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Sample records for alloimmune thrombocytopenic purpura

  1. Thrombotic Thrombocytopenic Purpura

    MedlinePlus

    ... the NHLBI on Twitter. What Is Thrombotic Thrombocytopenic Purpura? Thrombotic thrombocytopenic purpura (TTP) is a rare blood ... kee-ay). Petechiae may look like a rash. Purpura and Petechiae The photograph shows purpura (bruises) and ...

  2. Thrombotic thrombocytopenic purpura

    MedlinePlus

    ... medlineplus.gov/ency/article/000552.htm Thrombotic thrombocytopenic purpura To use the sharing features on this page, please enable JavaScript. Thrombotic thrombocytopenic purpura (TTP) is a blood disorder that causes blood ...

  3. What Causes Thrombotic Thrombocytopenic Purpura?

    MedlinePlus

    ... the NHLBI on Twitter. What Causes Thrombotic Thrombocytopenic Purpura? A lack of activity in the ADAMTS13 enzyme ( ... This leads to hemolytic anemia . Inherited Thrombotic Thrombocytopenic Purpura In inherited TTP, the ADAMTS13 gene is faulty. ...

  4. 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

  5. Genetics Home Reference: thrombotic thrombocytopenic purpura

    MedlinePlus

    ... Home Health Conditions thrombotic thrombocytopenic purpura thrombotic thrombocytopenic purpura Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Thrombotic thrombocytopenic purpura is a rare disorder that causes blood clots ( ...

  6. 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

  7. 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

  8. [Helicobacter pylori infection and idiopathic thrombocytopenic purpura].

    PubMed

    Franchini, Massimo; Veneri, Dino

    2005-03-01

    There are increasing data on the association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura and the significant increase in platelet count after bacterial eradication. The aim of this review was to consider the studies so far published on Helicobacter pylori infection and idiopathic thrombocytopenic purpura in order to evaluate a possible correlation between these two conditions. A review of the literature showed that 306 out of the 524 patients investigated (54.8%) were positive for Helicobacter pylori infection and that the bacterium was eradicated in 83% of cases. Eradication therapy was accompanied by a complete or partial platelet response in approximately half the cases. Overall, these data show that Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura is effective in increasing platelet count. However, since the studies so far published are few, sometimes controversial and involve small series of patients, further studies on larger numbers of patients with longer followup are needed to confirm these preliminary findings.

  9. Treatment of thrombotic thrombocytopenic purpura.

    PubMed

    Fontana, S; Kremer Hovinga, J A; Lämmle, B; Mansouri Taleghani, B

    2006-05-01

    Thrombotic thrombocytopenic purpura (TTP), characterized by thrombocytopenia and microangiopathic haemolytic anaemia, was almost universally fatal until the introduction of plasma exchange (PE) therapy in the 1970s. Based on clinical studies, daily PE has become the first-choice therapy since 1991. Recent findings may explain its effectiveness, which may include, in particular, the removal of anti-ADAMTS13 autoantibodies and unusually large von Willebrand factor multimers and/or supply of ADAMTS13 in acquired idiopathic or congenital TTP. Based on currently available data, the favoured PE regimen is daily PE [involving replacement of 1-1.5 times the patient's plasma volume with fresh-frozen plasma (FFP)] until remission. Adverse events of treatment are mainly related to central venous catheters. The potential reduction of plasma related side-effects, such as transfusion-related acute lung injury (TRALI) or febrile transfusion reactions by use of solvent-detergent treated (S/D) plasma instead of FFP is not established by controlled clinical studies. Uncontrolled clinical observations and the hypothesis of an autoimmune process in a significant part of the patients with acquired idiopathic TTP suggest a beneficial effect of adjunctive therapy with corticosteroids. Other immunosuppressive treatments are not tested in controlled trials and should be reserved for refractory or relapsing disease. There is no convincing evidence for the use of antiplatelet agents. Supportive treatment with transfusion of red blood cells or platelets has to be evaluated on a clinical basis, but the transfusion trigger for platelets should be very restrictive. Further controlled, prospective studies should consider the different pathophysiological features of thrombotic microangiopathies, address the prognostic significance of ADAMTS13 and explore alternative exchange fluids to FFP, the role of immunosuppressive therapies and of new plasma saving approaches as recombinant ADAMTS13 and

  10. [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.

  11. Thrombotic thrombocytopenic purpura in southeastern New England.

    PubMed

    Crowley, J P; Zaroulis, C G; O'Shea, P A; Clark, D D

    1983-05-01

    Eight patients with thrombotic thrombocytopenic purpura (TTP) originating within a 25-mile radius had their conditions diagnosed in a three-year period at a community teaching hospital in southeastern New England. In the preceding ten years, only one case of TTP had occurred in the same hospital. A niece-uncle relationship was present in two patients, and lymphocyte typing showed that they both shared an HLA haplotype. In the remaining patients, no social, familial, or environmental connection was established. Three patients died, all of whom were female. Six patients received exchange plasmapheresis with excellent responses in five. Autopsies in the three fatal cases showed widespread organ involvement with TTP but did not disclose evidence of any common underlying disease. This unusual occurrence should alert physicians to the possibility of localized outbreaks of TTP and the necessity of considering this diagnosis in all patients with unexplained thrombocytopenia. PMID:6383244

  12. SYSTEMIC INFECTIONS MIMICKING THROMBOTIC THROMBOCYTOPENIC PURPURA

    PubMed Central

    Booth, Kristina K.; Terrell, Deirdra R.; Vesely, Sara K.; George, James N.

    2012-01-01

    The absence of specific diagnostic criteria, the urgency to begin plasma exchange treatment, and the risk for complications from plasma exchange make the initial evaluation of patients with suspected thrombotic thrombocytopenic purpura (TTP) difficult. Systemic infections may mimic the presenting clinical features of TTP. In the Oklahoma TTP-HUS (hemolytic-uremic syndrome) Registry, 1989–2010, 415 consecutive patients have been clinically diagnosed with their first episode of TTP; in 31 (7%) the presenting clinical features were subsequently attributed to a systemic infection. All 31 patients had diagnostic criteria for TTP; 16 (52%) had the complete “pentad” of microangiopathic hemolytic anemia, thrombocytopenia, neurologic abnormalities, renal failure and fever. Four (16%) of 25 patients who had ADAMTS13 measurements had <10% activity; three patients had a demonstrable ADAMTS13 inhibitor. Compared to 62 patients with severe ADAMTS13 deficiency (<10%) who had no recognized alternative disorders, patients with systemic infections had more frequent fever, coma, renal failure, and the complete “pentad” of clinical features. Seventeen different infectious etiologies were documented. A systematic literature review identified 67 additional patients with a diagnosis of TTP or HUS and also a systemic infection. Among all 98 patients, infections with 41 different bacteria, viruses, and fungi were documented, suggesting that many different systemic infections may mimic the presenting clinical features of TTP. Initial plasma exchange treatment is appropriate in critically ill patients with diagnostic features of TTP, even if a systemic infection is suspected. Continuing evaluation to document a systemic infection is essential to determine the appropriateness of continued plasma exchange. PMID:21850657

  13. Thrombocytopenic Purpura Associated with Dietary Supplements Containing Citrus Flavonoids.

    PubMed

    Ghali, Alaa; Bourneau-Martin, Delphine; Dopter, Aymeric; Lainé-Cessac, Pascale; Belizna, Cristina; Urbanski, Geoffrey; Lavigne, Christian

    2015-01-01

    We report a case of thrombocytopenic purpura associated with the intake of two dietary supplements containing mainly citrus flavonoids. This is the first case to be notified to the French Agency for Food, Environmental and Occupational Health Safety (ANSES). It addresses the importance of an accurate medication history interview for each patient. PMID:26242500

  14. Coexisting Situs Inversus Totalis and Immune Thrombocytopenic Purpura

    PubMed Central

    Gundogdu, Kemal; Altintoprak, Fatih; Uzunoğlu, Mustafa Yener; Dikicier, Enis; Zengin, İsmail; Yağmurkaya, Orhan

    2016-01-01

    Situs inversus totalis is a rare congenital abnormality with mirror symmetry of mediastinal and abdominal organs. Immune thrombocytopenic purpura is an autoimmune disease with destruction of thrombocytes. This paper is presentation of surgical approach to a case with coexistence of these two conditions. PMID:26981307

  15. Thrombocytopenic Purpura Associated with Dietary Supplements Containing Citrus Flavonoids.

    PubMed

    Ghali, Alaa; Bourneau-Martin, Delphine; Dopter, Aymeric; Lainé-Cessac, Pascale; Belizna, Cristina; Urbanski, Geoffrey; Lavigne, Christian

    2015-01-01

    We report a case of thrombocytopenic purpura associated with the intake of two dietary supplements containing mainly citrus flavonoids. This is the first case to be notified to the French Agency for Food, Environmental and Occupational Health Safety (ANSES). It addresses the importance of an accurate medication history interview for each patient.

  16. Intravenous Rh immune globulin for treating immune thrombocytopenic purpura.

    PubMed

    Sandler, S G

    2001-11-01

    Intravenous Rh [corrected] immune globulin was licensed by the U. S. Food and Drug administration in 1995 for the treatment of acute and chronic immune thrombocytopenic purpura in children and chronic immune thrombocytopenic purpura in adults. In 1996, the American Society of Hematology published a practice guideline for immune thrombocytopenic purpura, but treatment recommendations of necessity were formulated using only results of early clinical trials with intravenous Rh immune globulin. To date, there are no published results of large-scale clinical trials comparing conventional doses of intravenous immune globulin with the most promising dose range for intravenous Rh immune globulin (50-75 microg/kg). However, clinical experience is accumulating to indicate that intravenous Rh immune globulin is as effective, probably safer, and easier to administer than intravenous immune globulin. Acute intravascular hemolysis after infusions of intravenous Rh immune globulin for immune thrombocytopenic purpura has been reported with an estimated incidence of 1 in 1,115 patients. The risk factors for this adverse event have not been defined.

  17. Thrombotic thrombocytopenic purpura: MR demonstration of reversible brain abnormalities

    SciTech Connect

    D'Aprile, P.; Carella, A.; Pagliarulo, R. ); Farchi, G. )

    1994-01-01

    We report a case of thrombotic thrombocytopenic purpura evaluated by MR, Multiple hyperintense foci on the TS-weighted images, observed principally in the brain stem and in the region of the basal nuclei, and neurologic signs disappeared after 15 days of therapy. 6 refs., 2 figs.

  18. [Laparoscopic splenectomy in immune thrombocytopenic purpura in pregnant women].

    PubMed

    Danishyan, K I; Soboleva, O A; Galstyan, G M; Zvereva, A V; Sorkina, O M

    2016-01-01

    The paper describes 4 cases of laparoscopic splenectomy in pregnant women with immune thrombocytopenic purpura. No complications of surgery were noted in all the patients. The postoperative period was marked by sustained clinical and hematological remission that made it possible to discontinue prednisolone therapy and to ensure an uncomplicated course of pregnancy and labor. PMID:27459624

  19. Immune thrombocytopenic purpura-related hemotympanum presenting with hearing loss.

    PubMed

    Fisgin, Tunc; Atmaca, Sinan; Duru, Feride; Ozyurek, Emel; Cetin, Recep; Albayrak, Davut

    2009-06-01

    A 5-year-old boy was admitted to our center with a major complaint of bilateral hearing loss for 2 days. He was diagnosed with acute immune thrombocytopenic purpura 3 months before the admission and treated with high-dose methylprednisolone 2 months ago. Physical examination revealed wet purpura in the oral mucosa, serous nasal discharge, multiple petechiae and ecchymosis of the lower lip. Otomicroscopic ear examination revealed the presence of bilateral hemotympanum. The patient denied head trauma, ear pain, fever, hypertension and medications, including salicylates. The patient received high-dose intravenous methylprednisolone because of low platelet count and wet purpura for 7 days and oral prophylactic amoxicillin-clavulanate for 14 days. The onset of the response to corticosteroids was rapid, and significant hematologic improvement was observed within a few days. The 2-week follow-up examination revealed intact tympanic membranes with normal color and mobility, and the patient restored normal hearing. In this patient, hemotympanum developed rapidly, and no predisposing cause other than immune thrombocytopenic purpura was found. However, presence of a serous nasal discharge may be a sign of viral upper respiratory tract infection. Therefore, it can be speculated that sneezing or coughing might have caused bilateral hemotympanum by increasing the middle ear pressure abruptly. We would like to emphasize that bleeding may occur in unusual sites and, unlike in healthy people, may cause bizarre symptoms in patients with bleeding diathesis. Hemotympanum can be considered among the indications to start treatment in patients with acute immune thrombocytopenic purpura. PMID:19530341

  20. Thrombotic thrombocytopenic purpura in the first trimester of pregnancy

    PubMed Central

    Sikka, Pooja; Chopra, Seema; Aggarwal, Neelam; Suri, Vanita; Chandrasekaran, Abi

    2013-01-01

    Thrombotic thrombocytopenic purpura (TTP) occurs more commonly in women and so can be associated with pregnancy. The time during pregnancy with greatest risk for development of TTP is near term and during the post partum period. TTP occurring in early trimester is uncommon and is also associated with great maternal and fetal mortality. We report a successful outcome of pregnancy in a woman with TTP in early first trimester who was treated with therapeutic plasma exchange. PMID:23559773

  1. Thrombotic thrombocytopenic purpura: The role of ADAMTS13.

    PubMed

    Rogers, Heesun J; Allen, Charles; Lichtin, Alan E

    2016-08-01

    Thrombotic thrombocytopenic purpura (TTP) is an uncommon, life-threatening disease requiring prompt diagnosis and initiation of therapeutic plasma exchange to improve patient survival. However, diagnosis is often difficult because of atypical presentations and signs and symptoms that resemble other conditions. Measurements of ADAMTS13 activity, ADAMTS13 inhibitor, and ADAMTS13 autoantibody are useful for diagnosing TTP, guiding therapy, and predicting relapse. PMID:27505881

  2. Immune Thrombocytopenic Purpura During Pregnancy: Laparoscopic Treatment

    PubMed Central

    Anglin, Beth V.; Rutherford, Cynthia; Ramus, Ronald; Lieser, Mark

    2001-01-01

    Background and Objectives: Laparoscopic surgical techniques in pregnancy have been accepted and pose minimal risks to the patient and fetus. We present the first reported case of a pregnant woman with immune thrombocytopenia purpura who underwent laparoscopic splenectomy during the second trimester. Methods and Results: The anesthesia, hematology, and obstetrics services closely followed the patient's preoperative and intraoperative courses. After receiving immunization, stress dose steroids, and prophylactic antibiotics, she underwent a successful laparoscopic splenectomy. After a short hospital stay, the patient was discharged home. Conclusion: Immune thrombocytopenia purpura can be an indication for splenectomy. As demonstrated in appendectomy, cholecystectomy, and our case presentation, laparoscopic splenectomy can be safely performed during pregnancy. PMID:11303997

  3. Immune Thrombocytopenic Purpura Presenting as Unprovoked Gingival Hemorrhage: a Case Report

    PubMed Central

    Bal, Mehmet V; Koyuncuoglu, Cenker Z; Saygun, Işıl

    2014-01-01

    Immune thrombocytopenic purpura is an autoimmune disease characterized by auto-antibody induced platelet destruction and reduced platelet production, leading to low blood platelet count. In this case report, the clinical diagnose of a patient with immune thrombocytopenic purpura and spontaneous gingival hemorrhage by a dentist is presented. The patient did not have any systemic disease that would cause any spontaneous hemorrhage. The patient was referred to a hematologist urgently and her thrombocyte number was found to be 2000/μL. Other test results were in normal range and immune thrombocytopenic purpura diagnose was verified. Then hematological treatment was performed and patient’s health improved without further problems. Hematologic diseases like immune thrombocytopenic purpura, in some cases may appear firstly in the oral cavity and dentists must be conscious of unexplained gingival hemorrhage. In addition, the dental treatment of immune thrombocytopenic purpura patients must be planned with a hematologist. PMID:25317211

  4. Thrombotic thrombocytopenic purpura in a case of brucellosis.

    PubMed

    Akbayram, Sinan; Dogan, Murat; Peker, Erdal; Akgun, Cihangir; Oner, Ahmet Faik; Caksen, Hüseyin

    2011-06-01

    Thrombotic thrombocytopenic purpura (TTP) is characterized by disseminated thrombotic occlusions located in the microcirculation and a syndrome of microangiopathic hemolytic anemia, thrombocytopenia, fever, and renal and neurologic abnormalities. Thrombotic thrombocytopenic purpura is encountered in a variety of clinical situations such as viral, bacterial, and mycobacterial infections, autoimmune disorders, drug reactions, connective tissue disease, and solid tumors. In this report, we present TTP in a case of brucellosis because of rare presentation. A 7-year-old girl was admitted with the complaints of headache, fever, hematuria, malaise, jaundice, epistaxis, and purpura. Her physical examination revealed conjunctival pallor, scleral icterus, petechial-purpuric skin lesions on both legs, and confusion. Laboratory tests showed hematocrit 14%; hemoglobin 4.8 g/dL; platelet count 6000/mm(3), and reticulocytosis 6%. Peripheral blood smear revealed fragmented red blood cells and a complete absence of platelets. The clinical and laboratory findings were consistent with TTP. Serum antibrucella titration agglutination test was found to be 1/1280 positive.

  5. Thrombotic Thrombocytopenic Purpura-Haemolytic Uremic Syndrome and pregnancy

    PubMed Central

    Mwita, Julius Chacha; Vento, Sandro; Benti, Tadele

    2014-01-01

    Thrombotic Thrombocytopenic Purpura-Haemolytic Uremic Syndrome (TTP-HUS) is a rare pregnancy and postpartum complication that may simulate the more common obstetric complications, preeclampsia and the syndrome of haemolysis, elevated liver functions tests, low platelets (HELLP). We describe a 26 years old patient who presented with peri-partum TTP-HUSand was initially treated as a case of HELLP syndrome without any improvement. A brief review of the current TTP-HUS treatment options in pregnancy is also presented. PMID:25309655

  6. 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.

  7. Accessory spleen compromising response to splenectomy for idiopathic thrombocytopenic purpura

    SciTech Connect

    Ambriz, P.; Munoz, R.; Quintanar, E.; Sigler, L.; Aviles, A.; Pizzuto, J.

    1985-06-01

    Accessory spleens were sought in 28 patients who had undergone splenectomy for chronic idiopathic thrombocytopenic purpura (ITP), using a variety of techniques. Abdominal scintigraphy with autologous erythrocytes labeled with Tc-99m and opsonized with anit-D IgG (radioimmune method) proved to be most useful, clearly demonstrating one or more accessory spleens in 12 cases (43%). Computed tomography (CT) was also helpful. Four out of five patients demonstrated an increased platelet count following surgery, the effectiveness of which was illustrated by the radioimmune scan. Patients who have had splenectomy for chronic ITP should be scanned using radioimmune techniques and CT to determine whether an accessory spleen is present.

  8. Two Mechanistic Pathways for Thienopyridine-Associated Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Bennett, Charles L.; Kim, Benjamin; Zakarija, Anaadriana; Bandarenko, Nicholas; Pandey, Dilip K.; Buffie, Charlie G.; McKoy, June M.; Tevar, Amul D.; Cursio, John F.; Yarnold, Paul R.; Kwaan, Hau C.; De Masi, Davide; Sarode, Ravindra; Raife, Thomas J.; Kiss, Joseph E.; Raisch, Dennis W.; Davidson, Charles; Sadler, J. Evan; Ortel, Thomas L.; Zheng, X. Long; Kato, Seiji; Matsumoto, Masanori; Uemura, Masahito; Fujimura, Yoshihiro

    2011-01-01

    Objectives We sought to describe clinical and laboratory findings for a large cohort of patients with thienopyridine-associated thrombotic thrombocytopenic purpura (TTP). Background The thienopyridine derivatives, ticlopidine and clopidogrel, are the 2 most common drugs associated with TTP in databases maintained by the U.S. Food and Drug Administration (FDA). Methods Clinical reports of TTP associated with clopidogrel and ticlopidine were identified from medical records, published case reports, and FDA case reports (n = 128). Duration of thienopyridine exposure, clinical and laboratory findings, and survival were recorded. ADAMTS13 activity (n = 39) and inhibitor (n = 30) were measured for a subset of individuals. Results Compared with clopidogrel-associated TTP cases (n = 35), ticlopidine-associated TTP cases (n = 93) were more likely to have received more than 2 weeks of drug (90% vs. 26%), to be severely thrombocytopenic (84% vs. 60%), and to have normal renal function (72% vs. 45%) (p < 0.01 for each). Compared with TTP patients with ADAMTS13 activity >15% (n = 13), TTP patients with severely deficient ADAMTS13 activity (n = 26) were more likely to have received ticlopidine (92.3% vs. 46.2%, p < 0.003). Among patients who developed TTP >2 weeks after thienopyridine, therapeutic plasma exchange (TPE) increased likelihood of survival (84% vs. 38%, p < 0.05). Among patients who developed TTP within 2 weeks of starting thienopyridines, survival was 77% with TPE and 78% without. Conclusions Thrombotic thrombocytopenic purpura is a rare complication of thienopyridine treatment. This drug toxicity appears to occur by 2 different mechanistic pathways, characterized primarily by time of onset before versus after 2 weeks of thienopyridine administration. If TTP occurs after 2 weeks of ticlopidine or clopidogrel therapy, therapeutic plasma exchange must be promptly instituted to enhance likelihood of survival. PMID:17868804

  9. 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.

  10. Harmful and beneficial antibodies in immune thrombocytopenic purpura.

    PubMed Central

    Imbach, P A

    1994-01-01

    Two facts support the definition of idiopathic thrombocytopenic purpura (ITP) as an immune disorder. First, antibodies against platelets, which often appear after a viral infection, provoke the increased elimination of these cells. Viral disease may change the complex immune response of the host at different levels. In chronic ITP, the consequences of the dysregulated immune system are autoantibodies, primarily against platelet glycoprotein IIb/IIIa. Second, pooled immunoglobulins from healthy blood donors may influence the imbalanced immune response in ITP. The initial study dose of 5 x 0.4 g of intact 7S IgG/kg body weight can now be reduced to 2 x 0.4 g/kg body weight in the majority of patients. The possible mechanisms of action of intravenous immune globulin (IVIG) are reviewed and updated in this article. The combination of effects on the humoral and cellular immune responses using IVIG in concert with cytokines may open up new therapeutic possibilities. PMID:8033430

  11. Association of primary biliary cirrhosis with idiopathic thrombocytopenic purpura

    PubMed Central

    Toshikuni, Nobuyuki; Yamato, Ryumei; Kobashi, Haruhiko; Nishino, Ken; Inada, Nobu; Sakanoue, Ritsuko; Suehiro, Mitsuhiko; Fujimura, Yoshinori; Yamada, Gotaro

    2008-01-01

    Although both primary biliary cirrhosis (PBC) and idiopathic thrombocytopenic purpura (ITP) are autoimmune diseases, the association of the 2 diseases is rare. Here, we report a case of ITP that developed during the follow-up of PBC in a 74-year-old man. The patient had been diagnosed with PBC 12 years previously, and had received treatment with ursodeoxycholic acid. The platelet count decreased from approximately 60 × 109/L to 8 × 109/L, and the association of decompensated liver cirrhosis (PBC) with ITP was diagnosed. Steroid and immune gamma globulin therapy were successful in increasing the platelet count. Interestingly, human leukocyte antigen genotyping detected the alleles DQB1*0601 and DRB1*0803, which are related to both PBC and ITP in Japanese patients. This case suggests common immunogenetic factors might be involved in the development of PBC and ITP. PMID:18416479

  12. 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.

  13. ADAMTS13 and von Willebrand Factor in Thrombotic Thrombocytopenic Purpura

    PubMed Central

    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. PMID:25587650

  14. Helicobacter pylori infection and immune thrombocytopenic purpura: an update.

    PubMed

    Franchini, Massimo; Veneri, Dino

    2004-08-01

    Data are accumulating on the association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) and the significant increase in platelet count after bacterial eradication. The aim of this review was to consider the studies so far published on H. pylori infection and ITP in order to evaluate a possible correlation between these two conditions. A review of the literature showed that 278 out of the 482 ITP patients investigated (58%) were positive for H. pylori infection and that the bacterium was eradicated in 88% of cases. Eradication therapy was accompanied by a complete or partial platelet response in approximately half the cases. Overall, these data show that H. pylori eradication in patients with ITP is effective in increasing platelet count. However, because the studies so far published are few, are sometimes controversial and involve small series of patients, further studies on larger numbers of patients with longer follow-up are needed to confirm these preliminary findings.

  15. Thrombotic Thrombocytopenic Purpura: Issues in Diagnosis and Treatment.

    PubMed

    Khatun, H; Morshed, M

    2015-10-01

    Thrombotic thrombocytopenic purpura (TTP) is a hematologic emergency fatal without prompt treatment. Plasma exchange (PEX), the treatment of choice for TTP, is not readily available and has major complications. We report seven cases of TTP, both acquired immune and secondary. Two patients had TTP secondary to malignancy and one secondary to SLE. Male to female ratio was 1:3 and median age at presentation 38 years. Six patients had moderate to very high level of LDH while one primary TTP had only mild elevation. Median haemoglobin and platelet at presentation were 6.3 gm/dL and 38 k/UL respectively. Median LDH value was 4595 u/L. All patients were treated with plasma exchange (PEX) except the two cases secondary to malignancy. One patient died of cardiac arrest during plasma exchange. None of the patients treated with PEX had relapsed over a median follow up of 18 months. PMID:26620016

  16. Treatment of immune thrombocytopenic purpura: focus on eltrombopag

    PubMed Central

    Rice, Lawrence

    2009-01-01

    Immune thrombocytopenic purpura (ITP) is a relatively common autoimmune disorder in which antibodies are produced to circulating platelets. Symptoms can be mild, but for most patients the risk of severe bleeding is unacceptable and treatment is required. Glucocorticoids followed by splenectomy had been the mainstays of therapy. High dose intravenous immunoglobulin and anti-RhD therapy are available for patients with severe illness, but produce only temporary benefit. Rituximab may provide more durable responses, danazol may be underutilized, and immunosuppressants and cytotoxic agents are less often required. Recently the pathophysiology of ITP has been more clearly elucidated, particularly the importance of decreased production of platelets in most patients and the very blunted rise that occurs in serum thrombopoietin (TPO). The isolation of TPO and better understanding of its role in thrombopoiesis has led to the development of new highly effective treatments. TPO analogs had some successes in treating highly refractory ITP patients but were taken out of development due to TPO-antibody induction. Two second-generation TPO-mimetics, romiplostim and the orally available eltrombopag, have recently been licensed in some territories for the treatment of ITP. Approval of eltrombopag was based on results from Phase II and III placebo-controlled clinical trials and a long-term extension study. About 80% of patients achieve significant increases in platelet count (11% of placebo patients), with reduced bleeding and reduced use of concomitant medications; responses are often durable with no tachyphylaxis. The side effects of eltrombopag are generally mild and not worse than placebo, although there are concerns about hepatic dysfunction, and the potentials for thromboses, marrow reticulin fibrosis, rebound thrombocytopenia and cataracts. This is an important new option for highly refractory patients, and its niche in earlier treatment (and for other thrombocytopenic

  17. Two cases of thrombocytopenic purpura at onset of Zika virus infection.

    PubMed

    Chraïbi, Samy; Najioullah, Fatiha; Bourdin, Carole; Pegliasco, Jean; Deligny, Christophe; Résière, Dabor; Meniane, Jean-Côme

    2016-10-01

    We report here two cases of thrombocytopenic purpura at onset of Zika virus infection. A 26-year-old woman and a 21-year-old man had thrombocytopenia above 5×10(9) platelets/L. Hemorrhagic symptoms were mucosal and subcutaneous bleeding and gross hematuria and they reported episode of conjunctivitis. In both cases blood and bone marrow analysis suggested thrombocytopenic purpura, blood PCR tests for Dengue (DENV), Chikungunya (CHIKV) and Zika virus (ZIKV) were negative. In both cases urinary PCR for ZIKV was positive, Prednisolone yielded early remission. Only three similar cases have been reported so far. In the Caribbean, DENV is also epidemic and responsible for severe thrombocytopenia. Coinfections can occur. Our report underlines the need to include a ZIKV assay in the diagnostic work-up of thrombocytopenic purpura in epidemic areas.

  18. Two cases of thrombocytopenic purpura at onset of Zika virus infection.

    PubMed

    Chraïbi, Samy; Najioullah, Fatiha; Bourdin, Carole; Pegliasco, Jean; Deligny, Christophe; Résière, Dabor; Meniane, Jean-Côme

    2016-10-01

    We report here two cases of thrombocytopenic purpura at onset of Zika virus infection. A 26-year-old woman and a 21-year-old man had thrombocytopenia above 5×10(9) platelets/L. Hemorrhagic symptoms were mucosal and subcutaneous bleeding and gross hematuria and they reported episode of conjunctivitis. In both cases blood and bone marrow analysis suggested thrombocytopenic purpura, blood PCR tests for Dengue (DENV), Chikungunya (CHIKV) and Zika virus (ZIKV) were negative. In both cases urinary PCR for ZIKV was positive, Prednisolone yielded early remission. Only three similar cases have been reported so far. In the Caribbean, DENV is also epidemic and responsible for severe thrombocytopenia. Coinfections can occur. Our report underlines the need to include a ZIKV assay in the diagnostic work-up of thrombocytopenic purpura in epidemic areas. PMID:27596376

  19. Lupus-associated thrombotic thrombocytopenic purpura-like microangiopathy

    PubMed Central

    Blum, Daniel; Blake, Geoffrey

    2015-01-01

    Recently reported cases of lupus complicated by a thrombotic thrombocytopenic purpura (TTP)-like syndrome suggest a survival benefit to early treatment with plasma exchange. The following is a report of the eighth such case in the last ten years. A 44-year-old lady known for lupus presented with the nephrotic syndrome and a renal biopsy was consistent with class 4G lupus nephritis. She was given high-dose steroids and cytotoxic therapy, but her induction therapy was complicated by the classic pentad of TTP. She was subsequently treated with another course of high-dose steroids, a different cytotoxic agent, and plasma exchange, with clinical resolution shortly thereafter. Similar to seven recently reported cases of microangiopathy in lupus, this lady’s TTP-like syndrome improved dramatically after initiation of plasma exchange, despite not having a severely deficient ADAMTS13. This has implications on both current clinical practice and on the pathogenesis of TTP-like syndromes in lupus. PMID:26558190

  20. Bortezomib in the treatment of refractory thrombotic thrombocytopenic purpura.

    PubMed

    Patriquin, Christopher J; Thomas, Mari R; Dutt, Tina; McGuckin, Siobhan; Blombery, Piers A; Cranfield, Tanya; Westwood, John P; Scully, Marie

    2016-06-01

    Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening condition caused by autoantibody-mediated inhibition of ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type-1 motif, 13). Therapeutic plasma exchange (TPE) improves survival, but disease may be refractory despite therapy. Management and treatment response of refractory TTP is variable, with rituximab and other immunosuppression often being used. Case reports have suggested a benefit of the proteasome inhibitor, bortezomib, possibly due to elimination of the autoreactive plasma cells producing anti-ADAMTS13 antibodies. We evaluated the effect of bortezomib in a series of primary refractory TTP patients unresponsive to intensive therapy. Bortezomib-treated patients were identified from consecutive cases managed at two UK referral centres. Demographic and clinical data were extracted from hospital records. ADAMTS13 activity was measured using a fluorescence resonance energy transfer VWF73 assay, and anti-ADAMTS13 IgG using enzyme-linked immunosorbent asssay. We identified six bortezomib-treated patients out of 51 consecutive cases of acute, acquired TTP. All patients received TPE, methylprednisolone and rituximab. Five of the six achieved complete remission with bortezomib, and one died of cardiac arrest due to underlying disease. No treatment-related adverse events were observed. Mean follow-up time after hospital discharge was 17 months (range: 3-33). Bortezomib appears effective in the treatment of a subgroup of cases with severe, refractory TTP. Prospective trials are required to further investigate this effect. PMID:27009919

  1. 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.

  2. Depression and cognitive impairment following recovery from thrombotic thrombocytopenic purpura.

    PubMed

    Han, Bowie; Page, Evaren E; Stewart, Lauren M; Deford, Cassandra C; Scott, James G; Schwartz, Lauren H; Perdue, Jedidiah J; Terrell, Deirdra R; Vesely, Sara K; George, James N

    2015-08-01

    After recovery from an acute episode of acquired thrombotic thrombocytopenic purpura (TTP), patients often describe problems with memory, concentration, and endurance. We have previously reported the occurrence of depression and cognitive impairment in these patients. In this study, we describe the frequency, severity, and clinical course of depression and cognitive impairment. Fifty-two (85%) out of 61 eligible Oklahoma Registry patients who had recovered from TTP, documented by ADAMTS13 activity <10%, have had at least one (median, four) evaluation for depression over 11 years using the Beck Depression Inventory-II; 31 (59%) patients screened positive for depression at least once; in 15 (29%), the results suggested severe depression at least once. Nine of these 15 patients had a psychiatric interview, the definitive diagnostic evaluation; the diagnosis of major depressive disorder was established in eight (89%) patients. In 2014, cognitive ability was evaluated in 33 patients by the Montreal Cognitive Assessment and the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Both tests detected significant cognitive impairment in the patients as a group. Fifteen out of the 33 patients had been evaluated by extensive cognitive tests in 2006. The 2014 RBANS results were significantly worse than the 2006 results for the overall score and two out of the five RBANS domains (immediate and delayed memory). Neither depression nor cognitive impairment was significantly associated with the occurrence of relapses or ADAMTS13 activity <10% during remission. These observations emphasize the importance of screening evaluations for depression and cognitive impairment after recovery from acquired TTP.

  3. Pulmonary Hyalinizing Granuloma Associated with Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Coleman, Christopher; Nassar, Aziza; McComb, Barbara

    2014-01-01

    Pulmonary hyalinizing granuloma (PHG) is a rare, benign lung disease of unknown etiology. It manifests as discrete, rounded nodules within the lung parenchyma. A 39-year-old woman presented for investigation after pulmonary nodules were found incidentally. Chest computed tomography showed multiple, discrete, non-enhancing pulmonary nodules bilaterally. Positron emission tomography (PET) was negative. Biopsy demonstrated a non-specific lymphoplasmacytic infiltrate. Open resection yielded two nodules consistent with hyalinizing granulomas. The differential for multiple pulmonary nodules is broad. PET scan can help rule out metastatic disease, although some cancers are not hypermetabolic on PET. Furthermore, some non-malignant conditions, including hyalinizing granuloma, can show increased activity on PET. PHG should be included in the differential of multiple pulmonary nodules, especially if nodule stability can be demonstrated and/or needle biopsies are non-diagnostic. Associated immune-mediated conditions, such as idiopathic thrombocytopenic purpura (ITP) in our patient, may also favor HG. In this case report we find an association between PHG and ITP. PMID:24744965

  4. Pulmonary hyalinizing granuloma associated with idiopathic thrombocytopenic purpura.

    PubMed

    Coleman, Christopher; Nassar, Aziza; McComb, Barbara

    2014-01-01

    Pulmonary hyalinizing granuloma (PHG) is a rare, benign lung disease of unknown etiology. It manifests as discrete, rounded nodules within the lung parenchyma. A 39-year-old woman presented for investigation after pulmonary nodules were found incidentally. Chest computed tomography showed multiple, discrete, non-enhancing pulmonary nodules bilaterally. Positron emission tomography (PET) was negative. Biopsy demonstrated a non-specific lymphoplasmacytic infiltrate. Open resection yielded two nodules consistent with hyalinizing granulomas. The differential for multiple pulmonary nodules is broad. PET scan can help rule out metastatic disease, although some cancers are not hypermetabolic on PET. Furthermore, some non-malignant conditions, including hyalinizing granuloma, can show increased activity on PET. PHG should be included in the differential of multiple pulmonary nodules, especially if nodule stability can be demonstrated and/or needle biopsies are non-diagnostic. Associated immune-mediated conditions, such as idiopathic thrombocytopenic purpura (ITP) in our patient, may also favor HG. In this case report we find an association between PHG and ITP. PMID:24744965

  5. 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.

  6. Pregnancy and Birth Outcomes among Women with Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Wyszynski, Diego F.; Carman, Wendy J.; Cantor, Alan B.; Graham, John M.; Kunz, Liza H.; Slavotinek, Anne M.; Kirby, Russell S.; Seeger, John

    2016-01-01

    Objective. To examine pregnancy and birth outcomes among women with idiopathic thrombocytopenic purpura (ITP) or chronic ITP (cITP) diagnosed before or during pregnancy. Methods. A linkage of mothers and babies within a large US health insurance database that combines enrollment data, pharmacy claims, and medical claims was carried out to identify pregnancies in women with ITP or cITP. Outcomes included preterm birth, elective and spontaneous loss, and major congenital anomalies. Results. Results suggest that women diagnosed with ITP or cITP prior to their estimated date of conception may be at higher risk for stillbirth, fetal loss, and premature delivery. Among 446 pregnancies in women with ITP, 346 resulted in live births. Women with cITP experienced more adverse outcomes than those with a pregnancy-related diagnosis of ITP. Although 7.8% of all live births had major congenital anomalies, the majority were isolated heart defects. Among deliveries in women with cITP, 15.2% of live births were preterm. Conclusions. The results of this study provide further evidence that cause and duration of maternal ITP are important determinants of the outcomes of pregnancy. PMID:27092275

  7. Platelet microparticles in immune thrombocytopenic purpura in pediatrics.

    PubMed

    Tantawy, Azza A G; Matter, Randa M; Hamed, Ahmed A; Shams El Din El Telbany, Manal A

    2010-05-01

    Immune thrombocytopenic purpura (ITP) is one of the most common hemorrhagic disorders in childhood. Platelet microparticles (PMPs) arise with platelet activation with procoagulant activity. Elevated PMP levels in adult ITP were reported to be thrombogenic in certain settings. However, their clinical significance in pediatric ITP was not studied. The aims of this study were to assess PMP levels in ITP in children and adolescents, and its correlation with clinical status and bleeding score. The study included 40 ITP patients (20 acute aged 9 +/- 2.19 years and 20 chronic aged 10.8 +/- 4.7 years) randomly selected from the Hematology Clinic, Children's Hospital, Ain Shams University, Cairo, Egypt, and 30 sex- and age-matched healthy controls aged 9 +/- 3.28 years. Patients were subjected to detailed history, assessment of bleeding score, complete hemogram, cytological bone marrow examination, and PMP quantification in peripheral blood by flow cytometry. Acute ITP patients had significant increase in PMPs, PMP/platelet count, and PMP percent compared to controls (P = .002, P < .0001, P < .0001, respectively) and compared to chronic ITP patients (P < .0001, P < .0001, P < .0001, respectively). PMPs were significantly decreased in chronic ITP patients compared to controls (P = .001), but PMP/platelet and PMP percent showed highly significant increase in chronic ITP (P < .0001). No correlation was evident between PMP levels and platelet count in either group (P > .05). Neither higher bleeding score nor thrombotic manifestations were observed in the studied ITP patients with high PMP levels. Elevated PMP levels may be protective against severe bleeding events in pediatric ITP. The role of PMP studies in deciding the management plan of childhood and adolescent ITP needs further evaluation.

  8. Late Results After Splenectomy in Adult Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Vecchio, Rosario; La Corte, Francesco; Marchese, Salvatore; Cacciola, Rossella R.; Cacciola, Emma

    2015-01-01

    Background: We performed a retrospective study on patients with idiopathic thrombocytopenic purpura (ITP) to evaluate the response to splenectomy in relation to preoperative platelet count. Materials and Methods: Two groups of patients operated on with laparoscopic or open splenectomy for ITP, with a platelet count ≤30,000/μL (study group: 22 patients) and >30,000/μL (control group: 18 patients), respectively, were compared. The two groups were homogeneous in relation to age, sex, length of preoperative steroid therapy, and time interval between diagnosis and surgery (Student t test with P > .1). The results of surgery were evaluated at one year after splenectomy. Positive response to surgery, according to the American Society of Hematologic Guidelines, was considered in patients with a postoperative platelet count ≥100,000/μL or in patients with a postoperative platelet count ≥30,000/μL and a twofold increase in platelet count from baseline, in the absence of bleeding. The postoperative platelet count increase rate was statistically related to preoperative platelet count in both the study and control groups. Statistical analysis was performed using the Student's t test for independent sample and the Pearson correlation in a 2-tailed test. Results: No relationship between preoperative platelet count and postoperative platelet percent increase was observed in the control group (r = –0.41; P = .089), whereas a significant negative correlation (r = –0.68; P = .0004) was found in the study group. Conclusions: A higher increase of postoperative percent platelet count may be predicted in patients with a low preoperative platelet count. PMID:25848175

  9. 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.

