystectomy was associated. Two patients required conversion to open splenectomy (3.5%). In three cases, a minilaparotomy was performed for spleen removal (5.2%). Accessory spleens were identified in three patients (5.2%). Complications (8.8%) included bleeding (two), abdominal collection (one) and pleural effusion (two). There was no mortality. Average operative time was 128 min (range 80-220). Average length of stay was 3 days (range 2-7). Mean blood loss was 80 ml (range 30-500) with a transfusion rate of 1.7% (one patient). Laparoscopic spleen surgery is safe, reliable and effective in the pediatric population with hematologic disorders and is associated with minimal morbidity, zero mortality, and a short length of stay. Ligasure vessel sealing system shortened operative time and blood loss. On the basis of the results, we consider laparoscopic approach the gold standard for the treatment of these patients even in a department of general surgery.

  3. Hematopoietic cell transplantation-associated thrombotic microangiopathy: a review of pathophysiology, diagnosis, and treatment

    PubMed Central

    Rosenthal, Joseph

    2016-01-01

    Transplant-associated thrombotic microangiopathy (TA-TMA) is a multifactorial disorder caused by systemic vascular endothelial injury that can be triggered by several mechanisms during the transplant process. Thrombotic microangiopathy may affect multiple systems and occurs in ~30% of patients undergoing hematopoietic stem cell transplantation. A subgroup of patients with thrombotic microangiopathy develop TA-TMA, and the other may develop other thrombotic microangiopathic disorders such as thrombotic thrombocytopenic purpura, a condition with similar finding but different pathophysiology involving ADAMTS-13. The mortality rates in patients who develop severe TA-TMA are in excess of 80%. Recent investigations show that complement system activation in patients with TA-TMA is a very poor prognostic sign and implicates complement dysregulation as a key pathway in the pathogenesis of TA-TMA and its disease phenotype. The original diagnostic criteria for TA-TMA included hematologic and renal injury markers, which are limited in their ability to detect only advanced disease, and therefore may result in delayed TA-TMA diagnosis in transplant patients. A recent set of diagnostic criteria added markers of complement activation, proteinuria, and hypertension, with predicted improved detection of early TA-TMA. Supportive care that includes elimination of potentially toxic agents such as calcineurin inhibitors and sirolimus, adequate antimicrobial treatment, and maintaining adequate renal functions using renal replacement therapy may be sufficient for treatment of mild-to-moderate TA-TMA. Plasma exchange, which is a potentially curative therapy in thrombotic thrombocytopenic purpura, has no proven efficacy in TA-TMA. Blocking the complement system with eculizumab is currently the most effective treatment to circumvent the poor outcome in patients with severe TA-TMA. PMID:27621680

  4. Hematopoietic cell transplantation-associated thrombotic microangiopathy: a review of pathophysiology, diagnosis, and treatment.

    PubMed

    Rosenthal, Joseph

    2016-01-01

    Transplant-associated thrombotic microangiopathy (TA-TMA) is a multifactorial disorder caused by systemic vascular endothelial injury that can be triggered by several mechanisms during the transplant process. Thrombotic microangiopathy may affect multiple systems and occurs in ~30% of patients undergoing hematopoietic stem cell transplantation. A subgroup of patients with thrombotic microangiopathy develop TA-TMA, and the other may develop other thrombotic microangiopathic disorders such as thrombotic thrombocytopenic purpura, a condition with similar finding but different pathophysiology involving ADAMTS-13. The mortality rates in patients who develop severe TA-TMA are in excess of 80%. Recent investigations show that complement system activation in patients with TA-TMA is a very poor prognostic sign and implicates complement dysregulation as a key pathway in the pathogenesis of TA-TMA and its disease phenotype. The original diagnostic criteria for TA-TMA included hematologic and renal injury markers, which are limited in their ability to detect only advanced disease, and therefore may result in delayed TA-TMA diagnosis in transplant patients. A recent set of diagnostic criteria added markers of complement activation, proteinuria, and hypertension, with predicted improved detection of early TA-TMA. Supportive care that includes elimination of potentially toxic agents such as calcineurin inhibitors and sirolimus, adequate antimicrobial treatment, and maintaining adequate renal functions using renal replacement therapy may be sufficient for treatment of mild-to-moderate TA-TMA. Plasma exchange, which is a potentially curative therapy in thrombotic thrombocytopenic purpura, has no proven efficacy in TA-TMA. Blocking the complement system with eculizumab is currently the most effective treatment to circumvent the poor outcome in patients with severe TA-TMA.

  5. The Efficacy and Safety of Miconazole Nitrate Mucoadhesive Tablets versus Itraconazole Capsules in the Treatment of Oral Candidiasis: An Open-Label, Randomized, Multicenter Trial

    PubMed Central

    Liu, Yang; Han, Ying; Lin, Mei; Wang, Wenmei; Guan, Xiaobing; Zhu, Shengrong; Zhang, Handong; Wang, Qintao; Chou, Lihong; Zhu, Xinghao; Hua, Hong

    2016-01-01

    Background Oral candidiasis (OC) is a common oral fungal infection. Recently, miconazole mucoadhesive tablets have been gaining attention for OC treatment. Despite trials in patients with human immunodeficiency virus and cancer, evidence of its application in the large-scale, general population with OC is lacking. This study aimed to evaluate the efficacy and safety of miconazole nitrate mucoadhesive tablets in comparison with itraconazole capsules for OC treatment. Methods The study was a randomized, open-label, parallel-armed, multicenter clinical trial. Totally, 343 patients diagnosed with OC, who met the inclusion criteria, were randomly assigned to either a treatment group that received miconazole nitrate mucoadhesive tablets (10 mg) once daily or a control group that received itraconazole capsules (100 mg QD) for 2 weeks, and were followed up for 2 weeks. The clinical cure, improvement of clinical symptoms/signs, mycologic cure, and safety were evaluated. Results The mucoadhesive tablets (n = 171) did not show inferiority to itraconazole (n = 172) in the treatment of OC. At the end of the 14-day treatment, the clinical cure rates were 45.29% and 41.76% in the miconazole and itraconazole groups, respectively (P = 0.3472). At the end of the 14-day follow-up, the clinical cure rates were 51.18% and 41.76% in the miconazole and itraconazole groups, respectively (P = 0.0329). Adverse events occurred in 53 subjects (33 in the miconazole group and 20 in the itraconazole group). There was no statistical difference in the safety profile between miconazole and itraconazole (P = 0.0533). Thrombocytopenic purpura, although rare, occurred in one patient in the miconazole group and was considered a drug-related, severe adverse event. Conclusion Miconazole nitrate mucoadhesive tablets may be as effective as systemic itraconazole capsule for OC treatment. Physicians should be cautious about thrombocytopenic purpura occurring as a rare and serious adverse event of miconazole

  6. Sustained response to combination therapy in a patient with chronic hepatitis C and thrombocytopenia secondary to alpha-interferon.

    PubMed

    Jiménez-Sáenz, M; Rojas, M; Piñar, A; Salas, E; Rebollo, J; Carmona, I; Herrerías-Esteban, J M; Herrerías-Gutiérrez, J M

    2000-05-01

    Recent data suggest that hepatitis C viral (HCV) infection may induce a significant autoimmune reaction to platelets, but the mechanism is unknown. Many patients with chronic hepatitis C, in fact, have high levels of platelet-associated immunoglobulin G (PAIgG) and HCV-RNA is present in the platelets of 100% of those patients with thrombocytopenia and high PAIgG levels. Hepatitis C virus infection has been associated with the development of thrombocytopenic purpura, sometimes triggered during interferon (IFN) therapy. In such cases, the treatment of the underlying disease is a difficult problem to solve. We report the case of a patient with chronic hepatitis C, who developed life-threatening thrombocytopenic purpura after a prolonged course of IFN-alpha2b over a 4-year period. Treatment with anti-immunoglobulin gammaglobulin (Polyglobin; Química Farmaceutica Bayer, Barcelona, Spain) had a transient effect on the platelet count, but prolonged therapy with prednisone was necessary for definitive relief of the haematological complication. Two years later, the patient was treated with combined therapy, including ribavirin (1200 mg/day) and IFN-alpha2b (5 mU, t.i.w.) for 12 months. This therapy induced a sustained response, both biochemical and virological, without haematological complications. This observation suggests that ribavirin may be of benefit in the treatment of immune-mediated thrombocytopenia in patients with chronic hepatitis C, preventing the harmful effect of IFN-alpha but also allowing both drugs to be combined so as to increase the probability of sustained remission of the liver disease.

  7. Therapeutic Effectiveness of Cryopreserved Autologous Platelets in the Treatment of Thrombocytopenic Dogs.

    DTIC Science & Technology

    1982-04-08

    Blood Processor 30 Platelets were obtained from three dogs by plateletpheresis prior to treatment with 800 rads of whole body irradiation and were...used for the plateletpheresis process. Platelet-rich plasma containing red blood cells was collected in a 125 ml pediatric bowl. A volume of ACD...isolated either from a unit of whole blood or from a healthy donor by plateletpheresis using the Haemonetics Blood Processor 30. A 30 ml volume of

  8. Erythrocyte dysplasia in peripheral blood smears from 5 thrombocytopenic dogs treated with vincristine sulfate.

    PubMed

    Collicutt, Nancy B; Garner, Bridget

    2013-12-01

    Secondary dyserythropoiesis has been associated with vincristine administration in dogs. Evaluation of bone marrow aspirates for the presence of morphologic abnormalities in the erythroid lineage aids in the diagnosis. However, morphologic features of circulating erythroid precursors in these cases have not been described previously. The purpose of this report was to describe the cytologic features of dyserythropoiesis in peripheral blood and also bone marrow smears in a case series of dogs with immune-mediated thrombocytopenia (IMT) treated with vincristine sulfate. Nineteen dogs receiving vincristine for treatment of IMT were identified by retrospectively searching a computerized medical record system. There were 5 dogs that had dysplastic erythroid precursors in peripheral blood smears within 7 days of vincristine treatment. Two of those 5 dogs also had evidence for erythrodysplasia in modified Wright's-stained bone marrow smears obtained postvincristine administration. Morphologic changes included bizarre or inappropriate mitotic figures, abnormal nuclear configurations (fragmentation, elongation, indentation, and binucleation), atypical nuclear remnants (Howell-Jolly bodies), or nuclear and cytoplasmic asynchrony within the erythroid precursors. A brief review of the literature with discussion of the etiologies for dyserythropoiesis is provided. The dyserythropoiesis was clinically insignificant in all 5 cases and resolved. However, pathologists and clinicians should be aware of these potential findings to prevent misdiagnosis of other conditions.