  10. Successful management of thrombotic thrombocytopenic purpura in a Jehovah's Witness without plasma exchange.

    PubMed

    Chai, Wanxing; Chaudhry, Abrar; Rabinowitz, Arthur P

    2015-02-01

    Thrombotic thrombocytopenic purpura (TTP) is a hematologic emergency characterized by microangiopathic hemolytic anemia and thrombocytopenia. Plasma exchange is the standard treatment. Treating TTP without plasma exchange is a challenge. Due to religious beliefs, Jehovah's Witnesses do not accept transfusions of blood products. We report a case of successful treatment of TTP in a Jehovah's Witness using plasma exchange with albumin replacement. PMID:24782109

  11. 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.

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

    PubMed

    Christopher, Kenneth; Horkan, Clare; Barb, Ilie T; Arbelaez, Christian; Hodgdon, Travis A; Yodice, Paul C

    2004-11-01

    Intravenous Rho (D) immune globulin (IV RhIG, WinRho SDF) has been shown to be a safe treatment for idiopathic thrombocytopenic purpura (ITP). Common side effects of IV RhIG include mild hemolysis, febrile reaction, and headache. Significant hemolysis with renal impairment following IV RhIG has been reported. We report a case of irreversible encephalopathy 48 hr following an infusion of IV RhIG for treatment of ITP.

  13. 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

  14. Pathogenesis, laboratory, and clinical characteristics of Helicobacter pylori-associated immune thrombocytopenic purpura.

    PubMed

    Franchini, Massimo; Plebani, Mario; Montagnana, Martina; Veneri, Dino; Lippi, Giuseppe

    2010-01-01

    Idiopathic thrombocytopenic purpura (ITP) is a common autoimmune disease mediated by autoantibodies against platelet glycoproteins. This hemorrhagic disorder may be primary or secondary to various illnesses, including lymphoproliferative, autoimmune, or infectious diseases. Among the latter causes, there is increasing laboratory and clinical evidence that documents a pathogenic role of Helicobacter pylori infection in ITP. The aim of this review is to analyze the current knowledge on the pathogenic, diagnostic, clinical, and therapeutic characteristics of H. pylori-associated ITP.

  15. 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. PMID:25879992

  16. [Association of idiopathic thrombocytopenic purpura and type 1 diabetes mellitus--a case report].

    PubMed

    Prusek, Katarzyna; Deja, Grażyna; Jarosz-Chobot, Przemysława

    2010-01-01

    The relation between type 1 diabetes mellitus and autoimmune thyroid diseases is well known. In the pathogenesis of both diseases, chronic autoimmunization plays an essential role. Specific autoantibodies are also responsible for the onset of idiopathic thrombocytopenic purpura. In the paper we present a case of an 11-year-old girl with insulin dependent diabetes in whom the idiopathic thrombocytopenic purpura without bleeding diathesis has been newly diagnosed. The patient had positive titres of thyroid autoantibodies, whilst she did not suffer from thyroid dysfunction. Due to inefficiency of intravenous gammaglobulins the patient was treated with a steroid therapy, which elevated the platelet counts to safe levels. However, the episodes of hyperglycemia have appeared as a side effect. The insulin therapy was modified and the girl was released in a good condition. In this case report, consideration should be given to the wide range of autoimmune diseases that can accompany type one diabetes mellitus--not only can we observe immune diabetic markers, but also thyroid autoantibodies and anti-platelet antibodies. Particular therapeutic dilemmas resulting in a difficult decision on steroid therapy while treating a diabetic patient with idiopathic thrombocytopenic purpura are also presented. PMID:21092704

  17. Presumptive thrombotic thrombocytopenic purpura following a hump-nosed viper (Hypnale hypnale) bite: a case report

    PubMed Central

    2014-01-01

    Hump-nosed viper bites are frequent in southern India and Sri Lanka. However, the published literature on this snakebite is limited and its venom composition is not well characterized. In this case, we report a patient with thrombotic thrombocytopenic purpura-like syndrome following envenoming which, to the best of our knowledge, has not been reported in the literature before. A 55-year-old woman from southern Sri Lanka presented to the local hospital 12 hours after a hump-nosed viper (Hypnale hypnale) bite. Five days later, she developed a syndrome that was characteristic of thrombotic thrombocytopenic purpura with fever, thrombocytopenia, microangiopathic hemolysis, renal impairment and neurological dysfunction in the form of confusion and coma. Her clinical syndrome and relevant laboratory parameters improved after she was treated with therapeutic plasma exchange. We compared our observations on this patient with the current literature and concluded that thrombotic thrombocytopenic purpura is a theoretically plausible yet unreported manifestation of hump-nosed viper bite up to this moment. This study also provides an important message for clinicians to look out for this complication in hump-nosed viper bites since timely treatment can be lifesaving. PMID:24987409

  18. Thrombotic thrombocytopenic purpura presenting as acute coronary syndrome.

    PubMed

    Mouabbi, Jason Aboudi; Zein, Rami; Kafri, Zyad; Al-Katib, Ayad; Hadid, Tarik

    2016-08-01

    In patients presenting with thrombotic thrombocytopenia purpura and non-ST elevation myocardial infarction, prompt initiation of plasma exchange takes precedence over other invasive diagnostic procedures for coronary artery disease. Such procedures should be delayed until clinical condition and laboratory parameters have been stabilized. PMID:27525072

  19. Dameshek W, Miller EB. The megakaryocytes in idiopathic thrombocytopenic purpura, a form of hypersplenism. 1946.

    PubMed

    2016-01-01

    This paper, by one of the legends of hematology, William Dameshek, and his colleague Edward Miller, is from the inaugural issue of Blood. By studying bone marrow specimens from controls, patients with acute or chronic immune thrombocytopenia, or patients with other thrombocytopenic disorders, the authors concluded that, in idiopathic thrombocytopenic purpura (ITP), production of platelets from megakaryocytes is defective, even while marrow megakaryocytes are greatly increased in number. This defect resolved after splenectomy. The authors appropriately credit E. Frank with having proposed defective platelet production from megakaryocytes in ITP in 1915. The idea that platelet production was defective in ITP was superseded or ignored for decades, but it has now been validated by the therapeutic effectiveness of the thrombopoietin mimetics in ITP.

  20. 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

    2016-01-01

    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/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. PMID:27026836

  1. [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.

  2. Advances in the pathogenesis, diagnosis and treatment of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.

    PubMed

    Franchini, Massimo; Zaffanello, Marco; Veneri, Dino

    2006-01-01

    The thrombotic microangiopathies are microvascular occlusive disorders characterized by hemolytic anemia caused by fragmentation of erythrocytes and thrombocytopenia due to increased platelet aggregation and thrombus formation, eventually leading to disturbed microcirculation with reduced organ perfusion. Depending on whether brain or renal lesions prevail, two different entities have been described: thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). However, not rarely the clinical distinctions between these two conditions remain questionable. Recent studies have contributed greatly to our current understanding of the molecular mechanisms leading to TTP and HUS. In this review, we briefly focus on the most important advances in the pathophysiology, diagnosis and treatment of these two thrombotic microangiopathies.

  3. Pulmonary hyalinizing granuloma. Bilateral pulmonary nodules associated with chronic idiopathic thrombocytopenic purpura.

    PubMed

    Satti, Mohamed B; Batouk, Abdelnasir A; Abdelaziz, Muntasir M; Ahmad, Mohamed F; Abdelaal, Mohamed A

    2005-09-01

    We report a case of a 30-year-old female who had been treated periodically with steroids for idiopathic thrombocytopenic purpura ITP over the last 10 years. Recently, during the course of investigation, she was found to have incidental asymptomatic multiple pulmonary nodules on chest CT. Following a needle biopsy to exclude malignancy, 2 nodules were excised and were histologically confirmed as pulmonary hyalinizing granuloma PHG. The remaining 2 nodules regressed on increasing her dose of steroids. The case is discussed with emphasis on the histological and radiological differential diagnosis, in addition to including ITP among the spectrum of immunologic conditions associated with PHG. PMID:16155671

  4. Surgical treatment of chronic idiopathic thrombocytopenic purpura: results in 107 cases

    SciTech Connect

    Cola, B.; Tonielli, E.; Sacco, S.; Brulatti, M.; Franchini, A.

    1986-07-01

    Between 1972 and 1985, 107 patients with chronic Idiopathic Thrombocytopenic Purpura underwent splenectomy. Platelet life span and sites of sequestration were studied with labelled platelets and external scanning. Medical treatment was always of scarce and transient effectiveness and had considerable side effects. Splenectomy had minimal complications and mortality and caused no hazard of overwhelming sepsis in adults. The results of splenectomy were very satisfying, especially when platelet sequestration was mainly splenic (remission in about 90% of patients). Surgical treatment is at present the most effective in patients with chronic ITP.

  5. 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

  6. Role of myeloid human cytomegalovirus infection in children's idiopathic thrombocytopenic purpura.

    PubMed

    Ding, Yan; Zhao, Lei; Mei, Hong; Zhang, Shu-Ling; Huang, Zhi-Hua

    2007-01-01

    This project explores the specificity of myeloid human cytomegalovirus (HCMV) infection in pathogenesis of idiopathic thrombocytopenic purpura (ITP). Eighty-one subjects with ITP were observed. HCMV early antigen and related myeloid cells in bone marrow, and platelet, HCMV IgM, and IgG in blood were tested. The results presented potent evidence that myeloid HCMV infection is a specific factor in children's ITP: patients of ITP with myeloid HCMV infection had a tendency for exacerbation, refractoriness, and chronic advance. However, HCMV did not affect the quantity of megakaryocyte, which showed the complicated relationships between HCMV and ITP.

  7. [Wilson's disease associated with olfactory paranoid syndrome and idiopathic thrombocytopenic purpura].

    PubMed

    Sagawa, Morihiko; Takao, Masaki; Nogawa, Shigeru; Mizuno, Masafumi; Murata, Mitsuru; Amano, Takahiro; Koto, Atsuo

    2003-10-01

    In this study we report an individual of Wilson's disease associated with olfactory paranoid syndrome and idiopathic thrombocytopenic purpura. The initial symptom of this female patient was olfactory paranoia at age 17. Although that psychiatric symptom was well controlled under pharmacological treatment for two years, she developed olfactory paranoia as well as sialorrhea, dysarthria and finger tremor at age 20. A year later rigidity was also present in the extremities. At age 23, idiopathic thrombocytopenic purpura was found based on hematological examinations. Because her extrapyramidal symptoms were progressive, she was referred to our department to evaluate her neurologic condition. She was diagnosed as having Wilson's disease based on (1) the presence of Kayser-Fleischer rings, (2) extrapyramidal signs, and (3) a decreased level of serum copper and ceruloplasmin. T2 and FLAIR images of brain MRI showed hyperintense lesions in the putamen, thalamus and pontine tegmentum. Diffusion-weighted images also showed hyperintense lesions in the thalamus and pontine tegmentum. The biopsy specimen of the liver revealed chronic hepatitis with copper accumulation. Since D-penicillamine treatment was initiated, she has shown no olfactory paranoia and exacerbation of ITP. Her gait disturbance has also improved. Olfactory paranoia and ITP are rare clinical complications of Wilson's disease. Further analysis may warrant consideration of the pathophysiological mechanism of the psychiatric, hematological and neuroradiological condition seen in Wilson's disease.

  8. Flow cytometric analysis of anti-platelet antibodies in idiopathic thrombocytopenic purpura.

    PubMed

    Latorraca, A; Lanza, F; Moretti, S; Ferrari, L; Reverberi, R; Galluccio, L; Castoldi, G

    1994-01-01

    Anti-platelet antibody measurement may be important in defining the pathogenesis of thrombocytopenic states. In this paper we compared three anti-human immunoglobulin reagents by using them to detect anti-platelet antibodies on the platelet surface and in the serum of 14 patients with chronic idiopathic thrombocytopenic purpura (ITP) and 22 thrombocytopenic disorders. Samples were analyzed by both flow cytometry and a fluorescence microscope. In ITP patients, the direct test was positive in 50% of the cases, while the indirect technique proved to be positive in a slightly higher number of those tested (56%). Furthermore, the number of positive cases was similar for the three reagents used in this study, although the mean percentage of positive platelets was higher for the kappa/lambda monoclonal reagent. These data further support the sensitivity and reproducibility of flow cytometry analysis, which was capable of detecting antiplatelet antibodies in all patients with transfused Cooley's disease (regarded as positive control), as well as in a significant number of patients with ITP or related diseases. On the basis of the data presented here, definitive proof regarding the presence of anti-platelet antibodies in patients with thrombocytopenia still has to be found, and further studies are needed in order to ascertain the autoimmune nature of these disorders. PMID:7926978

  9. Multiple domains of ADAMTS13 are targeted by autoantibodies against ADAMTS13 in patients with acquired idiopathic thrombotic thrombocytopenic purpura

    PubMed Central

    Zheng, X. Long; Wu, Haifeng M.; Shang, Dezhi; Falls, Erica; Skipwith, Christopher G.; Cataland, Spero R.; Bennett, Charles L.; Kwaan, Hau C.

    2010-01-01

    Background Type G immunoglobulins against ADAMTS13 are the primary cause of acquired (idiopathic) thrombotic thrombocytopenic purpura. However, the domains of ADAMTS13 which the type G anti-ADAMT13 immunoglobulins target have not been investigated in a large cohort of patients with thrombotic thrombocytopenic purpura. Design and Methods Sixty-seven patients with acquired idiopathic thrombotic thrombocytopenic purpura were prospectively collected from three major U.S. centers. An enzyme-linked immunosorbent assay determined plasma concentrations of anti-ADAMTS13 type G immunoglobulins, whereas immunoprecipitation plus western blotting determined the binding domains of these type G immunoglobulins. Results Plasma anti-ADAMTS13 type G immunoglobulins from 67 patients all bound full-length ADAMTS13 and a variant truncated after the eighth TSP1 repeat (delCUB). Approximately 97% (65/67) of patients harbored type G immunoglobulins targeted against a variant truncated after the spacer domain (MDTCS). However, only 12% of patients’ samples reacted with a variant lacking the Cys-rich and spacer domains (MDT). In addition, approximately 37%, 31%, and 46% of patients’ type G immunoglobulins interacted with the ADAMTS13 fragment containing TSP1 2-8 repeats (T2-8), CUB domains, and TSP1 5-8 repeats plus CUB domains (T5-8CUB), respectively. The presence of type G immunoglobulins targeted against the T2-8 and/or CUB domains was inversely correlated with the patients’ platelet counts on admission. Conclusions This multicenter study further demonstrated that the multiple domains of ADAMTS13, particularly the Cys-rich and spacer domains, are frequently targeted by anti-ADAMTS13 type G immunoglobulins in patients with acquired (idiopathic) thrombotic thrombocytopenic purpura. Our data shed more light on the pathogenesis of acquired thrombotic thrombocytopenic purpura and provide further rationales for adjunctive immunotherapy. PMID:20378566

  10. Thrombotic Thrombocytopenic Purpura associated with Clopidogrel: a case report and review of the literature

    PubMed Central

    Azarm, Taleb; Sohrabi, Ayatollah; Mohajer, Hamid; Azarm, Arezou

    2011-01-01

    Thrombotic Thrombocytopenic Purpura (TTP) is a life threatening, multisystem disease characterized by thrombocytopenia, microangiopathic hemolytic anemia, neurological changes, renal failure, and fever. These signs and symptoms are thought to be caused by microthrombi, composed of agglutinated platelets and fibrin, which deposit in the arterioles and capillaries without mediation by an inflammatory process. TTP can occur in the first two weeks of initiation of Clopidogrel therapy. Early signs of TTP may be a skin reaction, which may precede the onset of TTP or it may be other type of purpura or neurological changes. We report the clinical and laboratory findings in a 67 years old female patient in whom TTP developed soon after treatment with 40 mg/day oral Clopidogrel after 8 days. She developed thrombocytopenia (platelets count 12000 /mm3). Her clinical signs and symptoms were fever (39.6C), bleeding from the nose and gum, large skin bruises (purpura and ecchymoses), neurological changes including hallucinations, bizarre behavior, altered mental status (fluctuating), headache, and renal dysfunction. Physicians should be aware of the possibility early onset of this syndrome when initiate Clopidogrel treatment. PMID:22091257

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

    PubMed Central

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

    2016-01-01

    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.

  12. The role of splenectomy in multimodality treatment of thrombotic thrombocytopenic purpura.

    PubMed Central

    Schneider, P A; Rayner, A A; Linker, C A; Schuman, M A; Liu, E T; Hohn, D C

    1985-01-01

    Current treatment modalities for thrombotic thrombocytopenic purpura (TTP) include plasmapheresis (PP), splenectomy, steroids, dextran, other antiplatelet agents, and vinca alkaloids. Prior to the development of PP and use of multimodality treatment for TTP, mortality rates exceeded 50%. This report reviews 11 patients treated for TTP, demonstrates the successful use of splenectomy as salvage therapy, and defines our indications for splenectomy in the treatment of this disorder. Ten of 11 patients were initially treated with PP; three responded completely and one died of fulminant disease. Six patients had a transient partial response to plasmapheresis and were subsequently treated with splenectomy, steroids, and dextran-70. Initial plasmapheresis resulted in improvement in laboratory values and clinical status in those patients requiring splenectomy. Durable remission (6-48 months) was achieved in 91% of patients with minimal morbidity. PMID:2412500

  13. 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

  14. Neglect-induced pseudo-thrombotic thrombocytopenic purpura due to vitamin B12 deficiency.

    PubMed

    Asano, Takeshi; Narazaki, Hidehiko; Kaizu, Kiyohiko; Matsukawa, Shouhei; Takema-Tochikubo, Yuki; Fujii, Shuichi; Saitoh, Nobuyuki; Mashiko, Kunihiko; Fujino, Osamu

    2015-10-01

    Although thrombotic thrombocytopenic purpura (TTP) is rare, early diagnosis and treatment are important for decreasing the mortality rate. Acquired vitamin B12 deficiency is frequently overlooked because of its rarity in developed countries, particularly in children and adolescents. The hematological changes in vitamin B12 deficiency present as megaloblastic anemia, increased lactate dehydrogenase, vasoconstriction, increased platelet aggregation, and abnormal activation of the coagulation followed by microangiopathy as well as neutropenia and thrombocytopenia. We report herein the case of a 15-year-old girl who had been neglected, which might have caused pseudo-TTP through malnutrition, particularly vitamin B12 deficiency. When we encounter cases of TTP in children, clinicians must be aware of the possibility of malnutrition, particularly with vitamin B12 deficiency, even in developed countries, and investigate the cause of malnutrition including neglect. PMID:26387768

  15. 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. PMID:26684918

  16. The cost of treating immune thrombocytopenic purpura using intravenous Rh immune globulin versus intravenous immune globulin.

    PubMed

    Sandler, S G; Novak, S C; Roland, B

    2000-03-01

    Multiple factors, including efficacy, toxicity and cost, may influence the decision to treat immune thrombocytopenic purpura (ITP) with intravenous immune globulin (IVIG) or intravenous Rho (D) immune globulin (IV RhIG). We conducted a survey of 50 hospitals in 31 states to determine the costs for treating ITP using conventional doses for IVIG or IV RhIG, based on package insert recommendations. The average cost for a dose of IVIG ($2,771) was 71.7% ($1,157) more than that for a dose of IV RhIG ($1,614). In the absence of clearly defined differences in clinical outcomes when treating ITP with IVIG or IV RhIG, the difference in cost may be an important factor in selecting the treatment.

  17. Apheresis and the thrombotic thrombocytopenic purpura syndrome: current advances in diagnosis, pathophysiology, and management.

    PubMed

    Brailey, L L; Brecher, M E; Bandarenko, N

    1999-02-01

    Endeavors to optimize the management of thrombotic thrombocytopenic purpura (TTP) syndrome and improve mortality and relapse rates are hindered by its poorly understood pathophysiology. Variability in the application of therapeutic plasma exchange (TPE), including replacement fluid strategies, desirable endpoints in the platelet count, serum lactate dehydrogenase concentration, and the use of a TPE taper, limit comparisons among published studies. The diversity of adjunctive therapies such as antiplatelet agents, steroids, and splenectomy further clouds comparisons. Recent progress in the diagnosis, pathophysiology, and management of TTP syndrome are summarized. The possible role of occult infection and newly emerging associations such as ticlopidine therapy are discussed. Advances in possible pathogenic mechanisms, the rationale for different replacement fluids including the recently licensed solvent-detergent treated plasma, and progress in the apheresis management of TTP syndrome are presented.

  18. 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.

  19. 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. PMID:27313917

  20. Cytokine-induced killer cell therapy-associated idiopathic thrombocytopenic purpura: rare but noteworthy.

    PubMed

    Fu, Xiaomin; Zhang, Yong; Gao, Quanli; Lin, Jizhen; Zhang, Qinxian; Xu, Benling; Song, Yongping

    2016-09-01

    Idiopathic thrombocytopenic purpura (ITP) is characterized by a diminished platelet count, an autoimmune condition with antibodies against platelets and an increased tendency to bleed. The association between ITP and solid tumors is uncommon. Cytokine-induced killer (CIK) cell therapy is a well tolerated and promising cancer treatment with minimal toxicity. For the first time, CIK cell therapy was reported to be followed by ITP. The mechanism through which CIK induces ITP remains unclear. Imbalanced ratio of Th cells, decreased numbers or impaired function of Treg cells and excessive secretion of cytokines inducing abnormal activation of B cells may be among the possible reasons. Therefore, a better understanding of this rare condition will require further investigation of these cases. PMID:27485074

  1. 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. PMID:26770928

  2. Management of immune thrombocytopenic purpura in children: potential role of novel agents.

    PubMed

    Bredlau, Amy Lee; Semple, John W; Segel, George B

    2011-08-01

    The treatment of immune thrombocytopenic purpura (ITP) in children is controversial, requiring individualized assessment of the patient and consideration of treatment options. If the platelet count is >10 000/μL and the patient is asymptomatic, a 'watch and wait' strategy is appropriate since most children with ITP will recover completely without pharmacotherapy. If therapy is indicated because of bleeding or a platelet count <10 000/μL, then treatment with glucocorticoids, intravenous immunoglobulin (IVIg), or anti-D are possible initial choices. Glucocorticoid treatment is the least expensive and is our usual first choice of therapy. Its use assumes that the blood counts and blood film have been evaluated to ensure the absence of evidence of alternative diagnoses, such as thrombotic thrombocytopenic purpura or incipient acute leukemia. IVIg is expensive and often causes severe headache, nausea and vomiting, and requires hospitalization at our institution. Anti-D therapy is also expensive and can only be used in patients who are Rhesus D positive. These therapies, even if only transiently effective, can be repeated if necessary. Children usually recover from newly diagnosed ITP, with or without multiple courses of medical therapy. If the disease becomes 'persistent' with severe thrombocytopenia and/or bleeding, and is no longer responsive to the three first-line therapies, the next approach includes the use of thrombopoietin receptor agonists or rituximab. When the disease persists for more than 1 year, it is considered chronic, and, if symptomatic, it may become necessary to consider third-line therapies, including splenectomy, alternative immunosuppressive agents, or combination or investigative chemoimmunotherapy. This review considers the indications, mechanism of action, and effectiveness of the traditional and novel treatment options for patients with ITP.

  3. 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

  4. 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

  5. Anti-Ku antibody-positive scleroderma-dermatomyositis overlap syndrome developing Graves' disease and immune thrombocytopenic purpura.

    PubMed

    Kamei, Nozomu; Yamane, Kiminori; Yamashita, Yasuyo; Nakanishi, Shuhei; Watanabe, Hiroshi; Fujikawa, Rumi; Hiyama, Keiko; Ishioka, Shinichi; Mendoza, Ciro; Kohno, Nobuoki

    2002-12-01

    Graves' disease (GD) has been reported to be frequently complicated with other autoimmune diseases. However, it is rarely complicated with scleroderma-polymyositis overlap syndrome. Recently, we encountered a 35-year-old woman who developed GD and immune thrombocytopenic purpura during follow-up observation of scleroderma-dermatomyositis overlap syndrome. Platelet counts recovered after high-dose gamma-globulin therapy and bolus methylprednisolone therapy. The present case is the first report of a combination of scleroderma, dermatomyositis, GD, and immune thrombocytopenic purpura. The patient was anti-Ku antibody-positive and had relatively low natural killer T cell counts, both of which might contribute to the complication of multiple autoimmune diseases.

  6. 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

  7. Platelet destruction in autoimmune thrombocytopenic purpura: kinetics and clearance of indium-111-labeled autologous platelets

    SciTech Connect

    Stratton, J.R.; Ballem, P.J.; Gernsheimer, T.; Cerqueira, M.; Slichter, S.J.

    1989-05-01

    Using autologous /sup 111/In-labeled platelets, platelet kinetics and the sites of platelet destruction were assessed in 16 normal subjects (13 with and three without spleens), in 17 studies of patients with primary autoimmune thrombocytopenic purpura (AITP), in six studies of patients with secondary AITP, in ten studies of patients with AITP following splenectomy, and in five thrombocytopenic patients with myelodysplastic syndromes. In normal subjects, the spleen accounted for 24 +/- 4% of platelet destruction and the liver for 15 +/- 2%. Untreated patients with primary AITP had increased splenic destruction (40 +/- 14%, p less than 0.001) but not hepatic destruction (13 +/- 5%). Compared with untreated patients, prednisone treated patients did not have significantly different spleen and liver platelet sequestration. Patients with secondary AITP had similar platelet counts, platelet survivals, and increases in splenic destruction of platelets as did patients with primary AITP. In contrast, patients with myelodysplastic syndromes had a normal pattern of platelet destruction. In AITP patients following splenectomy, the five nonresponders all had a marked increase (greater than 45%) in liver destruction compared to five responders (all less than 40%). Among all patients with primary or secondary AITP, there was an inverse relationship between the percent of platelets destroyed in the liver plus spleen and both the platelet count (r = 0.75, p less than 0.001) and the platelet survival (r = 0.86, p less than 0.001). In a stepwise multiple linear regression analysis, total liver plus spleen platelet destruction, the platelet survival and the platelet turnover were all significant independent predictors of the platelet count. Thus platelet destruction is shifted to the spleen in primary and secondary AITP. Failure of splenectomy is associated with a marked elevation in liver destruction.

  8. 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.

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

    PubMed Central

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

    2009-01-01

    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 >150×109/L) or partial (platelet count between 50 and 150×109/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. PMID:21589818

  10. [Clinical significance of Helicobacter pylori in children with idiopathic thrombocytopenic purpura].

    PubMed

    Tang, Ying; Wang, Shu-Chun; Wang, Lu-Juan; Liu, Yong; Wang, Hai-Ying; Wang, Zhan-Ju

    2013-04-01

    This study was aimed to investigate the clinic significance of helicobacter pylori (HP) in children with idiopathic thrombocytopenic purpura (ITP). The infection of HP in 92 ITP children was determined by (13) C-Urea Breath Test, the same test was also performed on 66 healthy children. The 68 children infected with HP were randomly divided into 2 groups: single drug group treated only with corticosteroid and; combined drug group treated with corticosteroid and anti-helicobacter pylori treatment. The results showed that 68 patients infected with HP were found in 92 ITP children (74.7%), 26 patients infected with HP were observed in 66 healthy children (39.4%), which was lower than that in ITP children (74.7%, P < 0.05). After anti-helicobacter pylori therapy, the total effective rate and cure rate of ITP patients increased respectively from 73.5% to 94.1%, and the total recurrence rate (17.0%) was much lower than single drug group (47.1%, P < 0.05). Otherwise, after therapy the platelet count in both two groups increased continuously, and at the same time point, the platelet count in anti-helicobacter pylori group was higher than that in the single drug group (P < 0.05). It is concluded that the ITP children have a higher infection rate of HP, which may be involved in the pathogenesis of ITP. Anti-helicobacter pylori therapy would help to improve the therapeutic efficacy and reduce the recurrence of ITP children.

  11. 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

  12. Refractory Immune Thrombocytopenic Purpura and Cytomegalovirus Infection: A Call for a Change in the Current Guidelines.

    PubMed

    Shimanovsky, Alexei; Patel, Devbala; Wasser, Jeffrey

    2016-01-01

    Immune thrombocytopenic purpura (ITP) is characterized by a decreased platelet count caused by excess destruction of platelets and inadequate platelet production. In many cases, the etiology is not known, but the viral illness is thought to play a role in the development of some cases of ITP. The current (2011) American Society of Hematology ITP guidelines recommend initial diagnostic studies to include testing for HIV and Hepatitis C. The guidelines suggest that initial treatment consist of observation, therapy with corticosteroids, IVIG or anti D. Most cases respond to the standard therapy such that the steroids may be tapered and the platelet counts remain at a hemostatically safe level. Some patients with ITP are dependent on long-term steroid maintenance, and the thrombocytopenia persists with the tapering of the steroids. Recent case reports demonstrate that ITP related to cytomegalovirus (CMV) can persist in spite of standard therapy and that antiviral therapy may be indicated. Herein we report a case of a 26-year-old female with persistent ITP that resolved after the delivery of a CMV-infected infant and placenta. Furthermore, we review the current literature on CMV-associated ITP and propose that the current ITP guidelines be amended to include assessment for CMV, even in the absence of signs and symptoms, as part of the work-up for severe and refractory ITP, especially prior to undergoing an invasive procedure such as splenectomy.

  13. Refractory Immune Thrombocytopenic Purpura and Cytomegalovirus Infection: A Call for a Change in the Current Guidelines

    PubMed Central

    Shimanovsky, Alexei; Patel, Devbala; Wasser, Jeffrey

    2016-01-01

    Immune thrombocytopenic purpura (ITP) is characterized by a decreased platelet count caused by excess destruction of platelets and inadequate platelet production. In many cases, the etiology is not known, but the viral illness is thought to play a role in the development of some cases of ITP. The current (2011) American Society of Hematology ITP guidelines recommend initial diagnostic studies to include testing for HIV and Hepatitis C. The guidelines suggest that initial treatment consist of observation, therapy with corticosteroids, IVIG or anti D. Most cases respond to the standard therapy such that the steroids may be tapered and the platelet counts remain at a hemostatically safe level. Some patients with ITP are dependent on long-term steroid maintenance, and the thrombocytopenia persists with the tapering of the steroids. Recent case reports demonstrate that ITP related to cytomegalovirus (CMV) can persist in spite of standard therapy and that antiviral therapy may be indicated. Herein we report a case of a 26-year-old female with persistent ITP that resolved after the delivery of a CMV-infected infant and placenta. Furthermore, we review the current literature on CMV-associated ITP and propose that the current ITP guidelines be amended to include assessment for CMV, even in the absence of signs and symptoms, as part of the work-up for severe and refractory ITP, especially prior to undergoing an invasive procedure such as splenectomy. PMID:26740871

  14. A complement-dependent model of thrombotic thrombocytopenic purpura induced by antibodies reactive with endothelial cells.

    PubMed

    Ren, Guohui; Hack, Bradley K; Minto, Andrew W; Cunningham, Patrick N; Alexander, Jessy J; Haas, Mark; Quigg, Richard J

    2002-04-01

    Thrombotic thrombocytopenic purpura (TTP) is an immunologically mediated disease characterized by thrombocytopenia, hemolytic anemia, and pathologic changes in various organs, including the kidney, which are secondary to widespread thromboses. Central to TTP is platelet activation, which may occur from a variety of mechanisms, including endothelial cell activation or injury. In this study, injection of K6/1, a monoclonal antibody with widespread reactivity toward endothelia, led to dose-dependent thrombocytopenia in rats. This was magnified if animals were preimmunized with mouse IgG, thereby resulting in an accelerated autologous phase of injury. In this setting, significant anemia also resulted. Rats injected with K6/1 developed renal injury, consisting of tubular damage and glomerular thrombi. Thrombocytopenia and renal morphological abnormalities were eliminated if animals were complement depleted with cobra venom factor prior to K6/1 injection and worsened when the activity of the ubiquitous complement regulator Crry was inhibited with function-neutralizing antibodies. Therefore, we have developed a complement-dependent model of TTP in rats by injecting monoclonal antibodies reactive with endothelial cells. Antibody-directed complement activation leads to stimulation of platelets, through direct interactions with complement fragments and/or indirectly through endothelial cell activation or injury, with the subsequent development of TTP.

  15. When the picture is fragmented: Vitamin B12 deficiency masquerading as thrombotic thrombocytopenic purpura

    PubMed Central

    Panchabhai, Tanmay S.; Patil, Pradnya D.; Riley, Elizabeth C.; Mitchell, Charlene K.

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) has high mortality and necessitates prompt recognition of microangiopathic hemolytic anemia (MAHA) and initiation of plasmapheresis. We present a challenging diagnostic workup and management of a 42-year-old man who presented with anemia, thrombocytopenia, and schistocytes on peripheral smear, all pointing to MAHA. Plasmapheresis and steroid therapy were promptly initiated, but hemolysis continued. Further workup showed megaloblastic anemia, severe Vitamin B12 deficiency, high iron saturation, and absent reticulocytosis, none of which could be explained by TTP. Severe Vitamin B12 deficiency can lead to hemolytic anemia from the destruction of red cells in the marrow that have failed the process of maturation. However, this should not cause thrombotic microangiopathy. Previous reports of B12 deficiency presenting with MAHA and a TTP-like manifestation have identified acute hyperhomocysteinemia as a missing link between B12 deficiency and MAHA, so this possibility was further explored. Our patient similarly had significantly elevated serum homocysteine levels, confirming this suspicion of Vitamin B12 deficiency. Vitamin B12 replacement led to normalization of the elevated levels of homocysteine, the disappearance of schistocytes on the peripheral smear, and resolution of the microangiopathic hemolysis, thereby confirming the diagnosis. It is pertinent that intensivists not only know the importance of early recognition and treatment of TTP but are also familiar with rare conditions that can present in a similar fashion. PMID:27308258

  16. When the picture is fragmented: Vitamin B12 deficiency masquerading as thrombotic thrombocytopenic purpura.

    PubMed

    Panchabhai, Tanmay S; Patil, Pradnya D; Riley, Elizabeth C; Mitchell, Charlene K

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) has high mortality and necessitates prompt recognition of microangiopathic hemolytic anemia (MAHA) and initiation of plasmapheresis. We present a challenging diagnostic workup and management of a 42-year-old man who presented with anemia, thrombocytopenia, and schistocytes on peripheral smear, all pointing to MAHA. Plasmapheresis and steroid therapy were promptly initiated, but hemolysis continued. Further workup showed megaloblastic anemia, severe Vitamin B12 deficiency, high iron saturation, and absent reticulocytosis, none of which could be explained by TTP. Severe Vitamin B12 deficiency can lead to hemolytic anemia from the destruction of red cells in the marrow that have failed the process of maturation. However, this should not cause thrombotic microangiopathy. Previous reports of B12 deficiency presenting with MAHA and a TTP-like manifestation have identified acute hyperhomocysteinemia as a missing link between B12 deficiency and MAHA, so this possibility was further explored. Our patient similarly had significantly elevated serum homocysteine levels, confirming this suspicion of Vitamin B12 deficiency. Vitamin B12 replacement led to normalization of the elevated levels of homocysteine, the disappearance of schistocytes on the peripheral smear, and resolution of the microangiopathic hemolysis, thereby confirming the diagnosis. It is pertinent that intensivists not only know the importance of early recognition and treatment of TTP but are also familiar with rare conditions that can present in a similar fashion. PMID:27308258

  17. Thrombotic thrombocytopenic purpura after prophylactic cefuroxime axetil administered in relation to a liposuction procedure.

    PubMed

    Eskazan, Ahmet Emre; Salihoglu, Ayse; Gulturk, Emine; Ongoren, Seniz; Soysal, Teoman

    2012-04-01

    Thrombotic thrombocytopenic purpura (TTP) or Moschcowitz's syndrome is characterized by platelet and von Willebrand factor (vWF) deposition in arterioles and capillaries throughout the body, which results in organ ischemia. The diagnostic pentad characterizing TTP consists of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), fever, neurologic manifestations, and renal insufficiency. In terms of type, TTP can be either idiopathic or secondary. The causes of secondary TTP include pregnancy, infections, pancreatitis, collagen vascular disease, cancer, bone marrow transplantation, and drugs (including cephalosporins). Postoperative TTP has been reported after vascular surgery, renal and liver transplantations, and orthopedic, urologic, and abdominal surgical procedures. Therapeutic plasma exchange (TPE) therapy has reduced the mortality rates, but sometimes patients may have to receive immunosuppressive drugs including vincristine (VCR). This report describes a 42-year-old woman with TTP after prophylactic usage of cefuroxime axetil in relation to a liposuction procedure who was treated successfully with plasma exchange and VCR. The patient fully recovered after 17 TPEs and three doses of VCR. At this writing, her TTP still is in remission after 6 months of follow-up evaluation. To the authors' knowledge, this is the first report in the literature describing a patient with TTP after cefuroxime axetil administered in relation to a surgical procedure who was treated successfully with TPE and VCR.

  18. Renal failure after anti-D globulin treatment of idiopathic thrombocytopenic purpura.

    PubMed

    Kees-Folts, Deborah; Abt, Arthur B; Domen, Ronald E; Freiberg, Andrew S

    2002-02-01

    Idiopathic thrombocytopenic purpura (ITP) is a disorder of rapid destruction of antibody-coated platelets. Anti-D immune globulin has been used for treatment of ITP in the United States since 1995. Initial studies identified no significant side effects of treatment. However, a recent report highlighted occasional episodes of intravascular hemolysis after anti-D immune globulin. We describe two children with ITP who developed acute renal failure (ARF) after treatment with anti-D immune globulin and also analyze ten additional cases of ARF reported to the manufacturer, Cangene Corporation, through postmarketing surveillance. All episodes of ARF were associated with intravascular hemolysis. Four patients required dialysis. Patient age ranged from 1 to 82 years, but those requiring dialysis were all under age 15 years. Several patients with ARF had preexisting creatinine elevation. Three of the patients with ARF had serologic evidence of acute Epstein-Barr virus (EBV) infection. Renal biopsy in one patient showed acute tubular necrosis, with findings consistent with pigment nephropathy. Anti-D immune globulin, used to treat ITP, may be associated with intravascular hemolysis and resultant ARF. Renal function should be monitored in patients with evidence of intravascular hemolysis. Children and adolescents may have increased risk of ARF requiring dialysis.

  19. Vaccine administration and the development of immune thrombocytopenic purpura in children.

    PubMed

    Cecinati, Valerio; Principi, Nicola; Brescia, Letizia; Giordano, Paola; Esposito, Susanna

    2013-05-01

    The most important reasons cited by the opponents of vaccines are concerns about vaccine safety. Unlike issues such as autism for which no indisputable documentation of direct relationship with vaccine use is available, immune thrombocytopenic purpura (ITP) is an adverse event that can really follow vaccine administration, and may limit vaccine use because little is known about which vaccines it may follow, its real incidence and severity, the risk of chronic disease, or the possibility of recurrences after new doses of the same vaccine. The main aim of this review is to clarify the real importance of thrombocytopenia as an adverse event and discuss how it may interfere with recommended vaccination schedules. The available data clearly indicate that ITP is very rare and the only vaccine for which there is a demonstrated cause-effect relationship is the measles, mumps and rubella (MMR) vaccine that can occur in 1 to 3 children every 100,000 vaccine doses. However, also in this case, the incidence of ITP is significantly lower than that observed during the natural diseases that the vaccine prevents. Consequently, ITP cannot be considered a problem limiting vaccine use except in the case of children suffering from chronic ITP who have to receive MMR vaccine. In these subjects, the risk-benefit ratio of the vaccine should be weighed against the risk of measles in the community. PMID:23324619

  20. Acquired Idiopathic ADAMTS13 Activity Deficient Thrombotic Thrombocytopenic Purpura in a Population from Japan

    PubMed Central

    Matsumoto, Masanori; Bennett, Charles L.; Isonishi, Ayami; Qureshi, Zaina; Hori, Yuji; Hayakawa, Masaki; Yoshida, Yoko; Yagi, Hideo; Fujimura, Yoshihiro

    2012-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a type of thrombotic microangiopathy (TMA). Studies report that the majority of TTP patients present with a deficiency of ADAMTS13 activity. In a database of TMA patients in Japan identified between 1998 and 2008, 186 patients with first onset of acquired idiopathic (ai) ADAMTS13-deficient TTP (ADAMTS13 activity <5%) were diagnosed. The median age of onset of TTP in this group of patients was 54 years, 54.8% were female, 75.8% had renal involvement, 79.0% had neurologic symptoms, and 97.8% had detectable inhibitors to ADAMTS13 activity. Younger patients were less likely to present with renal or neurologic dysfunction (p<0.01), while older patients were more likely to die during the TTP hospitalization (p<0.05). Findings from this cohort in Japan differ from those reported previously from the United States, Europe, and Korea with respect to age at onset (two decades younger in the other cohort) and gender composition (60% to 100% female in the other cohort). We conclude that in one of the largest cohorts of ai-TTP with severe deficiency of ADAMTS13 activity reported to date, demographic characteristics differ in Japanese patients relative to those reported from a large Caucasian registry from Western societies. Additional studies exploring these findings are needed. PMID:22427934

  1. Residual plasmatic activity of ADAMTS13 is correlated with phenotype severity in congenital thrombotic thrombocytopenic purpura.

    PubMed

    Lotta, Luca A; Wu, Haifeng M; Mackie, Ian J; Noris, Marina; Veyradier, Agnes; Scully, Marie A; Remuzzi, Giuseppe; Coppo, Paul; Liesner, Ri; Donadelli, Roberta; Loirat, Chantal; Gibbs, Richard A; Horne, April; Yang, Shangbin; Garagiola, Isabella; Musallam, Khaled M; Peyvandi, Flora

    2012-07-12

    The quantification of residual plasmatic ADAMTS13 activity in congenital thrombotic thrombocytopenic purpura (TTP) patients is constrained by limitations in sensitivity and reproducibility of commonly used assays at low levels of ADAMTS13 activity, blunting efforts to establish genotype-phenotype correlations. In the present study, the residual plasmatic activity of ADAMTS13 was measured centrally by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (limit of detection = 0.5%) in 29 congenital TTP patients. The results were used to study correlations among ADAMTS13 genotype, residual plasmatic activity, and clinical phenotype severity. An ADAMTS13 activity above 0.5% was measured in 26 (90%) patients and lower levels of activity were associated with earlier age at first TTP episode requiring plasma infusion, more frequent recurrences, and prescription of fresh-frozen plasma prophylaxis. Receiver operating characteristic curve analysis showed that activity levels of less than 2.74% and 1.61% were discriminative of age at first TTP episode requiring plasma infusion < 18 years, annual rate of TTP episodes > 1, and use of prophylaxis. Mutations affecting the highly conserved N-terminal domains of the protein were associated with lower residual ADAMTS13 activity and a more severe phenotype in an allelic-dose dependent manner. The results of the present study show that residual ADAMTS13 activity is associated with the severity of clinical phenotype in congenital TTP and provide insights into genotype-phenotype correlations.

  2. [Acquired thrombotic thrombocytopenic purpura after vascular prosthesis implantation for impending rupture of an abdominal aortic aneurysm].

    PubMed

    Naito, Chiaki; Ogawa, Yoshiyuki; Yanagisawa, Kunio; Ishizaki, Takuma; Mihara, Masahiro; Handa, Hiroshi; Isonishi, Ayami; Hayakawa, Masaki; Matsumoto, Masanori; Nojima, Yoshihisa

    2016-03-01

    Acquired thrombotic thrombocytopenic purpura (TTP) is caused by autoantibodies against ADAMTS13. TTP patients run a rapidly fatal course unless immediate plasma exchange (PEX) is initiated upon diagnosis. Herein, we report a 72-year-old man with TTP, which developed after he underwent artificial blood vessel replacement surgery for an abdominal aneurysm with impending rupture. In the perioperative period, the patient received several platelet transfusions for severe thrombocytopenia (minimum platelet count: 0.6×10(4)/μl). Thereafter, he was admitted to our department for rapidly progressing coma with multiple cerebral infarctions, and was transferred to the ICU. Based on the tentative diagnosis of TTP, we immediately began PEX and steroid pulse therapy. The diagnosis was confirmed thereafter by markedly reduced ADAMTS13 activity (<0.5%) and his being positive for the ADAMTS13 inhibitor. We performed PEX for five consecutive days and administered high-dose prednisolone (PSL). On the second hospital day (HD), his platelet count rose along with improvement of his consciousness level. The ADAMTS13 inhibitor was not detected on the 10th HD. TTP did not relapse and his general condition improved despite tapering of PSL. In this case, by closely monitoring ADAMTS13-related parameters and minimizing the number of plasma exchanges, the patient was able to achieve a remission without the use of boosting inhibitors. PMID:27076251

  3. [Sudden death associated with myocardial damage caused by microthrombi in a patient with thrombotic thrombocytopenic purpura].

    PubMed

    Yamamoto, Kiyoko; Hattori, Yukinori; Shimada, Koki; Araki, Yoko; Adachi, Tatsuya; Tsushita, Keitaro

    2015-11-01

    We describe a 35-year-old woman with Down's syndrome who was admitted to a clinic with anorexia and vomiting. Since laboratory findings showed anemia (Hb 7.4 g/dl) and thrombocytopenia (0.5 × 10⁴/μl), she was transferred to our hospital for treatment. Further laboratory examinations revealed schistocytes, LDH elevation, and a negative Coombs' test. Thrombotic thrombocytopenic purpura (TTP) was suspected. Plasma exchange (PEX) and prednisolone administration were thus immediately initiated. Prior to these treatments, ADAMTS13 activity was less than 5% and inhibitors were detected at a level of 0.8 Bethesda U/ml. Although her platelet count had risen to 13.0 × 10⁴/μl by day 6 (post 4 sessions of PEX), it had decreased to 1.8 × 10⁴/μl on day 7. Despite ongoing PEX, thrombocytopenia persisted. On day 21, she suddenly died. Autopsy findings revealed no evidence of myocardial necrosis or coronary artery thrombosis. Extensive microthrombi were, however, detected in precapillary arterioles, capillaries, and post-capillary venules of the heart. Therefore, this patient's sudden death was clinically suspected to have been caused by cardiomyopathy, which had produced cardiogenic shock. PMID:26666721

  4. The role of N-acetylcysteine in the treatment of thrombotic thrombocytopenic purpura.

    PubMed

    Rottenstreich, Amihai; Hochberg-Klein, Sarit; Rund, Deborah; Kalish, Yosef

    2016-05-01

    Thrombotic thrombocytopenic purpura (TTP) is an acute, thrombotic microangiopathy with a high mortality rate if left untreated. Plasma exchange (PEX) is the current standard of care. However, a significant number of patients are refractory to this treatment. N-acetylcysteine (NAC) was recently suggested as a potential therapeutic adjunct for patients with TTP. This study reports a series of three patients with TTP successfully treated with NAC in addition to standard therapy. Detailed chart reviews on these patients were conducted. We discuss clinical features, laboratory findings and management of three patients who presented with microangiopathic hemolytic anemia and thrombocytopenia. Anti-ADAMTS13 antibodies and low levels of ADAMTS13 were detected and confirmed the diagnosis of acquired TTP. Based upon their severe presentation or lack of response to initial treatment with PEX, corticosteroids and other immunosuppressive agents, NAC was added. Under this combined treatment, all three patients hada significant clinical improvement of symptoms with concurrent normalization of platelet count and ADAMTS13 activity level. This report highlights the potential therapeutic utility of NAC in the treatment of TTP. Randomized controlled studies will be required to better characterize the risk-to-benefit ratio of NAC in the treatment of TTP. PMID:26245827

  5. Methorexate therapy in a patient with rheumatoid arthritis complicated by idiopathic thrombocytopenic purpura

    PubMed Central

    Komoğlu, Sabiha; Silte, Duygu; Sertbaş, Meltem; Sertbaş, Yaşar; Özdemir, Ali

    2015-01-01

    The association of rheumatoid arthritis (RA) and immune thrombocytopenic purpura (ITP) has been reported rarely. Methotrexate, which is used for RA treatment, causes thrombocytopenia. Therefore, in medical practice, physicians avoid using methotrexate for RA in patients who have both RA and ITP. Here, we report an RA case that also had ITP, which did not decrease in platelet count after methotrexate therapy. A 50-year-old woman was diagnosed with diabetes mellitus in 1990, RA in 1995, and ITP in 2000. She had received hydroxychloroquine for more than 5 years. She was treated with prednisolone 16 mg/daily between 2006 and 2007, but she discontinued this therapy because of weight gain. Laboratory findings were not remarkable, except for thrombocytopenia. We started methotrexate therapy 10 mg per week for treatment of RA, and hydroxychloroquine therapy was stopped due to nonresponse. The methotrexate dose was increased up to 15 mg/week. Her complete blood cell count was monitored frequently. We did not observe any decrease in platelet count, while active arthritis symptoms of the patient were relieved. This case shows that methotrexate may be used in patients diagnosed with RA that is associated with ITP under strict monitoring.

  6. Successful rituximab treatment in an elderly patient with recurrent thrombotic thrombocytopenic purpura.

    PubMed

    Matsubara, Etsuko; Yamanouchi, Jun; Hato, Takaaki; Takeuchi, Kazuto; Niiya, Toshiyuki; Yasukawa, Masaki

    2016-07-01

    An 81-year-old man presenting with fever, neurological symptoms, thrombocytopenia, and hemolytic anemia was diagnosed with acquired idiopathic thrombotic thrombocytopenic purpura (TTP). His disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) activity was <1% and the ADAMTS13 inhibitor titer was 3.2 BU/ml. He received plasma exchange and steroid administration until remission was achieved. Seven months later, he suffered from paralysis of the right hand, hemolytic anemia, and thrombocytopenia. We confirmed TTP recurrence based on ADAMTS13 activity <1% and an ADAMTS13 inhibitor titer of 19.4 BU/ml. Four infusions of rituximab were administered in addition to plasma exchange and steroid pulse therapy. Platelet count recovery was observed within 5 days. No severe side effects related to rituximab occurred. Although rituximab has not been approved for TTP in Japan, we report the efficacy and safety of rituximab in an elderly patient with recurrent TTP. We suggest that rituximab therapy should be started as soon as possible for recurrent TTP in patients with high titers of ADAMTS13 inhibitor. PMID:27498731

  7. 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. PMID:23011161

  8. 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

  9. Splenic dynamics of indium-111 labeled platelets in idiopathic thrombocytopenic purpura

    SciTech Connect

    Syrjaelae, M.T.Sa.; Savolainen, S.; Nieminen, U.; Gripenberg, J.; Liewendahl, K.; Ikkala, E. )

    1989-09-01

    Splenic dynamics of {sup 111}In-labeled platelets and platelet-associated IgG in 33 patients with idiopathic thrombocytopenic purpura (ITP) were studied. Two half-lives were calculated for the biexponential splenic time-activity curve after i.v. injection of {sup 111}In-labeled platelets. There was no difference in the mean half-life of the rapid component of the splenic curve (ST1) when patients with negative or slightly positive platelet suspension immunofluorescence test (PSIFT) were compared to those with strongly positive PSIFT (3.0 {plus minus} 0.7 min vs. 3.6 {plus minus} 0.4, p greater than 0.05). Mean half-life of the slow component of the splenic curve (ST2) was found to be longer in patients with a strongly positive than a negative or weakly positive PSIFT (26 {plus minus} 5 min vs. 13.2 {plus minus} 1.0 min, p less than 0.01). It seems that determination of the two components of the splenic time-activity curve provides a useful method for studying platelet kinetics in ITP.

  10. 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.

  11. [Long-term follow-up of chronic idiopathic thrombocytopenic purpura in children].

    PubMed

    Amendola, G; Danise, P; D'Arco, A

    2000-01-01

    Idiopathic thrombocytopenic purpura (ITP) is a common acquired bleeding disorder in infancy and childhood. Most children rapidly improve, exhibiting a rise in platelet count to hemostatically normal levels within weeks to several months. Traditionally, chronic ITP is defined as persistence of thrombocytopenia (platelet count < 150 x 10(9)/L) for greater than 6 months. The Authors retrospectively evaluated 16 patients with chronic ITP, identified during a 12-year period of time in their Department of Pediatrics. The most important clinical and hematological parameters of patients were analyzed, including age at diagnosis, type and response to the initial treatment, number of multiple treatments, and duration of follow-up. At the last evaluation (december 1999) one patient was lost to the follow-up; one died of overwhelming postsplenectomy sepsis; four still require intermittent or chronic infusions of intravenous gamma-globulin; seven are in stable partial remission (PLT > 50 x 10(9)/L < 150 x 10(9)/L) and do not require any treatment; three are in complete remission (PLT > 150 x 10(9)/L). Finally, the Authors discuss of the natural history and management of this rare disease. Presently there are insufficient trial data to support evidence-based treatment guidelines in childhood chronic ITP and therefore it is reasonable to encourage future multicentre collaboration.

  12. Does cryosupernatant plasma improve outcome in thrombotic thrombocytopenic purpura? No answer yet.

    PubMed

    Rock, Gail; Anderson, David; Clark, William; Leblond, Pierre; Palmer, Douglas; Sternbach, Marion; Sutton, David; Wells, George

    2005-04-01

    A randomized prospective trial compared cryosupernatant plasma (CSP) to fresh frozen plasma (FFP) for treatment of thrombotic thrombocytopenic purpura (TTP). A total of 236 patients were required: 28 patients were treated with CSP and 24 with FFP within 30 months. There were no differences in survival at 1 month. By day 9, 17 of 26 patients with CSP and 18 of 24 with FFP had a platelet count >100 x 10(9)/l. At entry, von Willebrand factor (VWF) multimers were normal in all patients (range 1.1-3.95 IU/ml). ADAMTS-13 levels showed large variations ranging from 10% to 100% activity. At entry, no individual had <5% VWF cleaving protease. By day 9 (end of cycle), 89% (FFP) and 67% (CSP) had levels >50% of the controls. At 6 months some patients showed inhibitors to the enzyme in spite of adequate or normal platelet counts. The data from this study do not show an apparent advantage to the use of CSP in TTP. A large number of patients will be required to determine appropriate replacement therapy. We were not able to find a statistically significant relationship between the low level of protease activity at presentation of TTP and response.

  13. Platelet Kinetics in Idiopathic Thrombocytopenic Purpura Patients Treated with Thrombopoietin Receptor Agonists

    PubMed Central

    Meyer, Oliver; Herzig, Eric; Salama, Abdulgabar

    2012-01-01

    Aim Thrombopoietin receptor agonists (Tpo RA) increase platelet counts in the majority of chronic autoimmune thrombocytopenia (idiopathic thrombocytopenic purpura; ITP) patients. It is unknown whether this treatment may also improve platelet survival (PS) in these patients. Methods In order to determine platelet survival (PS), autologous platelets were labeled with 111In oxine and retransfused in six patients under treatment with Tpo RA (romiplostim n = 3; eltrombopag n = 3). Results Stable platelet counts of greater than 100 × 103/μl were observed in all 6 patients. Platelet survival was decreased in all cases (mean 2.10 days; range 0.13–3.73 days). No correlation was found between platelet count and PS. Similarly, there was no significant relationship between platelet turnover and platelet count. However, a high platelet turnover, exceeding 25 or three times the norm was observed in 2 patients who presented the lowest PS (0.13 or 0.83 days). Two patients had a moderately shortened PS (1.91 or 2.42 days), and, correspondingly, a moderately increased platelet turnover rate (63,072 or 72,872 platelets/μl/day). Conclusion These results indicate that Tpo RA may not only overcompensate platelet destruction in ITP, but may interfere with other mechanisms, which, in some cases, results in a reduced platelet destruction rate. PMID:22896760

  14. 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

  15. Two cases of Vici syndrome associated with Idiopathic Thrombocytopenic Purpura (ITP) with a review of the literature.

    PubMed

    Huenerberg, Katherine; Hudspeth, Michelle; Bergmann, Shayla; Pai, Shashidhar; Singh, Balvir; Duong, Angie

    2016-05-01

    Vici syndrome is a rare congenital disorder first described in 1988. To date, 31 cases have been reported in the literature. The characteristic features of this syndrome include: agenesis of the corpus callosum, albinism, cardiomyopathy, variable immunodeficiency, cataracts, and myopathy. We report two Hispanic sisters with genetically confirmed Vici syndrome who both developed Idiopathic Thrombocytopenic Purpura. To our knowledge, this is an immunologic process that has been previously undescribed within the phenotype of Vici syndrome and should be added to the spectrum of variable immune dysregulation that can be found in these patients. PMID:26854214

  16. 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.

  17. Changes in Follicular Helper T Cells in Idiopathic Thrombocytopenic Purpura Patients

    PubMed Central

    Xie, Jue; Cui, Dawei; Liu, Yan; Jin, Jie; Tong, Hongyan; Wang, Lei; Ruan, Guoxiang; Lu, Yun; Yuan, Huiming

    2015-01-01

    Background: Idiopathic thrombocytopenic purpura (ITP) is a primary autoimmune disease with a decreased platelet count caused by platelet destruction mediated mainly by platelet antibodies. T follicular helper (TFH) cells have demonstrated important roles in autoimmune diseases. The aim of this study is to explore the might role of TFH cells in the patients of ITP. Methods: Twenty-three ITP patients and 12 healthy controls (HC) were enrolled in this study. The frequency of circulating TFH cells in both the patients and HC was analyzed by flow cytometry. Serum interleukin (IL)-21 and IL-6 levels were measured using ELISA, and platelet antibodies were tested using a solid phase technique. Additionally, IL-21, IL-6, Bcl-6 and c-Maf mRNA expressions in peripheral blood mononuclear cells (PBMCs) were detected using real-time PCR. Results: The percentages of circulating CXCR5+ CD4+TFH cells with ICOShigh or PD-1high expression were significantly higher in the ITP patients than in the HC. Moreover, the frequencies of circulating CXCR5+ CD4+TFH cells with inducible costimulator (ICOS)high or programmed death-1 (PD-1)high expression were notably higher in ITP with platelet-antibody-positive ( ITP (+) ) patients than in ITP with platelet-antibody-negative ( ITP (-) ) patients and HC, as were the serum IL-21 and IL-6 levels (significant). Moreover, a positive correlation was found between the CXCR5+CD4+TFH cells with ICOShigh or PD-1high expression and the serum IL-21 levels of ITP (+) patients. Additionally, the mRNA expression levels of IL-21, IL-6, Bcl-6 and c-Maf were significantly increased in ITP patients, especially in ITP (+) patients. Conclusions: This study demonstrated TFH cells and effector molecules might play an important role in the pathogenesis of ITP, which are possible therapeutic targets in ITP patients. PMID:25561904

  18. Single nucleotide polymorphisms of the inflammatory cytokine genes in adults with chronic immune thrombocytopenic purpura.

    PubMed

    Satoh, Takashi; Pandey, Janardan P; Okazaki, Yuka; Yasuoka, Hidekata; Kawakami, Yutaka; Ikeda, Yasuo; Kuwana, Masataka

    2004-03-01

    Single nucleotide polymorphisms (SNPs) of inflammatory cytokine genes were examined in 84 adult Japanese patients with chronic immune thrombocytopenic purpura (ITP) and 56 race-matched healthy controls. The SNPs examined were within the genes encoding tumour necrosis factor (TNF)-alpha (-238 G/A and -308 G/A), TNF-beta (+252 G/A), and interleukin (IL)-1beta (-511 C/T and +3953 T/C). Of these SNPs, the frequency of the TNF-beta (+252) G/G phenotype was significantly higher in ITP patients than in healthy controls (21% vs. 7%, P = 0.04, odds ratio = 3.6, 95% confidence interval 1.1-11.1), while no significant association was detected for the other SNPs. The distribution of the TNF-beta (+252) phenotype was not associated with human leucocyte antigen class II alleles or the therapeutic response in ITP patients. The frequency of circulating anti-glycoprotein IIb/IIIa antibody-producing B cells was significantly higher in ITP patients with the TNF-beta (+252) G/G phenotype than in those with the G/A or A/A phenotype (11.9 +/- 4.9 vs. 6.8 +/- 4.9 and 3.7 +/- 2.8 per 10(5) peripheral blood mononuclear cells; P = 0.02 and P < 0.001, respectively). These findings suggest that the SNP located at TNF-beta (+252) contributes to susceptibility to chronic ITP by controlling the autoreactive B-cell responses to platelet membrane glycoproteins.

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

    PubMed Central

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

    2015-01-01

    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. PMID:25728540

  20. 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. PMID:25728540

  1. CD16 and CD32 Gene Polymorphisms May Contribute to Risk of Idiopathic Thrombocytopenic Purpura.

    PubMed

    Xu, Jiannan; Zhao, Liyun; Zhang, Yan; Guo, Qingxu; Chen, Hui

    2016-01-01

    BACKGROUND Epidemiological studies have evaluated the associations of CD16 158F>V and CD32 131H>R gene polymorphisms with the risk of idiopathic thrombocytopenic purpura (ITP). MATERIAL AND METHODS Published studies on CD16 158F>V and CD32 131H>R polymorphisms with susceptibility to ITP were systematically reviewed until April 1, 2014. The Cochrane Library Database, Medline, CINAHL, EMBASE, Web of Science, and Chinese Biomedical Database (CBM) were used to search for relevant studies and then a meta-analysis was conducted by using Stata 12.0 software in order to produce consistent statistical results. RESULTS In total, 10 clinical case-control studies with 741 ITP patients and 1092 healthy controls were enrolled for quantitative data analysis. Results of this meta-analysis suggest that CD16 158F>V polymorphism had strong correlations with the susceptibility to ITP under 5 genetic models (all P<0.05). However, no similar associations were found between CD32 131H>R polymorphism and the susceptibility to ITP (all P>0.05). Subgroup analysis by ethnicity revealed that CD16 158F>V polymorphism was associated with the increased risk of ITP among both Caucasian and non-Caucasian populations. Nevertheless, no statistically significant correlations between CD32 131H>R polymorphism and the risk of ITP were observed among Caucasians and non-Caucasians (all P>0.05). CONCLUSIONS Our findings indicate that CD16 158F>V polymorphism may contribute to the increased risk of ITP, whereas CD32 131H>R polymorphism may not be an important risk factor for ITP. PMID:27315784

  2. Antiphospholipid antibodies (APLA) in immune thrombocytopenic purpura (ITP) and antiphospholipid syndrome (APS).

    PubMed

    Bidot, Carlos J; Jy, Wenche; Horstman, Lawrence L; Ahn, Eugene R; Yaniz, Miriam; Ahn, Yeon S

    2006-06-01

    Antiphospholipid antibodies (APLA) are associated with anti-phospholipid syndrome (APS), a thrombotic disorder, but they are also frequently detected in immune thrombocytopenic purpura (ITP), a bleeding disorder. To investigate possible differences of APLA between these two disorders, we assayed IgG and IgM APLA by ELISA in 21 patients with ITP and 33 with APS. The APLA reacting against two protein target antigens, beta(2)-glycoprotein 1 (beta2GP1) and FVII/VIIa, and four phospholipids [cardiolipin (CL), phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylethanolamine (PE)] as well as lupus anticoagulant (LA) were analyzed. We made the following observations: (i) IgG and IgM antibodies to beta2GP1 and IgM antibodies to FVII/VIIa were more common in APS than ITP, P < 0.05, while IgG antibodies against the phospholipids (aCL, aPC, aPS, aPE) were more common in ITP than APS, P < 0.05; (ii) multiple APLA > or =3 antigens) were more frequent in APS than ITP, P < 0.05; (iii) LA was frequently associated with APS but was absent in ITP; (iv) APLA is quite common in ITP: two-thirds were positive for at least one APLA. In summary, APLA are prevalent in ITP but their profile differs from APS. In APS, antibodies were predominantly against beta2GP1 and 80% had positive LA, while in ITP the APLA reacted most often with the phospholipids without LA. The difference in APLA may result in opposite clinical manifestations in two disorders.

  3. 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.

  4. Inhibitors of von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura.

    PubMed

    Tsai, H M; Li, A; Rock, G

    2001-01-01

    Thrombotic thrombocytopenic purpura (TTP), characterized by platelet thrombi in the arterioles and capillaries, is associated with antibodies that inhibit the activity of von Willebrand factor (vWF)-cleaving protease. Using a modified Bethesda method, we studied the inhibitor titers in patients who participated in the trial conducted by the Canadian Apheresis Group. Among the 41 patients investigated, the inhibitor titers at presentation were 1.4 +/- 1.7 U/mL (range -0.2-6.2 U/mL). Thirty-one patients (76%) had a titer > or = 0.2 U/mL, 8 patients (20%) had a titer > or = 2.0 U/mL but none had a titer > or = 10 U/mL. Among the 33 patients with an inhibitor titer < 2.0 U/mL (low titer group) and the 8 patients with an inhibitor titer > or = 2 U/mL (high titer group), 20 (61%) and 8 (100%) respectively had a platelet count < 25x10(9)/L (P = 0.04). Neurological abnormalities were among the presenting problems in 19 (58%) of the low titer and 6 (75%) of the high titer groups. Among the 23 patients who were randomized to plasma exchange, 5 patients had an inhibitor titer > or = 2 U/mL and none responded at the end of the first treatment cycle, while 8 of the 18 patients (44%) with a titer < 2 U/mL responded. This study shows that inhibitors of vWF-cleaving protease are of low titers in most cases of acquired TTP. A higher inhibitor titer is associated with a more advanced stage of the disease and may delay the response to plasma exchange.

  5. Plasma microRNA profiling of pediatric patients with immune thrombocytopenic purpura.

    PubMed

    Bay, Ali; Coskun, Enes; Oztuzcu, Serdar; Ergun, Sercan; Yilmaz, Fatih; Aktekin, Elif

    2014-06-01

    Immune thrombocytopenic purpura (ITP) is a commonly acquired autoimmune bleeding disorder in children. MicroRNAs (miRNAs) are small RNAs which are found in cells and circulation, and play a role in protein synthesis and regulation. In this study, we aimed to determine a biomarker for childhood ITP comparing the plasma miRNA levels of children having ITP with healthy children. A total of 86 patients with ITP and 56 healthy children followed up by the Department of Pediatric Hematology and Oncology in University of Gaziantep since July 2011 were enrolled in the study. The 86 patients with ITP were evaluated in two groups as 43 acute ITP (aITP) and 43 chronic ITP (cITP) patients. Plasma expression levels of 379 miRNAs were investigated by RT-PCR (quantitative RT-PCR) technique and they were compared between aITP, cITP, and control groups. For all miRNAs, the average of raw quantification cycle values of three groups separately in the analysis chip was accepted as the reference gene value, and normalization was done according to this value. Statistically significant differences were detected in seven miRNAs (miR-302c-3p, miR-483-5p, miR-410, miR-544a, miR-302a-3p, miR-223-3p, and miR-597) investigated between the groups with respect to the expression levels. The expression rates were found to be over 95% in miR-302c-3p and miR-483-5p, over 75% in miR-410, and over 40% in miR-544, miR-302a-3p, and miR-223-3p in all three groups. The detection of significant differences between plasma miRNA levels of aITP and cITP patients and healthy children may provide useful information in the prediction of the course of disease, determination of disease etiopathogenesis, and the development of new therapeutic modalities.

  6. Purpura

    MedlinePlus

    Blood spots; Skin hemorrhages ... and 10 mm (millimeters) in diameter. When purpura spots are less than 4 mm in diameter, they are called petechiae . Purpura spots larger than 1 cm (centimeter) are called ecchymoses. ...

  7. Eltrombopag for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a NICE single technology appraisal.

    PubMed

    Boyers, Dwayne; Jia, Xueli; Jenkinson, David; Mowatt, Graham

    2012-06-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of eltrombopag (GlaxoSmithKline) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with chronic immune or idiopathic thrombocytopenic purpura (ITP), as part of the their Single Technology Appraisal (STA) process. The Aberdeen Technology Assessment Review (TAR) Group, commissioned to act as the evidence review group (ERG), critically reviewed and supplemented the submitted evidence. This paper describes the company submission, the ERG review and NICE's subsequent decisions. The ERG critically appraised the clinical and cost-effectiveness evidence submitted by the manufacturer, independently searched for relevant literature, conducted a critical appraisal of the submitted economic models and explored the impact of altering some of the key model assumptions as well as combining relevant sensitivity analyses. Three trials were used to inform the safety and efficacy aspects of this submission; however, one high-quality randomized controlled trial (RAISE study) was the principal source of evidence and was used to inform the economic model. Eltrombopag had greater odds of achieving the primary outcome of a platelet count between 50 × 10^⁹/L and 400 × 10^⁹/L during the 6-month treatment period than placebo (odds ratio [OR] 8.2, 99% CI 3.6, 18.7). In the eltrombopag group, 50/83 (60%) of non-splenectomized patients and 18/49 (37%) of splenectomized patients achieved this outcome. The median duration of response was 10.9 weeks for eltrombopag (splenectomized 6 and non-splenectomized 13.4) compared with 0 for placebo. Eltrombopag patients required less rescue medication and had lower odds of bleeding events for both the splenectomized and the non-splenectomized patients. For a watch-and-rescue strategy of care, the comparator was placebo and the ERG found that substantial reductions in the cost of eltrombopag are needed

  8. [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.

  9. [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. PMID:24763012

  10. Refractory thrombotic thrombocytopenic purpura associated with oral contraceptives and factor V Leiden: a case report

    PubMed Central

    Tsirakis, George; Mantadakis, Elpis; Xylouri, Irini; Foudoulakis, Andreas; Vardaki, Eleftheria; Katsipi, Irene; Daphnis, Eugene; Samonis, George

    2009-01-01

    Introduction Thrombotic microangiopathies constitute a heterogeneous group of diseases characterised by microangiopathic haemolytic anaemia and thrombocytopaenia associated with platelet aggregation in the microcirculation responsible for ischaemic manifestations. Classically, thrombotic microangiopathies are described as encompassing two main syndromes: thrombotic thrombocytopaenic purpura and the haemolytic-uraemic syndrome Many cases of idiopathic thrombotic thrombocytopaenic purpura have, to date, been associated with severe ADAMTS13 metalloprotease deficiency while haemolytic uraemic syndrome usually occurs in the context of normal protease activity. Oestrogens and factor V Leiden have rarely been implicated in the pathogenesis of thrombotic microangiopathy. Case presentation We describe the case of a 17-year-old female with refractory thrombotic thrombocytopaenic purpura. The patient was receiving a new generation of oral contraceptives for dysmenorrhoea and had factor V Leiden. After undergoing prolonged and intense plasma exchange therapy for 40 days and high dose oral corticosteroids therapy for 90 days, our patient recovered fully. Conclusion Patients with refractory thrombotic thrombocytopaenic purpura should likely be evaluated for congenital thrombophilic disorders and for ingestion of drugs that have been associated with this rare form of thrombotic microangiopathy. Identification of these and as yet other unknown genetic and/or acquired risk factors may lead to more judicious treatment approaches. PMID:19829833

  11. The effect of platelet autoantibodies on the course of the disease and clinical response of patients with idiopathic thrombocytopenic purpura.

    PubMed

    Sikorska, A; Konopka, L; Maślanka, K

    2008-02-01

    In this study, we evaluated the response to treatment of 409 idiopathic thrombocytopenic purpura (ITP) patients who were tested for the presence of platelet-associated autoantibodies by direct-platelet immunofluorescence test (PIFT) and for the presence of plasma antibodies directed against the GPIIb/IIIa, GPIb and GPIa/IIa by monoclonal antibody immobilization of platelet antigens (MAIPA). In patients with platelet autoantibodies in comparison with patients without antibodies more frequently were observed the chronic form of disease (83.5%vs. 68.5%) and severe symptoms of haemorrhage diathesis (17.3%vs. 6.9%). Evaluation of the treatment response (to corticosteroids, immunosuppressive drugs and splenectomy) referred to patients with complete response, e.g. complete remission defined as platelet count of >100 x 10(9)/l for at least 2 years. The percentage of complete response in the whole population of ITP patients, both with and without autoantibodies regardless of the method of treatment, was similar (about 54%). However, the presence of platelet autoantibodies had effect on patients treated with corticosteroids: complete response approximately 71% (36/51) of patients with autoantibodies and in 60% (72/120) of patients without antibodies, as well as in patients treated with immunosuppressive drugs (cyclophosphamide, azathioprine, vincristin and vinblastin); complete response approximately 51% (11/21) of patients with autoantibodies and in 34.8% (6/17) of patients without autoantibodies. The presence of autoantibodies had no effect on the response of splenectomy patients. PMID:18190469

  12. Human/BALB radiation chimera engrafted with splenocytes from patients with idiopathic thrombocytopenic purpura produce human platelet antibodies.

    PubMed Central

    Dekel, B; Marcus, H; Shenkman, B; Shimoni, A; Shechter, Y; Canaan, A; Berrebi, A; Varon, D; Reisner, Y

    1998-01-01

    We have previously shown that lethally irradiated normal strains of mice, radioprotected with severe combined immunodeficient (SCID) bone marrow, can be engrafted with human peripheral blood mononuclear cells (PBMC). The human/mouse radiation chimera can mount marked humoral and cellular responses to recall antigens, as well as primary responses. In the present study, we adoptively transferred splenocytes from patients with chronic immune thrombocytopenic purpura (ITP) into lethally irradiated BALB/c mice, radioprotected with SCID bone marrow. High titres of total human immunoglobulin appeared as early as 2 weeks post-transplant and declined after 6 weeks, while human anti-human platelet antibodies were detected 2-8 weeks after the transfer of splenocytes. The immunoglobulin G (IgG) fraction contained antibodies against glycoprotein (GP) IIb/IIIa (CD41) or GPIb/IX (CD42). The human platelet antibodies showed a low level of cross-reactivity with mouse platelets, and thrombocytopenia in the animals was not observed. Splenocytes from individual ITP patients differed in their capacity to produce either human platelet antibodies or total human immunoglobulin. Furthermore, antibodies produced in the murine system were not always identical to the original antibodies present in the serum of the patients. The study of the serological aspects of autoantibodies against human platelets in an animal model might be useful for the investigation of potential therapeutics in ITP. PMID:9767425

  13. Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome associated with high-dose interleukin-2 for the treatment of metastatic melanoma.

    PubMed

    Alexandrescu, Doru T; Maddukuri, Prasad; Wiernik, Peter H; Dutcher, Janice P

    2005-01-01

    Various drugs have been associated with the development of thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Among the biologic agents, alpha-interferon therapy, used for treatment of hepatitis B and chronic myelogenous leukemia, has been associated with TTP in a few recent reports. The authors report the first case of TTP/HUS occurring in a metastatic melanoma patient receiving treatment with high-dose interleukin-2 (IL-2). A 57-year-old patient with malignant melanoma presented with seizures 3 days after completing the first week of high-dose IL-2, and the characteristic hematologic picture revealed TTP/HUS. This occurrence is unlikely to be explained by the association with malignant melanoma, which was not presenting with widespread visceral disease at the time of the occurrence, or by the use of other medications. Similar cytokine release profiles are encountered in TTP, HUS caused by Shiga toxin-1, HUS caused by E. coli O157, after IL-2 or IL-2-containing biochemotherapy, as well as in TTP caused by interferon-alpha. This cytokine profile could reflect a common cause, or just the presence of similar pathways involved. PMID:15725958

  14. Intracranial hemorrhage in acute and chronic childhood immune thrombocytopenic purpura over a ten-year period: an Egyptian multicenter study.

    PubMed

    Elalfy, Mohsen; Elbarbary, Nancy; Khaddah, Normine; Abdelwahab, Magy; El Rashidy, Farida; Hassab, Hoda; Al-Tonbary, Youssef

    2010-01-01

    Intracranial hemorrhage (ICH) is a rare but major cause of death in immune thrombocytopenic purpura (ITP). The authors reviewed data of 1,840 patient with ITP, from 5 pediatric hematology centers in Egypt from 1997 to 2007, to study the incidence and risk factors of ICH. Ten cases of ICH were identified with a median age at presentation of 7.5 years; 4 patients had acute ITP, 2 persistent and 4 chronic. The platelet count was <10 x 10(9)/l in 7 cases, and only 1 patient had a history of head trauma. Seven children were on treatment prior to or at the time of occurrence of ICH and all were treated by pharmacotherapy. Two children died shortly afterwards due to late referral to a specialized center. Our results suggest that treatment does not prevent ICH and that it can occur at any time during the course of the disease. Delayed referral can be considered a risk factor for unfavorable outcome of ICH, highlighting the importance of teaching sessions for patients and their parents to minimize subsequent morbidity and mortality of ICH in children with ITP. PMID:19955713

  15. Tumor necrosis factor-α -308G/A gene polymorphism in Egyptian children with immune thrombocytopenic purpura.

    PubMed

    El Sissy, Maha H; El Sissy, A H; Elanwary, Sherif

    2014-07-01

    Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by increased platelet destruction. Although the cause of ITP remains unclear, it is accepted that both environmental and genetic factors play an important role in the development of the disease. Children with ITP have a T-helper 1-type cytokine pattern with elevated levels of tumor necrosis factor-alpha (TNF-α) as in most autoimmune diseases. Researchers have shown that polymorphism in the TNF-α gene at position -308 affects gene transcriptions with increased TNF-α production. The current case-control study aimed at detecting the frequency of TNF-α -308G/A gene polymorphism as genetic markers in Egyptian children with ITP, and to clear out their possible role in choosing the treatment protocols of therapy, using PCR restriction fragment length polymorphism assay. Ninety-two ITP patients and 100 age and sex-matched healthy controls were recruited in the study. The results obtained revealed that the frequency of TNF-α -308A/A homotype in ITP patients was significantly higher than that of the controls, and conferred almost six-fold increased risk of ITP acquisition. The polymorphic A allele frequency was significantly higher in ITP patients than in the controls, conferring almost two-fold increased ITP risk. In conclusion, our study suggests the possibility that TNF-α -308 gene polymorphism may contribute to the susceptibility of childhood ITP in Egyptian children.

  16. A systematic review of randomized controlled trials for plasma exchange in the treatment of thrombotic thrombocytopenic purpura.

    PubMed

    Brunskill, S J; Tusold, A; Benjamin, S; Stanworth, S J; Murphy, M F

    2007-02-01

    The mainstay of treatment for thrombotic thrombocytopenic purpura (TTP) is plasma exchange (PE). A systematic review was undertaken to summarize the randomized controlled trial (RCT) evidence, to date, on PE as treatment for TTP. Seven randomized RCTs were identified till May 2005. A statistical reduction in mortality was found in patients receiving PE compared with patients receiving plasma infusion (relative risk 0.31, 95% confidence interval 0.12-0.79). No statistical difference in mortality was found in trials comparing different replacement fluids for PE. There were few differences in the response to treatment and the resolution of the presenting signs of TTP in any trial. Lack of data prevented a full assessment of the incidence of adverse events. None of the studies included measured patients' quality of life. Further research is required to determine the benefits and side effects associated with different replacement fluids for PE. It is recommended that there should be consistency in the diagnostic criteria, measurement of clinical outcomes and length of follow up. Continued support of existing TTP patient registries and establishment of new registries would facilitate this. PMID:17266701

  17. Acute renal failure after intravenous anti-D immune globulin in an adult with immune thrombocytopenic purpura.

    PubMed

    Chun, Nancy S; Savani, Bipin; Seder, Richard H; Taplin, Mary Ellen

    2003-12-01

    Intravenous anti-D immune globulin (anti-D IGIV) is indicated for the treatment of immune thrombocytopenic purpura (ITP) in nonsplenectomized patients who are Rh(D)-positive. Recent reports have described episodes of intravascular hemolysis (IVH) and acute renal failure (ARF) after anti-D IGIV. We report the first adult patient with ITP who required and received dialysis after IVH and ARF complicating treatment with anti-D IGIV. Whether the transfusion of 2 units of Rh(D)-positive red cells, indicated for the resulting anemia, exacerbated the IVH and renal failure is unclear. Three weeks after the administration of anti-D IGIV (13 days after two hemodialysis treatments), the patient's renal function had returned to normal. This case highlights the infrequent but potentially serious side effects of anti-D IGIV and the need to monitor a patient's renal function closely if there is evidence of IVH after infusion of anti-D IGIV. If red cell transfusion is indicated, we recommend the use of Rh(D)-negative red cell products.

  18. Thrombotic thrombocytopenic purpura-like syndromes following bone marrow transplantation: an analysis of associated conditions and clinical outcomes.

    PubMed

    Roy, V; Rizvi, M A; Vesely, S K; George, J N

    2001-03-01

    The diagnosis and treatment of thrombotic thrombocytopenic purpura (TTP) in patients following BMT are often uncertain and unsuccessful. To better understand the evaluation and management of these patients, we describe 17 patients treated with plasma exchange for a presumptive diagnosis of TTP following BMT during a 10 year period, 1989-1998. Because of the uncertainty of the diagnosis, these patients are described as having a 'TTP-like syndrome'. All 17 patients had received an allogeneic BMT. Comparison with the other 245 patients who had an allogeneic BMT during the same period demonstrated that patients with a TTP-like syndrome more frequently had unrelated and/or HLA-mismatched donors, and had also experienced more serious complications: grade III-IV acute GVHD and systemic bacterial, fungal, and viral infections. Three months after the diagnosis of the TTP-like syndrome, only four of 17 patients (24%) were alive; currently only one patient survives. These data emphasize: (1) the diagnosis of TTP following BMT is uncertain because of the presence of multiple BMT-associated complications. (2) The outcome of patients with TTP-like syndromes following BMT is poor. (3) Urgent intervention with plasma exchange when TTP is suspected following BMT may not always be appropriate. Alternative explanations for the signs and symptoms should be considered and treated aggressively. PMID:11319595

  19. Novel hypomorphic mutation in IKBKG impairs NEMO-ubiquitylation causing ectodermal dysplasia, immunodeficiency, incontinentia pigmenti, and immune thrombocytopenic purpura.