  9. Therapeutic effectiveness of cryopreserved autologous platelets in the treatment of thrombocytopenic dogs. Technical report

    SciTech Connect

    Melaragno, A.J.; Doty, A.J.; Dittmer, J.; Vecchione, J.J.; Valeri, C.R.

    1982-04-08

    Canine platelets were preserved in the frozen state with 6% DMSO in a -80 C mechanical freezer. The recovery of platelets after the freeze-thaw-wash procedure was about 70%, and posttransfusion recovery values were about 40% those of fresh platelets. The washed previously frozen platelets were hemostatically effective in supporting lethally irradiated dogs through prolonged periods of thrombocytopenia.

  10. Role of autophagy in megakaryocyte differentiation and platelet formation

    PubMed Central

    You, Tao; Wang, Qi; Zhu, Li

    2016-01-01

    Autophagy is a conserved biological process for digestion and recycling of cytoplasmic constituents in eukaryotic cells. Autophagy may trigger cell death or promote cell survival following various forms of stress. The emerging roles of autophagy in megakaryopoiesis, thrombopoiesis, and platelet function have been uncovered using not only in vitro and in vivo genetic models, but also in clinical observations of autophagic structure in patients with thrombocytopenic disorders. Inhibition of autophagy in early stage of megakaryocyte differentiation appears to impede megakaryocyte maturation, reduce platelet formation, and affect platelet function, whereas autophagic deficiency in mature megakaryocytes gives rise to abnormal platelet activation and function without changing platelet size and number. On the other hand, induction of autophagy by rapamycin in megakaryocytes exhibited substantial therapeutic benefits in patients with immune thrombocytopenic purpura (ITP). This mini-review is to highlight recent progresses in understanding the regulation of autophagy in megakaryopoiesis, thrombopoiesis and platelet function to bridge the gap between autophagy and megakaryocyte/platelet pathophysiology. PMID:27186320

  11. Pernicious Anemia Associated Cobalamin Deficiency and Thrombotic Microangiopathy: Case Report and Review of the Literature

    PubMed Central

    Spinowitz, Bruce; Charytan, Chaim; Galler, Marilyn

    2017-01-01

    A 43-year-old Hispanic male without significant previous medical history was brought to emergency department for syncope following a blood draw to investigate a 40 lbs weight loss during the past 6 months associated with decreased appetite and progressive fatigue. The patient also reported a 1-month history of jaundice. On examination, he was hemodynamically stable and afebrile with pallor and diffuse jaundice but without skin rash or palpable purpura. Normal sensations and power in all extremities were evident on neurological exam. Presence of hemolytic anemia, schistocytosis, thrombocytopenia, and elevated lactate dehydrogenase (LDH) was suggestive of thrombotic thrombocytopenic purpura (TTP). However, presence of leukopenia, macrocytes, and an inadequate reticulocyte response to the degree of anemia served as initial clues to an alternative diagnosis. Two and one units of packed red blood cells were transfused on day 1 and day 3, respectively. In addition, one unit of platelets was transfused on day 2. Daily therapeutic plasma exchange (TPE) was initiated and continued until ADAMTS-13 result ruled out TTP. A low cobalamin (vitamin B12) level was evident at initial laboratory work-up and subsequent testing revealed positive intrinsic factor-blocking antibodies supporting a diagnosis of pernicious anemia with severe cobalamin deficiency. Hematological improvement was observed following vitamin B12 supplementation. The patient was discharged and markedly improved on day 9 with outpatient follow-up for cobalamin supplementation. PMID:28265287

  12. A Case of a TSH-secreting Pituitary Adenoma Associated with Evans' Syndrome.

    PubMed

    Yasuda, Atsushi; Seki, Toshiro; Oki, Masayuki; Takagi, Atsushi; Inomoto, Chie; Nakamura, Naoya; Atsumi, Hideki; Baba, Tanefumi; Matsumae, Mitsunori; Sasaki, Noriko; Suzuki, Yasuo; Fukagawa, Masafumi

    2015-06-20

    We present a case of a TSH-secreting pituitary adenoma (TSHoma) associated with Evans' syndrome. A 30-year-old woman was referred to our hospital due to purpura and ecchymoses on her limb and body and epistaxis. Evans' syndrome was diagnosed based on idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia. She had a history of malocclusion and thyroid gland enlargement 4 years prior to admission. Endocrinological tests and magnetic resonance imaging also revealed that this patient had hyperthyroidism due to the TSHoma and that this adenoma concomitantly secreted GH. Recently, several cases of Evans' syndrome were associated with hyperthyroidism caused by autoimmune thyroid disease, such as Graves' disease, suggesting that these 2 conditions may have a common immunological basis. To the best of our knowledge, there is no case report of Evans' syndrome associated with hyperthyroidism due to TSHoma. Our report suggests that the excess of thyroid hormone itself promotes autoimmunity in Evans' syndrome. Thus, early treatment for hyperthyroidism is necessary in TSHomas because of the possibility that thyroid hormone normalization may prevent the development of Evans' syndrome.

  13. CRISPR/Cas9-mediated conversion of human platelet alloantigen allotypes.

    PubMed

    Zhang, Nanyan; Zhi, Huiying; Curtis, Brian R; Rao, Sridhar; Jobaliya, Chintan; Poncz, Mortimer; French, Deborah L; Newman, Peter J

    2016-02-11

    Human platelet alloantigens (HPAs) reside on functionally important platelet membrane glycoproteins and are caused by single nucleotide polymorphisms in the genes that encode them. Antibodies that form against HPAs are responsible for several clinically important alloimmune bleeding disorders, including fetal and neonatal alloimmune thrombocytopenia and posttransfusion purpura. The HPA-1a/HPA-1b alloantigen system, also known as the Pl(A1)/Pl(A2) polymorphism, is the most frequently implicated HPA among whites, and a single Leu33Pro amino acid polymorphism within the integrin β3 subunit is responsible for generating the HPA-1a/HPA-1b alloantigenic epitopes. HPA-1b/b platelets, like those bearing other low-frequency platelet-specific alloantigens, are relatively rare in the population and difficult to obtain for purposes of transfusion therapy and diagnostic testing. We used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9) gene-editing technology to transform Leu33 (+) megakaryocytelike DAMI cells and induced pluripotent stem cells (iPSCs) to the Pro33 allotype. CD41(+) megakaryocyte progenitors derived from these cells expressed the HPA-1b (Pl(A2)) alloantigenic epitope, as reported by diagnostic NciI restriction enzyme digestion, DNA sequencing, and western blot analysis using HPA-1b-specific human maternal alloantisera. Application of CRISPR/Cas9 technology to genetically edit this and other clinically-important HPAs holds great potential for production of designer platelets for diagnostic, investigative, and, ultimately, therapeutic use.

  14. CRISPR/Cas9-mediated conversion of human platelet alloantigen allotypes

    PubMed Central

    Zhang, Nanyan; Zhi, Huiying; Curtis, Brian R.; Rao, Sridhar; Jobaliya, Chintan; Poncz, Mortimer; French, Deborah L.

    2016-01-01

    Human platelet alloantigens (HPAs) reside on functionally important platelet membrane glycoproteins and are caused by single nucleotide polymorphisms in the genes that encode them. Antibodies that form against HPAs are responsible for several clinically important alloimmune bleeding disorders, including fetal and neonatal alloimmune thrombocytopenia and posttransfusion purpura. The HPA-1a/HPA-1b alloantigen system, also known as the PlA1/PlA2 polymorphism, is the most frequently implicated HPA among whites, and a single Leu33Pro amino acid polymorphism within the integrin β3 subunit is responsible for generating the HPA-1a/HPA-1b alloantigenic epitopes. HPA-1b/b platelets, like those bearing other low-frequency platelet-specific alloantigens, are relatively rare in the population and difficult to obtain for purposes of transfusion therapy and diagnostic testing. We used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9) gene-editing technology to transform Leu33+ megakaryocytelike DAMI cells and induced pluripotent stem cells (iPSCs) to the Pro33 allotype. CD41+ megakaryocyte progenitors derived from these cells expressed the HPA-1b (PlA2) alloantigenic epitope, as reported by diagnostic NciI restriction enzyme digestion, DNA sequencing, and western blot analysis using HPA-1b–specific human maternal alloantisera. Application of CRISPR/Cas9 technology to genetically edit this and other clinically-important HPAs holds great potential for production of designer platelets for diagnostic, investigative, and, ultimately, therapeutic use. PMID:26634302

  15. Pulmonary Changes in Lung Purpura and Some of the Other Collagen Diseases

    PubMed Central

    Schmidt, Herbert W.; Hargraves, Malcolm M.; Andersen, Howard A.; Daugherty, Guy W.

    1963-01-01

    The physician who specializes in pulmonary diseases has a most helpful aid in the form of chest roentgenography. This examination is secured routinely in many hospitals and clinics today. The roentgenogram is very accurate in finding pulmonary lesions. Accuracy in determining the type of lesion depends on the experience of the physician who is studying the patient. Pulmonary lesions occur in many systemic diseases. They may occur in some of the collagen diseases and at times they may be the first and also the most striking findings noted during the examination of a patient. For this reason, attention is called to some of the pulmonary findings encountered in certain of these diseases. Some of the clinical, roentgenologic and pathologic manifestations of necrotizing alveolitis, periarteritis nodosa, glomerulonephritis, disseminated lupus erythematosus, rheumatoid arthritis, and scleroderma are described. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7 PMID:13991999

  16. Myocardial infarction - a rare complication in Henoch-Schönlein purpura.

    PubMed Central

    Abdel-Hadi, O.; Greenstone, M. A.; Hartley, R. B.; Kidner, P. H.