    PubMed

    Ramírez-Alejo, Noé; Alcántara-Montiel, Julio C; Yamazaki-Nakashimada, Marco; Duran-McKinster, Carola; Valenzuela-León, Paola; Rivas-Larrauri, Francisco; Cedillo-Barrón, Leticia; Hernández-Rivas, Rosaura; Santos-Argumedo, Leopoldo

    2015-10-01

    NF-κB essential modulator (NEMO) is a component of the IKK complex, which participates in the activation of the NF-κB pathway. Hypomorphic mutations in the IKBKG gene result in different forms of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) in males without affecting carrier females. Here, we describe a hypomorphic and missense mutation, designated c.916G>A (p.D306N), which affects our patient, his mother, and his sister. This mutation did not affect NEMO expression; however, an immunoprecipitation assay revealed reduced ubiquitylation upon CD40-stimulation in the patient's cells. Functional studies have demonstrated reduced phosphorylation and degradation of IκBα, affecting NF-κB recruitment into the nucleus. The patient presented with clinical features of ectodermal dysplasia, immunodeficiency, and immune thrombocytopenic purpura, the latter of which has not been previously reported in a patient with NEMO deficiency. His mother and sister displayed incontinentia pigmenti indicating that, in addition to amorphic mutations, hypomorphic mutations in NEMO can affect females. PMID:26117626

  20. Occurrence of both hemolytic anemia and thrombocytopenic purpura (Evans' syndrome) in systemic lupus erythematosus. Relationship to antiphospholipid antibodies.

    PubMed

    Delezé, M; Oria, C V; Alarcón-Segovia, D

    1988-04-01

    Ten of 12 patients with systemic lupus erythematosus (SLE) who had hemolytic anemia and thrombocytopenic purpura (Evans' syndrome) during their course had evidence of antiphospholipid antibodies either because they had a false positive VDRL test (8 patients), a prolonged partial thromboplastin time (5 patients), a lupus anticoagulant (3/4 patients), and/or anticardiolipin antibodies as determined by an ELISA method (7 patients). Antibodies to cardiolipin were found in very high levels (up to 38 standard deviations above the mean of normal controls) and were of both IgG and IgM isotypes. The 2 patients with SLE and Evans' syndrome who did not have evidence of antiphospholipid antibodies were studied at the onset of SLE which occurred with Evans' syndrome. Although cardiolipin is not a constituent of the cell wall of either platelets or erythrocytes, other phospholipids that cross react antigenically with cardiolipin are and can be exposed through cell damage. This could be a mechanism whereby hemolytic anemia and thrombocytopenia could occur in the same patient with SLE. Whether absorption of the antiphospholipid antibody during the acute episode of hemocytopenia could occur, and thus prevent its detection at such time, remains undetermined.

  1. 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. PMID:19925495

  2. Ticlopidine- and clopidogrel-associated thrombotic thrombocytopenic purpura (TTP): review of clinical, laboratory, epidemiological, and pharmacovigilance findings (1989–2008)

    PubMed Central

    Zakarija, Anaadriana; Kwaan, Hau C.; Moake, Joel L.; Bandarenko, Nicholas; Pandey, Dilip K.; McKoy, June M.; Yarnold, Paul R.; Raisch, Dennis W.; Winters, Jeffrey L.; Raife, Thomas J.; Cursio, John F.; Luu, Thanh Ha; Richey, Elizabeth A.; Fisher, Matthew J.; Ortel, Thomas L.; Tallman, Martin S.; Zheng, X. Long; Matsumoto, Masanori; Fujimura, Yoshihiro; Bennett, Charles L.

    2012-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a fulminant disease characterized by platelet aggregates, thrombocytopenia, renal insufficiency, neurologic changes, and mechanical injury to erythrocytes. Most idiopathic cases of TTP are characterized by a deficiency of ADAMTS13 (a disintegrin and metalloprotease, with thrombospondin-1-like domains) metalloprotease activity. Ironically, use of anti-platelet agents, the thienopyridine derivates clopidogrel and ticlopidine, is associated with drug induced TTP. Data were abstracted from a systematic review of English-language literature for thienopyridine-associated TTP identified in MEDLINE, EMBASE, the public website of the Food and Drug Administration, and abstracts from national scientific conferences from 1991 to April 2008. Ticlopidine and clopidogrel are the two most common drugs associated with TTP in FDA safety databases. Epidemiological studies identify recent initiation of anti-platelet agents as the most common risk factor associated with risks of developing TTP. Laboratory studies indicate that most cases of thienopyridine-associated TTP involve an antibody to ADAMTS13 metalloprotease, present with severe thrombocytopenia, and respond to therapeutic plasma exchange (TPE); a minority of thienopyridine-associated TTP presents with severe renal insufficiency, involves direct endothelial cell damage, and is less responsive to TPE. The evaluation of this potentially fatal drug toxicity can serve as a template for future efforts to comprehensively characterize other severe adverse drug reactions. PMID:19180126

  3. Late side effects of high-dose steroid therapy on skeletal system in children with idiopathic thrombocytopenic purpura.

    PubMed

    Yildirim, Zühal Keskin; Büyükavci, Mustafa; Eren, Suat; Orbak, Zerrin; Sahin, Ali; Karakelleoğlu, Cahit

    2008-10-01

    Corticosteroids have been widely used in the treatment of idiopathic thrombocytopenic purpura (ITP). We evaluated the late side effects of high-dose methylprednisolone (HDMP) therapy on bone metabolism in children with ITP. Twenty-eight children with acute ITP treated with HDMP (30 mg/kg/d for 3 d then 20 mg/kg/d for 4 d) and 28 controls were enrolled in the study. Bone mineral density (BMD), urinary calcium creatinine ratio, urinary levels of deoxypyridinoline, serum levels of calcium, phosphate, parathyroid hormone, total alkaline phosphatase, and bone-specific alkaline phosphatase were measured in both groups. Magnetic resonance imaging of the femoral head was performed only in study group. The mean levels of serum phosphate, parathyroid hormone, urinary deoxypyridinoline, and calcium creatinine ratio were significantly increased in the study group. There was no significant difference between the 2 groups in terms of serum calcium, total alkaline phosphatase, bone-specific alkaline phosphatase, and BMD values. There was a statistically significant negative correlation between cumulative steroid dose and BMD values in study group (r = -0.379). Osteonecrosis was observed in 3 of 25 patients by magnetic resonance imaging. In conclusion, HDMP therapy, especially in high cumulative doses, increases the bone resorption and may cause osteonecrosis in children with ITP.

  4. Comparison of single port and three port laparoscopic splenectomy in patients with immune thrombocytopenic purpura: Clinical comparative study

    PubMed Central

    Barbaros, Umut; Aksakal, Nihat; Tukenmez, Mustafa; Agcaoglu, Orhan; Bostan, Mustafa Sami; Kilic, Berkay; Kalayci, Murat; Dinccag, Ahmet; Seven, Ridvan; Mercan, Selcuk

    2015-01-01

    AIM: Single-port laparoscopic surgery (SILS) has become increasingly popular during the last decades. This prospective study was undertaken to evaluate the feasibility of single-port laparoscopic splenectomy compared with conventional multiport laparoscopic splenectomy. MATERIALS AND METHODS: Between February 2, 2009 and August 29, 2011, a total of 40 patients with the diagnosis of immune thrombocytopenic purpura were included to study. Patients were alienated into two groups according to the procedure type including SILS and conventional multiport splenectomy. RESULTS: There were 19 patients in group 1, and 21 in group 2. Operative time was significantly shorter in group 1 versus group 2 (112.4 ± 13.56 vs 71.2 ±18.1 minutes, respectively, P < 0.05). One patient in group 1 had converted to laparatomy due to preoperative bleeding. Postoperative pain analyses (VAS Score) revealed superiority of SILS in the early post-operative days (P < 0.05). CONCLUSIONS: SILS splenectomy is a safe and effective alternative to standard laparoscopic splenectomy. PMID:26195874

  5. Rituximab in a child with autoimmune thrombotic thrombocytopenic purpura refractory to plasma exchange.

    PubMed

    Narayanan, Parameswaran; Jayaraman, Aparna; Rustagi, Rashi S; Mahadevan, S; Parameswaran, Sreejith

    2012-07-01

    A nine-year-old girl presented with headache, purpura and mild left hemiparesis. Laboratory evaluation revealed thrombotic microangiopathy with ADAMTS13 deficiency, with auto-antibodies to ADAMTS13. She was treated with plasma exchange and steroids, following which she improved transiently, relapsing within 2 months. The relapse was refractory to conventional therapy and rituximab was tried. She had good response to rituximab and has been in remission for the past 12 months. Rituximab may be a promising option for children with acquired TTP refractory to plasma exchange and steroids.

  6. 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

  7. Thrombotic thrombocytopenic purpura in a postoperative patient taking cephalexin responding to plasmapheresis: A case report and review of cephalosporin-induced TTP.

    PubMed

    Patel, Ritu; Amber, Kyle T

    2016-10-01

    The clinical presentation of thrombotic thrombocytopenic purpura (TTP) is often atypical delaying diagnosis and treatment. A number of drugs have been implicated in the development of TTP, including cyclosporine, tacrolimus, clopidogrel, and quinine. To our knowledge, only three cases of cephalosporin-induced TTP have been described, with two of these cases occurring with these use of cephalexin. We herein describe a case of TTP occurring in a postoperative patient taking cephalexin, requiring plasmapheresis. Following plasmapheresis, the patient's mental status and platelet count significantly improved. J. Clin. Apheresis 31:473-475, 2016. © 2015 Wiley Periodicals, Inc. PMID:26274019

  8. Comparison of anti-D immunoglobulin, methylprednisolone, or intravenous immunoglobulin therapy in newly diagnosed pediatric immune thrombocytopenic purpura.

    PubMed

    Celik, Muhittin; Bulbul, Ali; Aydogan, Gönül; Tugcu, Deniz; Can, Emrah; Uslu, Sinan; Dursun, Mesut

    2013-02-01

    This study aimed to evaluate the efficacy, cost, and effects of anti-D immunoglobulin (anti-D Ig), methylprednisolone, or intravenous immunoglobulin (IVIG) therapy on the development of chronic disease in children who are Rh-positive with diagnosed immune thrombocytopenic purpura (ITP). Children with newly diagnosed ITP and platelet count <20,000/mm(3) were prospectively randomized to treatment with anti-D Ig (50 μg/kg), methylprednisolone (2 mg/kg/day), or IVIG (0.4 g/kg/day, 5 days). Sixty children with a mean age of 6.7 years were divided into three equal groups. No difference was observed between platelet counts before treatment and on day 3 of treatment. However, platelet counts at day 7 were lower in the methylprednisolone group than in the IVIG group (P = 0.03). In the anti-D Ig group, hemoglobin and hematocrit levels were significantly lower at the end of treatment (P < 0.05). Chronic ITP developed in 30% of the anti-D Ig group, 35% of the methylprednisolone group, and 25% of the IVIG group, but no significant difference was noted among the groups. The cost analysis revealed that the mean cost of IVIG was 7.4 times higher than anti-D Ig and 10.9 times higher than methylprednisolone. In the treatment of ITP in childhood, one 50 μg/kg dose of anti-D Ig has similar effects to IVIG and methylprednisolone. Among patients who were treated with anti-D Ig, serious anemia was not observed, and the cost of treatment was less than that of IVIG treatment.

  9. Kinetics and sites of destruction of /sup 111/In-oxine-labeled platelets in idiopathic thrombocytopenic purpura: a quantitative study

    SciTech Connect

    Heyns, A.D.; Loetter, M.G.; Badenhorst, P.N.; de Kock, F.; Pieters, H.; Herbst, C.; van Reenen, O.R.; Kotze, H.; Minnaar, P.C.

    1982-04-01

    Kinetics and quantification of the sites of destruction of /sup 111/In-oxine-labeled autologous platelets were investigated in eight patients with idiopathic thrombocytopenic purpura. The mean platelet count was 17 +/- 9 X 10(9)/liter; platelets were separated by differential centrifugation and labeled with 5.6 +/- 2.5 MBq /sup 111/In. Whole body and organ /sup 111/In-platelet distribution was quantitated with a scintillation camera and a computer-assisted imaging system acquisition matrix. Areas of interest were selected with the computer and organ /sup 111/In-radioactivity expressed as a percentage of whole body activity. Mean platelet survival was 49.5 +/- 29.6 hr and the survival curves were exponential. Equilibrium percentage organ /sup 111/In-radioactivity was (normal values in parentheses): spleen 33.7 +/- 8.8 (31.1 +/- 10.2); liver 16.1 +/- 9.5 (13.1 +/- 1.3); thorax 22.8 +/- 3.7 (28.2 +/- 5.6). Percentage organ /sup 111/In-activity at the time when labeled platelets had disappeared from the circulation was: spleen 44.5 +/- 16.4 (40 +/- 16); liver 16.0 +/- 11.5 (32.4 +/- 7.2); thorax 19.7 +/- 6.0 (17.7 +/- 10.3). Thorax activity corresponds to bone marrow radioactivity. Three patterns of platelet sequestration were evident. Three patients had mainly splenic sequestration, two mainly hepatic sequestration, and three diffuse reticuloendothelial system sequestration with a major component of platelets destroyed in the bone marrow. Splenectomy was performed in two patients. The pattern of /sup 111/In-platelet sequestration was not predictive of response of glucocorticoid therapy or indicative of the necessity for splenectomy. Quantitative /sup 111/In-labeled autologous platelet kinetic studies provide a new tool for the investigation of platelet disorders.U

  10. Thrombotic thrombocytopenic purpura: outcome in 24 patients with renal impairment treated with plasma exchange. Canadian Apheresis Study Group.

    PubMed

    Rock, G; Shumak, K; Kelton, J; Blanchette, V S; Buskard, N; Nair, R; Spasoff, R

    1992-10-01

    The Canadian Apheresis Study Group recently completed a randomized clinical trial involving 102 patients with thrombotic thrombocytopenic purpura (TTP), in which treatment with plasma infusion and treatment with plasma exchange were compared. Thirty-three other patients were ineligible or refused to be randomly assigned in the trial. Of the 33 patients, 24 were assessed as ineligible because they would be unable to tolerate the fluid input that would occur if they were randomly assigned to receive plasma infusion. All 24 patients had oliguria and elevated creatinine and/or blood urea nitrogen level. These 24 patients were treated with acetylsalicyclic acid, dipyridamole, and plasma exchange according to the standardized protocol defined in the trial. Blood for tests of factors possibly involved in the pathogenesis of TTP was drawn before exchange and at intervals during and after exchange. The mean platelet count before exchange was 35.5 x 10(9) per L. In 12 of the 24 patients, the platelet count reached 150 x 10(9) per L or greater by 7 days after the initiation of plasma exchange. Three patients responded partially, in that their platelet count increased to at least twice that at presentation, but remained below 150 x 10(9) per L. One patient died during the first week. Of the eight other patients who experienced treatment failure at the 7-day assessment point, six subsequently responded, four while continuing to receive plasma exchange and two after plasma exchange had been discontinued. Of the 15 patients who either responded fully or responded partially by the end of the first cycle, all survived.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. The mechanisms of action of intravenous immunoglobulin and polyclonal anti-d immunoglobulin in the amelioration of immune thrombocytopenic purpura: what do we really know?

    PubMed

    Crow, Andrew R; Lazarus, Alan H

    2008-04-01

    Intravenous immunoglobulin (IVIg) has been used for more than 25 years to treat an ever-increasing number of autoimmune diseases including immune thrombocytopenic purpura. Although the exact mechanism of action of IVIg has remained elusive, many theories have been postulated, including mononuclear phagocytic system blockade/inhibition, autoantibody neutralization by anti-idiotype antibodies, pathogenic autoantibody clearance due to competitive inhibition of the neonatal immunoglobulin Fc receptor, cytokine modulation, complement neutralization, and immune complex formation leading to dendritic cell priming. Polyclonal anti-D immunoglobulin is a polyclonal IVIg product enriched for antibodies directed to the RhD antigen on red blood cells and that has also been successfully used to treat immune thrombocytopenia in RhD(+) patients. The primary theory to explain polyclonal anti-D immunoglobulin function has classically been mononuclear phagocytic system blockade, although modulation of Fcgamma receptor expression and/or immunomodulation may also play a role. Work using a murine model of immune thrombocytopenic purpura to further our understanding of the mechanism of action of these 2 therapeutic agents is a focus of this article.

  12. 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

  13. 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. PMID:27479501

  14. Successful treatment of sepsis-induced disseminated intravascular coagulation in a patient with idiopathic thrombocytopenic purpura using recombinant human soluble thrombomodulin.

    PubMed

    Koga, Tomohiro; Inoue, Daisuke; Okada, Akitomo; Aramaki, Toshiyuki; Yamasaki, Satoshi; Nakashima, Munetoshi; Kawakami, Atsushi; Eguchi, Katsumi

    2011-12-01

    Disseminated intravascular coagulation (DIC) may complicate a variety of disorders that contribute to mortality, particularly those related to bleeding. It is therefore very difficult to manage DIC in patients with known bleeding disorders. We treated a 62-year-old woman with idiopathic thrombocytopenic purpura (ITP) complicated with sepsis-induced DIC. She had been diagnosed with ITP 8 months prior to admission. Laboratory tests showed an elevation of d-dimer and endotoxin, while pyelonephritis was shown by abdominal computed tomography. Escherichia coli was detected by blood culture. Based on these findings, the patient was diagnosed with sepsis-induced DIC due to urinary tract infection. Thrombocytopenia was refractory despite the use of antibiotics and platelet transfusion, but it was promptly improved in response to recombinant human soluble thrombomodulin (rTM). We suggest that rTM provides a new therapeutic strategy for DIC patients with high hemorrhagic risk.

  15. High prevalence of sustained remission of idiopathic thrombocytopenic purpura after Helicobacter pylori eradication: a long-term follow-up study.

    PubMed

    Veneri, Dino; Krampera, Mauro; Franchini, Massimo

    2005-03-01

    We studied the effect of Helicobacter pylori (H. pylori) eradication in 43 consecutive H. pylori-infected patients with idiopathic thrombocytopenic purpura. H. pylori was eradicated with antibiotics in 41 of them (95.3%). The difference between the mean platelet count before and after therapy was statistically significant (54.3 x 10(9)/l vs. 119.1 x 10(9)/l; P < 0.001). A sustained remission was observed in 20 patients (48.8%), after a median follow-up of 31.2 months. None of the patients still infected by H. pylori after therapy reached normal platelet values. The long-term follow-up confirms the efficacy of H. pylori eradication in H. pylori-infected ITP patients.

  16. [A Case of Thrombotic Thrombocytopenic Purpura in a Patient Undergoing FOLFOX6 plus Panitumumab Therapy for Unresectable Recurrent Rectal Cancer with a Rapidly Progressive Course].

    PubMed

    Kato, Kuniyuki; Michishita, Yoshihiro; Oyama, Kenichi; Hatano, Yoshiaki; Nozawa, Tatsuru; Ishibashi, Masahisa; Konda, Ryuichiro; Sasaki, Akira

    2016-01-01

    A 71-year-old male patient began FOLFOX6 plus panitumumab treatment for unresectable recurrent rectal cancer. He developed thrombocytopenia after 2 courses of treatment and therefore a platelet transfusion was performed. The day after transfusion, the patient developed jaundice and hematuria. His lactate dehydrogenase levels had increased and a peripheral blood smear review revealed the presence of schistocytes. Anti-ADAMTS13 antibodies were present, and there was a reduction in ADAMTS13 activity. The patient was diagnosed with thrombotic thrombocytopenic purpura and treated with a plasma exchange. The day after the plasma exchange, his clinical condition rapidly worsened and he died. Thrombocytopenia due to chemotherapy often appears as myelosuppression. If conditions such as jaundice, indirect bilirubinemia, or hematuria appear during the course of chemotherapy, this condition must be considered as a differential diagnosis. PMID:26809542

  17. The expression of IFN-gamma, IL-4, Foxp3 and perforin genes are not correlated with DNA methylation status in patients with immune thrombocytopenic purpura.

    PubMed

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

    2010-01-01

    We investigated the relationship between the expression of IFN-gamma, IL-4, Foxp3 and perforin gene and the methylation status of their promoters in immune thrombocytopenic purpura (ITP) patients. Gene expression and DNA methylation were determined by quantitative PCR and bisulfite genomic sequencing, respectively. The expression of IFN-gamma was higher, while the expression of IL-4 was notably lower in ITP patients when compared with the controls. Most importantly, the Th1/Th2 (IFN-gamma/IL-4) was remarkably higher in ITP patients, showing that the ITP patients were mainly in the Th1 polarization response. Although the methylation rate of CpGs located at -409 of perforin was higher (p = 0.0376) and that of IFN-gamma were relatively higher (p = 0.0582) in ITP, we did not find the negative correlation between the expression of those genes and the methylation of their promoters. PMID:20100010

  18. 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.

  19. Randomized trial comparing intravenous immunoglobulin with methylprednisolone pulse therapy in acute idiopathic thrombocytopenic purpura. Danish I.T.P. Study Group.

    PubMed

    Rosthøj, S; Nielsen, S; Pedersen, F K

    1996-08-01

    Forty-three children with newly diagnosed idiopathic thrombocytopenic purpura (ITP), platelet count (PC) below 20 x 10(9)l-1, and either continued bleeding or failure to show a spontaneous rise in the PC after a 3 day observation period were randomized to treatment with either intravenous immunoglobulin (IVIG) infusions 1 g kg-1 (n = 23) or intravenous methylprednisolone pulse therapy (MPPT) 30 mg kg-1 (n = 20) on two consecutive days. After 72 h, IVIG had induced greater platelet responses (mean PC 188 x 10(9) versus 77 x 10(9)l-1, 2p < 0.001) and raised the PC to a haemostatically safe level above 50 x 10(9)l-1 more frequently (91 versus 50%, one-sided exact p = 0.003). Children responding poorly were then given the alternative treatment in addition. After 6 days, a normal PC of over 150 x 10(9)l-1 had been obtained more frequently in the group given first-line IVIG (70 versus 50%, p = 0.16). The relapse rates during 6 months of follow-up were not significantly different (26 versus 40%, p = 0.26). Cross-over treatment in 11 children with relapse confirmed the superior response to IVIG. The treatment given was restricted to the two initial infusions more often in the IVIG group (70 versus 35%, p = 0.05). These results indicate that IVIG may be preferable to MPPT as the initial treatment for ITP. PMID:8863869

  20. Anti-platelet antibodies associated with the Canale–Smith syndrome bind to the same platelet glycoprotein complexes as those of idiopathic thrombocytopenic purpura patients

    PubMed Central

    GRODZICKY, T; BUSSEL, J B; ELKON, K B

    2002-01-01

    The Canale–Smith syndrome (CSS) is an inherited disease characterized by massive lymphadenopathy, hepatosplenomegaly and systemic autoimmunity to erythrocytes and platelets. Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease in which approximately 60–80% of patients have anti-platelet antibodies directed against specific platelet glycoprotein complexes (GPCs) located on their membrane: GP IIb/IIIa, GPIb/IX, and GPIa/IIa. Almost all (95–100%) of the antibody-positive patients have antibodies directed against GPIIb/IIIa alone, or in combination with other glycoprotein targets. Our objective was to determine the specificities of the anti-platelet antibodies in CSS patients. The detection of anti-platelet antibodies was performed using a commercially available ELISA, the Pak-AUTO (GTI, Brookfield, WI), in which highly purified GPIIb/IIIa, GPIb/IX, and GPIa/IIa are immobilized on microtitre plates, incubated with serum or plasma, and subsequently developed with an antihuman polyclonal immunoglobulin. Of 14 CSS patients tested, 11 (79%) had anti-platelet antibodies in their serum directed toward at least one of the three major GPC, nine (82%) of which were against GPIIb/IIIa alone or in combination. Antibodies detected in the sera of ITP patients had similar specificities. No such antibodies were detected in samples from 25 consecutive normal controls. These results demonstrate that a genetically defined defect in lymphocyte apoptosis results in a humoral autoimmune response with anti-platelet specificities very similar to the common idiopathic form of autoimmune thrombocytopenia. PMID:11876752

  1. DNA methyltransferase 3B (DNMT3B -579G>T) promotor polymorphism and the susceptibility to pediatric immune thrombocytopenic purpura in Egypt.

    PubMed

    Khorshied, Mervat Mamdooh; El-Ghamrawy, Mona Kamal

    2012-12-10

    Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by increased platelet destruction. Although the etiology of ITP remains unclear, it is accepted that both environmental and genetic factors play an important role in the development of the disease. The present study aimed at exploring a novel molecular determinant that may influence the susceptibility and course of ITP in Egyptian children. To achieve our aim, genotyping of DNMT3B -579G>T promotor polymorphism by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. The current study was conducted on 140 ITP patients and 150 age and gender matched healthy controls. The results obtained revealed that DNMT3B -579 TT homotype was significantly higher in ITP patients and conferred almost three fold increased risk of ITP (OR=3.16, 95%CI=1.73-5.79). There was no statistically significant difference between ITP patients with wild or mutant genotypes as regards their clinical or laboratory data. Furthermore, there was no statistical difference in the distribution of DNMT3B -579G>T genotypes between acute and chronic ITP patients. In conclusion, DNMT3B -579G>T promotor polymorphism represents a novel genetic risk factor for ITP but not a predictor for tendency to chronicity in pediatric ITP in Egypt.

  2. Disseminated intravascular coagulation associated with acute hemoglobinemia or hemoglobinuria following Rh(0)(D) immune globulin intravenous administration for immune thrombocytopenic purpura.

    PubMed

    Gaines, Ann Reed

    2005-09-01

    The Food and Drug Administration (FDA) licensed Rh(o)(D) immune globulin intravenous (anti-D IGIV) on March 24, 1995, for treatment of immune thrombocytopenic purpura (ITP). A previous review described data on 15 patients who experienced acute hemoglobinemia or hemoglobinuria following anti-D IGIV administration for ITP or secondary thrombocytopenia. Eleven of those patients also experienced clinically compromising anemia, transfusion with packed red blood cells, renal insufficiency, dialysis, or death. That review suggested that patients receiving anti-D IGIV be monitored for those and other potential complications of hemoglobinemia, particularly disseminated intravascular coagulation (DIC). Through November 30, 2004, the FDA received 6 reports of DIC associated with "acute hemolysis" (or similar terms), 5 of which involved fatalities. The attending or consulting physicians assessed that acute hemolysis or DIC caused or contributed to each death. This review presents the first case series of DIC associated with acute hemoglobinemia or hemoglobinuria following anti-D IGIV administration for ITP. The purpose of this review is to increase awareness among physicians and other health care professionals that DIC may be a rare but potentially severe complication of anti-D IGIV treatment. Increased awareness of DIC as a diagnostic possibility may enable prompt recognition and medical intervention in affected patients.

  3. Efficacy, safety, and dose response of intravenous anti-D immune globulin (WinRho SDF) for the treatment of idiopathic thrombocytopenic purpura in children.

    PubMed

    Freiberg, A; Mauger, D

    1998-01-01

    We analyzed data from 20 children treated for acute or chronic idiopathic (immune) thrombocytopenic purpura (ITP) at a single institution to determine the relationship between dose of intravenous anti-D immune globulin (WinRho SDF; Nabi, Boca Raton, FL), increase in platelet count, and decrease in hemoglobin in the therapy of ITP. Higher doses of anti-D were clearly associated with a greater therapeutic response in the platelet count, with no increase in hemolysis for both acute and chronic ITP. A significant correlation was found between dose and peak increase in platelet count measured in the 14 days following administration. This effect was present for both acute ITP (17 infusions, P = .0001) and chronic ITP (30 infusions, P = .038). Although hemolysis was seen in nearly all infusions, with a median hemoglobin fall of 1.9 g/dL (range, 0 to 4.2), the decrease in hemoglobin was greater than 2.5 for only three infusions, and the largest fall in hemoglobin (4.2) was in a child with an underlying hemolytic anemia. Furthermore, for both acute and chronic ITP there was no relationship between the decrease in hemoglobin and the dose given (P = .22), nor between the increase in platelet count and fall in hemoglobin (P = .27). This analysis supports the use of higher doses of anti-D for the treatment of ITP, and demonstrates the need for a trial of high-dose anti-D (>100 microg/kg) in acute and chronic ITP.

  4. Helicobacter pylori infection and chronic immune thrombocytopenic purpura: long-term results of bacterium eradication and association with bacterium virulence profiles.

    PubMed

    Emilia, Giovanni; Luppi, Mario; Zucchini, Patrizia; Morselli, Monica; Potenza, Leonardo; Forghieri, Fabio; Volzone, Francesco; Jovic, Gordana; Leonardi, Giovanna; Donelli, Amedea; Torelli, Giuseppe

    2007-12-01

    Eradication of Helicobacter pylori may lead to improvement of chronic immune thrombocytopenic purpura (ITP), although its efficacy over time is uncertain. We report the results of H pylori screening and eradication in 75 consecutive adult patients with ITP. We also used molecular methods to investigate lymphocyte clonality and H pylori genotypes in the gastric biopsies from 10 H pylori-positive patients with ITP and 19 H pylori-positive patients without ITP with chronic gastritis. Active H pylori infection was documented in 38 (51%) patients and successfully eradicated in 34 (89%) patients. After a median follow-up of 60 months, a persistent platelet response in 23 (68%) of patients with eradicated infection was observed; 1 relapse occurred. No differences in mucosal B- or T-cell clonalities were observed between patients with ITP and control participants. Of note, the frequency of the H pylori cagA gene (P = .02) and the frequency of concomitant H pylori cagA, vacAs1, and iceA genes (triple-positive strains; P = .015) resulted statistically higher in patients with ITP than in control participants. All asymptomatic H pylori-positive patients with ITP were suffering from chronic gastritis. Our data suggest a sustained platelet recovery in a proportion of patients with ITP by H pylori eradication alone. Overrepresentation of specific H pylori genotypes in ITP suggests a possible role for bacterium-related factors in the disease pathogenesis. PMID:17652264

  5. Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura: a 20-year review from the Southern Network on Adverse Reactions (SONAR).

    PubMed

    Jacob, Sony; Dunn, Brianne L; Qureshi, Zaina P; Bandarenko, Nicholas; Kwaan, Hau C; Pandey, Dilip K; McKoy, June M; Barnato, Sara E; Winters, Jeffrey L; Cursio, John F; Weiss, Ivy; Raife, Thomas J; Carey, Patricia M; Sarode, Ravindra; Kiss, Joseph E; Danielson, Constance; Ortel, Thomas L; Clark, William F; Rock, Gail; Matsumoto, Masanori; Fujimura, Yoshihiro; Zheng, X Long; Chen, Hao; Chen, Fei; Armstrong, John M; Raisch, Dennis W; Bennett, Charles L

    2012-11-01

    Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ.

  6. Low-dose autologous in vitro opsonized erythrocytes. Radioimmune method and autologous opsonized erythrocytes for refractory autoimmune thrombocytopenic purpura in adults

    SciTech Connect

    Ambriz, R.; Munoz, R.; Pizzuto, J.; Quintanar, E.; Morales, M.; Aviles, A.

    1987-01-01

    Adult patients with chronic autoimmune thrombocytopenic purpura (ATP), which proved refractory to various treatments, received a single dose of autologous in vitro opsonized erythrocytes with 100 micrograms of anti-D IgG. In 1983, 30 of these patients were treated with autologous erythrocytes that had been opsonized and labeled with 25 mCi (740 MBq) of technetium Tc 99m; this treatment was designated as the radioimmune method. Favorable responses were noted in 36% of patients so treated. In 1985, another group of 16 patients with refractory ATP received therapy with autologous opsonized erythrocytes (AOPE) and 55% of these patients showed favorable responses. Five (17%) of the patients treated using the radioimmune method attained a complete, long-term (greater than 35 months) remission of their ATP, and five (31%) of the patients treated using AOPE remained in complete remission over 270 days after cessation of therapy. Major complications were not seen. We concluded that the interaction of macrophages with low-dose AOPE is a successful therapeutic approach in ATP refractory to standard treatment.

  7. 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.

  8. 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.

  9. Ticlopidine-, Clopidogrel-, and Prasugrel-Associated Thrombotic Thrombocytopenic Purpura: A 20-Year Review from the Southern Network on Adverse Reactions (SONAR)

    PubMed Central

    Jacob, Sony; Dunn, Brianne L.; Qureshi, Zaina P.; Bandarenko, Nicholas; Kwaan, Hau C.; Pandey, Dilip K.; McKoy, June M.; Barnato, Sara E.; Winters, Jeffrey L.; Cursio, John F.; Weiss, Ivy; Raife, Thomas J.; Carey, Patricia M.; Sarode, Ravindra; Kiss, Joseph E.; Danielson, Constance; Ortel, Thomas L.; Clark, William F.; Rock, Gail; Matsumoto, Masanori; Fujimura, Yoshihiro; Zheng, X. Long; Chen, Hao; Chen, Fei; Armstrong, John M.; Raisch, Dennis W.; Bennett, Charles L.

    2013-01-01

    Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ. PMID:23111862

  10. Thrombotic thrombocytopenic purpura following salvage chemotherapy with paclitaxel, ifosfamide and cisplatin in a patient with a refractory germ cell tumor: A case report and review of the literature

    PubMed Central

    ULAS, ARIFE; SILAY, KAMILE; AKINCI, SEMA; AKINCI, MUHAMMED BULENT; SENDUR, MEHMET ALI; DEDE, DIDEM SENER; POLAT, YUNUS HALIL; YALCIN, BULENT

    2015-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy that is characterized by microvascular thrombosis, thrombocytopenia, hemolysis and end organ damage. An extensive variety of drugs, including certain chemotherapeutic agents, have been associated with TTP. However, paclitaxel, cisplatin and ifosfamide regimen (TIP)-induced TTP has not previously been described. The present study reports the case of a 43-year-old patient with a refractory testicular germ cell tumor who developed acute TTP during TIP chemotherapy. Following the third cycle of TIP chemotherapy, the patient developed fever, anemia, thrombocytopenia and confusion. A diagnosis of TTP was established. Plasmapheresis was initiated as daily treatment in the first week, then continued every other day for 4 weeks. TIP chemotherapy was discontinued. The patient's clinical and neurological symptoms improved markedly after a week. Renal function and hemolysis improved, and the patient was discharged in a stable condition. The patient did not develop any complications and has been in remission for 5 months. The Naranjo adverse drug reaction probability scale indicated a likely association between TTP and the TIP chemotherapy regimen in this patient. This case is also investigated with regard to the associated literature to increase the awareness of TTP following chemotherapy. PMID:26622823

  11. Acute onset hemoglobinemia and/or hemoglobinuria and sequelae following Rh(o)(D) immune globulin intravenous administration in immune thrombocytopenic purpura patients.

    PubMed

    Gaines, A R

    2000-04-15

    Rh(o)(D) immune globulin intravenous (anti-D IGIV) was licensed by the United States Food and Drug Administration (FDA) in March 1995 to treat patients with immune thrombocytopenic purpura (ITP). Anti-D IGIV induces extravascular hemolysis, an expected adverse reaction that is consistent with the presumed mechanism of action. Between licensure and April 1999, the FDA received 15 reports of hemoglobinemia and/or hemoglobinuria following anti-D IGIV administration that met the case definition for this review. The mechanism responsible for hemoglobinemia and/or hemoglobinuria is unexplained. Review of these reports was prompted by the seriousness and the unexpectedness of treatment-associated sequelae experienced by 11 patients. Of these patients, 7 developed sufficient onset or exacerbation of anemia that orders were written for packed red blood cell transfusions, although only 6 patients were transfused. Eight patients experienced the onset or exacerbation of renal insufficiency, and 2 patients underwent dialysis. One patient died due to complications of exacerbated anemia. Six patients experienced 2 to 3 sequelae. Absent validated incidence data, a 1.5% estimated incidence rate from published clinical trial data and a 0.1% estimated reporting rate from FDA and drug utilization data were calculated for reported cases of hemoglobinemia and/or hemoglobinuria. This review presents the first case series of anti-D-IGIV-associated hemoglobinemia and/or hemoglobinuria and provides pretreatment and posttreatment clinical and laboratory findings of the case series patients. The primary purpose of this review is to increase awareness of this potentially serious occurrence among physicians and health care professionals who manage ITP patients treated with anti-D IGIV, thereby enabling prompt recognition and treatment of sequelae. (Blood. 2000;95:2523-2529)

  12. 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

  13. The D173G mutation in ADAMTS-13 causes a severe form of congenital thrombotic thrombocytopenic purpura. A clinical, biochemical and in silico study.

    PubMed

    Lancellotti, Stefano; Peyvandi, Flora; Pagliari, Maria Teresa; Cairo, Andrea; Abdel-Azeim, Safwat; Chermak, Edrisse; Lazzareschi, Ilaria; Mastrangelo, Stefano; Cavallo, Luigi; Oliva, Romina; De Cristofaro, Raimondo

    2016-01-01

    Congenital thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy, inherited with autosomal recessive mode as a dysfunction or severe deficiency of ADAMTS-13 (A Disintegrin And Metalloprotease with ThromboSpondin 1 repeats Nr. 13), caused by mutations in the ADAMTS-13 gene. About 100 mutations of the ADAMTS-13 gene were identified so far, although only a few characterised by in vitro expression studies. A new Asp to Gly homozygous mutation at position 173 of ADAMTS-13 sequence was identified in a family of Romanian origin, with some members affected by clinical signs of TTP. In two male sons, this mutation caused a severe (< 3%) deficiency of ADAMTS-13 activity and antigen level, associated with periodic thrombocytopenia, haemolytic anaemia and mild mental confusion. Both parents, who are cousins, showed the same mutation in heterozygous form. Expression studies of the mutant ADAMTS-13, performed in HEK293 cells, showed a severe decrease of the enzyme's activity and secretion, although the protease was detected inside the cells. Molecular dynamics found that in the D173G mutant the interface area between the metalloprotease domain and the disintegrin-like domain significantly decreases during the simulations, while the proline-rich 20 residues linker region (LR, 285-304) between them undergoes extensive conformational changes. Inter-domain contacts are also significantly less conserved in the mutant compared to the wild-type. Both a decrease of the inter-domain contacts along with a substantial conformational rearrangement of LR interfere with the proper maturation and folding of the mutant ADAMTS-13, thus impairing its secretion.

  14. Novel Recombinant Glycosylphosphatidylinositol (GPI)-Anchored ADAMTS13 and Variants for Assessment of Anti-ADAMTS13 Autoantibodies in Patients with Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Li, Dengju; Xiao, Juan; Paessler, Michele; Zheng, X. Long

    2011-01-01

    Summary Immunoglobulin Gs (IgGs) against ADAMTS13 are major causes of acquired (idiopathic) thrombotic thrombocytopenic purpura (TTP). We report here a novel cell-based assay using glycosylphosphatidylinositol (GPI)-anchored ADAMTS13 or variants expressed on cell membrane for assessment of autoantibodies in patients with TTP. We showed that IgGs from all 26 patients with acquired TTP bound to cells expressing a GPI anchored full-length ADAMTS13 (gFL) and a variant truncated after the spacer domain (gS). Also, IgGs from 25/26 (96.7%) of these TTP patients bound to cells expressing a GPI-anchored C-terminal fragment, TSP1 2-8 plus CUB (gT2C). In contrast, none of the 20 healthy blood donors showed detectable binding of their IgGs to the cells expressing gFL, gS, and gT2C. A moderate, but statistically significant correlation was observed between plasma concentrations of anti-ADAMTS13 IgG and positive cells expressing gFL (r=0.65), gS (r=0.67), and gT2C (r=0.42). These results suggest that the microtiter-plate assay and the cell-based assay may detect differential antigenic epitopes. Moreover, antigens clustered on cell membrane may enhance antibody binding affinity, thereby increasing analytical sensitivity. Finally, our assay was able to determine kinetic changes of plasma levels of anti-ADAMTS13 IgGs in TTP patients during plasma therapy. Together, our findings suggest that the novel cell-based assay may be applicable for rapid identification and mapping of anti-ADAMTS13 autoantibodies in patients with acquired TTP. PMID:21901237

  15. Inhibitory autoantibodies against ADAMTS-13 in patients with thrombotic thrombocytopenic purpura bind ADAMTS-13 protease and may accelerate its clearance in vivo

    PubMed Central

    SHELAT, S. G.; SMITH, P.; AI, J.; ZHENG, X. L.