    1981-01-01

    A 29-year-old man with previous Henoch-Schönlein disease presented with multiple systemic emboli and a myocardial infarction. Subsequent investigation by angiography showed normal coronary arteries. This appears to be the first reported case of Henoch-Schönlein disease and myocardial infarction probably due to coronary vasculitis. Images Fig. 1 PMID:7301688

  17. Cyclosporin A in the treatment of refractory immune thrombocytopenia purpura in children.

    PubMed

    Gesundheit, B; Cividalli, G; Freeman, A; Yatziv, S; Koren, G; Baruchel, S

    2001-05-01

    Patients with refractory autoimmune thrombocytopenia do not respond to standard therapy with high-dose corticosteroids, intravenous immunoglobulin, and splenectomy. We describe the cases of two patients with refractory autoimmune thrombocytopenia treated with oral cyclosporin A (CsA) to evaluate the efficacy of this alternative therapy. Blood pressure and hepatic and renal function were in the normal range before initiation of treatment. Induction therapy with pulses of high-dose methylprednisolone was used for 3 consecutive days to improve the initial immune suppression. Gradual dose reduction of CsA, according the platelet count, minimized the long-term adverse effects of CsA. Oral CsA with pulses of high-dose methylprednisolone induced remission of the thrombocytopenia. Gradual weaning of CsA over months, according the platelet count, produced no observable adverse effects of the CsA. Rapid dose reduction caused thrombocytopenia, which resolved with higher dosages of CsA. Our cases show the efficacy of CsA for refractory immune thrombocytopenia. This therapeutic option with oral CsA as an additional salvage option may avoid splenectomy and the adverse effects of long-term corticosteroids. Larger clinical investigations are necessary to establish the indications and therapeutic regimen for CsA in immune thrombocytopenia.

  18. Indian Tick Typhus Presenting as Purpura Fulminans with Review on Rickettsial Infections

    PubMed Central

    Hulmani, Manjunath; Alekya, P; Kumar, V Jagannath

    2017-01-01

    Rickettsial diseases are some of the most covert reemerging infections of the present times. They are generally incapacitating and notoriously difficult to diagnose; untreated cases can have fatality rates as high as 30%–35%, but when diagnosed properly, they are often easily treated but lack of definite diagnostic tools and the hazards of handling these microorganisms aggravate the difficulties of diagnosis and treatment. PMID:28216718

  19. Perplexing purpura in two females: Rare case of autoerythrocyte sensitization syndrome

    PubMed Central

    Tainwala, Ram R.; Phiske, Meghna; Raghuwanshi, Abhijith; Mathapati, Sukesh; Manjare, Ashwini K.; Jerajani, Hemangi R.

    2013-01-01

    Autoerythrocyte sensitization syndrome is a psychologically induced painful bruising condition. Two female, 19 and 30-year-old presented with recurrent episodes of painful ecchymotic bruising over accessible areas of body. In the younger female, episodes were since 3 years and were precipitated by stress and trivial trauma. The elder female presented with similar lesions since 3 months which were spontaneous in presentation. There were no obvious psychiatric manifestations in either. Clinically, ecchymotic changes in various stages of development were seen. Routine hemogram and coagulation profile were normal. Histopathology showed extravasated erythrocytes, perivascular neutrophils and fibrinoid deposition. Intradermal injection of autologous whole blood produced a painful ecchymotic reaction after 2 h similar to the presenting lesions. Psychiatric evaluation revealed mild mixed depression – anxiety disorder in the younger female while the latter revealed no abnormalities. The diagnosis of autoerythrocyte sensitization syndrome was made based on clinical history and findings, positive autoerythrocyte sensitization test, psychiatric evaluation and absence of any other clinical or laboratory pathology. PMID:24350012

  20. Giant electron-dense chains, clusters and granules in megakaryocytes and platelets with normal dense bodies: an inherited thrombocytopenic disorder.

    PubMed

    White, James G

    2003-03-01

    A woman and her male child were referred because of life-long thrombocytopenia, moderately increased platelet size, and absence of laboratory findings suggesting immune thrombocytopenia or defective platelet function. Evaluation of their platelets in the electron microscope revealed the presence of large organelles never seen before in human platelets. Examination of bone marrow from the mother and her son in an earlier study revealed that the giant platelet organelles originated in megakaryocytes. The present study has focused on the continuing development of the aberrant organelles in circulating platelets. The smallest subunits were electron-dense fragments and hollow-cored bodies observed in the dense tubular system (DTS). The dense fragments formed chains that became thicker, resulting in clusters, and clusters formed the large electron opaque bodies. Hollow-cored, almost hexagonal subunits also formed chains that interacted with each other to form target-like organelles. The multi-layered target organelles tended to become completely electron dense and difficult to distinguish from the opaque bodies. How two different types of aberrant organelles can develop in the same megakaryocyte/platelet system and both originate from channels of the DTS is unknown. Partial clarification stemming from analytical electron microscopy and ultrastructural cytochemistry will be presented in a subsequent report.

  1. Th-17 Alloimmune Responses in Renal Allograft Biopsies From Recipients of Kidney Transplants Using Extended Criteria Donors During Acute T Cell-Mediated Rejection.

    PubMed

    Matignon, M; Aissat, A; Canoui-Poitrine, F; Grondin, C; Pilon, C; Desvaux, D; Saadoun, D; Barathon, Q; Garrido, M; Audard, V; Rémy, P; Lang, P; Cohen, J; Grimbert, P

    2015-10-01

    Although renal transplantation using expanded criteria donors has become a common practice, immune responses related to immunosenescence in those kidney allografts have not been studied yet in humans. We performed a retrospective molecular analysis of the T cell immune response in 43 kidney biopsies from patients with acute T cell-mediated rejection including 25 from recipients engrafted with a kidney from expanded criteria donor and 18 from recipients grafted with optimal kidney allograft. The clinical, transplant and acute T cell-mediated rejection characteristics of both groups were similar at baseline. The expression of RORγt, Il-17 and T-bet mRNA was significantly higher in the elderly than in the optimal group (p = 0.02, p = 0.036, and p = 0.01, respectively). Foxp3 mRNA levels were significantly higher in elderly patients experiencing successful acute T cell-mediated rejection reversal (p = 0.03). The presence of IL-17 mRNA was strongly associated with nonsuccessful reversal in elderly patients (p = 0.008). Patients with mRNA IL17 expression detection and low mRNA Foxp3 expression experienced significantly more treatment failure (87.5%) than patients with no mRNA IL17 expression and/or high mRNA Foxp3 expression (26.7%; p = 0.017). Our study suggests that the Th17 pathway is involved in pathogenesis and prognosis of acute T cell-mediated rejection in recipients of expanded criteria allograft.

  2. A low effective dose of interleukin-7 is sufficient to maintain cord blood T cells alive without potentiating allo-immune responses.

    PubMed

    Pascal, Laurent; Hivert, Bénédicte; Trauet, Jacques; Deberranger, Eva; Dessaint, Jean-Paul; Yakoub-Agha, Ibrahim; Labalette, Myriam

    2015-04-01

    Slow reconstitution of T cell immunity remains a critical issue after umbilical cord blood (CB) transplantation. Although this may be a consequence of the low cell dose, it may also reflect the propensity of naïve T cells, which predominate in CB, to undergo apoptotic cell death. Exogenous interleukin 7 (IL-7) can prevent apoptosis of naïve T cells, but at high concentrations, IL-7 may also expand alloreactive T cells, thereby aggravating the risk of graft-versus-host disease. We evaluated the survival of CB T cells from 34 healthy full-term pregnancies, and we found wide interdonor variation, from 17.4% to 79.7%, of CB T cells that were still alive after being rested for 4 days in culture medium without cytokine supplementation. The viability of CB T cells was negatively correlated to infant birth weight (Spearman's ρ = .376; P = .031) and positively correlated to venous CB pH (ρ = .397; P = .027); both associations were confirmed by multivariate analysis (P = .023 and P = .005, respectively). A low supplemental concentration (100 pg/mL) of recombinant human IL-7 was sufficient to maintain the viability of cryopreserved/thawed CB T cells, with most (>80%) cells remaining in a quiescent state and without significant changes in their CD4/CD8 ratio and the proportion of CD4(+) CD31(+) PTK7(+) recent thymic emigrants. IL-7 at 100 pg/mL did not lead to any significant enhancement of the alloreactive response of CB T cells, as evaluated by proliferation rates (thymidine incorporation and carboxyfluorescein diacetate succinimidyl ester dilution) and interferon-gamma production (ELISPOT). This effective concentration of IL-7 is far lower than that obtained in vivo after pharmacological administration of the cytokine. This study suggests that administration of lower doses of recombinant human IL-7 than used in previous clinical trials may be sufficient to sustain the viability of infused CB T cells and, thus, help to accelerate naïve T cell reconstitution without potentiating their alloreactivity.

  3. CBP 1011: Colirest, Hematrol.

    PubMed

    2003-01-01

    InKine Pharmaceutical Co. is developing an oral compound, CBP 1011, for the treatment of immune thrombocytopenic purpura (ITP) [Hematrol] and for the treatment of inflammatory bowel disorders, ulcerative colitis and Crohn's disease (Colirest). This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. CBP 1011 or medroxyprogesterone, is a progesterone agonist and inhibits pro-inflammatory mediators such as interleukin-6 and tumour necrosis factor (TNF). CBP 1011 was originally developed by CorBec Pharmaceuticals, which in 1997 was aquired by Panax and then intergrated into InKine Pharmaceuticals. According to a company spokesperson, InKline is pursuing outlicensing opportunities for Hematrol since the company's current commercial focus is on gastrointestinal products. In June 2000, InKine announced the completion of a study comparing the bioavailability of a commercially viable tablet formulation of CBP 1011 to the original capsule formulation that is currently being used in the company's phase III studies in patients with idiopathic thrombocytopenic purpura. Preliminary results from this study indicate that the bioavailability of the tablet formulation does not differ significantly from that of the capsule formulation. The trial enrolled ITP patients (i) who are HIV positive, (ii) who are chronic ITP sufferers despite having had a splenectomy, (iii) who are older, or (iv) who have less severe thrombocytopenia. In preclinical trials, CBP 1011 was shown to decrease lymphocyte infiltration into the bowel compared with the control. Studies also show that it possibly offers safety benefits over steroid therapies. In June 2001, InKine commenced enrolment for a pivotal phase III trial in the treatment of Crohn's disease. This randomised, double-blind trial will enrol approximately 250 patients and will compare two doses of CBP 1011 (400 and 1000mg) with placebo. In April 2003, the US Patent and Trademark

  4. Human platelet antigen genotyping using a fluorescent SSCP technique with an automatic sequencer.

    PubMed

    Quintanar, A; Jallu, V; Legros, Y; Kaplan, C

    1998-11-01

    The typing of human platelet antigens (HPA) can be useful in many clinical situations such as neonatal alloimmune thrombocytopenia, post-transfusion purpura, and platelet transfusion refractoriness. The fluorescent-based single-strand conformation polymorphism (F-SSCP) technique is a fast and convenient way to perform HPA genotyping. Universal sequences from phage M13 were introduced at both ends of specific PCR-products by using 5'-tailed primers. A short second round of PCR with universal primers coupled to Cy-5 enabled the PCR-products to be fluorescently labelled. F-SSCP was performed by gel electrophoresis on an automated fluorescent DNA analyser. Genotyping of the three major HPA systems carried by the GP IIb-IIIa complex showed the F-SSCP technique to be accurate and reliable. A single gel procedure has been sufficient to detect HPA genetic polymorphisms tested to date. Neither restriction enzyme, radioactive material, nor any other hazardous chemicals such as ethidium bromide were required. This technique enabled us to genotype HPA-1, -3 and -4 alleles easily and to diagnose materno-fetal incompatibility in a rare alloantigenic system. F-SSCP is a promising technique for the detection of new mutations and/or DNA polymorphisms on a large scale.

  5. Typing for human platelet alloantigens.

    PubMed

    Juji, T; Saji, H; Satake, M; Tokunaga, K

    1999-01-01

    Antibodies to platelet alloantigens, and sometimes to isoantigens, induce severe clinical problems such as neonatal alloimmune thrombocytopenia (NAIT), post-transfusion purpura (PTP) and refractoriness to platelet transfusions (PTR). For example, NAIT affects approximately 1 in 5,000 live births. It is essential, therefore, to screen pregnant women for platelet antibodies in order to save babies' lives. Almost 40 years ago, two platelet alloantigen systems were discovered using relatively simple methods, namely the platelet agglutination test and the complement fixation test. However, these methods were not sensitive enough to identify all antibodies in mothers and patients, even in those with severe clinical problems. Tremendous effort has been devoted to establish more sensitive and reliable methods. In recent years, excellent new serological and immunochemical methods have been established and several new platelet antigen systems have been discovered. Simultaneously, newly developed molecular genetic techniques have been introduced for the typing and analysis of human platelet alloantigen systems. These methods allow DNA typing for cases in which serological typing is not available. In this article, the history of studies on human platelet alloantigen systems and isoantigens, the nomenclature of platelet alloantigen systems and their alleles, the present status of antibody detection and typing techniques and, finally, ethnic variations in platelet antigen profiles are reviewed.

  6. [Plasmapheresis in haematology].

    PubMed

    Woźniak, Krzysztof; Urbanowska, Elżbieta; Snarski, Emilian

    2015-01-01

    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.

  7. Granulocyte-associated IgG in neutropenic disorders

    SciTech Connect

    Cines, D.B.; Passero, F.; Guerry, D.; Bina, M.; Dusak, B.; Schreiber, A.D.

    1982-01-01

    We applied a radiolabeled antiglobulin test to a study of patients with a variety of neutropenic disorders. After defining the nature of the interaction of radiolabeled anti-IgG with the neutrophil, we studied 16 patients with neutropenia of uncertain etiology and adequate bone marrow granulocyte precursors. Twelve of these 16 patients had increased neutrophil-associated IgG (PMN-IgG). Patients with the highest levels of PMN-IgG had the lowest neutrophil counts. The majority of patients with neutropenia and increased PMN-IgG had an underlying immunologic disorder that included immune thrombocytopenic purpura in 5 patients and autoimmune hemolytic anemia in 1 patient. In some patients, elevated PMN-IgG preceded other evidence for immunologic disease. The direct antiglobulin test helped to distinguish neutropenic patients with increased PMN-IgG both from patients with neutropenia due to a known nonimmune disorder and from nonneutropenic patients with rheumatoid arthritis or systemic lupus erythematosis. Each of four patients with increased neutrophil-associated IgG treated with systemic corticosteroids responded clinically with an associated fall in neutrophil IgG and a rise in the circulating neutrophil count. The radiolabeled antiglobulin test appears useful in defining a subpopulation of patients with neutropenia due to an underlying immunologic disorder.

  8. Atypical Hemolytic Uremic Syndrome Secondary to Lupus Nephritis, Responsive to Eculizumab

    PubMed Central

    Raufi, Alexander G.; Scott, Shruti; Darwish, Omar; Harley, Kevin; Kahlon, Kanwarpal; Desai, Sheetal; Lu, Yuxin; Tran, Minh-Ha

    2016-01-01

    Among the spectrum of disease manifestations associated with systemic lupus erythematosus, lupus nephritis is particularly concerning due to the potential for renal failure. This autoimmune attack may not, however, be limited to the kidney and is increasingly being recognized as a trigger for atypical Hemolytic Uremic Syndrome (aHUS). Atypical HUS falls under the spectrum of the thrombotic microangiopathies (TMAs) – a group of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ damage. Although plasma exchange is considered first-line therapy for thrombotic thrombocytopenic purpura – a TMA classically associated with autoimmune depletion of ADAMTS-13 – aHUS demonstrates less reliable responsiveness to this modality. Instead, use of the late complement inhibitor Eculizumab has emerged as an effective modality for the management of such patients. Diagnosis of aHUS, however, is largely clinically based, relying heavily upon a multidisciplinary approach. Herein we present the case of a patient with atypical HUS successfully treated with Eculizumab in the setting of Class IV-G (A) lupus nephritis and hypocomplementemia. PMID:27781079

  9. Pregnant Woman with Atypical Hemolytic Uremic Syndrome Delivered a Healthy Newborn under Eculizumab Treatment

    PubMed Central

    Demir, Erol; Yazici, Halil; Ozluk, Yasemin; Kilicaslan, Isin; Turkmen, Aydin

    2016-01-01

    Pregnancy-associated thrombotic microangiopathy is a very rare condition; however, it significantly increases fetal or maternal morbidity and mortality. Pregnancy may trigger atypical hemolytic uremic syndrome (aHUS) or thrombotic thrombocytopenic purpura. The risk for pregnancy-associated aHUS is highest during the second pregnancy. The outcome is usually poor with 50–60% mortality; renal dysfunction and hypertension are the rule in those who survive the acute episode. After the development of complement regulation mechanisms and aHUS pathogenesis, eculizumab has been widely used as a first-line treatment in aHUS. Eculizumab has been produced to minimize immunogenicity and Fc-mediated functions, including recruitment of inflammatory cells and complement activation, and using eculizumab in first-line treatment improves kidney function. Recent studies showed that early diagnosis and rapid use of eculizumab in first-line treatment improve outcomes. We demonstrate a case with pregnancy-triggered aHUS occurring in the second trimester, who was successfully treated and delivered a healthy baby under eculizumab treatment. PMID:28101502

  10. Fecal microbiota transplantation broadening its application beyond intestinal disorders.

    PubMed

    Xu, Meng-Que; Cao, Hai-Long; Wang, Wei-Qiang; Wang, Shan; Cao, Xiao-Cang; Yan, Fang; Wang, Bang-Mao

    2015-01-07

    Intestinal dysbiosis is now known to be a complication in a myriad of diseases. Fecal microbiota transplantation (FMT), as a microbiota-target therapy, is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases. New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota. This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas, including metabolic diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors. A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces, with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity, along with increased levels of butyrate-producing intestinal microbiota. Case reports of FMT have also shown favorable outcomes in Parkinson's disease, multiple sclerosis, myoclonus dystonia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura. FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis.

  11. [Biology of von Willebrand factor].

    PubMed

    Girma, Jean-Pierre

    2006-01-01

    Von Willebrand factor (VWF) is a multimeric glycoprotein synthesized by megakaryocytes and endothelial cells. It is stored in platelets and endothelial cells and secreted towards subendothelium and plasma. VWF multimers consist of linear arrangements of identical subunits with a molecular weight of 270 kDa. The longest multimers reach more than 20 x 10(6) Da in storage granules. In the circulation, the multimer size is limited by the specific protease ADAMTS13. In primary hemostasis, VWF plays a key role as a molecular bridge in adhesion between platelets and subendothelium and between platelets during their aggregation. These functions, which involve the interaction with platelet glycoprotein lb, are mainly enhanced by VWF immobilization onto hydrophobic surfaces (collagen, cell membrane) and by high shear rates found in microcirculation and stenosed arteries. In these functions, the higher molecular weight forms are the most efficient. Under such hemodynamic conditions, proteolytic activity of ADAMTS13 is also optimal and limits the multimer size to about 15 x 10(6) Da as soon as their secretion. Thus ADAMTS13 appears as a key physiologic regulator of the VWF platelet functions. In the microcirculation, the lack of ADAMTS13 activity can result in the formation of VWF-rich platelet aggregates responsible for thrombotic thrombocytopenic purpura.