    2008-01-01

    Summary Background Many patients with acquired thrombotic thrombocytopenic purpura (TTP) harbor autoantibodies that may bind and/or inhibit ADAMTS-13 proteolytic activity and accelerate its clearance in vivo. Methods To test this hypothesis, we determined ADAMTS-13 activity and antigen levels in parallel plasma samples from patients clinically diagnosed with TTP. Collagen binding, GST-VWF73 and FRETS-VWF73 assays were used to determine ADAMTS-13 activity and to detect inhibitory autoantibodies. Enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation plus Western blotting (IP/WB) were used to detect total anti-ADAMTS-13 IgG (inhibitory and non-inhibitory). Results Among 40 patients with TTP (21 idiopathic and 19 non-idiopathic), inhibitory autoantibodies were detected (by FRETS-VWF73) in 52% of idiopathic and 0% of non-idiopathic TTP patients. In contrast, non-inhibitory IgG autoantibodies were detected in 29% of idiopathic and 50% of non-idiopathic TTP patients. The concentration of inhibitory IgG autoantibody in idiopathic TTP patients was significantly higher than that of non-inhibitory IgG in either idiopathic or non-idiopathic TTP patients. Idiopathic TTP patients demonstrated significantly reduced ADAMTS-13 activity compared with non-idiopathic patients, but only slightly lower ADAMTS-13 antigen levels. Interestingly, patients with inhibitory autoantibodies exhibited significantly lower ADAMTS-13 antigen levels than those with only non-inhibitory IgG autoantibodies or no autoantibody. Serial plasma exchanges increased levels of ADAMTS-13 activity and antigen concurrently in patients with inhibitory autoantibodies. Conclusion The identification of severe ADAMTS-13 deficiency and autoantibodies or inhibitors appears to be assay-dependent; the inhibitory IgG autoantibodies, in addition to binding and inhibiting ADAMTS-13 proteolytic activity, may accelerate ADAMTS-13 clearance in vivo. PMID:16879212

  16. 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

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

    2011-09-01

    On 11(th) 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 50×10(9)/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

  17. Analysis of B- and T-cell clonality and HLA class II alleles in patients with idiopathic thrombocytopenic purpura: correlation with Helicobacter pylori infection and response to eradication treatment.

    PubMed

    Veneri, Dino; De Matteis, Giovanna; Solero, Pietro; Federici, Francesca; Zanuso, Carla; Guizzardi, Elisabetta; Arena, Silvia; Gaio, Monica; Pontiero, Patrizia; Ricetti, Maria M; Franchini, Massimo

    2005-08-01

    Many authors have recently found a positive correlation between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP), the most common autoimmune hematological disorder. In order to clarify the pathogenic mechanism of H. pylori-associated ITP, we have investigated 52 consecutive ITP adult patients for Helicobacter pylori infection, B- and T-cell clonality and HLA class II alleles. Thirty-four ITP patients (65.4%) were infected by H. pylori and bacterium eradication was accompanied by a long-term platelet response in 17 (53.1%) of them. A B-cell clonality was found in three patients (5.8%, two patients H. pylori-negative and one patient H. pylori-positive). The ITP patients with H. pylori infection showed a HLA-DRB1*11, *14 and -DQB1*03 frequencies significantly higher and a -DRB1*03 frequency significantly lower than in H. pylori-negative patients. Moreover, an HLA-DQB1*03 pattern was associated with a higher probability of platelet response to eradication treatment. If our study documents the efficacy of eradication treatment in H. pylori-infected ITP patients, it may also help to identify different subgroups of ITP patients with probably different pathogeneses of thrombocytopenia and, finally, different responses to eradication treatment.

  18. A phase-II sequential case-series study of all patients presenting to four plasma exchange centres with presumed relapsed/refractory thrombotic thrombocytopenic purpura treated with rituximab.

    PubMed

    Clark, William F; Rock, Gail; Barth, David; Arnold, Donald M; Webert, Kathyrn E; Yenson, Paul R; Kelton, John G; Li, Lihua; Foley, Steven R

    2015-07-01

    The primary objective of this phase II study was to evaluate the efficacy of rituximab in the management of adult patients with physician-diagnosed presumed thrombotic thrombocytopenic purpura (TTP); relapsed or refractory. We conducted a multicentre study in four Canadian hospital-based apheresis units. Forty patients with presumed TTP (20 refractory and 20 relapsing) were sequentially enrolled and all received rituximab in a standardized manner. A complete response was documented in 14 of 19 refractory patients by week 8 and 15/16 were alive and in remission at 52 weeks (one patient was lost to follow-up, one was a non-responder, and three died). Among relapsing patients, 16/18 had a complete response at week 8 and 18/18 at week 52 (one patient lost to follow-up and one withdrew). At 1 year, all relapsing and 85% of refractory patients survived. Of 38/40 patients who had ADMATS13 testing at study entry, 13/19 refractory and 10/19 relapsing patients had ADAMTS13 < 10% (typical TTP); whereas 6/19 refractory and 9/19 relapsing cases had ADAMTS13 > 10% (other thrombotic microangiopathy; TMA). Refractory-typical TTP in contrast to refractory-other TMA and all relapsing patients treated with plasma exchange and rituximab, were less likely to be responsive and more likely to die or relapse. PMID:25855259

  19. 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

  20. Effects of cytotoxin-associated gene A (CagA) positive Helicobacter pylori infection on anti-platelet glycoprotein antibody producing B cells in patients with primary idiopathic thrombocytopenic purpura (ITP)

    PubMed Central

    Cheng, Yuan-Shan; Kuang, Li-Ping; Zhuang, Chun-Lan; Jiang, Jia-Dian; Shi, Man

    2015-01-01

    Objective: To explore the effects of cytotoxin-associated gene A (CagA) positive Helicobacter pylori (H. pylori or HP) infection on circulating B cells producing specific platelet glycoprotein antibodies and the association between therapeutic outcomes in primary idiopathic thrombocytopenic purpura (ITP) patients. Methods: A total of 76 newly diagnosed primary ITP patients were included in the study which was conducted at the first affiliated hospital of Shantou University Medical college, in Shantou city China, between January 2013 and January 2014. These patients were tested for H. pylori infection by 13C urea breath test and for anti-CagA antibody in H. pylori positive cases by enzyme-linked immunosorbent assay (ELISA) method. Anti-GPIb and anti-GPIIb/IIIa antibody-producing B cells were measured using an enzyme-linked immunospot (ELISPOT) assay in all ITP patients and 30 controls. Anti-nuclear antibody (ANA) was also detected in ITP patients. Results: The numbers of anti-GPIIb/IIIa antibody-producing B cells in HP+CagA+ patients were higher than in HP+CagA- or HP- patients. However, anti-GPIb antibody-producing B cells were found higher in HP- patients. Analysis of treatment outcomes showed that a therapeutic response was more likely in patients presenting anti-GPIIb/IIIa B cells, but the poor response was found to be associated with anti-GPIb B cells and ANA presences. Conclusion: CagA antigen of H. pylori may induce anti-GPIIb/IIIa antibodies production by a molecular mimicry mechanism. Anti-GPIIb/IIIa and anti-GPIb antibody producing B Cells detection is useful for predicting treatment effects of primary ITP. PMID:25878627

  1. Foetal and neonatal alloimmune thrombocytopaenia

    PubMed Central

    Kaplan, Cecile

    2006-01-01

    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 1/1 000 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. PMID:17032445

  2. 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 ...

  3. [Fetal-neonatal alloimmune thrombocytopenia].

    PubMed

    Muñiz-Díaz, E; Ginovart Galiana, G

    2003-06-01

    Fetal-neonatal alloimmune thrombocytopenia is the commonest cause of severe thrombocytopenia in the newborn. This disorder is due to the destruction of fetal platelets by a maternal platelet-specific antibody caused by fetal-maternal incompatibility. The most serious complication is intracranial hemorrhage (10-30 % of newborns), which may cause death (10 % of the reported cases) or irreversible neurological sequelae (20 %). The diagnosis is usually made after birth when most affected neonates have petechiae, purpura or overt bleeding. The degree of severity varies according to platelet count. Current methods allow detection of maternal platelet alloantibodies (usually HPA-1a). Clinical grounds and the exclusion of other causes of neonatal thrombocytopenia are required to establish an accurate diagnosis. Recurrence of this disease is very high and has prompted clinicians to develop antenatal prophylactic programs in subsequent pregnancies. However, the optimal treatment of at-risk pregnancies remains controversial. The early diagnosis of this process allows effective therapy based on the infusion of compatible platelets and IgG immunoglobulins when hemorrhage is not obvious. Antenatal management of subsequent pregnancies can prevent recurrence of thrombocytopenia and intracranial hemorrhage. The aim of this review is to draw pediatricians' attention to the importance of this probably under-diagnosed disease in which early diagnosis can prevent potentially severe complications.

  4. 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

  5. Progressive Pigmentary Purpura

    MedlinePlus

    ... Category: Share: Yes No, Keep Private Progressive Pigmentary Purpura Share | Progressive pigmentary purpura (we will call it PPP) is a group ... conditions ( Schamberg's disease , Lichenoid dermatitis of Gourgerot-Blum, purpura annularis telangiectodes of Majocchi and Lichen aureus). Schamberg's ...

  6. Henoch-Schonlein Purpura

    MedlinePlus

    ... Types of Vasculitis / Henoch-Schönlein Purpura Henoch-Schönlein Purpura Fast Facts First Description Who gets Henoch-Schönlein ... to serious kidney involvement. Who gets Henoch-Schönlein Purpura (the “typical” patient)? Usually, HSP affects a child ...

  7. Fetal/Neonatal Alloimmune Thrombocytopenia: Pathogenesis, Diagnostics and Prevention.

    PubMed

    Brojer, Ewa; Husebekk, Anne; Dębska, Marzena; Uhrynowska, Małgorzata; Guz, Katarzyna; Orzińska, Agnieszka; Dębski, Romuald; Maślanka, Krystyna

    2016-08-01

    Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a relatively rare condition (1/1000-1/2000) that was granted orphan status by the European Medicines Agency in 2011. Clinical consequences of FNAIT, however, may be severe. A thrombocytopenic fetus or new-born is at risk of intracranial hemorrhage that may result in lifelong disability or death. Preventing such bleeding is thus vital and requires a solution. Anti-HPA1a antibodies are the most frequent cause of FNAIT in Caucasians. Its pathogenesis is similar to hemolytic disease of the newborn (HDN) due to anti-RhD antibodies, but is characterized by platelet destruction and is more often observed in the first pregnancy. In 75 % of these women, alloimmunization by HPA-1a antigens, however, occurs at delivery, which enables development of antibody-mediated immune suppression to prevent maternal immunization. As for HDN, the recurrence rate of FNAIT is high. For advancing diagnostic efforts and treatment, it is thereby crucial to understand the pathogenesis of FNAIT, including cellular immunity involvement. This review presents the current knowledge on FNAIT. Also described is a program for HPA-1a screening in identifying HPA-1a negative pregnant women at risk of immunization. This program is now performed at the Institute of Hematology and Transfusion Medicine in cooperation with the Department of Obstetrics and Gynecology of the Medical Centre of Postgraduate Education in Warsaw as well as the UiT The Arctic University of Norway. PMID:26564154

  8. Safety and Efficacy Study of Romiplostim to Treat ITP in Pediatric Subjects

    ClinicalTrials.gov

    2016-01-13

    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

  9. Fetal and Neonatal Alloimmune Thrombocytopenia

    PubMed Central

    Espinoza, J P; Caradeux, J; Norwitz, Errol R; Illanes, S E

    2013-01-01

    Fetomaternal alloimmune thrombocytopenia (FMAIT) is a relatively uncommon disease, but is the leading cause of severe thrombocytopenia in the newborn. It can cause severe complications and long-term disabilities. The main objective of screening is to reduce both the morbidity and mortality associated with FMAIT, primarily by preventing intracranial hemorrhage. However, controversy surrounds both pre- and antenatal management. This article discusses pathogenesis, screening, diagnosis, and both pre- and neonatal management of FMAIT. PMID:23687553

  10. [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.

  11. 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.

  12. 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

    2015-01-01

    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. PMID:26610057

  13. Exercise-induced purpura.

    PubMed

    Leung, A K; Grant, R M; Truscott, R

    1990-09-01

    A 11-year-old boy developed purpura on the back and chest on more than 5 occasions following vigorous exercise. This eruption should be added to the list of differential diagnosis of the dermatosis experienced by athletes.

  14. Fetal and Neonatal Alloimmune Thrombocytopenia

    PubMed Central

    CONSTANTINESCU, Simona; ZAMFIRESCU, Vlad; VLADAREANU, Prof. Radu

    2012-01-01

    ABSTRACT Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the commonest cause of severe neonatal thrombocytopenia. FNAIT is usually suspected in neonates with bleeding or severe, unexplained, and/or isolated postnatal thrombocytopenia. Affected fetuses should be managed in referral centers with experience in the ante-natal management of FNAIT. Close collaboration is required between specialists in fetal medicine, obstetrics, hematology/transfusion medicine, and pediatrics. The mother and her partner should be provided with detailed information about FNAIT and its potential clinical consequences, and the benefits and risks of different approaches to ante-natal management. There has been huge progress in the ante-natal management of FNAIT over the last 20 years. However, the ideal effective treatment without significant side effects to the mother or fetus has yet to be determined. Key issues: Fetal and neonatal alloimmune thrombocytopenia is a condition that is underdiagnosed. Immunization seldom occurs in the first pregnancy. Immunization takes place in association with delivery in most cases. Anti-HPA-1a level is a predictor for the severity of thrombocytopenia. PMID:23482913

  15. Thrombocytopenic syndromes in pregnancy.

    PubMed

    Yan, Matthew; Malinowski, Ann K; Shehata, Nadine

    2016-03-01

    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

  16. A new approach to detect reticulated platelets stained with thiazole orange in thrombocytopenic patients.

    PubMed

    Fujii, T; Shimomura, T; Fujimoto, T T; Kimura, A; Fujimura, K

    2000-03-15

    Recent studies have shown that reticulated platelets stained with Thiazole Orange (T.O.) are useful markers for thrombopoiesis. The percentage of T.O. positive platelets tends to be inconsistent using the original method, especially when the peripheral blood platelet count is very low. We measured T.O. positive platelet levels in patients with severe thrombocytopenic disorders, using concentrated platelet-rich plasma and carrying out a two-color analysis involving T.O. and an anti-glycoprotein IIb/IIIa monoclonal antibody. This method allowed us to obtain consistent T.O. positive platelet rates in patients with thrombocytopenia whose platelet counts were below 20 approximately 30x10(9)/l. By this method, the T.O. positive rates of platelets from idiopathic thrombocytopenic purpura patients were found to be significantly higher than in the control group. The T.O. positive rates of other thrombocytopenic disorders were similar to those of the control group. These results are consistent with those previously reported. We conclude that our technique of measuring of T.O. positive platelets using platelet-rich plasma is useful for analyzing severe thrombocytopenic disorders.

  17. 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.

  18. 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)

  19. Hemin controls T cell polarization in sickle cell alloimmunization

    PubMed Central

    Zhong, Hui; Bao, Weili; Friedman, David; Yazdanbakhsh, Karina

    2014-01-01

    Patients with sickle cell disease (SCD) often require transfusions to treat and prevent worsening anemia and other SCD complications. However, transfusions can trigger alloimmunization against transfused red blood cells (RBCs) with serious clinical sequelae. Risk factors for alloimmunization in SCD remain poorly understood. We recently reported altered regulatory T cell (Treg) and T helper (Th) responses with higher circulating Th1 (IFN-γ+) cytokines in chronically transfused SCD patients with alloantibodies as compared to those without alloantibodies. Since monocytes play a critical role in polarization of T cell subsets and participate in clearance of transfused RBCs, we tested the hypothesis that in response to RBC breakdown product, hemin, monocyte control of T cell polarization will differ between alloimmunized and non-alloimmunized SCD patients. Exogenous hemin induced Treg polarization in purified T-cell-monocyte cocultures from healthy volunteers through monocyte anti-inflammatory heme degrading enzyme HO-1. Importantly, hemin primarily through its effect on CD16+ monocytes induced an anti-inflammatory (higher Treg/lower Th1) polarization state in non-alloimmunized SCD group, whereas it had little effect in the alloimmunized group. Non-alloimmunized SCD CD16+ monocytes expressed higher basal levels of HO-1. Furthermore, IL-12, which contributed to a pro-inflammatory polarization state (low Treg/high Th1) in SCD, was dampened in hemin-treated stimulated monocytes from non-alloimmunized SCD patients, but not in alloimmunized group. These data suggest that unlike alloimmunized patients, non-alloimmunized SCD CD16+ monocytes in response to transfused RBC breakdown products promote an anti-inflammatory state that is less conductive to alloimmunization. PMID:24879794

  20. Fatal purpura fulminans and Waterhouse-Friderichsen syndrome from fulminant Streptococcus pneumoniae sepsis in an asplenic young adult.

    PubMed

    Hale, Andrew J; LaSalvia, Mary; Kirby, James E; Kimball, Allison; Baden, Rachel

    2016-01-01

    Asplenic patients are at increased risk for sepsis and fulminant infection. Sepsis in these patients is typically secondary to encapsulated bacteria, with Streptococcus pneumoniae being the most frequent pathogen. Rare complications of severe sepsis include purpura fulminans and bilateral adrenal hemorrhage (Waterhouse-Friderichsen syndrome). We present the case of a 36-year-old woman, healthy except for splenectomy years prior for idiopathic thrombocytopenic purpura treatment, who presented with fever. Upon presentation to our hospital, three hours after symptoms onset, she had purpura fulminans and shock. Despite timely antimicrobials and maximal resuscitative efforts, her disease progressed and she expired 12 hours after symptoms onset. Autopsy revealed bilateral adrenal hemorrhage; acute adrenal crisis likely contributed to her refractory shock. Prior to her presentation, she had not received guideline-based post-splenectomy care. Sepsis in asplenic patients can be fulminant and rapidly fatal. Streptococcus pneumoniae remains the most frequent cause, despite decreasing rates in recent years related to widespread pneumococcal vaccination. Guideline-based vaccinations and "pill-in-pocket" therapy can be life-saving for asplenic patients. Purpura fulminans represents an extreme manifestation of disseminated intravascular coagulation, is more common in asplenic patients, and portends a poor prognosis. Waterhouse-Friderichsen syndrome can be seen concurrently with purpura fulminans and further portends a poor prognosis; pre-mortem diagnosis requires a high index of suspicion. PMID:27583208

  1. Neonatal alloimmune thrombocytopenia: pathogenesis, diagnosis and management

    PubMed Central

    Peterson, Julie A.; McFarland, Janice G.; Curtis, Brian R.; Aster, Richard H.

    2014-01-01

    Summary Neonatal alloimmune thrombocytopenia, (NAIT) is caused by maternal antibodies raised against alloantigens carried on fetal platelets. Although many cases are mild, NAIT is a significant cause of morbidity and mortality in newborns and is the most common cause of intracranial haemorrhage in full-term infants. In this report, we review the pathogenesis, clinical presentation, laboratory diagnosis and prenatal and post-natal management of NAIT and highlight areas of controversy that deserve the attention of clinical and laboratory investigators. PMID:23384054

  2. Advances in alloimmune thrombocytopenia: perspectives on current concepts of human platelet antigens, antibody detection strategies, and genotyping

    PubMed Central

    Hayashi, Tomoya; Hirayama, Fumiya

    2015-01-01

    Alloimmunisation to platelets leads to the production of antibodies against platelet antigens and consequently to thrombocytopenia. Numerous molecules located on the platelet surface are antigenic and induce immune-mediated platelet destruction with symptoms that can be serious. Human platelet antigens (HPA) cause thrombocytopenias, such as neonatal alloimmune thrombocytopenia, post-transfusion purpura, and platelet transfusion refractoriness. Thirty-four HPA are classified into 28 systems. Assays to identify HPA and anti-HPA antibodies are critically important for preventing and treating thrombocytopenia caused by anti-HPA antibodies. Significant progress in furthering our understanding of HPA has been made in the last decade: new HPA have been discovered, antibody-detection methods have improved, and new genotyping methods have been developed. We review these advances and discuss issues that remain to be resolved as well as future prospects for preventing and treating immune thrombocytopenia. PMID:26057488

  3. Henoch-Schönlein Purpura

    MedlinePlus

    ... PDF, 345 KB)​​​​​ Alternate Language URL Henoch-Schönlein Purpura Page Content On this page: What is Henoch- ... to Remember Clinical Trials What is Henoch-Schönlein purpura (HSP)? Henoch-Schönlein purpura is a disease that ...

  4. 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.

  5. Case report: solid-phase platelet crossmatching to support the alloimmunized patient.

    PubMed

    O'Connell, B A

    1995-01-01

    Platelet crossmatching by a solid-phase red cell adherence assay was used to provide compatible platelets for two alloimmunized patients with leukemia. In this study, a successful platelet transfusion was defined as giving a corrected count increment (CCI) of >7,500 in a posttransfusion sample. For patient A, a total of 205 random platelet concentrates (PCs) were crossmatched. Eleven were considered compatible. These 11 PCs were transfused during five transfusion episodes. Four of the five transfusions produced CCIs of >7,500 and were considered successful. Individually, eight of the eleven units were considered in vivo compatible, and five of the eight donors of these units agreed to become apheresis donors. Platelets from three of these five apheresis donors gave CCIs of >7,500. For patient B, 1,074 random PCs were crossmatched, and 332 were considered compatible. These units were administered during 78 different transfusions. Seventy-one of these transfusion episodes resulted in CCIs of >7,500. In addition, 19 apheresis donors were identified by platelet crossmatching, and they provided platelets for 38 of 39 successful transfusions for Patient B. Platelet crossmatching should therefore be considered when a blood bank is called upon to support a refractory thrombocytopenic patient.

  6. Modulation of Alloimmunity by Heat Shock Proteins.

    PubMed

    Borges, Thiago J; Lang, Benjamin J; Lopes, Rafael L; Bonorino, Cristina

    2016-01-01

    The immunological mechanisms that evolved for host defense against pathogens and injury are also responsible for transplant rejection. Host rejection of foreign tissue was originally thought to be mediated mainly by T cell recognition of foreign MHC alleles. Management of solid organ transplant rejection has thus focused mainly on inhibition of T cell function and matching MHC alleles between donor and host. Recently, however, it has been demonstrated that the magnitude of the initial innate immune responses upon transplantation has a decisive impact on rejection. The exact mechanisms underlying this phenomenon have yet to be characterized. Ischemic cell death and inflammation that occur upon transplantation are synonymous with extracellular release of various heat shock proteins (Hsps), many of which have been shown to have immune-modulatory properties. Here, we review the impact of Hsps upon alloimmunity and discuss the potential use of Hsps as accessory agents to improve solid organ transplant outcomes. PMID:27555846

  7. Modulation of Alloimmunity by Heat Shock Proteins

    PubMed Central

    Borges, Thiago J.; Lang, Benjamin J.; Lopes, Rafael L.; Bonorino, Cristina

    2016-01-01

    The immunological mechanisms that evolved for host defense against pathogens and injury are also responsible for transplant rejection. Host rejection of foreign tissue was originally thought to be mediated mainly by T cell recognition of foreign MHC alleles. Management of solid organ transplant rejection has thus focused mainly on inhibition of T cell function and matching MHC alleles between donor and host. Recently, however, it has been demonstrated that the magnitude of the initial innate immune responses upon transplantation has a decisive impact on rejection. The exact mechanisms underlying this phenomenon have yet to be characterized. Ischemic cell death and inflammation that occur upon transplantation are synonymous with extracellular release of various heat shock proteins (Hsps), many of which have been shown to have immune-modulatory properties. Here, we review the impact of Hsps upon alloimmunity and discuss the potential use of Hsps as accessory agents to improve solid organ transplant outcomes. PMID:27555846

  8. Modulation of Alloimmunity by Heat Shock Proteins.

    PubMed

    Borges, Thiago J; Lang, Benjamin J; Lopes, Rafael L; Bonorino, Cristina

    2016-01-01

    The immunological mechanisms that evolved for host defense against pathogens and injury are also responsible for transplant rejection. Host rejection of foreign tissue was originally thought to be mediated mainly by T cell recognition of foreign MHC alleles. Management of solid organ transplant rejection has thus focused mainly on inhibition of T cell function and matching MHC alleles between donor and host. Recently, however, it has been demonstrated that the magnitude of the initial innate immune responses upon transplantation has a decisive impact on rejection. The exact mechanisms underlying this phenomenon have yet to be characterized. Ischemic cell death and inflammation that occur upon transplantation are synonymous with extracellular release of various heat shock proteins (Hsps), many of which have been shown to have immune-modulatory properties. Here, we review the impact of Hsps upon alloimmunity and discuss the potential use of Hsps as accessory agents to improve solid organ transplant outcomes.

  9. Alloimmunization in multitransfused liver disease patients: Impact of underlying disease

    PubMed Central

    Bajpai, Meenu; Gupta, Shruti; Jain, Priyanka

    2016-01-01

    Introduction: Transfusion support is vital to the management of patients with liver diseases. Repeated transfusions are associated with many risks such as transfusion-transmitted infection, transfusion immunomodulation, and alloimmunization. Materials and Methods: A retrospective data analysis of antibody screening and identification was done from February 2012 to February 2014 to determine the frequency and specificity of irregular red-cell antibodies in multitransfused liver disease patients. The clinical and transfusion records were reviewed. The data was compiled, statistically analyzed, and reviewed. Results: A total of 842 patients were included in our study. Alloantibodies were detected in 5.22% of the patients. Higher rates of alloimmunization were seen in patients with autoimmune hepatitis, cryptogenic liver disease, liver damage due to drugs/toxins, and liver cancer patients. Patients with alcoholic liver disease had a lower rate of alloimmunization. The alloimmunization was 12.7% (23/181) in females and 3.17% (21/661) in males. Antibodies against the Rh system were the most frequent with 27 of 44 alloantibodies (61.36%). The most common alloantibody identified was anti-E (11/44 cases, 25%), followed by anti-C (6/44 cases, 13.63%). Conclusion: Our findings suggest that alloimmunization rate is affected by underlying disease. Provision of Rh and Kell phenotype-matched blood can significantly reduce alloimmunization. PMID:27605851

  10. Fetal alloimmune thrombocytopenia and maternal intravenous immunoglobulin infusion

    PubMed Central

    Giers, Günther; Wenzel, Folker; Stockschläder, Markus; Riethmacher, Regina; Lorenz, Horst; Tutschek, Boris

    2010-01-01

    Background Different therapeutic approaches have been used in fetal-neonatal alloimmune thrombocytopenia, but many centers administer immunoglobulin G infusions to the pregnant woman. We studied the effect of maternal antenatal immunoglobulin infusions on fetal platelet counts in pregnancies with fetal alloimmune thrombocytopenia. Design and Methods We retrospectively analyzed the clinical courses of fetuses with fetal alloimmune thrombocytopenia whose mothers were treated with immunoglobulin G infusions in a single center between 1999 and 2005. In a center-specific protocol, weekly maternal immunoglobulin G infusions were given to 25 pregnant women with previously affected neonates and four women with strong platelet antibodies, but no previous history of fetal alloimmune thrombocytopenia; before each infusion diagnostic fetal blood sampling was performed to determine fetal platelet counts and immunoglobulin G levels. Results There were 30 fetuses with fetal alloimmune thrombocytopenia, confirmed by initial fetal blood sampling showing fetal platelet counts between 4×109/L and 130×109/L and antibody-coated fetal platelets using a glycoprotein specific assay. Despite weekly antenatal maternal immunoglobulin G infusions fetal platelet counts did not change significantly. Maternal and fetal immunoglobulin G levels, measured before every infusion, increased significantly with the number of maternal immunoglobulin G infusions. Conclusions In this group of fetuses with fetal alloimmune thrombocytopenia no consistent increase of fetal platelets was achieved as a result of regular maternal immunoglobulin G infusions. PMID:20534698

  11. Alloimmunization in multitransfused liver disease patients: Impact of underlying disease

    PubMed Central

    Bajpai, Meenu; Gupta, Shruti; Jain, Priyanka

    2016-01-01

    Introduction: Transfusion support is vital to the management of patients with liver diseases. Repeated transfusions are associated with many risks such as transfusion-transmitted infection, transfusion immunomodulation, and alloimmunization. Materials and Methods: A retrospective data analysis of antibody screening and identification was done from February 2012 to February 2014 to determine the frequency and specificity of irregular red-cell antibodies in multitransfused liver disease patients. The clinical and transfusion records were reviewed. The data was compiled, statistically analyzed, and reviewed. Results: A total of 842 patients were included in our study. Alloantibodies were detected in 5.22% of the patients. Higher rates of alloimmunization were seen in patients with autoimmune hepatitis, cryptogenic liver disease, liver damage due to drugs/toxins, and liver cancer patients. Patients with alcoholic liver disease had a lower rate of alloimmunization. The alloimmunization was 12.7% (23/181) in females and 3.17% (21/661) in males. Antibodies against the Rh system were the most frequent with 27 of 44 alloantibodies (61.36%). The most common alloantibody identified was anti-E (11/44 cases, 25%), followed by anti-C (6/44 cases, 13.63%). Conclusion: Our findings suggest that alloimmunization rate is affected by underlying disease. Provision of Rh and Kell phenotype-matched blood can significantly reduce alloimmunization.

  12. [Treatment of chronic refractory idiopathic thrombocytopenia purpura. 10 years experience at the Salvador Zubiran National Institute of Nutrition].

    PubMed

    Pita-Ramírez, L; Hurtado-Monroy, R; Labardini-Méndez, J

    1992-01-01

    A total of 126 patients with chronic idiopathic thrombocytopenic purpura were diagnosed from January 1980 to January 1990 in our institute. In this group of patients, 21 were refractory to prednisone therapy, splenectomy or both, or had had a relapse after a good response with these treatments. They were given other therapies. There was enough information for evaluation in 16 of the 21 patients. The treatment responses were classified according to the post-therapy platelet counts: complete response (CR) = > 150 x 10(9)/L for more than three months; partial response (PR) = 50-150 x 10(9)/L for more than three months; any response (AR) = CR + PR; no response (NR) = < 50 x 10(9)/L. There were 15 women and one male. The median age was 41 years (range 11 to 65). 6-mercaptopurine was given in all patients with CR = 31.2%, PR = 18.8%, AR = 50% and NR = 50%. Seven patients received cyclophosphamide with CR = 28.6%, PR = 14.3%, AR = 42.9% and NR = 57%. Vincristine was given in four patients with only one PR. Interferon alpha 2B was given in four patients with two transitory PR. One patient received colchicine and vitamin C without response. It is concluded that 6-mercaptopurine and cyclophosphamide are useful drugs in refractory thrombocytopenic purpura. PMID:1485028

  13. Severe intracranial haemorrhage in neonatal alloimmune thrombocytopenia

    PubMed Central

    Silva, Francisco; Morais, Sofia; Sevivas, Teresa; Veiga, Ricardo; Salvado, Ramon; Taborda, Adelaide

    2011-01-01

    Neonatal alloimmune thrombocytopenia is a rare (1/1000–5000 births) life-threatening disorder, caused by fetomaternal incompatibility for a fetal human platelet alloantigen inherited from the father, with production of maternal alloantibodies against fetal platelets, leading to severe thrombocytopenia and potential bleeding. Intracranial haemorrhage is the most feared complication. This report presents the case of a term newborn infant, born from caesarean section after a normal pregnancy, presenting signs of skin bleeding with different ages. Obstetric history included a previous spontaneous abortion after amniocentesis. Severe thrombocytopenia (4×109/l platelets) was found and brain ultrasound showed multiple intracranial haemorrhages. Human platelet antigen (HPA) phenotyping showed maternal negative HPA-1a and paternal positive HPA-1a platelets. Strongly positive anti-HPA-1a and weakly positive anti-human leukocyte antigen class I alloantibodies were found in the mother. Multiple platelet transfusions, intravenous immunoglobulin and corticosteroid were given but favourable response was accomplished only after a compatible platelet transfusion. Brain MRI showed multiple subacute and chronic haemorrhages. PMID:22679192

  14. Prediction of neonatal alloimmune thrombocytopenia using PCR.

    PubMed

    Marshall, L R; Jones, C; Munro, T E

    1994-01-01

    Neonatal alloimmune thrombocytopenia (NAIT) is a potentially fatal condition and in the majority of cases is associated with maternal antibodies to the HPA-1a (PLA1) haplotype. Early diagnosis in utero can enhance survival rates. The application of DNA genomic analysis and PCR technology for the determination of the HPA-1a/HPA-1b (PLA1/PLA2) locus is described and applied in a family study where the fetus was diagnosed to have NAIT. This rapid technique differentiated between the 3 haplotypes HPA-1a/HPA-1a, HPA-1b/HPA-1b and HPA-1a/HPA-1b using the polymorphism at base 196 of the GPIIIa gene. This is the first Australian report on the establishment of this technology for platelet genotype typing and the application in the diagnosis of NAIT. This technique can be performed on DNA extracted from any nucleated cells and avoids the difficulty of requiring fetal platelets for serological typing when NAIT is suspected. The PCR technique of genomic DNA analysis has an important application in the prediction and management of this potentially severe condition.

  15. 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.

  16. Aging augments IL-17 T-cell alloimmune responses.

    PubMed

    Tesar, B M; Du, W; Shirali, A C; Walker, W E; Shen, H; Goldstein, D R

    2009-01-01

    As increasing numbers of elderly patients require solid organ transplantation, the need to better understand how aging modifies alloimmune responses increases. Here, we examined whether aged mice exhibit augmented, donor-specific memory responses prior to transplantation. We found that elevated donor-specific IL-17, but not IFN-gamma, responses were observed in aged mice compared to young mice prior to transplantation. Further characterization of the heightened IL-17 alloimmune response with aging demonstrated that memory CD4(+) T cells were required. Reduced IL-2 alloimmune responses with age contributed to the elevated IL-17 phenotype in vitro, and treatment with an anti-IL-17 antibody delayed the onset of acute allograft rejection. In conclusion, aging leads to augmented, donor-specific IL-17 immune responses that are important for the timing of acute allograft rejection in aged recipients. IL-17 targeting therapies may be useful for averting transplant rejection responses in older transplant recipients.

  17. 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.

  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. [Use of Groupamatic in surveying fetomaternal alloimmunizations].

    PubMed

    Massaro, A L; Martinelli, A

    1978-03-01

    The A.V.I.S. Blood Transfusion Center of Turin performs the screening of foetomaternal allo-immunizations for the S. Anna Hospital of Turin. This hospital includes 3 hospital departments and 3 obstetrical and gynaecological university departments. The number of births in one year is roughly 13.000, i.e. 50 mother-baby couples, are tested every day. The identification system and the sampling process are described. The program used on the Groupamatic system includes: 1.) First run: Blood typing of mother blood with screening of alloantibodies. Second run: Blood typing control, screening of immune anti-A and anti-B antibodies, syphilis screening. 2.) Washing of cord blood red blood cells: First run: Washed red blood cells ABO and Rhesus typing, direct Coombs test. Second run: Blood typing control. Automatic screening of maternal irregular alloantibodies and automatic indirect Coombs test on washed cordblood red cells are simultaneously controlled with standard manual techniques. Sampling and testing are processed within 24 hours after birth. The set of results concerning mother-baby couples are grouped on one card and sent to the hospital department for a quick MHNN prophylaxy. Results of tests performed on 6.351 pregnancies studied until birth are presented. The automated direct Coombs test was positive with: 1--95% of new borns from mother who have a high immune allo antibody anti-A/B titer (IgG after treatment with two Mercapto etanol greater than I/64). 2--100% of new borns from mother who have irregular allo antibodies in Rh, Kell, Duffy or Kidd systems.

  20. How we use WinRho in patients with idiopathic thrombocytopenic purpura.

    PubMed

    Stotler, Brie A; Schwartz, Joseph

    2015-11-01

    Primary immune thrombocytopenia (ITP) is an autoimmune disease that affects children and adults. WinRho SDF is a D immune globulin product that is Food and Drug Administration approved for the treatment of ITP in D+ pediatric and adult patients. WinRho is a plasma-derived biologic product dispensed from blood banks. Transfusion medicine physicians serve as a resource to health care providers regarding blood component and derivative usage and, as such, should be familiar with the use of WinRho for ITP, including the dosage, administration, and contraindications. This report details the transfusion medicine consultation practice and guidelines at a tertiary care academic medical center for the usage of WinRho SDF in patients with ITP. PMID:26094894

  1. Management of chronic immune thrombocytopenic purpura: targeting insufficient megakaryopoiesis as a novel therapeutic principle

    PubMed Central

    Rank, Andreas; Weigert, Oliver; Ostermann, Helmut

    2010-01-01

    Traditionally, anti-platelet autoantibodies accelerating platelet clearance from the peripheral circulation have been recognized as the primary pathopysiological mechanism in chronic immune thrombocytopenia (ITP). Recently, increasing evidence supports the co-existence of insufficient megakaryopoiesis. Inadequate low thrombopoietin (TPO) levels are associated with insufficient proliferation and differentiation of megakaryocytes, decreased proplatelet formation, and subsequent platelet release. Recently two novel activators of TPO receptors have been made available: romiplostim and eltrombopag. In several phase III studies, both agents demonstrated increase of platelet counts in about 80% of chronic ITP patients within 2 to 3 weeks. These agents substantially broaden the therapeutic options for patients with chronic ITP although long-term results are still pending. This review will provide an update on the current conception of underlying mechanisms in ITP and novel, pathophysiologically based treatment options. PMID:20531970

  2. Intravenous usage of gammaglobulin: humoral immunodeficiency, immune thrombocytopenic purpura, and newer indications.

    PubMed

    Bussel, J B; Cunningham-Rundles, C

    1985-01-01

    Intravenous gammaglobulin is effective therapy of ITP and other autoantibody-mediated immune cytopenias. All children as well as adults unresponsive to splenectomy or with known immune deficiency are probably the best candidates for treatment with IVGG. Its major advantage, in addition to its efficacy of treatment and possible remission-inducing effect, is that it has the fewest side effects of any treatment of ITP so that it is the best maintenance therapy of patients when effective. Future uses of IVGG remain to be determined. Premature infants with a high mortality from sepsis and with hypogammaglobulinemia due to termination of pregnancy prior to transplacental antibody transfer may benefit from IVGG. A preliminary study suggested such benefit and also showed safety of IVGG treatment in that there was no impaired immune responsiveness of these prematures at 2 years of age (28). Another potential usage of IVGG involves the treatment of the hypogammaglobulinemia associated with certain types of malignancy. Patients with CLL, especially in the advanced stages, are often hypogammaglobulinemic. Multiple myeloma and Waldenstrom's macroglobulinemia are two other B-cell malignancies associated with antibody production defects which might benefit from antibody replacement therapy. Therapeutic IgG levels may be harder to obtain due to hypercatabolism of immunoglobulin. The issue of immune hyporesponsiveness during intensive chemotherapy is also unexplored. Secondary antibody responses do not seem to be impaired, but primary responses, as tested in numerous immunization studies, are decidedly impaired. Certain protocols, especially those treating high-risk acute leukemias and neuroblastoma during induction therapy are intensive with high rates of sepsis, and may warrant trials of prophylactic IVGG. Similarly, some form of humoral prophylaxis is becoming an important part of the handling of the patient undergoing bone marrow transplantation not only to prevent bacterial sepsis but also to prevent cytomegalovirus (CMV) interstitial pneumonitis. A likely additional usage is gammaglobulin replacement for patients undergoing plasmapheresis, especially if performed multiple times. Finally, the broad spectrum of antibacterial and antiviral antibodies present in the preparations (such as anti-CMV, anti-Group B strep, and antiendotoxin) and the ease and safety of delivery allow the preparations to be used in situations where a hyperimmune preparation might be desired and/or where more than one pathogen is possible. In summary, IVGG is a treatment capable of safely conferring significant benefits to selected patients.(ABSTRACT TRUNCATED AT 400 WORDS)

  3. How we use WinRho in patients with idiopathic thrombocytopenic purpura.

    PubMed

    Stotler, Brie A; Schwartz, Joseph

    2015-11-01

    Primary immune thrombocytopenia (ITP) is an autoimmune disease that affects children and adults. WinRho SDF is a D immune globulin product that is Food and Drug Administration approved for the treatment of ITP in D+ pediatric and adult patients. WinRho is a plasma-derived biologic product dispensed from blood banks. Transfusion medicine physicians serve as a resource to health care providers regarding blood component and derivative usage and, as such, should be familiar with the use of WinRho for ITP, including the dosage, administration, and contraindications. This report details the transfusion medicine consultation practice and guidelines at a tertiary care academic medical center for the usage of WinRho SDF in patients with ITP.

  4. Rituximab for the treatment of childhood chronic idiopathic thrombocytopenic purpura and hemophilia with inhibitors.

    PubMed

    Franchini, Massimo; Zaffanello, Marco; Veneri, Dino; Lippi, Giuseppe

    2007-07-01

    Rituximab, a monoclonal chimeric antibody to the CD20 antigen, is an effective treatment for non-Hodgkin lymphomas. Moreover, rituximab has also shown efficacy in various autoimmune disorders. In this review, we will focus on the use of rituximab in childhood disorders of hemostasis associated with inhibitor formation. Although the results presented suggest that rituximab can be useful in the treatment of this subset of pediatric patients, most of the data come from isolated case reports or descriptions of small, uncontrolled series. Therefore, large, prospective, and randomized trials are needed to confirm the positive, preliminary results.