  12. Rapid high-resolution electrophoresis of multimeric von Willebrand Factor using a thermopiloted gel apparatus.

    PubMed

    Smejkal, Gary B; Shainoff, John R; Kottke-Marchant, Kandice M

    2003-02-01

    Rapid and highly reproducible nonreducing agarose gel electrophoresis (NRAGE) of von Willebrand Factor (vWF) multimers was performed using a thermostated minigel apparatus that monitors and precisely controls internal gel temperature. The substitution of lithium dodecyl sulfate (LiDS) for sodium dodecyl sulfate (SDS) allowed electrophoresis to be performed below the 16 degrees C Krafft point of SDS and facilitated NRAGE of vWF over the entire range of 0-35 degrees C. Internal gel temperature was regulated by a thermocouple probe inserted directly into the gel during electrophoresis which interfaced with a thermopilot that continually measures and adjusts temperature to within +/- 0.5 degrees C. At 10 degrees C operative temperature, NRAGE at 1.5% agarose concentration was completed in 20 min at 250 V. Electrophoresis could be performed in only 10 min at 500 V, but at such high voltages, localized temperature fluctuations as much as 6 degrees C resulted in perturbation of banding patterns in those vicinities. In the optimized method, both high molecular weight multimers and proteolytic fragments of vWF were separable suggesting clinical applicability of this system for the diagnosis of von Willebrand Disease and thrombotic thrombocytopenic purpura.

  13. New Diagnostic Strategies for Detection of Helicobacter pylori Infection in Pediatric Patients

    PubMed Central

    Gold, Benjamin D.; Gilger, Mark A.; Czinn, Steven J.

    2014-01-01

    Helicobacter pylori (H pylori) is a common chronic bacterial infection that is an important cause of peptic ulcer disease and gastroduodenal disease in children. H pylori is also associated with extragastric manifestations, including growth reduction, iron-deficiency anemia, and idiopathic thrombocytopenic purpura. Current guidelines recommend endoscopy with biopsy for the definitive demonstration of H pylori infection. In contrast to serology, the fecal antigen test and the urea breath test provide reliable, sensitive, and specific results for detecting active H pylori infection in children before and after treatment. The first-line treatment option for pediatric patients is triple therapy with a proton pump inhibitor and 2 antibiotics, which include amoxicillin and clarithromycin or metronidazole. Decreasing eradication rates and the emergence of antibiotic-resistant strains of H pylori have led to the use of other treatments, such as sequential therapy or triple therapy with newer antibiotics, particularly in geographic areas with high rates of antibiotic resistance. Patients should be tested after treatment to confirm eradication, as the absence of symptoms does not necessarily mean that H pylori is no longer present. This clinical roundtable monograph provides an overview of H pylori infection, as well as expert insight into the diagnosis and management of H pylori infection in children. PMID:26491414

  14. Refractory platelet transfusion in a patient with CD36 deficiency due to pseudothrombocytopenia.

    PubMed

    Yin, Xiao-Lin; Shen, Wei-Dong; Chen, Yong-Sheng; Zhou, Yan; Zhang, Xin-Huan

    2011-01-01

    Type I CD36 deficiency is defined by the absence of CD36 on both platelets and monocytes. Pseudothrombocytopenia (PTCP) is characterized by a false reduction in the number of platelets in ethylenediaminetetraacetic acid (EDTA)-anticoagulated blood. Here we report a rare case of concomitant CD36 deficiency and PTCP. The patient was a 7-year-old boy who suffered comminuted fractures of the left humeral condyle. In the pre-operative examination, he was found to have thrombopenia and assumed to have idiopathic thrombocytopenic purpura. After immunotherapy and platelet transfusion, the platelet count remained low, suggesting that the patient was refractory to platelet transfusion. Serum was collected for the detection of platelet antibodies, and antibodies against CD36 were found. Flow cytometry verified the absence of CD36 on both the platelets and monocytes of this patient. However, the platelet count was normal when capillary blood smears were analysed; in addition, platelet coagulation was noted under the microscope when EDTA-anticoagulated peripheral blood was used. The patient underwent surgery without platelet transfusion and recovered uneventfully.

  15. Relationships between platelet counts, platelet volumes and reticulated platelets in patients with ITP: evidence for significant platelet count inaccuracies with conventional instrument methods.

    PubMed

    Diquattro, M; Gagliano, F; Calabrò, G M; Tommasi, M; Scott, C S; Mancuso, G; Palma, B; Menozzi, I

    2009-04-01

    The platelet count has a primary role in the diagnosis and treatment of idiopathic thrombocytopenic purpura (ITP). This study analysed the accuracy of ITP patient platelet counts determined by Abbott CD-Sapphire (impedance/optical) and Bayer Advia 120 (optical) analyses, compared with a reference immunoplatelet method. Instrument platelet estimates showed broad equivalence in the higher range of observed values, but significant discrepancies against the immunoplatelet count were seen when platelet counts were <10 x 10(9)/l. CD-Sapphire mean platelet volume (MPV) results revealed increased (>12 fl) platelet volumes in eight of eight ITP patients with counts of <20 x 10(9)/l compared with 6/6 and 5/13 patients with platelet counts of 20-50 and >50 x 10(9)/l. In contrast, Bayer Advia MPV values showed no relationship with the platelet count. Increased reticulated platelets were associated with an increasing CD-Sapphire MPV (R(2) = 0.61) and a decreasing platelet count. High (>40%) reticulated platelet values were seen in 9/9 patients with immunoplatelet counts of <20 x 10(9)/l compared with 0/19 patients with platelet counts above 20 x 10(9)/l. There may be a need for caution in the interpretation of platelet counts in ITP patients obtained with conventional instrument methods, and therapeutic decisions should ideally be validated by reference immunoplatelet procedures.

  16. Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative.

    PubMed

    Bendapudi, Pavan K; Li, Ang; Hamdan, Ayad; Uhl, Lynne; Kaufman, Richard; Stowell, Christopher; Dzik, Walter; Makar, Robert S

    2015-12-01

    The Harvard TMA Research Collaborative is a multi-institutional registry-based effort to study thrombotic microangiopathies (TMA). Laboratory and clinical parameters were recorded for 254 cases of suspected autoimmune thrombotic thrombocytopenic purpura (TTP). Patients with severe ADAMTS13 deficiency (activity ≤10%, N = 68) were more likely to be young, female and without a history of cancer treatment or transplantation. While all patients with severe deficiency were diagnosed with autoimmune TTP, those without severe deficiency frequently had disseminated intravascular coagulation, drug-associated TMA and transplant-related TMA. Patients with severe ADAMTS13 deficiency had superior overall survival at 360 d compared to those without severe deficiency (93·0% vs. 47·5%, P < 0·0001). Almost all patients with severe deficiency received therapeutic plasma exchange (TPE), but the use of TPE in patients with ADAMTS13 activity >10% varied significantly across the institutions in our consortium (13·2-63·8%, P < 0·0001). Nevertheless, 90-d mortality was not different in patients with ADAMTS13 activity >10% between the three hospitals (P = 0·98). Our data show that patients with severe ADAMTS13 deficiency represent a clinically distinct cohort that responds well to TPE. In contrast, TMA without severe ADAMTS13 deficiency is associated with increased mortality that may not be influenced by TPE.

  17. Managing thrombocytopenia associated with cancer chemotherapy.

    PubMed

    Kuter, David J

    2015-04-01

    Thrombocytopenia is a common problem in cancer patients. Aside from bleeding risk, thrombocytopenia limits chemotherapy dose and frequency. In evaluating thrombocytopenic cancer patients, it is important to assess for other causes of thrombocytopenia, including immune thrombocytopenia, coagulopathy, infection, drug reaction, post-transfusion purpura, and thrombotic microangiopathy. The incidence of chemotherapy-induced thrombocytopenia varies greatly depending on the treatment used; the highest rates of this condition are associated with gemcitabine- and platinum-based regimens. Each chemotherapy agent differs in how it causes thrombocytopenia: alkylating agents affect stem cells, cyclophosphamide affects later megakaryocyte progenitors, bortezomib prevents platelet release from megakaryocytes, and some treatments promote platelet apoptosis. Thrombopoietin is the main regulator of platelet production. In numerous studies, recombinant thrombopoietin raised the platelet count nadir, reduced the need for platelet transfusions, reduced the duration of thrombocytopenia, and allowed maintenance of chemotherapy dose intensity. Two thrombopoietin receptor agonists now available, romiplostim and eltrombopag, are potent stimulators of platelet production. Although few studies have been completed to demonstrate their ability to treat chemotherapy-induced thrombocytopenia, these agents may be useful in treating this condition in some situations. Chemotherapy dose reduction and platelet transfusions remain the major treatments for affected patients.

  18. Pathogenesis of Thrombotic Microangiopathies

    PubMed Central

    Zheng, X. Long; Sadler, J. Evan

    2008-01-01

    Profound thrombocytopenia and microangiopathic hemolytic anemia characterize thrombotic microangiopathy, which includes two major disorders: thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). TTP has at least three types: congenital or familial, idiopathic, and nonidiopathic. The congenital and idiopathic TTP syndromes are caused primarily by deficiency of ADAMTS13, owing to mutations in the ADAMTS13 gene or autoantibodies that inhibit ADAMTS13 activity. HUS is similar to TTP, but is associated with acute renal failure. Diarrhea-associated HUS accounts for more than 90% of cases and is usually caused by infection with Shiga-toxin-producing Escherichia coli (O157:H7). Diarrhea-negative HUS is associated with complement dysregulation in up to 50% of cases, caused by mutations in complement factor H, membrane cofactor protein, factor I or factor B, or by autoanti-bodies against factor H. The incomplete penetrance of mutations in either ADAMTS13 or complement regulatory genes suggests that precipitating events or triggers may be required to cause thrombotic microangiopathy in many patients. PMID:18215115

  19. Unwinding the von Willebrand factor strings puzzle.

    PubMed

    De Ceunynck, Karen; De Meyer, Simon F; Vanhoorelbeke, Karen

    2013-01-10

    von Willebrand factor (VWF) is amongst others synthesized by endothelial cells and stored as ultra-large (UL) VWF multimers in Weibel-Palade bodies. Although UL-VWF is proteolysed by ADAMTS13 (a disintegrin-like and metalloprotease domain with thrombospondin type-1 motif, number 13) on secretion from endothelial cells, in vitro experiments in the absence of ADAMTS13 have demonstrated that a proportion of these UL-VWF multimers remain anchored to the activated endothelium. These multimers unravel, bind platelets, and wave in the direction of the flow. These so-called VWF "strings" have also been visualized in vivo, lining the lumen of activated mesenteric veins of Adamts13(-/-) mice. Various studies have demonstrated the extraordinary length of these VWF strings, the availability of their platelet binding and ADAMTS13 cleavage sites, and the possible nature of their endothelial attachment. VWF strings are also capable of tethering leukocytes and parasite-infected red blood cells. However, the majority of studies have been performed in the absence of ADAMTS13, a condition only experienced in thrombotic thrombocytopenic purpura. A normal functional role of VWF strings in healthy persons or in other disease pathologies remains unclear. In this review, we discuss some of the puzzling characteristics of VWF strings, and we debate whether the properties of VWF strings in the absence of ADAMTS13 might be relevant for understanding (patho)physiologic mechanisms.

  20. Peptibodies

    PubMed Central

    Shimamoto, Grant; Gegg, Colin; Boone, Tom; Quéva, Christophe

    2012-01-01

    Peptibodies or peptide-Fc fusions are an attractive alternative therapeutic format to monoclonal antibodies. They consist of biologically active peptides grafted onto an Fc domain. This approach retains certain desirable features of antibodies, notably an increased apparent affinity through the avidity conferred by the dimerization of two Fcs and a long plasma residency time. Peptibodies can be made in E. coli using recombinant technology. The manufacturing process involves fermentation and downstream processing, including refolding and multiple column chromatographic steps, that result in overall yields and quality suitable for commercial development. Romiplostim, marketed under the brand name Nplate®, is the first peptibody to be approved by the United States Food and Drug Administration and the European Medicines Agency and is indicated for the treatment of immune thrombocytopenic purpura. AMG 386, a peptibody antagonist to angiopoietins 1 and 2, is being evaluated in Phase 3 clinical testing in combination with chemotherapy in women with ovarian cancer. AMG 819, a peptibody targeting nerve growth factor for pain has also progressed to clinical trials. These peptibodies illustrate the versatility of the modality. PMID:22820181

  1. Epidemiological characteristics of rubella and congenital rubella syndrome in the 2012-2013 epidemics in Tokyo, Japan.

    PubMed

    Sugishita, Yoshiyuki; Shimatani, Naotaka; Katow, Shigetaka; Takahashi, Takuri; Hori, Narumi

    2015-01-01

    A large rubella outbreak has been observed since June 2012 in Tokyo, Japan, and a rapid increase in the number of congenital rubella syndrome (CRS) cases have also been reported in Japan since October 2012. All the clinically diagnosed and laboratory-confirmed rubella cases reported in Tokyo from January 2012 to December 2013 and all the laboratory-confirmed CRS cases from January 2012 to March 2014 were analyzed. In total, 4,116 rubella cases were reported in Tokyo. Of these, 77.2% (n=3,176) were male; the highest number of cases occurred in males aged 35-39 years and in females aged 20-24 years. Complications included arthralgia/arthritis (19.4%), thrombocytopenic purpura (0.5%), hepatic dysfunction (0.3%), and encephalitis (0.1%). The circulating rubella virus in Tokyo was genotype 2B. The most possible site of transmission was the workplace. Because of the rubella epidemic, 16 CRS cases were reported in Tokyo from March 2013 to February 2014. Domestic infection with rubella was proven for all mothers of 16 cases. This situation suggests that Japan is still working to achieve rubella elimination.

  2. Interpreting the developmental dance of the megakaryocyte: a review of the cellular and molecular processes mediating platelet formation.

    PubMed

    Machlus, Kellie R; Thon, Jonathan N; Italiano, Joseph E

    2014-04-01

    Platelets are essential for haemostasis, and thrombocytopenia (platelet counts <150 × 10(9) /l) is a major clinical problem encountered across a number of conditions, including immune thrombocytopenic purpura, myelodysplastic syndromes, chemotherapy, aplastic anaemia, human immunodeficiency virus infection, complications during pregnancy and delivery, and surgery. Circulating blood platelets are specialized cells that function to prevent bleeding and minimize blood vessel injury. Platelets circulate in their quiescent form, and upon stimulation, activate to release their granule contents and spread on the affected tissue to create a physical barrier that prevents blood loss. The current model of platelet formation states that large progenitor cells in the bone marrow, called megakaryocytes, release platelets by extending long, branching processes, designated proplatelets, into sinusoidal blood vessels. This review will focus on different factors that impact megakaryocyte development, proplatelet formation and platelet release. It will highlight recent studies on thrombopoeitin-dependent megakaryocyte maturation, endomitosis and granule formation, cytoskeletal contributions to proplatelet formation, the role of apoptosis, and terminal platelet formation and release.

  3. Apical sorting of ADAMTS13 in vascular endothelial cells and Madin-Darby canine kidney cells depends on the CUB domains and their association with lipid rafts

    PubMed Central

    Shang, Dezhi; Zheng, X. Wu; Niiya, Masami; Zheng, X. Long

    2006-01-01

    ADAMTS13 biosynthesis appeared to occur mainly in hepatic stellate cells, but detection of ADAMTS13 mRNA in many other tissues suggests that vascular endothelium may also produce ADAMTS13. We showed that ADAMTS13 mRNA and protein were detectable in human umbilical vein endothelial cells, aortic endothelial cells, and endothelium-derived cell line (ECV304). ADAMTS13 in cell lysate or serum-free conditioned medium cleaved von Willebrand factor (VWF) specifically. ADAMTS13 and VWF were localized to the distinct compartments of endothelial cells. Moreover, ADAMTS13 was preferentially sorted into apical domain of ECV304 and Madin-Darby canine kidney (MDCK) cells. Apical sorting of ADAMTS13 depended on the CUB domains and their association with lipid rafts. A mutation in the second CUB domain of ADAMTS13 (4143-4144insA), naturally occurring in patients with inherited thrombotic thrombocytopenic purpura, resulted in a significant reduction of ADAMTS13 secretion and a reversal of its polarity in MDCK cells. These data demonstrated that ADAMTS13 is synthesized and secreted from endothelial cells; the apically secreted ADAMTS13 from endothelial cells may contribute significantly to plasma ADAMTS13 proteases. The data also suggest a critical role of the CUB domains and a novel cargo-selective mechanism for apical sorting of a soluble ADAMTS protease in polarized cells. PMID:16597588

  4. Lupus Anticoagulant Positivity in Pediatric Patients With Prolonged Activated Partial Thromboplastin Time: A Single-Center Experience and Review of Literature.

    PubMed

    Malbora, Baris; Bilaloglu, Eris

    2015-01-01

    The presence of lupus anticoagulants (LAs) is an important cause of activated partial thromboplastin time (aPTT) prolongation found in children after an infection or during screening tests before surgical intervention. The authors retrospectively reviewed the charts of 68 patients who have been consulted from surgery departments with prolonged aPTT. These patients were reevaluated with aPTT analysis after 1 week. Thirteen patients had normal aPTTs. Therefore, 55 patients remained with prolonged aPTTs. LA positivity was detected in 39 patients. Sixteen of these had prolonged aPTT prior to surgery (41%). Others with LA positivity had systemic lupus erythematosus (SLE; n = 6), infection (n = 5), leukemia (n = 3), hemolytic uremic syndrome (n = 2), epistaxis (n = 2), antiphospholipid syndrome (APS; n = 1), chronic immune thrombocytopenic purpura (n = 1), acute poststreptococcal glomerulonephritis (n = 1), central nervous system (CNS) thrombosis (n = 1), and congenital heart disease (n = 1). None of the patients had bleeding history. LA positivity rarely leads to bleeding and/or thrombosis. Specific therapy is usually not needed. Further prospective multicenter studies are required to understand clinical outcomes and laboratory correlation in children with positive LA.

  5. High-dose immunoablative therapy with hematopoietic stem cell support in the treatment of severe autoimmune disease: current status and future direction.

    PubMed

    Tyndall, Alan; Koike, Takao

    2002-08-01

    In the past 5 years approximately 500 patients worldwide suffering from severe autoimmune disease (AD) have received an autologous hematopoietic stem cell transplantation (HSCT) as treatment following high-dose chemotherapy. The EBMT and EULAR data base contains 370 registrations, the most frequently transplanted ADs being multiple sclerosis (MS), systemic sclerosis (SSc), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), systemic lupus erythematosus (SLE) and idiopathic thrombocytopenic purpura (ITP). Around 70% responded initially well, with durable remission/stabilization seen more frequently in MS and SSc than in RA and SLE, the latter having around 2/3 relapses, the majority of which respond to simple agents. Overall 8% transplant-related mortality was seen with large inter AD differences (12.5% in SSc and only one patient in RA) probably reflecting the degree of vital organ involvement at the time of transplant. This phase I/II data has led to a running phase III randomized trial in SSc called the Autologous Stem cell Transplantation International Scleroderma (ASTIS) trial, and it will soon begin in MS (ASTIMS) and RA (ASTIRA). The concept of immunological "re-setting" has evolved, and needs to be confirmed by longer follow-up and the multicentre, international phase III randomized studies.

  6. Granulocyte-associated IgG in neutropenic disorders

    SciTech Connect

    Cines, D.B.; Passero, F.; Guerry, D. IV; Bina, M.; Dusak, B.; Schreiber, A.D

    1982-01-01

    We applied a radiolabeled antiglobulin test to a study of patients with a variety of neutropenic disorders. After defining the nature of the interaction of radiolabeled anti-IgG with the neutrophil, we studied 16 patients with neutropenia of uncertain etiology and adequate bone marrow granulocyte precursors. Twelve of these 16 patients had increased neutrophil-associated IgG (PMN-IgG). Patients with the highest levels of PMN-IgG had the lowest neutrophil counts. The majority of patients with neutropenia and increased PMN-IgG had an underlying immunologic disorder that included immune thrombocytopenic purpura in 5 patients and autoimmune hemolytic anemia in 1 patient. In some patients, elevated PMN-IgG preceded other evidence for immunologic disease. The direct antiglobulin test helped to distinguish neutropenic patients with increased PMN-IgG both from patients with neutropenia due to a known nonimmune disorder and from noneutropenic patients with rheumatoid arthritis or systemic lupus erythematosis. Each of four patients with increased neutrophil-associated IgG treated with systemic corticosteroids responded clinically with an associated fall in neutrophil IgG and a rise in the circulating neutrophil count. The radiolabeled antiglobulin test appears useful in defining a subpopulation of patients with neutropenia due to an underlying immunologic disorder.