  5. 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

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

    PubMed

    Frontario, S Christopher N; 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

  7. 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.

  8. 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

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

    PubMed

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

    2016-09-01

    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.

  10. Henoch-Schönlein purpura

    MedlinePlus

    Ardoin SP, Fels E. Vasculitis syndromes. In: Kliegman RM, Stanton B, St. Geme J, Schor N, Behrman ... Elsevier Saunders; 2011:chap 161. Marcdante KJ, Kliegman RM. Henoch-Schöenlein purpura. In: Marcdante KJ, Kliegman RM, ...

  11. An improbable and unusual case of thrombotic thrombocytopenia purpura.

    PubMed

    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. 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

  13. ALLOIMMUNIZATION IN SICKLE CELL DISEASE: CHANGING ANTIBODY SPECIFICITIES AND ASSOCIATION WITH CHRONIC PAIN AND DECREASED SURVIVAL

    PubMed Central

    Telen, Marilyn J.; Afenyi-Annan, Araba; Garrett, Melanie E.; Combs, Martha Rae; Orringer, Eugene P.; Ashley-Koch, Allison E.

    2014-01-01

    BACKGROUND: Alloimmunization remains a significant complication of transfusion and has been associated with multiple factors, including inflammation, an important pathophysiologic mechanism in sickle cell disease (SCD). We explored whether alloimmunization is associated with disease severity in SCD. STUDY DESIGN AND METHODS Adult SCD patients were enrolled in a study of outcome modifying genes in SCD. Historical records of patients with SCD at two participating institutions were reviewed for data on antigen phenotype and alloimmunization. Differences in demographic, clinical and laboratory findings, end organ damage, and overall disease severity were then compared between alloimmunized and non-alloimmunized patients. RESULTS Of 319 patients, 87 (27%) were alloimmunized. Alloantibody specificities differed from those previously described, especially due to the significantly higher frequency of anti-S. Although alloimmunization was not associated with frequency of vaso-occlusive episodes, a higher percentage of alloimmunized patients had chronic pain, as defined by daily use of short acting narcotics (p=0.006), long acting narcotics (p=0.013), or both (p=0.03). Additionally, alloimmunized patients had poorer survival (HR=1.92, p=0.01) and were more likely to have avascular necrosis (p=0.024), end-organ damage (p=0.049) and red cell autoantibodies (p<0.001), even after controlling for the effects of age, gender, and hemoglobin diagnosis. Alloimmunization was not associated with other SCD related complications, such as acute chest syndrome or stroke. CONCLUSIONS Alloimmunization in SCD may be associated with chronic pain, risk of end-organ damage, and shorter survival. These novel findings suggest new directions for the investigation of immune response-mediated pathways common to alloimmunization and chronic pain. PMID:25444611

  14. Alloimmunization of patients by blood units harboring distinct DEL variants.

    PubMed

    St-Louis, Maryse; Lebrun, André; Goldman, Mindy; Lavoie, Marianne

    2013-01-01

    The alloimmunization potential of many RHD variants is unknown, and it can be explored by lookback and traceback studies. Hema-Quebec (HQ) investigated the RHD status of 3980 D- repeat blood donors. Thirteen were found to be RHD positive: 4 RHD*1p, and 1 RHD*487delACAG, which show a Dphenotype;and 1 RHD*885T and 7 RHD*(93-94insT) causing a DEL phenotype when C antigen is present. Look back studies were done to verify the alloimmunization potential of these eight DEL donors. Coincidentally, Canadian Blood Services (CBS)performed a trace back study by investigating the RHD status of donors after aD- recipient developed anti-Dafter transfusion of two D- red blood cell (RBC) units. Donor genotyping was done either manually (HQ) or using the Progenika Bloodchip platform(CBS). Donations were traced through computer records. Letters were sent to hospital blood bank physicians to verify the presence of anti-Din recipients and to donors to request repeat samples.A total of 118 RBC units were transfused, 82 to D- recipients.Anti-D was found in three patients transfused with RHD*(93-94insT) DEL red blood cells. One donor presenting the same DEL variant was involved in the trace back study. Even without strong evidence clearly demonstrating the alloimmunization potential of DEL variants, whenever HQ or CBS identifies a donor harboring a DEL phenotype, his or her D status will be changed from DtoD+ to protect against the potential alloimmunization risk. PMID:24689683

  15. Influenza vaccination and humoral alloimmunity in solid organ transplant recipients.

    PubMed

    Vermeiren, Pieter; Aubert, Vincent; Sugamele, Rocco; Aubert, John-David; Venetz, Jean-Pierre; Meylan, Pascal; Pascual, Manuel; Manuel, Oriol

    2014-09-01

    Annual influenza vaccination is recommended in solid organ transplant (SOT) recipients. However, concerns have been raised about the impact of vaccination on antigraft alloimmunity. We evaluated the humoral alloimmune responses to influenza vaccination in a cohort of SOT recipients between October 2008 and December 2011. Anti-HLA antibodies were measured before and 4-8 weeks after influenza vaccination using a solid-phase assay. Overall, 169 SOT recipients were included (kidney = 136, lung = 26, liver = 3, and combined = 4). Five (2.9%) of 169 patients developed de novo anti-HLA antibodies after vaccination, including one patient who developed donor-specific antibodies (DSA) 8 months after vaccination. In patients with pre-existing anti-HLA antibodies, median MFI was not significantly different before and after vaccination (P = 0.73 for class I and P = 0.20 for class II anti-HLA antibodies) and no development of de novo DSA was observed. Five episodes of rejection (2.9%) were observed within 12 months after vaccination, and only one patient had de novo anti-HLA antibodies. The incidence of development of anti-HLA antibodies after influenza vaccination in our cohort of SOT recipients was very low. Our findings indicate that influenza vaccination is safe and does not trigger humoral alloimmune responses in SOT recipients.

  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. [Difficulties of the care of public antigen alloimmunization].

    PubMed

    Ben Amor, I; Rekik, T; Louati, N; Lahiani, W; Rekik, H; Peyrard, T; Menif, H; Gargouri, J

    2016-05-01

    Alloimmunization against high-frequency erythrocyte antigens is a problematic situation in terms of laboratory diagnosis, transfusion and obstetrical management. We report the case of a pregnant woman alloimmunized against public Ag. We detail the difficulties of alloantibody (Ab) identification and transfusion management of the deliveries. A 29-year-old pregnant woman was hospitalized in gynecology and obstetrics departments at 36 weeks of gestation for assessment of hydrops fetalis. Antibody identification test revealed the presence of a pan-reactive antibody. Investigations realized in CNRGS (Paris) concluded in anti-GE2+anti-RH3+autoantibody. The red cell phenotype was GE: -2,3. A therapeutic interruption of the pregnancy was indicated. A program of autologous transfusion was organized with withdrawal of 2 units of blood. The 2nd pregnancy took place normally. Before delivery, an autologous blood reserve consisting of 2 red cell packs and 2 fresh frozen plasma was withdrawn and transfused after delivery. The management of anti-public alloimmunization poses several problems. The first one is of diagnostic nature with, on the one hand, the difficulty of Ab identification by the available red cell panels and, on the other hand, the possible presence of alloantibodies of transfusional or obstetric interest masked by anti-public Ab. The second is represented by transfusional care of these patients. In the absence of a national reserve of frozen rare blood, the autologous transfusion remains the only alternative. However, it can answer only a limited number of indications and only in case of moderate blood loss.

  18. [Epidemiology of anti-D allo-immunization during pregnancy].

    PubMed

    Branger, B; Winer, N

    2006-02-01

    The number of women exposed to a risk of anti-D allo-immunization who require care depends on the number of pregnancies, the distribution of blood groups in the Rhesus D system, and the number of allo-immunization risk situations as well as the chosen prevention protocol. In 2004, there were 790,000 pregnancies in metropolitan France. The total number of conceptions (adding abortions, voluntary interruptions, ectopic pregnancies and in utero fetal deaths) would be to the order of 1,100,000 to 1,200,000. Since 15% of the French population is RhD-negative, 15% of pregnant women or women who have delivered are RhD-negative, which would correspond to 160,000 to 180,000 women exposed to a risk of anti-D allo-immunization. Two strategies could be evaluated: prevention targeting risk factors and systematic prevention from 28 weeks gestation. Both strategies involve treatment with anti-D anti-globulins to RhD-negative women with an RhD-positive newborn. Targeted prevention would involve 160,000 to 190,000 doses for 130,000 to 150,000 women. The systematic approach would consist in 300,000 to 340,000 doses for 250,000 to 280,000 women. This number could be lowered by reserving treatment for women with a RhD-positive partner (210,000 to 230,000 doses for 260,000 to 290,000 women), but this would require a precise contract between the physician and the woman. Another way to reduce the number of doses would be to determine the Rh group of the fetus either by ovular samples or by genotyping on maternal blood. This would give about 200,000 to 220,000 doses for 240,000 to 270,000 women. In light of the literature, the systematic protocol would probably reduce the number of immunized women, the current estimation being 700 women still immunized in France and the goal being a reduction to a residual 200. The number of infants at risk of in utero maternal allo-immunization (fetal death, anasark, anemia) or after birth (jaundice, severe anemia) is not known in France and could be the

  19. Neonatal alloimmune thrombocytopenia due to HLA-A2 antibody.

    PubMed

    Chow, M P; Sun, K J; Yung, C H; Hu, H Y; Tzeng, J L; Lee, T D

    1992-01-01

    A male, full-term baby with thrombocytopenia was born by a G3P2A1 mother who was not associated with autoimmune disease. Platelet antibody screening was positive by using lymphocytotoxicity test, platelet suspension immunofluorescence test and solid-phase red cell adherence test. The identified HLA antibody was of A2 specificity. It was confirmed by testing the mother's and the baby's sera against the lymphocytes and platelets of 10 HLA-A2-positive donors. The possibility of platelet-specific antibody as the cause of neonatal alloimmune thrombocytopenia was ruled out by testing against platelets of 10 HLA-A2-negative donors and the known platelet-specific antigens utilizing immobilized, purified platelet glycoprotein as targets. The mother's serum reacted strongly with both the father's and the baby's platelets and lymphocytes. This neonatal thrombocytopenia was most likely due to the maternal HLA antibody, which was induced by her antecedent gestations.

  20. Pruritis and palpable purpura from leeches in the Australian Rainforest

    PubMed Central

    Seiverling, Elizabeth V.; Khalsa, Amrit; Ahrns, Hadjh T.

    2014-01-01

    Leeches are prevalent in the Australian Rainforest. We report two cases of leech bites resulting in pruritis and palpable purpura. The dermatologic sequelae of leech bites, differential diagnosis of pruritic palpable purpura, leech bite treatment, prevention, and complications are reviewed. PMID:26839767

  1. Henoch-Schönlein purpura with preceding abdominal pain.

    PubMed

    Toshihiko, Kakiuchi; Tomonobu, Aoki

    2015-06-01

    Diagnosing HSP can be difficult, especially when abdominal symptoms precede the onset of characteristic palpable purpura (Chen MJ et al. 2005, World Gastroenterol., 11, 2354). Therefore, it is necessary to consider the possibility of HSP in patients with prolonged strong abdominal pain, even in cases without purpura.

  2. Henoch–Schönlein purpura with preceding abdominal pain

    PubMed Central

    Toshihiko, Kakiuchi; Tomonobu, Aoki

    2015-01-01

    Key Clinical Message Diagnosing HSP can be difficult, especially when abdominal symptoms precede the onset of characteristic palpable purpura (Chen MJ et al. 2005, World Gastroenterol., 11, 2354). Therefore, it is necessary to consider the possibility of HSP in patients with prolonged strong abdominal pain, even in cases without purpura. PMID:26185663

  3. Henoch-Schönlein purpura with preceding abdominal pain.

    PubMed

    Toshihiko, Kakiuchi; Tomonobu, Aoki

    2015-06-01

    Diagnosing HSP can be difficult, especially when abdominal symptoms precede the onset of characteristic palpable purpura (Chen MJ et al. 2005, World Gastroenterol., 11, 2354). Therefore, it is necessary to consider the possibility of HSP in patients with prolonged strong abdominal pain, even in cases without purpura. PMID:26185663

  4. Alloimmunization due to red cell antibodies in Rhesus positive Omani Pregnant Women: Maternal and Perinatal outcome

    PubMed Central

    Al-Dughaishi, Tamima; Al-Rubkhi, Ikhlass S.; Al-Duhli, Maymoona; Al-Harrasi, Yusra; Gowri, Vaidyanathan

    2015-01-01

    Objective: This study is aimed to determine the prevalence of alloimmunization due to antibodies to red blood cell (RBC) antigens (other than rhesus [Rh] antigen) and report the maternal, perinatal, and neonatal outcomes. Materials and Methods: A retrospective review of medical records of all patients with minor RBCs antibodies alloimmunization who were followed and delivered at Sultan Qaboos University Hospital, Oman from June 2011 to June 2013. Maternal characteristics, antibody type, antibody titer in addition to perinatal and neonatal outcomes were reviewed. Results: There were 1160 patients with Rh positive status in the study. The most common ABO blood group was O, followed by A, B, and AB. We found 33 out of 1160 Rh positive women alloimmunized with minor RBCs antibodies that gave a prevalence of minor RBCs alloimmunization of 2.7%. The most frequent antibody was anti-E 38%, followed by anti-c 17% and anti-kell 17%. 6 of these 33 patients were identified to have significant antibody titer, and two cases showed evidence of fetal anemia. Only one case required an intrauterine blood transfusion. The most common neonatal complication was jaundice in 53%, followed by respiratory distress syndrome in 28%. Two cases complicated by neonatal anemia required a postnatal blood transfusion. Conclusion: Alloimmunization with anti-E, anti-c, and anti-kell were the most common antibodies among the study group. Minor RBCs alloimmunization was an important cause of neonatal morbidity. PMID:26420934

  5. Current problems and future directions of transfusion-induced alloimmunization: summary of an NHLBI working group.

    PubMed

    Zimring, James C; Welniak, Lis; Semple, John W; Ness, Paul M; Slichter, Sherrill J; Spitalnik, Steven L

    2011-02-01

    In April 2010, a working group sponsored by the National Heart, Lung, and Blood Institute was assembled to identify research strategies to improve our understanding of alloimmunization caused by the transfusion of allogeneic blood components and to evaluate potential approaches to both reduce its occurrence and manage its effects. Significant sequelae of alloimmunization were discussed and identified, including difficulties in maintaining chronic transfusion of red blood cells and platelets, hemolytic disease of the newborn, neonatal alloimmune thrombocytopenia, and rejection of transplanted cells and tissues. The discussions resulted in a consensus that identified key areas of future research and developmental areas, including genetic and epigenetic recipient factors that regulate alloimmunization, biochemical specifics of transfused products that affect alloimmunization, and novel technologies for high-throughput genotyping to facilitate extensive and efficient antigen matching between donor and recipient. Additional areas of importance included analysis of unappreciated medical sequelae of alloimmunization, such as cellular immunity and its effect upon transplant and autoimmunity. In addition, support for research infrastructure was discussed, with an emphasis on encouraging collaboration and synergy of animal models biology and human clinical research. Finally, training future investigators was identified as an area of importance. In aggregate, this communication provides a synopsis of the opinions of the working group on the above issues and presents both a list of suggested priorities and the rationale for the topics of focus. The areas of research identified in this report represent potential fertile ground for the medical advancement of preventing and managing alloimmunization in its different forms and mitigating the clinical problems it presents to multiple patient populations. PMID:21251006

  6. Early occurrence of red blood cell alloimmunization in patients with sickle cell disease.

    PubMed

    Sins, Joep W R; Biemond, Bart J; van den Bersselaar, Sil M; Heijboer, H; Rijneveld, Anita W; Cnossen, Marjon H; Kerkhoffs, Jean-Louis H; van Meurs, Alfred H; von Ronnen, F B; Zalpuri, Saurabh; de Rijke, Yolanda B; Ellen van der Schoot, C; de Haas, Masja; van der Bom, Johanna G; Fijnvandraat, Karin

    2016-08-01

    Red blood cell (RBC) alloimmunization is a major complication of transfusion therapy in sickle cell disease (SCD). Identification of high-risk patients is hampered by lack of studies that take the cumulative transfusion exposure into account. In this retrospective cohort study among previously non-transfused SCD patients in the Netherlands, we aimed to elucidate the association between the cumulative transfusion exposure, first alloimmunization and independent risk factors. A total of 245 patients received 11 952 RBC units. Alloimmunization occurred in 43 patients (18%), half of them formed their first alloantibody before the 8th unit. In patients with exposure to non-extended matched transfusions (ABO and RhD) the cumulative alloimmunization risk increased up to 35% after 60 transfused units. This was significantly higher compared to a general transfused population (HR 6.6, CI 4.2-10.6). Receiving the first transfusion after the age of 5 was an independent risk factor for alloimmunization (HR 2.3, CI 1.0-5.1). Incidental, episodic transfusions in comparison to chronic scheme transfusions (HR 2.3, CI 0.9-6.0), and exposure to non-extended matched units in comparison to extended matching (HR 2.0, CI 0.9-4.6) seemed to confer a higher alloimmunization risk. The majority of first alloantibodies are formed after minor transfusion exposure, substantiating suggestions of a responder phenotype in SCD and stressing the need for risk factor identification. In this study, older age at first transfusion, episodic transfusions and non-extended matched transfusions appeared to be risk factors for alloimmunization. Am. J. Hematol. 91:763-769, 2016. © 2016 Wiley Periodicals, Inc. PMID:27102719

  7. 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.

  8. 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

  9. Low frequency of anti-D alloimmunization following D+ platelet transfusion: the Anti-D Alloimmunization after D-incompatible Platelet Transfusions (ADAPT) study.

    PubMed

    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

    2015-02-01

    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 d following the first D+ platelet transfusion. Data were collected on 485 D- recipients of D+ platelets in 11 centres between 2010 and 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 d (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

  10. Low frequency of anti-D alloimmunization following D+ platelet transfusion: the Anti-D Alloimmunization after D-incompatible Platelet Transfusions (ADAPT) study.

    PubMed

    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

    2015-02-01

    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 d following the first D+ platelet transfusion. Data were collected on 485 D- recipients of D+ platelets in 11 centres between 2010 and 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 d (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.

  11. Quantitative kinetics of In-111 autologous (In-AP) and homologous (Cr-HP) platelets in immune thrombocytopenic purpura (ITP)

    SciTech Connect

    Lotter, M.G.; Heyns, A.D.P.; Badenhorst, P.N.; Minnaar, P.C.

    1984-01-01

    Contrary to the accepted view, the authors have found that platelet turnover is not always increased in ITP if the mean platelet survival time (PS) is measured with In-AP. The authors investigated the possible cause of the discrepancy by comparing kinetics of In-AP with those of Cr-HP in 10 patients with ITP. PS was estimated with the multiple hit model. The equilibrium and final in vivo distribution of In-AP was quantitated with the geometrical mean method. The patients could be divided into either those with splenic or diffuse RES platelet destruction. The authors conclude that in ITP platelet survival of In-AP is significantly (P < .05) longer than that of Cr-HP. Platelet turnover measured with In-AP is only normal in patients with mainly splenic platelet sequestration. Results with Cr-HP give a false impression of PS. It seems that in ITP those patients with severe disease also have a platelet production defect.

  12. Recurrent adult onset Henoch-Schonlein Purpura: a case report.

    PubMed

    Gaskill, Neil; Guido, Bruce; Mago, Cynthia

    2016-01-01

    Henoch-Schonlein purpura is an immunoglobulin A (IgA)-immune complex mediated leukocytoclastic vasculitis that classically manifests with palpable purpura, abdominal pain, arthritis, and hematuria or proteinuria. The condition is much more predominant in children (90% of cases) and commonly follows an upper respiratory infection. We present a case of recurrent Henoch-Schonlein purpura (HSP) complicated by nephritis in an adult female initially categorized as IgA nephropathy (IgAN). We review the pathophysiologic basis of HSP nephritis as the variant of HSP accompanied by renal involvement and its pathogenetic commonality with IgA nephropathy. PMID:27617937

  13. Bleeding into the skin

    MedlinePlus

    ... under the tissue in larger flat areas (called purpura ), or in a very large bruised area (called ... in the newborn) Aging skin (ecchymosis) Idiopathic thrombocytopenic purpura (petechiae and purpura) Henoch-Schonlein purpura (purpura) Leukemia ( ...

  14. Successful management of neonatal alloimmune thrombocytopenia in the second pregnancy: a case report

    PubMed Central

    Conti, Fabiana Mendes; Hibner, Sergio; Costa, Thiago Henrique; Dezan, Marcia Regina; Aravechia, Maria Giselda; Pereira, Ricardo Antonio D'Almeida; Kondo, Andrea Tiemi; D'Amico, Élbio Antônio; Mota, Mariza; Kutner, José Mauro

    2014-01-01

    ABSTRACT Neonatal alloimmune thrombocytopenia is a serious disease, in which the mother produces antibodies against fetal platelet antigens inherited from the father; it is still an underdiagnosed disease. This disease is considered the platelet counterpart of the RhD hemolytic disease of the fetus and newborn, yet in neonatal alloimmune thrombocytopenia the first child is affected with fetal and/or neonatal thrombocytopenia. There is a significant risk of intracranial hemorrhage and severe neurological impairment, with a tendency for earlier and more severe thrombocytopenia in subsequent pregnancies. This article reports a case of neonatal alloimmune thrombocytopenia in the second pregnancy affected and discusses diagnosis, management and the clinical importance of this disease. PMID:24728253

  15. Autoantibody formation after alloimmunization inducing bystander immune hemolysis.

    PubMed

    Mota, M; Bley, C; Aravechia, M G; Hamerschlak, N; Sakashita, A; Kutner, J M; Castiho, L

    2009-01-01

    The development of RBC autoantibodies resulting from or associated with allogeneic blood transfusions is not an easily determined complication of RBC transfusions. This report discusses one patient who developed RBC autoantibodies in association with an allogeneic blood transfusion and alloimmunization leading to a temporary bystander immune hemolysis. A 72-year-old woman was hospitalized as a result of severe anemia and received two units of ABO- and D-compatible RBCs. She had a history of two pregnancies 40 years before, but no history of RBC transfusion, and her antibody screen was negative. On the tenth day after transfusion her hemoglobin dropped, and alloanti-c was identified in her serum and eluate. At this time she received another two units of compatible blood according to her phenotype (group O, R1R1, K:-1). After 48 hours, she developed joint pain, pyrexia, and hemoglobinuria, and her Hb dropped from 9.2 g/dL to 5.3 g/ dL. The direct antiglobulin test was positive, an IgG autoantibody was present in the eluate, and the antibody investigation revealed the presence of anti-Jk(b) in addition to the previously identified alloanti-c. Her genotype was determined, and, based on the findings, two additional units were selected, found to be compatible, and transfused without incident. Transfusions were discontinued, and she was treated with IVIG and corticosteroids. Her Hb increased to 9.7 g/dL, and the patient made an uneventful recovery. It was concluded that transfusion of incompatible RBCs induced the formation of an autoantibody in this patient, resulting in lysis of bystander RBCs. The need for additional blood transfusion was successfully avoided by treatment with IVIG, steroid therapy, and rituximab.

  16. Genetics Home Reference: immune thrombocytopenia

    MedlinePlus

    ... develop frequent bruising or red or purple spots (purpura) on the skin caused by bleeding just under ... of immune thrombocytopenia: Genetic Testing Registry: Idiopathic thrombocytopenic purpura Johns Hopkins Medicine MedlinePlus Encyclopedia: Idiopathic Thrombocytopenic Purpura ( ...

  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. 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).

  19. Intrauterine transfusion for fetal anemia due to red blood cell alloimmunization: 14 years experience in Leuven

    PubMed Central

    Pasman, S.A.; Claes, L.; Lewi, L.; Van Schoubroeck, D.; Debeer, A.; Emonds, M.; Geuten, E.; De Catte, L.; Devlieger, R.

    2015-01-01

    Objective: The purpose of this study is to report on the pregnancy and neonatal outcome of intrauterine transfusion (IUT) for red blood cell (RBC-)alloimmunization. Material and Methods: Retrospective cohort study of all IUT for RBC-alloimmunization in the University Hospital of Leuven, between January 2000 and January 2014. The influence of hydrops, gestational age and technique of transfusion on procedure related adverse events were examined. Results: 135 IUTs were performed in 56 fetuses. In none of the cases fetal or neonatal death occurred. Mild adverse events were noted in 10% of IUTs, whereas severe adverse events occurred in 1.5%. Hydrops and transfusion in a free loop were associated with an increased risk of adverse events whereas gestational age (GA) at transfusion after 34 weeks was not. Median GA at birth was 35.6 weeks and 9% was born before 34 weeks. Besides phototherapy 65.4% required additional neonatal treatment for alloimmune anemia. Non-hematologic complications occurred in 23.6% and were mainly related to preterm birth. Conclusion: In experienced hands, IUT for RBC-alloimmunization is a safe procedure in this era. Patients should be referred to specialist centers prior to the development of hydrops. IUT in a free loop of cord and unnecessary preterm birth are best avoided. PMID:26175890

  20. 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

  1. Alloimmune Activation Promotes Anti-Cancer Cytotoxicity after Rat Liver Transplantation

    PubMed Central

    Lacotte, Stéphanie; Oldani, Graziano; Slits, Florence; Orci, Lorenzo A.; Rubbia-Brandt, Laura; Morel, Philippe; Mentha, Gilles; Toso, Christian

    2014-01-01

    Liver transplantation for hepatocellular carcinoma (HCC) results in a specific condition where the immune response is potentially directed against both allogeneic and cancer antigens. We have investigated the level of anti-cancer immunity during allogeneic immune response. Dark Agouti-to-Lewis and Lewis-to-Lewis rat liver transplantations were performed and the recipients anti-cancer immunity was analysed at the time of alloimmune activation. The occurrence of rejection in the allogeneic recipients was confirmed by a shorter survival (p<0.01), increased liver function tests (p<0.01), the presence of signs of rejection on histology, and a donor-specific ex vivo mixed lymphocyte reaction. At the time of alloimmune activation, blood mononuclear cells of the allogeneic group demonstrated increased anti-cancer cytotoxicity (p<0.005), which was related to an increased natural killer (NK) cell frequency (p<0.05) and a higher monocyte/macrophage activation level (p<0.01). Similarly, liver NK cell anti-cancer cytotoxicity (p<0.005), and liver monocyte/macrophage activation levels (p<0.01) were also increased. The alloimmune-associated cytotoxicity was mediated through the NKG2D receptor, whose expression was increased in the rejected graft (p<0.05) and on NK cells and monocyte/macrophages. NKG2D ligands were expressed on rat HCC cells, and its inhibition prevented the alloimmune-associated cytotoxicity. Although waiting for in vivo validation, alloimmune-associated cytotoxicity after rat liver transplantation appears to be linked to increased frequencies and levels of activation of NK cells and monocyte/macrophages, and is at least in part mediated through the NKG2D receptor. PMID:24651497

  2. Alloimmune activation promotes anti-cancer cytotoxicity after rat liver transplantation.

    PubMed

    Lacotte, Stéphanie; Oldani, Graziano; Slits, Florence; Orci, Lorenzo A; Rubbia-Brandt, Laura; Morel, Philippe; Mentha, Gilles; Toso, Christian

    2014-01-01

    Liver transplantation for hepatocellular carcinoma (HCC) results in a specific condition where the immune response is potentially directed against both allogeneic and cancer antigens. We have investigated the level of anti-cancer immunity during allogeneic immune response. Dark Agouti-to-Lewis and Lewis-to-Lewis rat liver transplantations were performed and the recipients anti-cancer immunity was analysed at the time of alloimmune activation. The occurrence of rejection in the allogeneic recipients was confirmed by a shorter survival (p<0.01), increased liver function tests (p<0.01), the presence of signs of rejection on histology, and a donor-specific ex vivo mixed lymphocyte reaction. At the time of alloimmune activation, blood mononuclear cells of the allogeneic group demonstrated increased anti-cancer cytotoxicity (p<0.005), which was related to an increased natural killer (NK) cell frequency (p<0.05) and a higher monocyte/macrophage activation level (p<0.01). Similarly, liver NK cell anti-cancer cytotoxicity (p<0.005), and liver monocyte/macrophage activation levels (p<0.01) were also increased. The alloimmune-associated cytotoxicity was mediated through the NKG2D receptor, whose expression was increased in the rejected graft (p<0.05) and on NK cells and monocyte/macrophages. NKG2D ligands were expressed on rat HCC cells, and its inhibition prevented the alloimmune-associated cytotoxicity. Although waiting for in vivo validation, alloimmune-associated cytotoxicity after rat liver transplantation appears to be linked to increased frequencies and levels of activation of NK cells and monocyte/macrophages, and is at least in part mediated through the NKG2D receptor.

  3. [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. PMID:27399026

  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. Study of red blood cell alloimmunization in multitransfused thalassemic children of Jammu region

    PubMed Central

    Dogra, Ashu; Sidhu, Meena; Kapoor, Raman; Kumar, Dinesh

    2015-01-01

    Introduction: Thalassemia is one of the most common genetic disorder of hemoglobin synthesis in Jammu region. Although RBC transfusion is life saving for these patients, it may be associated with some complications like RBC alloimmunization. Thus, the aim of this study was to determine the frequency of alloimmunization and the most common alloantibodies involved. Material and Methods: This was a descriptive study involving a total of 70 thalassemic patients in the age range of 2-17 years receiving regular blood transfusions, registered at SMGS Blood Bank, Jammu. Relevant clinical and laboratory data was collected with reference to age at the start of transfusions, total number of transfusions received and splenectomy status. Antibodies screening, antibody identification, and cross matching was done on allpatient samples included in the study, during the period between November 2009 and October 2010. Results: In this study, a total of six alloantibodies six patients (8.5%) and one autoantibody (1.42%) was detected. All identified alloantibodies belonged to Rh system (i.e. anti-E, in 3 patients (50%), anti D, in one patient (16.66%)) and Kell system (anti-K, in two patients (33.34%)). Higher frequency of alloimmunization was found, with increase in number of transfusions and in those who received transfusions after 1 year of age. Alloimmunization was not significantly associated with gender and splenectomy status (P-value > 0.05). Conclusion: Red cell alloantibodies developed in 8.5% of thalassemic patients and 1.42% had autoantibodies. The most common alloantibodies identified were anti Rh system antibodies (anti-E and anti-D) present in 50% and 16.66% of patients respectively. Alloimmunization is not an uncommon problem faced by blood banks and finding compatible units for regularly transfused thalassemic patients may become very difficult. In order to reduce alloimmunization, a policy for performing extended red cell phenotyping of these patients is essential and

  6. 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. PMID:25312036

  7. Plasmapheresis and intravenous immune globulin for the treatment of D alloimmunization in pregnancy.

    PubMed

    Novak, Deborah J; Tyler, Lisa N; Reddy, Ramakrishna L; Barsoom, Michael J

    2008-01-01

    The alloimmunized pregnancy can result in fetal and newborn mortality due to fetal anemia. Control of fetal anemia has not been possible until recently, and management consists of following the degree of fetal anemia during gestation until intrauterine transfusion is feasible to support the fetus until delivery. Cordocentesis and intrauterine transfusion have potential complications that have been well documented. Control of fetal anemia via immune modulation utilizing plasmapheresis and intravenous immune globulin administration has been attempted alone and in combination with varying results. We present a case report of an Rh(D) alloimmunized pregnancy, in which successful management consisted of initial therapeutic plasmapheresis (TPE) followed by intravenous immunoglobulin (IVIG) administration until delivery at 37 weeks gestation without the need for intrauterine transfusion.

  8. 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.

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

    PubMed

    McAdams, Ryan M

    2016-04-01

    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.

  10. Purpura fulminans associated with acute West Nile virus encephalitis.

    PubMed

    Shah, Sheevam; Fite, Laura Paul; Lane, Natalie; Parekh, Palak

    2016-02-01

    Purpura fulminans is a progressive thrombotic disorder that presents with widespread purpura due to deficiency or dysfunction of protein C or protein S. Lesions present as well-demarcated erythematous macules that progress to irregular areas of hemorrhagic necrosis.West Nile virus is a member of the Flaviviridae family transmitted to humans through the bite of various mosquito species. It manifests as West Nile fever in 25% of those infected and less commonly as neuroinvasive disease. An African American man in his fortiespresented with altered mental status and was noted to have evidence of disseminated intravascular coagulation according to his lab data. He then developed dusky skin discoloration and systemic flaccid bullae with desquamation. Biopsy was consistent with purpura fulminans and the patient eventually developed symmetric peripheral gangrene, requiring amputations of all four extremities. Infectious work up revealed positive testing for IgM and IgG antibodies in serum and cerebrospinal fluid leading to the diagnosis of acute West Nile Virus encephalitis. We present this case to describe the rarely reported association of purpura fulminans with West Nile Virus infection.

  11. Risk estimation of HNA-3 incompatibility and alloimmunization in Thai populations.

    PubMed

    Nathalang, Oytip; Intharanut, Kamphon; Siriphanthong, Kanokpol; Nathalang, Siriporn; Leetrakool, Nipapan

    2015-01-01

    Severe transfusion-related acute lung injury (TRALI) is often due to antibodies in blood components directed against human neutrophil antigen (HNA)-3a. This study aimed to report the genotype frequencies of the HNA-3 system and to estimate the potential risk of HNA-3 incompatibility and alloimmunization in two Thai populations. Eight hundred DNA samples obtained from 500 unrelated healthy blood donors at the National Blood Centre, Thai Red Cross Society, Bangkok and 300 samples from the Blood Bank, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand were included. HNA-3 genotyping was performed using an in-house polymerase chain reaction with sequence-specific primer (PCR-SSP) technique. The observed frequencies of the HNA-3a/3a, HNA-3a/3b, and HNA-3b/3b genotypes were 0.528, 0.380, and 0.092 in central Thais and 0.600, 0.350, and 0.050 in northern Thais, respectively. The frequencies were used to estimate HNA-3 incompatibility and risk of HNA-3a alloimmunization. The HNA-3 incompatibility in central Thais (33.28%) was higher than northern Thais (28.75%), corresponding to a significantly higher probability of HNA-3a alloimmunization (P<0.05) similar to Japanese and Chinese populations. This study showed the high risk of HNA-3 incompatibility and alloimmunization, especially in central Thai blood donors. A molecular-based identification of the HNA-3 genotype of female donors is suggested to reduce the risk of TRALI following plasma and whole blood allogeneic transfusion.

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

    PubMed Central

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

    2016-01-01

    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. PMID:25963831

  13. Genetics of Transfusion Recipient Alloimmunization: Can Clues from Susceptibility to Autoimmunity Pave the Way?

    PubMed Central

    Tatari-Calderone, Zohreh; Luban, Naomi L.C.; Vukmanovic, Stanislav

    2014-01-01

    Summary The search for genetic determinants of alloimmunization in sickle cell disease transfusion recipients was based on two premises: i) that polymorphisms responsible for stronger immune and/or inflammatory responses and hemoglobin βS mutation were co-selected by malaria; and ii) that stronger responder status contributes to development of lupus. We found a marker of alloimmunization in the gene encoding for Ro52 protein, also known as Sjögren syndrome antigen 1 (SSA1) and TRIM21. Surprisingly, the nature of the association was opposite of that with lupus; the same variant of a polymorphism (rs660) that was associated with lupus incidence was also associated with induction of tolerance to red blood cell antigens during early childhood. The dual function of Ro52 can explain this apparent contradiction. We propose that other lupus/autoimmunity susceptibility loci may reveal roles of additional molecules in various aspects of alloimmunization induced by transfusion as well as during pregnancy. PMID:25670931

  14. Associations of Rhesus and non-Rhesus maternal red blood cell alloimmunization with stillbirth and preterm birth

    PubMed Central

    Fan, Jing; Lee, Brian K; Wikman, Agneta T; Johansson, Stefan; Reilly, Marie

    2014-01-01

    Background: Although the risks of adverse pregnancy outcomes associated with anti-D antibodies are well-recognized, much less is known concerning alloimmunization with other red blood cell antibodies detected during routine maternal screening. To date, most reports of adverse pregnancy outcomes associated with non-anti-D antibodies have been from small case studies. The aim of this study was to examine the associations of maternal alloimmunization with specific red blood cell antibodies and the risks of preterm birth and stillbirth in the Swedish population. Methods: All antibody screening, outcome and covariate data were obtained through linkages of Swedish national health and data registers. Follow-up in these population-based registers was available up to 31 December 2002. The final study sample consisted of 1 022 569 singleton births from 668 952 mothers during 1987–2002. Results: In total, 1.3% of the 1 022 569 study pregnancies were alloimmunized. In adjusted logistic regression models, compared with having no antibodies, alloimmunization with anti-D, anti-E, anti-C and anti-c was associated with increased risk of both stillbirth and preterm birth. In addition, anti-Kell was associated with increased risk of preterm birth and anti-Lea with increased risk of stillbirth. Compared with firstborn children, risk of preterm birth associated with alloimmunization was greater in subsequent births Conclusions: In the largest study to date, alloimmunization with Rhesus, K- and -Lea red blood cell antibodies increased the risk of preterm birth and/or stillbirth. The association of anti-Lea with stillbirth was an unexpected finding. Further study of the consequences of non-anti-D alloimmunization is warranted. PMID:24801308

  15. [Randomized comparison of intravenous immunoglobulin and methylprednisolone pulse therapy in children with newly diagnosed idiopathic thrombocytic purpura. The Danish ITP Study Group].

    PubMed

    Rosthøj, S; Nielsen, S M; Pedersen, F K

    1998-03-01

    Forty three children with newly diagnosed idiopathic thrombocytopenic purpura (ITP), platelet count (pl.c.) below 20 x 10(9)/l, and either clinically significant bleeding or failure to show a spontaneous platelet rise within three days of admission were randomly allocated to treatment with intravenous infusions of either immunoglobulin (IVIG) 1 g/kg or methylprednisolone (MPPT) 30 mg/kg on two consecutive days. Prompt induction of partial remission with pl.c. > 50 x 10(9)/l after 72 hours was seen in 21/23 given IVIG versus 10/20 given MPPT (exact p = 0.003); mean pl.c.s after 72 hours were 188 versus 77 x 10(9)/l (2p < 0.001). Poor responders were then given the alternative infusions in addition. After six days, complete remission with pl.c. > 150 x 10(9)/l was achieved in 16/23 versus 10/20 (p = 0.16). During six months follow-up, there were no significant differences regarding relapse rates or chronic course. Eleven children with relapse were crossed over to the alternative treatment arm: the estimated treatment effect in pl.c. after 72 hours was 134 x 10(9)/l in favour of IVIG. These results indicate that IVIG infusions may be preferable to high-dose corticosteroids as initial treatment for children with ITP. PMID:9522658

  16. Vasculitic purpura in vinyl chloride disease: a case report

    SciTech Connect

    Magnavita, N.; Bergamaschi, A.; Garcovich, A.; Giuliano, G.

    1986-05-01

    Vinyl chloride (VC), a volatile substance mostly used for polyvinyl chloride (PVC) synthesis, is a systemic toxicant particularly noxious to endothelium. Angiosarcoma of the liver, Raynaud's phenomenon, scleroderma-like lesions, acroosteolysis and neuritis are known to be typical vinyl chloride-associated manifestations (VC disease). A so far unknown feature of the disease is purpura. This was first observed by the authors in a worker of a PVC-producing plant. The skin eruption was characterized by small purpuric maculae with tiny, palpable spots and papulae, mostly concentrated on the lower part of the legs, changing into bullae, pustules and crusts and tending to spontaneous regression after withdrawal from VC exposure. A skin biopsy revealed marked inflammatory reaction with a mostly lymphocytic and histiocytic infiltration around and in the walls of dermal arterioles. The finding of increased circulating immune complexes and anti-smooth muscle autoantibodies strengthens the hypothesis that immunologic changes play a role in the appearance of ''vinylic purpura.''

  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. The Influence of Clinical and Biological Factors on Transfusion-Associated Non-ABO Antigen Alloimmunization: Responders, Hyper-Responders, and Non-Responders.

    PubMed

    Gehrie, Eric A; Tormey, Christopher A

    2014-11-01

    In the context of transfusion medicine, alloimmunization most often refers to the development of antibodies to non-ABO red blood cell (RBC) antigens following pregnancy, transfusion, or transplantation. The development of RBC alloantibodies can have important clinical consequences, particularly in patients who require chronic transfusions. It has been suggested that alloimmunization is more common in some clinical circumstances and patient populations than in others. As such, individuals that develop alloantibodies are frequently referred to as 'responders' in the medical literature. In contrast, individuals that do not develop alloantibodies despite repeated exposures to non-self blood group antigens have been referred to as 'non-responders'. The purpose of this article is to review the phenomenon of RBC alloimmunization in the context of responders and non-responders to: i) establish a basic framework for alloimmunization as reported across several diverse patient populations; ii) more fully explore literature reports which support the concept of responders/non-responders regarding blood group antigen alloimmunization; iii) summarize the mechanisms that have been shown to predispose an individual to alloimmunization to determine how these factors may differentiate 'responders' from 'non-responders'; and iv) briefly discuss some practical approaches to prevent alloimmunization in patients who may be prone to alloantibody development.

  19. Receipt of older RBCs does not predispose D-negative recipients to anti-D alloimmunization.

    PubMed

    Yazer, Mark H; Triulzi, Darrell J

    2010-09-01

    The effect of the age of RBCs on anti-RBC alloimmunization has not been investigated in previous studies of the RBC storage lesion. D-negative recipients of at least 1 D-positive RBC unit were identified. Responders produced an anti-D, while nonresponders had not made anti-D when the database was searched. The 2 groups were matched for age, sex, length of serologic follow-up, and hospital location. There were 29 responders and 58 nonresponders. The median number of all RBCs transfused to the responders was 6, vs 10 for the nonresponders (P < .01); the median age of the RBCs was 15 vs 14 days, respectively (P = .70). Responders received a median of 3 D-positive RBC units vs 4 D-positive RBCs for nonresponders (P = .02); median ages of the D-positive RBCs were 16 vs 14 days, respectively (P = .21). There was no association between the age of transfused RBCs and the likelihood of anti-D alloimmunization.

  20. Successful prevention of post-transfusion Rh alloimmunization by intravenous Rho (D) immune globulin (WinRho SD).

    PubMed

    Anderson, B; Shad, A T; Gootenberg, J E; Sandler, S G

    1999-03-01

    Alloimmunization to the D blood group antigen following the transfusion of D-positive red blood cells to a D-negative recipient may be prevented in most persons by a prompt and adequate dose of Rho (D) immune globulin (RhIG). Until recently, the only RhIG approved by the US Food and Drug Administration (FDA) for this indication required intramuscular injection, an inconvenient and painful route for the relatively large volume that may be required. We describe the successful prevention of Rh alloimmunization following the unintentional transfusion of D-positive red blood cells to a D-negative infant by the intravenous infusion of WinRho SD, a new RhIG that is FDA-approved for prevention of post-transfusion Rh alloimmunization by intravenous administration. We believe that this more convenient and less painful approach should be the treatment of choice for preventing Rh alloimmunization following the transfusion of D-positive red cells to a D-negative recipient.

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

    PubMed

    Lozo, Svjetlana; Atabeygi, Amir; 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. 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).

  3. 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

  4. Special Blood Donation Procedures

    MedlinePlus

    ... type of abnormal antibody formation), and thrombotic thrombocytopenic purpura (a rare clotting disorder). In cytapheresis, excess numbers ... generally does not cure them. However, thrombotic thrombocytopenic purpura can be cured with apheresis. Directed or designated ...

  5. What Causes Thrombocytopenia?

    MedlinePlus

    ... Transfusion Disseminated Intravascular Coagulation Immune Thrombocytopenia Thrombotic Thrombocytopenic Purpura Send a link to NHLBI to someone by ... low platelet count. Two examples are thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC). TTP is ...

  6. Platelet associated antibodies

    MedlinePlus

    ... of the following: For unknown reasons (idiopathic thrombocytopenic purpura, or ITP ) Side effect of certain drugs such ... 2012:chap 134. Read More Antibody Idiopathic thrombocytopenic purpura (ITP) Platelet count Serum globulin electrophoresis Thrombocytopenia Update ...

  7. Drug-related Henoch-Schönlein Purpura.

    PubMed

    Escudero, A; Lucas, E; Vidal, J B; Sánchez-Guerrero, I; Martínez, A; Illán, F; Ramos, J

    1996-01-01

    We report the case of a patient with Henoch-Schönlein Purpura related to a treatment with cefuroxime and diclofenac who presented important systemic manifestations including a glomerulonephritis with IgA mesangial deposits. Skin testing with beta lactam antibiotics and diclofenac were negative in immediate and late reaction as well as RAST test to penicillins G and V. No cautious administration of drugs was done because of the illness severity. Although a reaction to diclofenac could not be excluded we thought that the more probably implicated drug was cefuroxime because the patient referred a purpuric rash after the intake of cephradine for a mastitis, ten years ago. PMID:8882757

  8. [Use of anti-D (Rh) IgG or intramuscular polyvalent human immunoglobulin in the treatment of chronic autoimmune thrombocytopenic purpura].

    PubMed

    Vizcaíno, G; Diez-Ewald, M; Arteaga-Vizcaíno, M; Torres, E

    1992-01-01

    The present study compares the effect of the intramuscular injection of low doses of IgG anti-D or human polyvalent immunoglobulin (Ig) on the platelet count of patients with CATP. Forty patients (14 children, 26 adults), 11 who had undergone splenectomy, were divided in the following groups of treatment: 20 patients received a single injection of 300 micrograms of IgG anti-D, 6 patients received the same dose as above plus 0.5 mg/kg daily of prednisone v.o and 14 patients received 640 mg of polyvalent Ig. Each patient was sequentially studied by measuring peripheral blood parameters, reticulocyte index, direct Coombs' test and C3-C4 determinations. Their blood group and Rh factor had been previously determined. The platelet response was evaluated as refractory (no response) and favorable (platelet increment over 50,000/microliters compared with initial platelet count). Patients with a favorable response over a month were considered as a prolonged remission. The results showed a favorable platelet response in 74% of the patients that received a single injection of IgG anti-D alone (one of the patients was Rh negative) or associated to prednisone, and 42.8% of the cases when polyvalent Ig was used. The patients who had not undergone splenectomy obtained better results than the group with splenectomy (62% vs 45%) and children showed a better response than adults (78.5% vs 46.1%). Forty five percent of prolonged remissions (including the Rh negative patient) were obtained with both schemes of IgG anti-D administration and only 28.5% when polyvalent Ig was used. The remissions were significantly longer with IgG anti-D (p < 0.01). The hematological and serological parameters did not show any significant modifications in all the cases and there was no adverse effects with the treatment. In conclusion, the intramuscular injection of immunoglobulins, especially IgG anti-D, produce an increase in the platelet count in some patients with CATP, several of them can obtain prolonged remissions, particularly children and patients that had not received immunoglobulins previously. This treatment is safe, ambulatory, easy to administer, and relatively inexpensive.

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

    PubMed Central

    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. PMID:26823908

  10. 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

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

    PubMed

    Hagihara, Masao; 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

  12. Correlation of Notch1/Hes1 Genes Expression Levels in Egyptian Paediatric Patients with Newly Diagnosed and Persistent Primary Immune(Idiopathic) Thrombocytopenic Purpura.

    PubMed

    Gawdat, Rania Mohsen; Hammam, Amira Ahmed; Ezzat, Dina Ahmed

    2016-09-01

    Notch signalling is involved in the development of several autoimmune diseases, one of such diseases is ITP. The aim of this study was to investigate and compare the expression levels of Notch1 receptor and its target Hes1 gene in Egyptian paediatric ITP patients. Real-time quantitative reverse transcriptase polymerase chain reaction was used to analyse the expression levels of Notch1 and Hes1 in 42 children with primary ITP (22 newly diagnosed and 20 persistent) cases. Twenty age and sex matched non-ITP controls were included. The expression levels of Notch1 were higher in newly diagnosed and persistent cases than controls with high statistical significant difference (P value < 0.001, P < 0.001) respectively, similarly as regards the expression levels of HES1 (P value < 0.001, P < 0.007) respectively. A significant positive correlation was found between Notch1 and Hes1 expression levels in newly diagnosed cases (r = 0.587, P value = 0.004). There was an association between levels of both genes in most of ITP patients but Hes1 was markedly elevated than Notch1 in few cases. High expression levels of Notch1/Hes1 indicated the important role of Notch signalling in both newly diagnosed and persistent ITP. High expression levels of Hes1 than Notch1 may shed light on its value as a therapeutic target for future research in ITP. PMID:27429531

  13. Urological Manifestations of Henoch-Schonlein Purpura: A Review

    PubMed Central

    Dalpiaz, Amanda; Schwamb, Richard; Miao, Yimei; Gonka, Jacquelyn; Walzter, Wayne; Khan, Sardar A.

    2015-01-01

    Henoch-Schonlein purpura (HSP) is an immune-mediated systemic vasculitis generally found in children. The standard manifestations of HSP are palpable purpura, arthritis, abdominal pain, and renal complications. Although less common, there are significant urological manifestations associated with HSP. The primary objective of this review is to encourage better understanding and management of HSP by emphasizing the common and rare manifestations of HSP, how they are diagnosed, and the latest treatment options for mild to severe complications. Medline searches of HSP and its urological manifestations were conducted along with searches on current diagnostic and treatment methods. Urological manifestations of HSP involve the kidney, ureter, bladder, prostate, scrotum, testicle, and penis. Diagnosis and management of HSP are not always clear due to differential diagnosis and diversity of symptom presentation. Treatment for HSP is mainly supportive and includes use of nonsteroidal anti-inflammatory drugs for pain relief. In more severe cases, glucocorticoids, methylprednisolone, plasmapheresis, and peritoneal and hemodialysis are reported successful. It is important to note different symptoms of HSP in order to distinguish HSP from other diseases. Early diagnosis may prevent severe complications. Treatment options vary from conservative to invasive depending on the severity of the disease and time frame of diagnosis. PMID:26889120

  14. Henoch-Schonlein purpura nephritis: pathophysiology, treatment, and future strategy.

    PubMed

    Davin, Jean-Claude

    2011-03-01

    Henoch-Schönlein purpura nephritis is a rare kidney disease leading to chronic kidney disease in a non-negligible percentage of patients. Although retrospective studies suggest beneficial effects of some therapies, prospective randomized clinical trials proving treatment efficacy are still lacking. The dilemma of spontaneous recovery even in patients with severe clinical and histologic presentation and of late evolution to chronic kidney disease in patients with mild initial symptoms renders it difficult for clinicians to expose patients to treatment protocols that are not evidence-based. A better understanding of the pathophysiology of progression to chronic kidney disease in Henoch-Schönlein purpura patients could be achieved by designing prospective international multicenter studies looking at determinants of clinical and histopathological evolution as well as possible circulating and urinary markers of progression. Such studies should be supported by a database available on the web and a new histologic classification of kidney lesions. This paper reports clinical, pathologic, and experimental data to be used for this strategy and to assist clinicians and clinical trial designers to reach therapeutic decisions.

  15. 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. PMID:26344048

  16. 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.

  17. 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.

  18. Alloimmune IgG binds and modulates cardiac beta-adrenoceptor activity.

    PubMed Central

    Sterin-Borda, L; Cremaschi, G; Pascual, J; Genaro, A; Borda, E

    1984-01-01

    Purified IgG from murine alloimmune sera directed against class I products from the major histocompatibility complex of the mouse, could bind to the beta-adrenoceptors and stimulate contractile activity of myocardium. Immune IgG inhibited the binding of (-) 3H-DHA to beta-adrenoceptors of mouse myocardial membranes behaving as a competitive inhibitor. Moreover, immune IgG induced positive inotropic and chronotropic effects on isolated mouse atria. These effects could be blocked by beta-adrenoceptors antagonists. Data prove that immune IgG directed against specific alloantigens are able to recognize the beta-adrenoceptors and mimic the stimulation of the beta-adrenoceptor agonist. PMID:6090043

  19. /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.

  20. 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

  1. Micromanaging alloimmunity.

    PubMed

    Ford, Mandy L

    2016-07-01

    Increasing evidence indicates that microbes have a large influence on immune function. Previous studies have linked pathogenic microorganisms with decreased allograft tolerance and subsequent rejection. In this issue of the JCI, Lei and colleagues demonstrate that commensal organisms also influence the host response to allograft transplantation. Using murine skin and cardiac transplant models, the authors demonstrate that allograft rejection is accelerated in mice with a normal microbiome compared with germ-free animals and antibiotic-treated mice. The increased graft rejection observed in conventional animals was due to enhanced T cell priming and was mediated through type I IFN. Together, these results suggest that altering a patient's microbial community prior to transplant could improve allograft acceptance.

  2. Megakaryocyte size and concentration in the bone marrow of thrombocytopenic and nonthrombocytopenic neonates.

    PubMed

    Sola-Visner, Martha C; Christensen, Robert D; Hutson, Alan D; Rimsza, Lisa M

    2007-04-01

    Thrombocytopenia is frequent among sick neonates, but little is known about its underlying mechanisms. It is known, however, that neonatal megakaryocytes are smaller and of lower ploidy than their adult counterparts and that smaller megakaryocytes produce fewer platelets than larger, more polyploid, megakaryocytes. We hypothesized that neonatal megakaryocytes would not increase their size in response to thrombocytopenia, thus limiting the ability of neonates to mount a response. To test this, we obtained marrow specimens from thrombocytopenic and nonthrombocytopenic neonates and adults. Megakaryocytes were immunohistochemically stained, quantified using an eyepiece reticle, and measured using an image analysis system with incorporated electronic micrometer. We found that, after adjusting for differences in cellularity, neonates and adults had similar megakaryocyte concentrations. When samples from the same sources were compared (tibial clot and vertebral body sections in neonates, iliac crest biopsies in adults), there were also no differences in megakaryocyte concentration between thrombocytopenic and nonthrombocytopenic subjects. The megakaryocyte diameter, however, was greater in adults than in neonates (19.4 +/- 3.0 versus 15.3 +/- 1.7 microm, p<0.0001). Thrombocytopenic adults also had a higher proportion of large megakaryocytes than nonthrombocytopenic adults (p<0.001). This was not observed among thrombocytopenic neonates, suggesting a developmental limitation in their ability to increase megakaryocyte size. PMID:17515875

  3. Acute Scrotal Swelling in Henoch-Schonlein Purpura: Case Report and Review of the Literature

    PubMed Central

    Modi, Sunny; Mohan, Muhunthan; Jennings, Andrew

    2016-01-01

    Henoch-Schönlein purpura (HSP) is a systemic vasculitis characterized classically by purpura, arthritis and abdominal pain. Epididymitis/orchitis is rarely seen as a complication of HSP. Testicular or scrotal involvement has been reported in children with Henoch-Schonlein purpura and must be distinguished from testicular torsion. We report a case of a 5 year old boy diagnosed with Henoch-Schönlein purpura with acute scrotal swelling. He was managed successfully with conservative approach. The history, clinical examination findings and scrotal ultrasound evaluation should suffice to make the correct diagnosis and avoid surgery. Steroid treatment and/or antibiotics appeared to be effective for this condition. PMID:27169017

  4. 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. PMID:23985086

  5. 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.

  6. Maternal alloimmunization against the rare platelet-specific antigen HPA-9b (Maxa) is an important cause of neonatal alloimmune thrombocytopenia

    PubMed Central

    Peterson, Julie A.; Balthazor, Stephanie M.; Curtis, Brian R.; McFarland, Janice G.; Aster, Richard H.

    2006-01-01

    BACKGROUND Neonatal alloimmune thrombocytopenia (NATP) is an important cause of morbidity and mortality in the newborn. Optimal management of subsequent pregnancies requires knowledge of the alloantigen that caused maternal immunization, but this is possible only in a minority of cases. This study investigated whether this can be explained in part by maternal immunization against the “rare” alloantigen HPA-9b (Maxa), implicated previously only in a single NATP case. STUDY DESIGN AND METHODS Archived paternal DNA from unresolved cases of NATP and normal individuals was typed for platelet (PLT)-specific antigens with real-time polymerase chain reaction and direct sequencing. PLT-specific alloantibodies were characterized by flow cytometry and solid-phase enzyme-linked immunosorbent assay. Recombinant GPIIb/IIIa was expressed in stably transfected Chinese hamster ovary cells. Clinical information was obtained directly from attending physicians. RESULTS Six of 217 fathers were positive for the presence of HPA-9b (Maxa), an incidence about seven times that in the general population. In each of five cases studied, maternal serum samples reacted with intact paternal PLTs and paternal GPIIb/IIIa. Only one of three serum samples tested recognized recombinant GPIIb/IIIa carrying the HPA-9b (Maxa) mutation. These seemingly discrepant reactions may reflect different requirements for oligosaccharides linked to residues close to the mutation in GPIIb that determines HPA-9b (Maxa). NATP in the affected children was severe and was associated with intracranial hemorrhage in three of six infants on whom information was obtained. CONCLUSIONS Maternal immunization against HPA-9b (Maxa) is an important cause of NATP and should be considered in cases of apparent NATP not resolved on the basis of maternal-fetal incompatibility for “common” PLT antigens. PMID:16131382

  7. Henoch-Schönlein Purpura Associated with Gangrenous Appendicitis: A Case Report

    PubMed Central

    SEMEENA, NK; ADLEKHA, Shashikant

    2014-01-01

    Henoch-Schönlein Purpura (HSP) is a leucocytoclastic vasculitis of unclear aetiology characterised by symmetrical, non-traumatic, nonthrombocytopenic purpura mostly involving the lower limbs and buttocks, as well as arthritis, gastrointestinal manifestations, and occasional nephritis. A 35 years old male presented with purpuric rash on the lower extremities, abdominal pain, fever, arthralgia, and melaena. A diagnosis of HSP with appendicitis was made, which is an exceedingly rare phenomenon. PMID:24876811

  8. 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.

  9. Purpura fulminans secondary to rickettsial infections: A case series

    PubMed Central

    Katoch, Saloni; Kallappa, Ravindra; Shamanur, Murugesh B.; Gandhi, Sneha

    2016-01-01

    Purpura fulminans (PF) is a descriptive term used to describe a heterogeneous group of disorders characterized by rapidly progressive purpuric lesions that may develop into extensive areas of skin necrosis, and peripheral gangrene. This rare disorder is associated with laboratory evidence of consumptive coagulopathy and is often fatal. PF is usually associated with many infections, most notably with meningococcal, staphylococcal, and streptococcal infections. However, there are very few reports of this entity with spotted fever and scrub typhus from India. Rickettsial infections are an underdiagnosed group of diseases presenting as acute febrile illness, with high mortality in untreated cases. Of the available tests, Weil–Felix is a handy and economical tool for early diagnosis of this fatal disease especially in resource poor settings. We present four infants with PF secondary to rickettsial fever diagnosed by the Weil–Felix test. PMID:26955583

  10. Neonatal alloimmune thrombocytopenia caused by human leucocyte antigen-B27 antibody.

    PubMed

    Thude, H; Schorner, U; Helfricht, C; Loth, M; Maak, B; Barz, D

    2006-04-01

    Neonatal alloimmune thrombocytopenia (NAIT) occurs when maternal alloantibodies to antigens presented on foetal platelets cause their immune destruction. Whether human leucocyte antigen (HLA) antibodies can cause NAIT is controversial. Here, a patient was described who suffered from a NAIT caused by an HLA-B27 antibody. Sera from the mother and the newborn were tested for human platelet antigen antibodies and HLA antibodies by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay, solid phase-linked immunosorbent assay (ELISA), lymphocytotoxicity assay (LCT) and flow cytometric analysis. No antibodies against cluster designation (CD)109 and platelet glycoproteins of the father were found in patient's and mother's serum. However, HLA ELISA was used to identify HLA antibody in both sera. The antibody was specified as HLA-B27 antibody. Typing results showed that the father descended HLA-B27 antigen on patient and his brother. The mother was HLA-B27 negative. It is most conceivable that the previous pregnancy of the mother induced the production of anti-HLA-B27 antibody, which crossed the placenta and subsequently caused an NAIT in the case presented. PMID:16623921

  11. A case of severe Rh (D) alloimmunization pregnant woman delivery an infant with limited treatment.

    PubMed

    Xu, Wenhao

    2013-10-01

    A 35-year-old woman with histories of frequent failed pregnancies was pregnant after having five plasma exchange procedures during which she was given Rh (D) positive plasma as replacement and her anti-D antibody titer went from 512 to 1024. Antenatal surveillance of the fetus showed no abnormality. At 36 weeks gestation she delivered an infant who initially had no significant clinical problems but was severely anemic on the following days. Using exchange transfusion and blood transfusions the infant's hemoglobin was normal at 4 months of age. Thus, the Rh (D) status of donor plasma should be considered when used as the replacement in plasma exchange for Rh (D) negative women. Severe Rh (D) alloimmunization pregnant woman may delivery an infant who seem in good condition at birth. If severe Rhesus isoimmunisation of the infant is confirmed, whole blood exchange should be done as early as possible and the infant must be considered to be at risk for late anemia. Clinical judgment plays a vital role in the decision to transfuse red cells or not.

  12. 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

  13. Mathematical model of platelet turnover in thrombocytopenic and nonthrombocytopenic preterm neonates.

    PubMed

    Kulshrestha, Mudit; Sola-Visner, Martha; Widness, John A; Veng-Pedersen, Peter; Mager, Donald E

    2015-01-01

    Neonatal thrombocytopenia affects 22-35% of all neonates admitted to neonatal intensive care units. The purpose of this study was to develop a mathematical model for characterizing platelet (PLT) kinetics in thrombocytopenic preterm neonates. Immature PLT fraction (IPF) and PLT counts were measured for up to 35 days after birth in 27 very low birth weight preterm neonates. PLT transfusions were administered to 8 of the 27 (24%) subjects. The final model included a series of four transit compartments to mimic the production and survival of IPF and PLT. Model parameters were estimated using nonlinear mixed effects modeling with the maximum likelihood expectation maximization algorithm. The model adequately captured the diverse phenotypes expressed by individual subject profiles. Typical population survival values for IPF and PLT life spans in nonthrombocytopenic patients were estimated at 0.912 and 10.7 days, respectively. These values were significantly shorter in thrombocytopenic subjects, 0.429 and 2.56 days, respectively. The model was also used to evaluate the influence of growth and laboratory phlebotomy loss on the time course of IPF and PLT counts. Whereas incorporating body weight was essential to correct for expanding blood volume due to growth, phlebotomy loss, a possible covariate, did not significantly influence PLT kinetics. This study provides a platform for identifying potential covariates that influence the interindividual variability in model parameters regulating IPF and PLT kinetics and for evaluating future pharmacological therapies for treating thrombocytopenic neonates. PMID:25362135

  14. A case of neutrophilic dermatosis who develop palpable purpura during the use of montelukast

    PubMed Central

    Çetin, Gözde Yıldırım; Sayarlıoğlu, Hayriye; Erhan, Çiğdem; Kahraman, Hasan; Cıralık, Harun; Sayarlıoğlu, Mehmet

    2014-01-01

    In this case report, we present a female patient with neutrophilic dermatosis (ND) occurring as palpable purpura after using montelukast. Neutrophilic dermatoses (NDs) are characterized by skin lesions in which mature neutrophils are predominantly located in the epidermis and dermis in the absence of any infective pathology. Classification of the NDs is based upon the recognition of clinical and pathologic features, as well as the identification of associated diseases, like Sweet’s syndrome, pyoderma gangrenosum, generalized pustular psoriasis, and Behçet’s disease. Cutaneous findings in NDs are variable and can include vesiculopustules, plaques, nodules, or ulcerations. Drug-induced NDs are not uncommon, but ND with palpable purpura is uncommon. The current patient appeared with a rare presentation as palpable purpura without vasculitis regarding ND. It is important that this is the first case report. PMID:27708908

  15. [Henoch-Schönlein Purpura with lung abscess].

    PubMed

    Nakazawa, Junji; Watanabe, Atsushi; Nakajima, Tomohiro; Mishina, Taijiro; Miyajima, Masahiro; Higami, Tetsuya

    2013-09-01

    A 72-year-old man had underwent left lower lobectomy for squamous cell carcinoma in our hospital in 2008. Postoperative stage was I A (T1N0M0). In 2010, follow-up chest computed tomography (CT) images showed similar cavitary nodules in segments 2 and 8 of the right lung with positive uptake on fluorodeoxyglucose-positron emission tomography (FDG-PET) images. Physical examination, blood tests, and levels of serum tumor markers showed no abnormality. Transbronchial lung biopsy revealed the absence of malignant cells. Segment 8 of the right lower lobe with the nodule was partially resected, and pathological examination demonstrated lung abscess. He was discharged but was hospitalized in another hospital for purpuric rash, fever, and arthralgia. Microscopic albuminuria was noted, and renal biopsy revealed nephritis with immunoglobulin A( IgA)deposition. He was made a diagnosis of Henoch-Schönlein purpura. Oral steroid therapy( prednisolone 60 mg/d) was initiated, resulting in the improvement of symptoms and disapearance of the cavitary nodule in the right lung segment 2. PMID:24008637

  16. Neonatal alloimmune thrombocytopenia in Taiwan due to an antibody against a labile component of HPA-3a (Baka).

    PubMed

    Lin, M; Shieh, S H; Liang, D C; Yang, T F; Shibata, Y

    1995-01-01

    We report on two siblings who developed severe neonatal alloimmune thrombocytopenia (NAIT) due to an alloantibody against a labile component or components of the HPA-3a (Baka) antigen. The antibody reacted only with fresh, unfixed platelets by the solid-phase red cell adherence test, immunofluorescence test and mixed passive haemagglutination test. In the latter method, weakly fixed platelets also gave a weak positive reaction. Monoclonal-antibody-specific immobilization of platelet antigens and immunoblotting tests gave negative results. Our findings may possibly help to explain why in some cases of NAIT no platelet-specific antibody is demonstrable in tests with fixed or solubilized platelets.

  17. Neonatal alloimmune thrombocytopenia in the Irish population: a discrepancy between observed and expected cases

    PubMed Central

    Davoren, A; McParland, P; Barnes, C A; Murphy, W G

    2002-01-01

    Aims: To estimate the rate of detection of neonatal alloimmune thrombocytopenia (NAITP) in the Irish population, to investigate clinical presentation and outcome in affected infants, and to determine the extent, if any, to which this condition is underdiagnosed at present. Methods: Cases were collected in a retrospective fashion from a review of platelet serology laboratory records from January 1992 to December 2000. Clinical data were obtained from hospital records. Testing for maternal antiplatelet antibody was by one or more of the following: the platelet suspension immunofluorescence test, a commercial antigen capture enzyme linked immunosorbent assay (GTI-PakPlus™), and the monoclonal antibody immobilisation of platelet antigens assay. Platelet antigen typing was by the polymerase chain reaction technique with sequence specific primers. Results: Twenty seven serologically verified cases of NAITP were identified in 18 families. Maternal antibody to human platelet antigen 1a accounted for 25 of the 27 confirmed cases. Twenty one of 26 infants were born with severe thrombocytopenia. Nineteen of 27 infants had bleeding manifestations at birth. Petechiae and bruising were most commonly observed (n = 17). There were no documented cases of intracranial haemorrhage in this group but systematic cranial ultrasound was not performed. Conclusions: Screening studies in predominantly white populations have estimated the incidence of NAITP to be between 1 in 1000 and 1 in 2000 live births. With 50 000 births each year in Ireland, these results give a clinical detection rate for NAITP of just 1 case in 16 500 live births, strongly suggesting that NAITP is currently underdiagnosed. Antenatal screening to detect women at risk of having babies with NAITP is now scientifically feasible and should be considered. PMID:11919215

  18. Clinical and blood bank factors in the management of platelet refractoriness and alloimmunization.

    PubMed

    Friedberg, R C; Donnelly, S F; Boyd, J C; Gray, L S; Mintz, P D

    1993-06-15

    Numerous independent and interdependent factors are involved in the posttransfusion platelet response. Factors such as ABO match and platelet age are related to circumstances potentially under the control of the blood bank physician and therefore may permit circumvention by an active transfusion service. On the other hand, factors such as fever or sepsis may be unavoidable, being related more to the individual patient or clinical condition. To evaluate which factors could be circumvented, we prospectively followed the 1-hour corrected count increments (CCIs) for 962 single-donor apheresis platelet transfusions to 71 refractory hematologic oncology inpatients, with concomitant recording of implicated factors. Stepwise regression analysis allowed for determination of which concurrent and confounding clinical-, patient-, and blood bank-related factors significantly affected the CCIs. Although many implicated factors proved to be independently associated with an increased or decreased CCI, we found that no single variable consistently explained the CCI variation across the patient population. Each patient appeared sensitive to one or a few particular factors, but because of marked intraindividual variation, it was not possible to identify a priori which factors were important for a given patient. The single exception was a solid-phase red blood cell adherence assay used to cross-match platelets, but only for alloimmunized patients. We also evaluated the utility of requesting HLA-matched platelets from the local suppliers and maintained a clear distinction between platelets simply ordered as HLA matched and actually HLA-identical platelets. Accounting for the confounding clinical-, patient-, and blood bank-related factors, the cross-match assay was a better predictor of an adequate CCI than ordering platelets as HLA matched.

  19. 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.

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

    PubMed

    Prathiba Rajalakshmi, Parameswaran; Srinivasan, Kalyanasundaram

    2015-03-28

    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

  1. 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

  2. Interaction between ICOS-B7RP1 and B7-CD28 costimulatory pathways in alloimmune responses in vivo.

    PubMed

    Salama, Alan D; Yuan, Xueli; Nayer, Ali; Chandraker, Anil; Inobe, Manabu; Uede, Toshimutsu; Sayegh, Mohamed H

    2003-04-01

    The B7-CD28 pathway is one of the foremost costimulatory pathways involved in T-cell activation. Recently, a number of additional costimulatory pathways have been described and preliminary data suggest that they play important roles in alloimmunity. However, the interactions between these different pathways are not well understood. We studied the effect of targeting ICOS ligand, B7RP1, in a rat cardiac transplant model, with and without concomitant blockade of the B7 pathway using CTLA4Ig. In a fully mismatched WF to LEW vascularized cardiac allograft model, without therapy, grafts were acutely rejected (MST 10.8 +/- 1.6 days). Early (day of transplant) B7RP1 blockade with ICOSIg alone had little effect on graft survival and rather than being additive with B7 blockade, ICOSIg abrogated the prolonged graft survival induced by CTLA4Ig treatment. By contrast, delayed (day 2 post-transplant) blockade of B7RP1 did not have such an effect. These findings were not related to cytokine deviation but may be in part related to the pattern of down-regulation of B7.2 expression following early B7RP1 blockade. This is the first report describing the complex interactions between ICOS-B7RP1 and B7-CD28 costimulatory pathways in alloimmunity in vivo. PMID:12694060

  3. Provision of HPA-1a (PlA1)-negative platelets for neonatal alloimmune thrombocytopenia: screening, testing, and transfusion protocol.

    PubMed

    Munizza, M; Nance, S; Keashen-Schnell, M A; Sherwood, W; Murphy, S

    1999-01-01

    HPA-1a-negative platelet products are not routinely available for newborns with alloimmune thrombocytopenia. In this article we describe a program established to identify normal pheresis donors who are HPA-1a-negative and to organize their future donations so that our regional blood center would always have an HPA-1a-negative platelet product available. The solid phase red cell adherence assay was used for initial screening of platelet pheresis products. HPA-1a-negative donors were confirmed with the platelet suspension immunofluorescence test using three anti-HPA-1a sera. Screening of 2600 plateletpheresis donor samples identified 40 HPA-1a-negative donors. Of these, 36 are active and are coded for recognition on the daily pheresis inventory sheet. Theoretically, assuming four donations per year and donors' cooperation with scheduling, these 36 donors would enable us to have at least one HPA-1a-negative product available every day. In addition, a decision tree for patient management using platelet serology and availability of HPA-1a-negative products was developed. The GTI-PAK trade mark 12 is the major technique used for serologic screening of mothers of patients thought to have neonatal alloimmune thrombocytopenia. By screening pheresis donors and developing a clinical decision tree, HPA-1a-negative products, a rare resource, can be fully utilized.

  4. Prevalence of Alloimmunization to Human Platelet Antigen Glycoproteins and Human Leucocyte Antigen Class I in β Thalassemia Major Patients in Western India.

    PubMed

    Philip, Joseph; Kumar, Sudeep; Chatterjee, T; Mallhi, R S

    2014-12-01

    Present management of β thalassemia major by regular packed red blood cell (PRBC) transfusions poses risk of alloimmunization not only to red blood cell antigens, but also to human platelet antigens (HPA) and Human leucocyte antigens class I (HLA I). However data in this context is very limited in Indian population. The aim of the study was to determine the prevalence of alloimmunization to HPA and HLA I in β thalassemia major patients who have received multiple PRBC transfusions over the years. A cross sectional study was performed at our tertiary care blood bank. β thalassemia major patients of more than 6 years of age were included who were receiving fresh, leucoreduced and irradiated PRBC units regularly with annual requirement of more than ten PRBC transfusions. A total of 9 out of 80 (11.25 %) patients were found to be alloimmunized for HPA antigens of various specificity and 24 out of 80 (30 %) developed antibodies to HLA I. The awareness of development of alloimmunization to HPA and HLA antigens in multi PRBC transfused thalassemics, despite use of leucofilters will prompt us, to look for improvement in our current PRBC preparations to minimise platelet alloimmunisation. Further studies are required to validate the findings and build the base line data in this regard. This is of importance, especially in view of providing suitable cross-matched platelets when required in future especially when considering future haematopoietic stem cell transplantation (HSCT).

  5. Group A Escherichia coli-Related Purpura Fulminans: an Unusual Manifestation Due to an Unusual Strain?

    PubMed Central

    Amara, Marlène; Bonacorsi, Stéphane; Bedel, Jérôme; Mira, Jean-Paul; Laurent, Virginie; Socha, Koryna; Bruneel, Fabrice; Pangon, Béatrice; Bédos, Jean-Pierre

    2014-01-01

    We describe an exceptional case of life-threatening group A Escherichia coli-induced purpura fulminans. Genotyping of common polymorphisms in genes involved in innate immunity or coagulation did not reveal known susceptibility to such a manifestation. Genetic analysis of the strain revealed an unusual conserved virulence plasmidic region, pointing out its potential virulence. PMID:25232165

  6. 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. PMID:21377319

  7. Thromboelastometric Monitoring of the Hemostatic Effect of Platelet Concentrates Transfusion in Thrombocytopenic Children Undergoing Chemotherapy

    PubMed Central

    Solomon, Cristina; Cadamuro, Janne; Jones, Neil

    2015-01-01

    Prophylactic platelet concentrates transfusion represents a therapeutic choice in patients with chemotherapy-induced thrombocytopenia. This prospective, non-interventional study evaluated the effects of platelet concentrates transfusion on thromboelastometric parameters of platelet function in 36 transfusion occasions for 11 thrombocytopenic children undergoing chemotherapy. Pre- and posttransfusion (1-2 hours) blood samples were analyzed using standard coagulation tests and thromboelastometry (ROTEM) measurements (EXTEM and FIBTEM tests). Platelet component of the clot was calculated based on the EXTEM and FIBTEM maximum clot elasticity (MCE) results. After transfusion, mean platelet count increased from 16.5 × 109/L to 43.0 × 109/L (P < .001) and platelet component increased from 34.1 to 73.0 (P < .001). Statistically significant increases for posttransfusion EXTEM parameters A10, A20, and maximum clot firmness (MCF) were observed compared to pretransfusion values (P < .001). The EXTEM α-angle values increased posttransfusion (P < .05). The FIBTEM measurements were comparable pre- and posttransfusion. The study showed that platelet concentrates transfusion in thrombocytopenic children undergoing chemotherapy improves platelet-related coagulation pattern. PMID:25525046

  8. 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

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

    PubMed Central

    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.

    2013-01-01

    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. PMID:23656729

  10. 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

  11. 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.

  12. Association of endothelial nitric oxide synthase gene polymorphism with the risk of Henoch-Schönlein purpura/Henoch-Schönlein purpura nephritis.

    PubMed

    Zhong, Weiqiang; Zhou, Tian-Biao; Jiang, Zongpei

    2015-04-01

    Association between endothelial nitric oxide synthase (eNOS) gene polymorphism and Henoch-Schönlein purpura (HSP)/Henoch-Schönlein purpura nephritis (HSPN) risk is still controversial. A meta-analysis was performed to evaluate the association between eNOS gene polymorphism and HSP/HSPN susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Three articles were identified for the analysis of association between eNOS gene polymorphism and HSPN/HSP risk. eNOS G894T gene polymorphism was not associated with HSPN susceptibility and the risk of patients with HSP developing into HSPN. Interestingly, eNOS G894T T allele and GG genotype were associated with HSP susceptibility, but not the TT genotype. eNOS T786C TT genotype was associated with HSPN susceptibility, but not C allele and CC genotype. Furthermore, eNOS T786C gene polymorphism was not associated with HSP risk and the risk of patients with HSP developing into HSPN. In conclusion, eNOS T786C TT genotype was associated with and eNOS G894T T allele and GG genotype were associated with HSP susceptibility. However, more studies should be performed in the future. PMID:25585947

  13. Immune-mediated thrombocytopenias: basic and immunological aspects.

    PubMed

    Porcelijn, L; von dem Borne, A E

    1998-06-01

    Acute idiopathic or autoimmune thrombocytopenic purpura (AITP) is a disorder found mainly in children, usually preceded by a viral infection, with a higher incidence in the autumn and winter. The platelet-specific autoantibodies in acute childhood AITP are more often of the IgM class. Chronic AITP occurs mostly in adults. The platelet immunofluorescence test (PIFT) detects platelet-specific autoantibodies with a sensitivity of 65-75%. The autoantibodies in chronic AITP are classified as IgG in 95%, IgM in 26% and IgA in 4% of cases. The antibodies are usually bound to platelets and are detectable as free circulating antibodies in about 40%. AITP in pregnancy may cause neonatal AITP by autoantibodies of the IgG class which pass the placenta barrier. The rare neonatal alloimmune thrombocytopenic purpura (NAITP) are caused by IgG alloantibodies against HPA-1a in 75-90%, HPA1b in 3-5%, HPA 3a in 4-5%, HPA5b in 6-19% and against private platelet antigens in 3%. To confirm the diagnosis of NAITP requires extensive serological testing of the child, and the parents have to be typed for the important platelet-specific antigens by PIFT, monoclonal antibody immobilisation of platelet antigens (MAIPA) and/or enzyme-linked immunosorbent assay (ELISA) techniques. Three mechanisms of drug-induced thrombocytopenias are described. Platelets of both the donor and the patient are destroyed in post-transfusion thrombocytopenic purpura (PTP) but PTP does not occur again if incompatible platelets are re-administered. PMID:10097811

  14. 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

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

    PubMed

    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

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

    PubMed

    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

  17. Sirolimus for Autoimmune Disease of Blood Cells

    ClinicalTrials.gov

    2016-04-22

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

  18. Bruising and Bleeding

    MedlinePlus

    ... or purple dots (petechiae), red or purple patches (purpura), bruises (ecchymoses), or small blood vessels that are ... syndrome HIV infection Immune thrombocytopenia Leukemia Thrombotic thrombocytopenic purpura Increased number of platelets (which often causes excessive ...

  19. Platelet Count

    MedlinePlus

    ... rash Small purplish spots on the skin called purpura, caused by bleeding under the skin Testing may ... Idiopathic thrombocytopenia (ITP), also known as immune thrombocytopenic purpura, is the result of antibody production against platelets. ...

  20. How Is Immune Thrombocytopenia Treated?

    MedlinePlus

    ... Blood Transfusion Bone Marrow Tests Thrombocytopenia Thrombotic Thrombocytopenic Purpura Send a link to NHLBI to someone by ... who have bleeding symptoms, other than merely bruising (purpura), usually are treated. Children who have mild ITP ...

  1. Large-scale DNA typing for human platelet alloantigens by PCR-PHFA (preferential homoduplex formation assay).

    PubMed

    Fujiwara, K; Isa, K; Oka, T; Maekawajiri, S; Yamane, A; Akaza, T; Tadokoro, K; Juji, T; Shibata, Y; Tokunaga, K

    1996-10-01

    Alloimmunization against human platelet alloantigens (HPA) is known to be involved in disorders such as neonatal alloimmune thrombocytopenic purpura, posttransfusion purpura, and refractoriness to platelet transfusion therapy. HPA typing is essential in diagnosis and management of patients. Therefore a reliable and speedy method is necessary for HPA typing. We have successfully applied a new DNA typing method, PCR-preferential homoduplex formation assay (PHFA) method, to typing for the HPA-1, -2, -3, -4, -5 and -6 systems. This method is based on DNA strand competition during hybridization under a precisely controlled temperature gradient between a double-labelled amplicon (standard DNA), prepared from biotin- and DNP-labelled primers, and an unlabelled amplicon (sample DNA). The results obtained by PCR-PHFA typing were in good agreement with the allotypes determined by serological typing and by other DNA typing methods. The PCR-PHFA method can be easily automated, is suitable for typing both small and large numbers of samples, and thus is applicable to routine HPA typing.

  2. Anaphylactoid Purpura Manifested after Acute Gastroenteritis with Severe Dehydration in an 8-Year-Old Male Child: A Case Report.