  7. Therapeutic potential of fecal microbiota transplantation.

    PubMed

    Smits, Loek P; Bouter, Kristien E C; de Vos, Willem M; Borody, Thomas J; Nieuwdorp, Max

    2013-11-01

    There has been growing interest in the use of fecal microbiota for the treatment of patients with chronic gastrointestinal infections and inflammatory bowel diseases. Lately, there has also been interest in its therapeutic potential for cardiometabolic, autoimmune, and other extraintestinal conditions that were not previously considered to be associated with the intestinal microbiota. Although it is not clear if changes in the microbiota cause these conditions, we review the most current and best methods for performing fecal microbiota transplantation and summarize clinical observations that have implicated the intestinal microbiota in various diseases. We also discuss case reports of fecal microbiota transplantations for different disorders, including Clostridium difficile infection, irritable bowel syndrome, inflammatory bowel diseases, insulin resistance, multiple sclerosis, and idiopathic thrombocytopenic purpura. There has been increasing focus on the interaction between the intestinal microbiome, obesity, and cardiometabolic diseases, and we explore these relationships and the potential roles of different microbial strains. We might someday be able to mine for intestinal bacterial strains that can be used in the diagnosis or treatment of these diseases.

  8. Cyclosporin A Impairs the Secretion and Activity of ADAMTS13 (A Disintegrin and Metalloprotease with Thrombospondin Type 1 Repeat)*

    PubMed Central

    Hershko, Klilah; Simhadri, Vijaya L.; Blaisdell, Adam; Hunt, Ryan C.; Newell, Jordan; Tseng, Sandra C.; Hershko, Alon Y.; Choi, Jae Won; Sauna, Zuben E.; Wu, Andrew; Bram, Richard J.; Komar, Anton A.; Kimchi-Sarfaty, Chava

    2012-01-01

    The protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat) cleaves multimers of von Willebrand factor, thus regulating platelet aggregation. ADAMTS13 deficiency leads to the fatal disorder thrombotic thrombocytopenic purpura (TTP). It has been observed that cyclosporin A (CsA) treatment, particularly in transplant patients, may sometimes be linked to the development of TTP. Until now, the reason for such a link was unclear. Here we provide evidence demonstrating that cyclophilin B (CypB) activity plays an important role in the secretion of active ADAMTS13. We found that CsA, an inhibitor of CypB, reduces the secretion of ADAMTS13 and leads to conformational changes in the protein resulting in diminished ADAMTS13 proteolytic activity. A direct, functional interaction between CypB (which possesses peptidyl-prolyl cis-trans isomerase (PPIase) and chaperone functions) and ADAMTS13 is demonstrated using immunoprecipitation and siRNA knockdown of CypB. Finally, CypB knock-out mice were found to have reduced ADAMTS13 levels. Taken together, our findings indicate that cyclophilin-mediated activity is an important factor affecting secretion and activity of ADAMTS13. The large number of proline residues in ADAMTS13 is consistent with the important role of cis-trans isomerization in the proper folding of this protein. These results altogether provide a novel mechanistic explanation for CsA-induced TTP in transplant patients. PMID:23144461

  9. Detection of Intracellular ADAMTS13, a Secreted Zinc-metalloprotease, via Flow Cytometry

    PubMed Central

    S., Geetha; Allen, Courtni E.; Hunt, Ryan; Plum, Elizabeth; Garfield, Susan; Friedman, Scott L.; Soejima, Kenji; Sauna, Zuben E.; Kimchi-Sarfaty, Chava

    2009-01-01

    Background ADAMTS13 is a secreted metalloprotease that cleaves von Willebrand Factor multimers and maintains proper homeostasis. A severe deficiency in ADAMTS13 triggers a disorder known as thrombotic thrombocytopenic purpura (TTP). At present, ADAMTS13 expression levels are determined by immunoblotting. Methods We established a flow cytometry methodology to detect intracellular ADAMTS13 in liver and kidney cells using a polyclonal antibody, BL154G, and several monoclonal antibodies previously used to detect ADAMTS13 by immunoblotting. Results were validated using confocal microscopy, immunoblotting and an activity assay (FRETS-VWF73). Results We show that labeling ADAMTS13 with specific antibodies and detection by flow cytometry yields results that are comparable to previously established methods for ADAMTS13 detection. Specifically, we compared the endogenous expression levels of ADAMTS13 in various liver cell lines using flow cytometry and obtained results that parallel immunoblot analysis. Knock-down of ADAMTS13 expression via targeted siRNA resulted in significantly reduced median signal, displaying the sensitivity of this detection method. A further analysis of reliability and specificity was achieved through plasmid DNA and transfection reagent dose response studies. Conclusions The flow cytometry method described here is useful in determining the expression of both endogenous and recombinant forms of intracellular ADAMTS13. Flow cytometry is a convenient, efficient and cost effective way to measure the expression levels of ADAMTS13. PMID:19526483

  10. Characterization of Conformation-Sensitive Antibodies to ADAMTS13, the von Willebrand Cleavage Protease

    PubMed Central

    Sauna, Zuben E.; Okunji, Chinyere; Hunt, Ryan C.; Gupta, Tanvi; Allen, Courtni E.; Plum, Elizabeth; Blaisdell, Adam; Grigoryan, Vahan; S, Geetha; Fathke, Robert; Soejima, Kenji; Kimchi-Sarfaty, Chava

    2009-01-01

    Background The zinc metalloprotease ADAMTS13 is a multidomain protein that cleaves von Willebrand Factor (VWF) and is implicated in Thrombotic Thrombocytopenic Purpura (TTP) pathogenesis. Understanding the mechanism of this protein is an important goal. Conformation sensitive antibodies have been used to monitor protein conformation and to decipher the molecular mechanism of proteins as well as to distinguish functional and non-functional mutants. Methodology/Principal Findings We have characterized several antibodies against ADAMTS13, both monoclonal and polyclonal. We have used flow cytometry to estimate the binding of these antibodies to ADAMTS13 and demonstrate that antibodies raised against the TSP and disintegrin domains detect conformation changes in the ADAMTS13. Thus for example, increased binding of these antibodies was detected in the presence of the substrate (VWF), mainly at 37°C and not at 4°C. These antibodies could also detect differences between wild-type ADAMTS13 and the catalytically deficient mutant (P475S). The flow cytometry approach also allows us to estimate the reactivity of the antibody as well as its apparent affinity. Conclusions/Significance Our results suggest that these antibodies may serve as useful reagents to distinguish functional and non-functional ADAMTS13 and analyze conformational transitions to understand the catalytic mechanism. PMID:19654870

  11. Clinical Application of Partial Splenic Embolization

    PubMed Central

    Guan, Yong-Song; Hu, Ying

    2014-01-01

    Partial splenic embolization (PSE) is one of the intra-arterial therapeutic approaches of diseases. With the development of interventional radiology, the applications of PSE in clinical practice are greatly extended, while various materials are developed for embolization use. Common indications of PSE include hypersplenism with portal hypertension, hereditary spherocytosis, thalassemia, autoimmune hemolytic anemia, splenic trauma, idiopathic thrombocytopenic purpura, splenic hemangioma, and liver cancer. It is also performed to exclude splenic artery aneurysms from the parent vessel lumen and prevent aneurysm rupture, to treat splenic artery steal syndrome and improve liver perfusion in liver transplant recipients, and to administer targeted treatment to areas of neoplastic disease in the splenic parenchyma. Indicators of the therapeutic effect evaluation of PSE comprise blood routine test, changes in hemodynamics and in splenic volume. Major complications of PSE include the pulmonary complications, severe infection, damages of renal and liver function, and portal vein thrombosis. The limitations of PSE exist mainly in the difficulties in selecting the arteries to embolize and in evaluating the embolized volume. PMID:25538966

  12. Breast Cancer-Associated Thrombotic Microangiopathy

    PubMed Central

    Regierer, Anne C.; Kuehnhardt, Dagmar; Schulz, Carsten-Oliver; Flath, Bernd; Jehn, Christian F.; Scholz, Christian W.; Possinger, Kurt; Eucker, Jan

    2011-01-01

    Background Thrombotic microangiopathy (TMA) is defined as thrombocytopenia and microangiopathic hemolytic anemia. Cancer-associated TMA, a rare but fatal condition, seems an entity distinct from classical thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS). Patients and Methods All patients with breast cancer-associated TMA treated at our institution between 2003 and 2008 were analyzed retrospectively. To elucidate pathophysiological mechanisms, we measured the serum activity of the metalloprotease ADAMTS13. Results 8 patients were identified. All showed bone marrow infiltration of breast cancer as well as thrombocytopenia, schistocytes, and hemolytic anemia. ADAMTS13 activity was mildly decreased in 4/6 patients (20–108%, normal range 30–120%), but none showed severely low levels as is characteristic of classical TTP. 6 patients were treated with anthracycline-containing fractionated chemotherapy, 5/6 patients experienced partial response. Overall survival was 13 months. Fractionated chemotherapy was well tolerated. Conclusions Cancer-associated TMA has an underlying mechanism different from classical TTP. While bone marrow infiltration might be of major relevance, ADAMTS13 deficiency seems to be an epiphenomenon. Fractionated chemotherapy resulted in higher remission rates and comparatively long survival. PMID:22419897

  13. Plasma components: properties, differences, and uses.

    PubMed

    Benjamin, Richard John; McLaughlin, Lisa Swinton

    2012-05-01

    General use of plasma components includes replacement for multiple coagulation factor deficiencies, for treatment of single coagulation factor deficiencies for which a concentrate is unavailable, and as a replacement fluid used in therapeutic plasma exchange for thrombotic thrombocytopenic purpura. Four major products currently transfused are fresh-frozen plasma (FFP), plasma frozen within 24 hours of phlebotomy (FP24), cryoprecipitate-poor plasma (CPP), and thawed plasma. FP24, CPP, and thawed plasma contain decreased amounts of labile coagulation factors. Pathogen reduction technology has included solvent/detergent, methylene blue, and ultraviolet light irradiation with psoralen or riboflavin treatment and is available in Europe but not in the United States. Pathogen-reduced plasma may contain reduced levels of certain coagulant and/or anticoagulant factors compared to FFP. Clinical findings with pathogen-reduced plasma have provided an impetus to the US Food and Drug Administration to promulgate specific requirements for approval of novel plasma products, some of which may be too burdensome for the industry to readily overcome.

  14. Inactivation of Escherichia coli O157:H7 by essential oil from Cinnamomum zeylanicum.

    PubMed

    Senhaji, Ouafae; Faid, Mohamed; Kalalou, Ichraq

    2007-04-01

    Escherichia coli O157:H7 is a pathogen strain, which causes hemorrhagic colitis, hemolytic uremic syndrome and thrombotic thrombocytopenic purpura in humans. The control of bacterial cells in foods is an important factor to reduce foodborne diseases due to E. coli O157:H7. Assays to inactivate E. coli O157:H7 were carried out by using the cinnamon oil obtained by steam distillation for 6 hours. When E. coli O157:H7 cells were incubated at 37 degrees C for 2 hours in the presence of 0.025% of the essential oil from cinnamon, a dramatic decrease was observed in the viable counts (from 10(7) to 3.10(4) CFU/mL-1). In the presence of 0.05% of the oil, most of cells were killed after 30 min, suggesting that the antimicrobial activity of essential oil is bactericidal against E. coli. The minimal inhibitory concentration of the essential oil from cinnamon was around 625 ppm against E. coli O157:H7 and E. coli ATCC 25921, around 1250 ppm against E. coli ATCC25922 and around 2500 ppm against E. coli ATCC11105.

  15. Wide allelic heterogeneity with predominance of large IDS gene complex rearrangements in a sample of Mexican patients with Hunter syndrome.

    PubMed

    Alcántara-Ortigoza, M A; García-de Teresa, B; González-Del Angel, A; Berumen, J; Guardado-Estrada, M; Fernández-Hernández, L; Navarrete-Martínez, J I; Maza-Morales, M; Rius-Domínguez, R

    2016-05-01

    Hunter syndrome or mucopolysaccharidosis type II (MPSII) is caused by pathogenic variants in the IDS gene. This is the first study that examines the mutational spectrum in 25 unrelated Mexican MPSII families. The responsible genotype was identified in 96% of the families (24/25) with 10 novel pathogenic variants: c.133G>C, c.1003C>T, c.1025A>C, c.463_464delinsCCGTATAGCTGG, c.754_767del, c.1132_1133del, c.1463del, c.508-1G>C, c.1006+1G>T and c.(-217_103del). Extensive IDS gene deletions were identified in four patients; using DNA microarray analysis two patients showed the loss of the entire AFF2 gene, and epilepsy developed in only one of them. Wide allelic heterogeneity was noted, with large gene alterations (e.g. IDS/IDSP1 gene inversions, partial to extensive IDS deletions, and one chimeric IDS-IDSP1 allele) that occurred at higher frequencies than previously reported (36% vs 18.9-29%). The frequency of carrier mothers (80%) is consistent with previous descriptions (>70%). Carrier assignment allowed molecular prenatal diagnoses. Notably, somatic and germline mosaicism was identified in one family, and two patients presented thrombocytopenic purpura and pancytopenia after idursulfase enzyme replacement treatment. Our findings suggest a wide allelic heterogeneity in Mexican MPSII patients; DNA microarray analysis contributes to further delineation of the resulting phenotype for IDS and neighboring loci deletions.

  16. Vitamin B12 and Vitamin D Deficiencies: An Unusual Cause of Fever, Severe Hemolytic Anemia and Thrombocytopenia

    PubMed Central

    Mishra, Vikas A.; Harbada, Rishit; Sharma, Akhilesh

    2015-01-01

    The array of diagnostic workup for pyrexia of unknown origin (PUO) generally revolves in searching for infections, inflammatory/autoimmune, and endocrine etiologies. A differential diagnosis of fever, hemolytic anemia, and thrombocytopenia can have etiologies varying from infections like malaria, dengue, cytomegalovirus, Ebstein barr virus, Parvovirus, infective endocarditis, to autoimmune disorder (systemic lupus erythromatosis), vasculitis, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura (TTP), autoimmune hemolytic anemia/Evan's syndrome, paroxysmal nocturnal hemoglobinuri (PNH), or drugs. Nutritional deficiencies (especially vitamin B12 deficiency) as a cause of fever, hemolytic anemia, and thrombocytopenia are very rare and therefore rarely thought of. Severe vitamin B12 deficiency may cause fever and if accompanied by concurrent hyper-homocysteinemia and hypophosphatemia can sometimes lead to severe hemolysis mimicking the above-mentioned conditions. We present a case that highlights vitamin B12 and vitamin D deficiency as an easily treatable cause of PUO, hemolytic anemia, and thrombocytopenia, which should be actively looked for and treated before proceeding with more complicated and expensive investigation or starting empiric treatments. PMID:25811010

  17. Helicobacter pylori: Friend or foe?

    PubMed Central

    Malnick, Stephen David Howard; Melzer, Ehud; Attali, Malka; Duek, Gabriel; Yahav, Jacob

    2014-01-01

    Helicobacter pylori (H. pylori) is a Gram-negative spiral bacterium that is present in nearly half the world’s population. It is the major cause of peptic ulcer disease and a recognized cause of gastric carcinoma. In addition, it is linked to non-ulcer dyspepsia, vitamin B12 deficiency, iron-deficient anemia and immune thrombocytopenic purpura. These conditions are indications for testing and treatment according to current guidelines. An additional indication according to the guidelines is “anyone with a fear of gastric cancer” which results in nearly every infected person being eligible for eradication treatment. There may be beneficial effects of H. pylori in humans, including protection from gastroesophageal reflux disease and esophageal adenocarcinoma. In addition, universal treatment will be extremely expensive (more than $32 billion in the United States), may expose the patients to adverse effects such as anaphylaxis and Clostridium difficile infection, as well as contributing to antibiotic resistance. There may also be an as yet uncertain effect on the fecal microbiome. There is a need for robust clinical data to assist in decision-making regarding treatment of H. pylori infection. PMID:25083071

  18. Helicobacter pylori: friend or foe?

    PubMed

    Malnick, Stephen David Howard; Melzer, Ehud; Attali, Malka; Duek, Gabriel; Yahav, Jacob

    2014-07-21

    Helicobacter pylori (H. pylori) is a Gram-negative spiral bacterium that is present in nearly half the world's population. It is the major cause of peptic ulcer disease and a recognized cause of gastric carcinoma. In addition, it is linked to non-ulcer dyspepsia, vitamin B12 deficiency, iron-deficient anemia and immune thrombocytopenic purpura. These conditions are indications for testing and treatment according to current guidelines. An additional indication according to the guidelines is "anyone with a fear of gastric cancer" which results in nearly every infected person being eligible for eradication treatment. There may be beneficial effects of H. pylori in humans, including protection from gastroesophageal reflux disease and esophageal adenocarcinoma. In addition, universal treatment will be extremely expensive (more than $32 billion in the United States), may expose the patients to adverse effects such as anaphylaxis and Clostridium difficile infection, as well as contributing to antibiotic resistance. There may also be an as yet uncertain effect on the fecal microbiome. There is a need for robust clinical data to assist in decision-making regarding treatment of H. pylori infection.

  19. Role of fluid shear stress in regulating VWF structure, function and related blood disorders.

    PubMed

    Gogia, Shobhit; Neelamegham, Sriram

    2015-01-01

    Von Willebrand factor (VWF) is the largest glycoprotein in blood. It plays a crucial role in primary hemostasis via its binding interaction with platelet and endothelial cell surface receptors, other blood proteins and extra-cellular matrix components. This protein is found as a series of repeat units that are disulfide bonded to form multimeric structures. Once in blood, the protein multimer distribution is dynamically regulated by fluid shear stress which has two opposing effects: it promotes the aggregation or self-association of multiple VWF units, and it simultaneously reduces multimer size by facilitating the force-dependent cleavage of the protein by various proteases, most notably ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type repeats, motif 1 type 13). In addition to these effects, fluid shear also controls the solution and substrate-immobilized structure of VWF, the nature of contact between blood platelets and substrates, and the biomechanics of the GpIbα-VWF bond. These features together regulate different physiological and pathological processes including normal hemostasis, arterial and venous thrombosis, von Willebrand disease, thrombotic thrombocytopenic purpura and acquired von Willebrand syndrome. This article discusses current knowledge of VWF structure-function relationships with emphasis on the effects of hydrodynamic shear, including rapid methods to estimate the nature and magnitude of these forces in selected conditions. It shows that observations made by many investigators using solution and substrate-based shearing devices can be reconciled upon considering the physical size of VWF and the applied mechanical force in these different geometries.

  20. Catastrophic antiphospholipid syndrome in pregnancy, a diagnosis that should not be missed.

    PubMed

    Hoayek, Jennifer G; Moussa, Hind N; Rehman, Hina A; Nasab, Susan Hosseini; Blackwell, Sean C; Sibai, Baha M

    2016-12-01

    Catastrophic antiphospholipid syndrome (CAPS) is an accelerated form of the antiphospholipid antibody syndrome resulting in multi-organ ischemia and failure. It is a rare and life-threatening condition that can be easily mistaken with hemolysis elevated liver enzymes low platelets syndrome, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome. In order to make a diagnosis, it is required to have multi-organ thrombosis over 1 week affecting at least three organs or systems, and to have positive antiphospholipid antibody on two occasions (6 weeks apart), and histopathologic confirmation of small vessel occlusion. However, due to similarities in clinical and laboratory findings between CAPS and some other obstetric complications, potential misdiagnosis or delay in diagnosis are common, increasing the risk of adverse maternal and perinatal outcomes. In this review we summarized information presented in previous studies, focusing on CAPS related to pregnancy. We reviewed diagnostic criteria, differential diagnosis, and common presentation ranging from malaise, abdominal pain, dyspnea, hypertension, to altered mental status and seizures. We also discussed management in pregnancy and included a detailed algorithm with steps to take. Of note, the most significant reduction in mortality was seen in patients receiving triple therapy which will be discussed in this review.