    PubMed

    Thakkar, Umang G; Vanikar, Aruna V; Trivedi, Hargovind L

    2015-12-01

    Anaphylactoid purpura, also known as Henoch-Schönleinpurpura (HSP), is an IgA-mediated vasculitis that tends to be a benign disease of childhood. Up to 50% of cases are preceded by an upper tract respiratory infection caused by group-A beta-hemolytic streptococcus and present with the common tetrad of abdominal pain, arthritis, purpuric rash, and renal involvement. The majority of patients recover completely. Here we document a rare case of anaphylactoid purpura which manifested with skin lesions in the form of palpable purpura following about of acute gastroenteritis with severe dehydration; it was treated with a short regimen of steroid therapy, which resulted in the complete remission of the disease. We conclude that prompt diagnosis and multidisciplinary intervention will lead to appropriate management-consisting of the installation of early short-course steroid therapy and thus, prevent further complications and the recurrence of the disease. PMID:26602584

  3. Expanded Non-human Primate Tregs Exhibit A Unique Gene Expression Signature and Potently Downregulate Allo-immune Responses

    PubMed Central

    Anderson, Alan; Martens, Christine; Hendrix, Rose; Stempora, Linda; Miller, Wes; Hamby, Kelly; Russell, Maria; Strobert, Elizabeth; Blazar, Bruce R.; Pearson, Thomas C.; Larsen, Christian P.; Kean, Leslie S.

    2009-01-01

    We have established two complementary strategies for purifying naturally occurring regulatory T cells (Tregs) from rhesus macaques in quantities which would be sufficient for use as an in vivo cellular therapeutic. The first identified Tregs based on their being CD4+/CD25bright. The second incorporated CD127, and purified Tregs based on their expression of CD4 and CD25 and their low expression of CD127. Using these purification strategies, we were able to purify as many as 1×106 Tregs from 120cc of peripheral blood. Culture of these cells with anti-CD3, anti-CD28 and IL-2 over 21 days yielded as much as 450-fold expansion, ultimately producing as many as 4.7×108 Tregs. Expanded Treg cultures potently inhibited alloimmune proliferation as measured by a CFSE-MLR assay even at a 1:100 ratio with responder T cells. Furthermore, both responder-specific and third-party Tregs downregulated alloproliferation similarly. Both freshly isolated and cultured Tregs had gene expression signatures distinguishable from concurrently isolated bulk CD4+ T cell populations, as measured by single-plex RT-PCR and gene array. Moreover, an overlapping yet distinct gene expression signature seen in freshly isolated compared to expanded Tregs identifies a subset of Treg genes likely to be functionally significant. PMID:18801023

  4. Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia.

    PubMed

    Sonneveld, Myrthe E; Natunen, Suvi; Sainio, Susanna; Koeleman, Carolien A M; Holst, Stephanie; Dekkers, Gillian; Koelewijn, Joke; Partanen, Jukka; van der Schoot, C Ellen; Wuhrer, Manfred; Vidarsson, Gestur

    2016-07-01

    Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. The clinical outcome varies from asymptomatic, to petechiae or intracranial haemorrhage, but no marker has shown reliable correlation with severity, making screening for FNAIT impractical and highly inefficient. We recently found IgG Fc-glycosylation towards platelet and red blood cell antigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. The lowered core-fucosylation increases the affinity of the pathogenic antibodies to FcγRIIIa and FcγRIIIb, and hence platelet destruction. Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). Besides a significant decrease in Fc-fucosylation after the first pregnancy (P = 0·0124), Fc-glycosylation levels remained stable during and after pregnancy and in subsequent pregnancies. Multiple logistic regression analysis identified anti-HPA-1a -fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity, making these parameters a feasible marker in screening for severe cases of FNAIT. PMID:27017954

  5. Effects of increased von Willebrand factor levels on primary hemostasis in thrombocytopenic patients with liver cirrhosis.

    PubMed

    Wannhoff, Andreas; Müller, Oliver J; Friedrich, Kilian; Rupp, Christian; Klöters-Plachky, Petra; Leopold, Yvonne; Brune, Maik; Senner, Mirja; Weiss, Karl-Heinz; Stremmel, Wolfgang; Schemmer, Peter; Katus, Hugo A; Gotthardt, Daniel N

    2014-01-01

    In patients with liver cirrhosis procoagulant and anticoagulant changes occur simultaneously. During primary hemostasis, platelets adhere to subendothelial structures, via von Willebrand factor (vWF). We aimed to investigate the influence of vWF on primary hemostasis in patients with liver cirrhosis. Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100) closure times with collagen and epinephrine (Col-Epi, upper limit of normal ≤ 165 s) or collagen and ADP (Col-ADP, upper limit of normal ≤ 118 s). If Col-Epi and Col-ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72 included cirrhotic patients, 32 (44.4%) showed a pathological result for the PFA-100. They had mean closure times (± SD) of 180 ± 62 s with Col-Epi and 160 ± 70 s with Col-ADP. Multivariate analysis revealed that hematocrit (P = 0.027) and vWF-antigen levels (P = 0.010) are the predictors of a pathological PFA-100 test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count ≥ 150/nL and hematocrit ≥ 27.0%, pathological PFA-100 results were found. In thrombocytopenic (< 150/nL) patients with cirrhosis, normal PFA-100 results were associated with higher vWF-antigen levels (462.3 ± 235.9% vs. 338.7 ± 151.6%, P = 0.021). These results were confirmed by multivariate analysis in these patients as well as by adding recombinant vWF or polyclonal anti-vWF antibody that significantly shortened or prolonged closure times, respectively. In conclusion, primary hemostasis is impaired in cirrhotic patients. The effect of reduced platelet count in cirrhotic patients can at least be partly compensated by increased vWF levels. Recombinant vWF could be an alternative to platelet transfusions in the future.

  6. Purpura Fulminans Associated with Hemiparesis Following Measles Infection in a Nigerian Girl: A Case Report

    PubMed Central

    Ibrahim, Aliyu

    2013-01-01

    Purpura fulminans is a life-threatening hematologic emergency characterized by extensive skin necrosis with hemorrhagic infarction, hypotension and gangrene which may arise from severe sepsis; mostly gram negative sepsis though also associated with some gram positive organisms, similarly viral infections like varicella and measles have been implicated; it may also arise from congenital deficiency of the anticoagulants protein C, S, and antithrombin III; and it may also be idiopathic. Its clinical manifestation may be quite extensive resulting in multiorgan failure. Treatment will require aggressive management with use of fresh frozen plasma, heparin, antibiotics, and surgical debridement of necrotic tissue. PMID:26664850

  7. Koebner's Phenomenon in Childhood Henoch-Schönlein Purpura: A Report of Two Cases.

    PubMed

    Sharma, Shreya; Chandrasekaran, Venkatesh; Krishnamurthy, Sriram; Mekala, Suresh; Mahadevan, Subramanian

    2016-07-01

    Koebner's phenomenon occurs rarely in connection with Henoch-Schönlein purpura (HSP). We report two children with HSP who developed Koebner's phenomenon on the second day after the onset of rash. The first was an 11-year-old girl with rheumatic heart disease who presented with abdominal pain for 1 month and subsequently developed rash and nephritis. The second patient was a 7-year-old girl who presented with rash and polyarthritis. To the best of our knowledge, Koebner's phenomenon in childhood HSP has not been reported. PMID:27282588

  8. Adult Onset Henoch-Schonlein Purpura and Intussusception: A Rare Presentation

    PubMed Central

    Nahas, Joseph

    2016-01-01

    We present an unusual case of a young 26-year-old male who was diagnosed with Henoch-Schonlein Purpura (HSP). Initial presentation was primarily mild gastrointestinal symptoms, which progressed to a life threatening intussusception and subsequently resolved with prompt glucocorticoid use rather than typical surgical intervention. Of importance, the patient's initial gastrointestinal symptoms without associated skin manifestations made the diagnosis difficult. In conclusion, it is important to recognize uncommon presentations of HSP as it may lead to life threatening complications and surgical intervention may be avoided with prompt treatment.

  9. [Successful treatment of allergic purpura nephritis associated with thrombotic microangiopathy using plasma exchange: a case report].

    PubMed

    Kuwabara, Takashige; Ohnishi, Takahiro; Kakuta, Yutaka; Nomura, Shinsuke; Joh, Kensuke

    2004-01-01

    A 73-year-old man, who had an allergy to shellfish, was admitted to our hospital because of proteinuria, hematuria, purpura and extremity edema after eating oysters. Laboratory data on admission were proteinuria 2.0 g/day, hematuria 3+, serum creatinine (Cr) 1.2 mg/dl, total protein 6.3 g/dl, and albumin 3.1 g/dl. He presented a high fever with neutrophilia and rapid deterioration of renal function after admission. Based on the skin biopsy, we made a diagnosis of leukocytoclastic vasculitis with IgA deposition. Oral prednisolone (40 mg/day) following drip intravenous methylprednisolone (500 mg/day, 3 days) was administered. However, renal function and urinary findings showed no sign of improvement. In the first renal biopsy, although there were no crescentic formations, most of the glomeruli showed thrombotic microangiopathy and endocapillary proliferation with IgA deposition and electron dense deposits. Therefore, a plasma exchange was performed resulting in an improvement of the renal function. The serum Cr. level was reduced from 2.7 to 0.8 mg/dl and proteinuria from 3.7 to 0.1 g/day. In the second biopsy, the electron dense deposits with an IgA deposition had disappeared. These findings suggested that plasma exchange was effective in leading remission in a case of allergic purpura nephritis associated with thrombotic microangiopathy.

  10. [PREVFNAIT prevention of foetal/neonatal alloimmune thrombocytopenia (FNAIT) in Polish foetuses and newborns--the PREVFNAIT program].

    PubMed

    Uhrynowska, Małgorzata Ewa; Dębska, Marzena; Guz, Katarzyna; Orzińska, Agnieszka; Wróbel, Agnieszka; Maślanka, Krystyna; Dębski, Romuald; Brojer, Ewa

    2015-01-01

    The scientific goals related to the grant include 1) estimation of FNAIT prevalence in Poland and 2) search for biomarkers to predict the risk of the antibody production and severity of fetal thrombocytopenia. Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT) is caused by destruction of fetal blood platelets due to maternal antibodies. This condition, which most commonly results from incompatibility between the mother and the fetus for the Human Platelet Antigen-1a (HPA-1a), may lead to intracranial hemorrhage, damage of the central nervous system (CNS) and even death of the fetus or the newborn. It can be the cause of strokes in term newborns. FNAIT is usually attributed to the presence of anti-HPA-1a antibodies. Its incidence rate is estimated at approximately 1/1000-2000 live births. In the absence of a screening program, it is usually diagnosed after birth of a child with symptoms of thrombocytopenia or CNS hemorrhage. Monitoring of antibody production and thrombocytopenia treatment to effectively minimize the risk of stroke are therefore launched only at the next pregnancy. Testing indications are broader to include fetal ultrasound for symptoms of stroke to the CNS, ventricular enlargement or hydrocephalus, and obstetric failure. Diagnostic process is also recommended prior to the planned cordocentesis, in vitro fertilization and in sisters of mothers with children with FNAIT history. HPA-1a testing remains the best method for diagnosing pregnancies at risk. The detection frequency for FNAIT in Poland remains low. Therefore, the Institute of Hematology and Transfusion Medicine (IHTM) will have performed such HPA-1a antigen testing in 30 000 Polish women within the framework of the PREVFNAIT program by March 2016. HPA-1a negative women (2% of the population) are a risk group for production of anti- HPA-1a antibodies responsible for FNAIT therefore all of them will be monitored for the presence and activity of anti-HPA-1a antibodies. Such testing will be

  11. Polymorphisms in canine platelet glycoproteins identify potential platelet antigens.

    PubMed

    Callan, Mary Beth; Werner, Petra; Mason, Nicola J; Meny, Geralyn M; Raducha, Michael G; Henthorn, Paula S

    2013-08-01

    Human alloimmune thrombocytopenic conditions caused by exposure to a platelet-specific alloantigen include neonatal alloimmune thrombocytopenia, posttransfusion purpura, and platelet transfusion refractoriness. More than 30 platelet-specific alloantigens have been defined in the human platelet antigen (HPA) system; however, there is no previous information on canine platelet-specific alloantigens. Using the HPA system as a model, we evaluated the canine ITGB3, ITGA2B, and GP1BB genes encoding GPIIIa (β3), GPIIb (αIIb), and GPIbβ, respectively, which account for 21 of 27 HPA, to determine whether amino acid polymorphisms are present in the orthologous canine genes. A secondary objective was to perform a pilot study to assess possible association between specific alleles of these proteins and a diagnosis of idiopathic thrombocytopenic purpura (ITP) in dogs. By using genomic DNA from dogs of various breeds with and without ITP, sequencing of PCR products encompassing all coding regions and exon-intron boundaries for these 3 genes revealed 4 single-nucleotide polymorphisms in ITGA2B resulting in amino acid polymorphisms in the canine genome, 3 previously reported and 1 newly identified (Gly[GGG]/Arg[AGG] at amino acid position 576 of ITGA2B. Of 16 possible ITGA2B protein alleles resulting from unique combinations of the 4 polymorphic amino acids, 5 different protein isoforms were present in homozygous dogs and explain all of the genotype combinations in heterozygous dogs. There was no amino acid polymorphism or protein isoform that was specific for a particular breed or for the diagnosis of ITP. PMID:24209971

  12. Immunoglobulin A multiple myeloma presenting with Henoch-Schönlein purpura associated with reduced sialylation of IgA1.

    PubMed

    Van Der Helm-Van Mil, Annette H M; Smith, Alice C; Pouria, Shideh; Tarelli, Edward; Brunskill, Nigel J; Eikenboom, Heroen C J

    2003-09-01

    Henoch-Schönlein purpura is characterized by immunoglobulin A1 (IgA1) depositions in blood vessels of the skin or in glomeruli, resulting from altered hinge region O-glycosylation. Henoch-Schönlein purpura is seldom reported as a complication of IgA1 myeloma, even when the circulating IgA concentration is very high. We report two patients with IgA1 myeloma presenting with Henoch-Schönlein purpura. The O-glycosylation of these patients' IgA1 was studied. Both patients showed increased binding to peanut agglutinin lectin, suggesting a low degree of sialylation of the hinge region of IgA1 that was confirmed by mass spectrometry. IgA multiple myeloma, secreting IgA1 molecules with decreased sialylation, presenting with a Henoch-Schönlein purpura-like syndrome was diagnosed.

  13. Immunoglobulin A multiple myeloma presenting with Henoch-Schönlein purpura associated with reduced sialylation of IgA1.

    PubMed

    Van Der Helm-Van Mil, Annette H M; Smith, Alice C; Pouria, Shideh; Tarelli, Edward; Brunskill, Nigel J; Eikenboom, Heroen C J

    2003-09-01

    Henoch-Schönlein purpura is characterized by immunoglobulin A1 (IgA1) depositions in blood vessels of the skin or in glomeruli, resulting from altered hinge region O-glycosylation. Henoch-Schönlein purpura is seldom reported as a complication of IgA1 myeloma, even when the circulating IgA concentration is very high. We report two patients with IgA1 myeloma presenting with Henoch-Schönlein purpura. The O-glycosylation of these patients' IgA1 was studied. Both patients showed increased binding to peanut agglutinin lectin, suggesting a low degree of sialylation of the hinge region of IgA1 that was confirmed by mass spectrometry. IgA multiple myeloma, secreting IgA1 molecules with decreased sialylation, presenting with a Henoch-Schönlein purpura-like syndrome was diagnosed. PMID:12956761

  14. The Development of Severe Neonatal Alloimmune Thrombocytopenia due to Anti-HPA-1a Antibodies Is Correlated to Maternal ABO Genotypes

    PubMed Central

    Ahlen, Maria Therese; Husebekk, Anne; Killie, Mette Kjær; Kjeldsen-Kragh, Jens; Olsson, Martin L.; Skogen, Bjørn

    2012-01-01

    Background. Maternal alloantibodies against HPA-1a can cross placenta, opsonize foetal platelets, and induce neonatal alloimmune thrombocytopenia (NAIT). In a study of 100, 448 pregnant women in Norway during 1995–2004, 10.6% of HPA-1a negative women had detectable anti-HPA-1a antibodies. Design and Methods. A possible correlation between the maternal ABO blood group phenotype, or underlying genotype, and severe thrombocytopenia in the newborn was investigated. Results. We observed that immunized women with blood group O had a lower risk of having a child with severe NAIT than women with group A; 20% with blood group O gave birth to children with severe NAIT, compared to 47% among the blood group A mothers (relative risk 0.43; 95% CI 0.25–0.75). Conclusion. The risk of severe neonatal alloimmune thrombocytopenia due to anti-HPA-1a antibodies is correlated to maternal ABO types, and this study indicates that the observation is due to genetic properties on the maternal side. PMID:22110529

  15. 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.

  16. 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

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

    PubMed

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

    2015-01-01

    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. PMID:26464409

  18. 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.

  19. Pneumococcal Sepsis Complicated by Splenic Abscesses and Purpura Fulminans in a 15-Month-Old Child

    PubMed Central

    Pangonis, Scott; Patamasucon, Pisespong; Fitzpatrick, Ellen

    2016-01-01

    Streptococcus pneumoniae is an invasive organism that causes a wide range of common diseases, including sinusitis, acute otitis media, and pneumonia. Splenic abscesses and purpura fulminans (PF) are rare complications of pneumococcal disease. Splenic abscesses caused by S pneumoniae have only been reported in the adult literature. PF has been described in the pediatric population as a rare complication in patients with invasive pneumococcal disease (IPD) with and without underlying immunological disorders such as asplenia. Here, we report a patient with IPD complicated by splenic abscesses and PF. Our patient initially presented with bacteremia, septic shock, and disseminated intravascular coagulation. She subsequently developed PF and splenic abscesses. She survived her illness after receiving a total of 8 weeks of antibiotic therapy. This case highlights 2 rare complications of IPD and demonstrates the need to keep pneumococcal disease in the differential diagnosis even in children whose vaccination status is up to date. PMID:27006958

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

    PubMed

    Kukrety, Shweta; Vimalachandran, Pradeepa; Kunadharaju, Rajesh; Mehta, Vishisht; Colanta, Agnes; Abu Hazeem, Mahmoud

    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

  1. 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

  2. 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

  3. [Henoch-Schönlein purpura in a cocaine consumer man with HIV infection and ANCA-p positivity].

    PubMed

    De Paoli, María C; Moretti, Dino; Scolari Pasinato, Carlos M; Buncuga, Martín G

    2016-01-01

    The Henoch-Schönlein purpura (HSP) is a small vessel vasculitis with IgA immune complex deposition. The presentation in adults is rare and severe. Reported cases of HSP in patients infected with HIV are scarce. Neutrophil cytoplasmic antibodies (ANCA) are commonly found in other systemic vasculitis, but rarely in HSP and even more unusual the perinuclear pattern. Beside small vessel vasculitis, positivity of ANCA can be detected in a number of different pathological conditions in association with infectious processes, including HIV, or cocaine use, and especially the pattern of ANCA-p, associated with drugs, inflammatory bowel or autoimmune diseases. We report the case of a 35 years old man with toxic habits (cocaine, marijuana) who consulted for abdominal pain, hematochezia and purpura on lower extremities, and later fever, joint pain and progression of purpura associated with nephritic syndrome and ANCA-p (+). During hospitalization HIV infection was detected. Renal biopsy showed IgA nephropathy with favorable response to corticosteroid and antiproteinuric treatment. The communication of the case is due to the rarity of the presentation and therapeutic diagnostic challenge. It remains to elucidate the role of ANCA in the pathogenesis and management of adult PSH. PMID:27576285

  4. Polyangitis overlap syndrome: a fatal case combined with adult Henoch-Schönlein purpura and polyarteritis nodosa.

    PubMed

    Watanabe, Kazuo; Abe, Hiroyuki; Mishima, Tomoko; Ogura, Go; Suzuki, Toshimitsu

    2003-08-01

    Henoch-Schönlein purpura (HSP) is a rather common disease characterized by systemic hypersensitivity vasculitis in the skin and other visceral organs. It has a favorable prognosis unless it is complicated by severe glomerular disease. We report a distinctive fatal case of systemic vasculitis combined with HSP and polyarteritis nodosa (PN) in a 56-year-old man who died of progressive renal failure one month after the onset of the disease. He complained of arthralgia, purpura of both lower extremities, nasal bleeding and tarry stool, and acute renal failure was noted at the time of admission to hospital. A skin biopsy from the purpura lesion exhibited leucocytoclastic vasculitis with IgA deposition, and HSP was considered. However, renal failure progressed rapidly and subsequently was complicated by acute myocardial infarction. Postmortem examination revealed PN type necrotizing vasculitis in the kidneys, heart and mesentery resulting in acute multiple infarctions of these organs. We think the current case was a polyangitis overlap syndrome. It is important to suspect the polyangitis overlap syndrome positively when progressive acute renal failure is seen in a patient with HSP and to begin appropriate therapy immediately.

  5. Developing recombinant HPA-1a–specific antibodies with abrogated Fcγ receptor binding for the treatment of fetomaternal alloimmune thrombocytopenia

    PubMed Central

    Ghevaert, Cedric; Wilcox, David A.; Fang, Juan; Armour, Kathryn L.; Clark, Mike R.; Ouwehand, Willem H.; Williamson, Lorna M.

    2008-01-01

    Fetomaternal alloimmune thrombocytopenia (FMAIT) is caused by maternal generation of antibodies specific for paternal platelet antigens and can lead to fetal intracranial hemorrhage. A SNP in the gene encoding integrin β3 causes a clinically important maternal-paternal antigenic difference; Leu33 generates the human platelet antigen 1a (HPA-1a), whereas Pro33 generates HPA-1b. As a potential treatment to prevent fetal intracranial hemorrhage in HPA-1a alloimmunized pregnancies, we generated an antibody that blocks the binding of maternal HPA-1a–specific antibodies to fetal HPA-1a1b platelets by combining a high-affinity human HPA-1a–specific scFv (B2) with an IgG1 constant region modified to minimize Fcγ receptor–dependent platelet destruction (G1Δnab). B2G1Δnab saturated HPA-1a+ platelets and substantially inhibited binding of clinical HPA-1a–specific sera to HPA-1a+ platelets. The response of monocytes to B2G1Δnab-sensitized platelets was substantially less than their response to unmodified B2G1, as measured by chemiluminescence. In addition, B2G1Δnab inhibited chemiluminescence induced by B2G1 and HPA-1a–specific sera. In a chimeric mouse model, B2G1 and polyclonal Ig preparations from clinical HPA-1a–specific sera reduced circulating HPA-1a+ platelets, concomitant with transient thrombocytopenia. As the Δnab constant region is uninformative in mice, F(ab′)2 B2G1 was used as a proof of principle blocking antibody and prevented the in vivo platelet destruction seen with B2G1 and polyclonal HPA-1a–specific antibodies. These results provide rationale for human clinical studies. PMID:18654666

  6. Characterization of a human platelet antigen-1a-specific monoclonal antibody derived from a B cell from a woman alloimmunized in pregnancy.

    PubMed

    Eksteen, Mariana; Tiller, Heidi; Averina, Maria; Heide, Gøril; Kjaer, Mette; Ghevaert, Cedric; Michaelsen, Terje E; Ihle, Øistein; Husebekk, Anne; Skogen, Bjørn; Stuge, Tor B

    2015-06-15

    Human platelet Ag (HPA)-1a, located on integrin β3, is the main target for alloantibodies responsible for fetal and neonatal alloimmune thrombocytopenia (FNAIT) in the white population. There are ongoing efforts to develop an Ab prophylaxis and therapy to prevent or treat FNAIT. In this study, an mAb specific for HPA-1a, named 26.4, was derived from an immortalized B cell from an alloimmunized woman who had an infant affected by FNAIT. It is the only HPA-1a-specific human mAb with naturally paired H and L chains. Specific binding of mAb 26.4, both native and recombinant forms, to platelets and to purified integrins αIIbβ3 (from platelets) and αVβ3 (from trophoblasts) from HPA-1a(+) donors was demonstrated by flow cytometry and surface plasmon resonance technology, respectively. No binding to HPA-1a(-) platelets or integrins was detected. Moreover, the Ab binds with higher affinity to integrin αVβ3 compared with a second HPA-1a-specific human mAb, B2G1. Further in vitro experimentation demonstrated that mAb 26.4 can opsonize HPA-1a(+) platelets for enhanced phagocytosis by monocytes, inhibit binding of maternal polyclonal anti-HPA-1a Abs, and weakly inhibit aggregation of HPA-1a-heterozygous platelets, the latter with no predicted clinical relevance. Thus, mAb 26.4 is highly specific for HPA-1a and could potentially be explored for use as a prophylactic or therapeutic reagent for FNAIT intervention and as a phenotyping reagent to identify women at risk for immunization.

  7. Flow cytometric analysis of thiazole orange uptake by platelets: a diagnostic aid in the evaluation of thrombocytopenic disorders.

    PubMed

    Kienast, J; Schmitz, G

    1990-01-01

    Thiazole orange (TO), a fluorescent dye originally synthesized for reticulocyte analysis, is characterized by a large fluorescence enhancement and high quantum yield on binding to nucleic acids, particularly RNA. In addition, the dye readily permeates live cell membranes. We applied TO staining, followed by fluorescence-activated flow cytometric analysis, to platelets in whole blood samples from hematologically normal subjects and patients with various quantitative platelet disorders. The percentage of TO-positive platelets in 50 control subjects was 8.6 +/- 2.8% (mean +/- SD) ranging from 2.8% to 15.8%. In 21 thrombocytopenic patients whose bone marrow contained normal to increased numbers of megakaryocytes, the percentage of fluorescently labeled platelets was significantly elevated (P less than .0001) to 26.9 +/- 10.9% (range, 13.3% to 57.1%). In contrast, the proportion of positively stained platelets in 23 patients with thrombocytopenia due to impaired platelet production (various conditions with reduced marrow megakaryocytes) did not significantly differ from the controls, whereas the absolute counts of TO-positive platelets were significantly lowered (P less than .0001). Differences in the distributions of the percentage values as well as of the absolute counts for TO-positive platelets between the two patient groups were again highly significant (P less than .0001). Both the sensitivity and the specificity of this method in distinguishing between these categories of thrombocytopenia were greater than or equal to 95%. We conclude that flow cytometric analysis of platelets after staining with TO is a sensitive and specific test that rapidly provides information on the thrombopoietic activity in thrombocytopenic disorders. Our data further suggest that increased amounts of residual RNA characterize platelets released under conditions of "stress thrombopoiesis."

  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. Corticosteroids May Improve Clinical Outcomes During Hospitalization for Henoch-Schönlein Purpura

    PubMed Central

    Weiss, Pamela F.; Klink, Andrew J.; Localio, Russell; Hall, Matt; Hexem, Kari; Burnham, Jon M.; Keren, Ron; Feudtner, Chris

    2012-01-01

    OBJECTIVE To characterize the effect of corticosteroid exposure on clinical outcomes in children hospitalized with new-onset Henoch-Schönlein purpura (HSP). PATIENTS AND METHODS We conducted a retrospective cohort study of children discharged with an International Classification of Diseases, Clinical Modification code of HSP between 2000 and 2007 by using inpatient administrative data from 36 tertiary care children’s hospitals. We used stratified Cox proportional hazards regression models to estimate the relative effect of time-varying corticosteroid exposure on the risks of clinical outcomes that occur during hospitalization for acute HSP. RESULTS During the 8-year study period, there were 1895 hospitalizations for new-onset HSP. After multivariable regression modeling adjustment, early corticosteroid exposure significantly reduced the hazard ratios for abdominal surgery (0.39 [95% confidence interval (CI): 0.17– 0.91]), endoscopy (0.27 [95% CI: 0.13– 0.55]), and abdominal imaging (0.50 [95% CI: 0.29 – 0.88]) during hospitalization. CONCLUSIONS In the hospital setting, early corticosteroid exposure was associated with benefits for several clinically relevant HSP outcomes, specifically those related to the gastrointestinal manifestations of the disease. PMID:20855386

  11. Variation in inpatient therapy and diagnostic evaluation of children with Henoch Schönlein purpura

    PubMed Central

    Weiss, Pamela F.; Klink, Andrew J.; Hexem, Kari; Burnham, Jon M.; Leonard, Mary B.; Keren, Ron; Localio, Russell; Feudtner, Chris

    2009-01-01

    Objective To describe variation regarding inpatient therapy and evaluation of children with Henoch Schönlein purpura (HSP) admitted to children’s hospitals across the United States. Study design We conducted a retrospective cohort study of children discharged with a diagnosis of HSP between 2000 and 2007 using inpatient administrative data from 36 children’s hospitals. We examined variation among hospitals in the use of medications, diagnostic tests, and intensive care services using multivariate mixed effects logistic regression models. Results During the initial HSP hospitalization (N=1,988), corticosteroids were the most common medication (56% of cases), followed by opioids (36%), NSAIDs (35%), and anti-hypertensives (11%). After adjustment for patient characteristics, hospitals varied significantly in their use of corticosteroids, opioids, and NSAIDs; the use of diagnostic abdominal imaging, endoscopy, laboratory testing, and renal biopsy; and the utilization of intensive care services. By contrast, hospitals did not differ significantly regarding administration of anti-hypertensives or performance of skin biopsy. Conclusions The significant variation identified may contribute to varying HSP clinical outcomes between hospitals, warrants further investigation, and represents a potentially important opportunity to improve quality of care. PMID:19643437

  12. Current views of the relationship between Helicobacter pylori and Henoch-Schonlein purpura in children

    PubMed Central

    Xiong, Li-Jing; Mao, Meng

    2016-01-01

    Helicobacter pylori (H. pylori) is one of the factors involved in the pathogenesis of various gastrointestinal diseases and may play a potential role in certain extra-intestinal diseases. H. pylori infection are mainly acquired during childhood, and it has been reported that in endemic areas of China the infection rates are extraordinarily higher in HSP children, particular those with abdominal manifestations. Furthermore, eradication therapy may ameliorate Henoch-Schonlein purpura (HSP) manifestations and decrease the recurrence of HSP. Therefore, results suggested that detection of H. pylori infection by appropriate method ought to be applied in HSP children. Current evidences indicate that local injury of gastric mucosa and immunological events induced by H. pylori infection are involved in the development of HSP. Increased serum IgA, cryoglobulins, C3 levels, autoimmunity, proinflammatory substances and molecular mimicry inducing immune complex and cross-reactive antibodies caused by H. pylori infection might play their roles in the course of HSP. However, there are no investigations confirming the causality between H. pylori infection and HSP, and the pathogenesis mechanism is still unclear. More bench and clinical studies need to be executed to elaborate the complex association between H. pylori and HSP. PMID:26862506

  13. 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.

  14. IgA myeloma presenting as Henoch-Schönlein purpura with nephritis.

    PubMed

    Zickerman, A M; Allen, A C; Talwar, V; Olczak, S A; Brownlee, A; Holland, M; Furness, P N; Brunskill, N J; Feehally, J

    2000-09-01

    IgA nephropathy (IgAN) and Henoch-Schönlein purpura (HSP) are both characterized by IgA-mediated tissue injury, including mesangial proliferative glomerulonephritis. Abnormalities of IgA1 glycosylation are described in IgA nephropathy and HSP nephritis. IgA-antineutrophil cytoplasmic antibodies (ANCA) have been inconsistently described in the serum of patients with HSP. In IgA myeloma, the paraprotein-mediated renal lesion is typically cast nephropathy; IgAN or HSP have only rarely been reported in myeloma even when an IgA paraprotein is circulating in large concentrations. We report the case of a 50-year-old man with IgA myeloma who presented with HSP including nephritis and rapidly progressive renal failure. His IgA1 had altered O-glycosylation in the pattern seen in IgAN and also contained an IgA-ANCA. This case adds further weight to the evidence that IgA1 O-glycosylation abnormalities predispose to mesangial IgA deposition and also that IgA-ANCA may have a pathogenic role in the development of HSP. PMID:10977812

  15. 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

  16. [A case of disseminated nontuberculous mycobacteriosis during purpura associated with hypergammaglobulinemia and hepatitis type C].

    PubMed

    Ueno, Shiro; Miyauchi, Shunichi; Umekita, Kunihiko; Kusumoto, Norio; Takajo, Ichiro; Kuroki, Masayuki; Kai, Yasufumi; Nagatomo, Yasuhiro; Okayama, Akihiko

    2008-11-01

    A 74-year-old woman with hepatitis due to hepatitis C virus followed up using oral predonisolone (3 mg/day) for two years because of hypergammaglobulinemia-associated purpura reported fever and lumbago in February 2005. Upon admission in June, she was found in chest-computed tomography to have atelectasia in the right middle lung lobe and a nodule with a cavity in the right lower lobe. She tested positive for tuberculous glycolipid antibody. Gallium scintigraphy showed an abnormal accumulation in the lower lumbar vertebra. Magnetic resonance imaging showed abnormal enhancement at L4, L5, and their intervertebral disc. Mycobacterium intracellulare (M. intracellulare) was detected in blood culture, bronchoalveolar lavage, and a biopsy specimen from the intervertebral disc, yielding a diagnosis of disseminated nontuberculous mycobacteriosis (NTM) due to M. intracellulare. She was treated with clarithromycin (CAM), ethambutol (EB), and rifampicin (RFP), but EB and RFP were discontinued due to of the fever they induced. She was then treated with a combination of CAM, levofloxacin, and streptomycin and followed up as an out patient. Based on case reports of disseminated NTM infection in Japan, the prognosis is poor and a protocol must be established for its treatment. PMID:19086421

  17. 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

    2014-01-01

    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.

  18. Henoch-Schönlein purpura complicated by acalculous cholecystitis and intussusception, and following recurrence with appendicitis.

    PubMed

    Özkaya, Ahmet Kağan; Güler, Ekrem; Çetinkaya, Ahmet; Karakaya, Ali Erdal; Göksügür, Yalçın; Katı, Ömer; Güler, Ahmet Gökhan; Davutoğlu, Mehmet

    2016-05-01

    Henoch-Schönlein purpura (HSP) is the most common childhood systemic vasculitis. Gastro-intestinal involvement occurs in two-thirds of patients. The characteristic skin lesions generally precede abdominal symptoms or present concurrently. A 7-year-old boy presented with intussusception and acalculous cholecystitis and had a cholecystectomy. Two weeks later he was re-admitted with features typical of HSP which responded to corticosteroids. Eleven months later he presented with abdominal pain and recurrence of HSP and, at laparotomy, there was acute appendicitis. This is the first case of a child presenting with HSP complicated by acalculous cholecystitis. PMID:27077617

  19. 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

  20. Predictors of hospital length of stay in pediatric Henoch-Schönlein purpura.

    PubMed

    Cohen, Neta; Mimouni, Francis B; Friedel, Nadav; Amarilyo, Gil

    2015-09-01

    Henoch-Schönlein purpura (HSP) is a common, benign vasculitis in childhood which occasionally follows a protracted course and prolonged length of hospital stay. We aimed to determine clinical and laboratory characteristics that allow prediction of prolonged length of hospital stay (4 or more days) in HSP patients. We have retrospectively reviewed all HSP cases that were admitted to the Dana Duek Children's hospital between 2000 and 2013. Univariable analysis was performed to study the variables that were statistically related to length of hospital stay. These variables along with other clinically relevant variables were analyzed using stepwise backward multiple regression analysis. Variables that remained significant in the final analysis were correlated with length of stay, were each given specific weight (according to their contribution to the final R(2)) and were used to assemble an HSP presentation severity score. Out of 107 charts that were screened, 89 children were retrieved for analysis. In univariate analysis, variables that were associated with prolonged (>4 days) length of stay were: abdominal pain as initial sole presentation, C-reactive protein (CRP) 45 mg/dL (1 or 0 point) and patient's age > 6 years (0.5 or 0 points). A score of ≥3 in patients diagnosed with HSP predicted a prolonged length of stay with a positive predictive value of 93 %. The HSP presentation severity score index that we describe here may serve as a practical tool to assess severity of HSP which may eventually reflected as prolonged length of hospital stay. This score should be validated in the future in an ongoing prospective study. PMID:25804958

  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. Human Regulatory T Cells with Alloantigen Specificity Are More Potent Inhibitors of Alloimmune Skin Graft Damage than Polyclonal Regulatory T Cells

    PubMed Central

    Sagoo, Pervinder; Ali, Niwa; Garg, Garima; Nestle, Frank O.; Lechler, Robert I.; Lombardi, Giovanna

    2013-01-01

    Graft rejection by the immune system is a major cause of transplant failure. Lifelong immunosuppression decreases the incidence of graft rejection; however, nonspecific immunosuppression results in increased susceptibly to infection and cancer. Regulatory T cells (Tregs), which suppress the activation of the immune system and induce tolerance, are currently under evaluation for use in clinical transplantation. Ex vivo expanded polyclonal Tregs that are introduced into transplant recipients alter the balance of T effector cells to Tregs; however, experimental data suggest that alloantigen-specific Tregs would be more effective at preventing graft rejection. We have developed a method to enrich alloantigen-specific human Tregs based on the coexpression of activation markers, CD69 and CD71. These Tregs could be readily expanded in vitro and demonstrated potent antigen-specific suppression. In a humanized mouse model of alloimmune-mediated injury of human skin grafts, alloantigen-specific Tregs resulted in a significant reduction in clinically relevant indicators of dermal tissue injury when compared with polyclonal Tregs, restoring a histology comparable to healthy skin. This method of human allospecific Treg selection should be scalable to the clinic. The improved in vivo efficacy of alloantigen-specific Tregs over polyclonal Tregs shown here suggests that generating “customized” Tregs with defined anti-donor allospecificities may improve current practice in clinical immunotherapy. PMID:21593402

  3. Hemolytic disease of the newborn associated with anti-Jra alloimmunization in a twin pregnancy: the first case report in Korea.

    PubMed

    Kim, Hyungsuk; Park, Min-Jeong; Sung, Tae-Jung; Choi, Ji Seon; Hyun, Jungwon; Park, Kyoung Un; Han, Kyou-Sup

    2010-10-01

    Jr(a) is a high-frequency antigen found in all ethnic groups. However, the clinical significance of the anti-Jr(a) antibody has remained controversial. Most studies have reported mild hemolytic disease of the newborn and fetus (HDNF) in Jr(a)-positive patients. Recently, fatal cases of HDNF have also been reported. We report the first case of HDNF caused by anti-Jr(a) alloimmunization in twins in Korea. A 33-yr-old nulliparous woman with no history of transfusion or amniocentesis was admitted at the 32nd week of gestation because of vaginal bleeding caused by placenta previa. Anti-Jr(a) antibodies were detected in a routine laboratory examination. An emergency cesarean section was performed at the 34th week of gestation, and 2 premature infant twins were delivered. Laboratory examination showed positive direct antiglobulin test and Jr(a+) phenotype in the red blood cells and the presence of anti-Jr(a) antibodies in the serum in both neonates. The infants underwent phototherapy for neonatal jaundice; this was followed by conservative management. They showed no further complications and were discharged on the 19th postpartum day. Preparative management to ensure the availability of Jr(a-) blood, via autologous donation, and close fetal monitoring must be performed even in cases of first pregnancy in Jr(a-) women.

  4. Interleukin 12 levels during the initial phase of septic shock with purpura in children: relation to severity of disease.

    PubMed

    Hazelzet, J A; Kornelisse, R F; van der Pouw Kraan, T C; Joosten, K F; van der Voort, E; van Mierlo, G; Suur, M H; Hop, W C; de Groot, R; Hack, C E

    1997-09-01

    Plasma levels of interleukin 12 (IL-12), a cytokine consisting of two different polypeptide subunits (p40 and p35), were measured together with interferon gamma (IFN-gamma) and other cytokines in 46 children with septic shock and purpura. The median (range) plasma IL-12 p40 level on admission was 457 (244-2677) pg/ml in non-survivors vs 189 (< 40-521) pg/ml in survivors (P = < 0.001). IL-12 p70 levels were elevated in only nine patients. IL-12 p40 plasma levels were positively correlated with tumour necrosis factor alpha (TNF-alpha), IL-6, IL-8, IL-10 and PRISM-score, whereas they were negatively correlated with C-reactive protein (CRP), whole blood cell (WBC) and serum glucose levels. Twelve (29%) of the patients had detectable levels of IFN-gamma. Thus, circulating levels of IL-12 p40 and to a lesser extent those of IL-12 p70, are elevated in children with septic shock and purpura, and correlate with severity of disease and outcome.

  5. 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

  6. Henoch-Schönlein purpura from vasculitis to intestinal perforation: A case report and literature review.

    PubMed

    Lerkvaleekul, Butsabong; Treepongkaruna, Suporn; Saisawat, Pawaree; Thanachatchairattana, Pornsri; Angkathunyakul, Napat; Ruangwattanapaisarn, Nichanan; Vilaiyuk, Soamarat

    2016-07-14

    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

  7. Fetal intracranial haemorrhages caused by fetal and neonatal alloimmune thrombocytopenia: an observational cohort study of 43 cases from an international multicentre registry

    PubMed Central

    Tiller, Heidi; Kamphuis, Marije M; Flodmark, Olof; Papadogiannakis, Nikos; David, Anna L; Sainio, Susanna; Koskinen, Sinikka; Javela, Kaija; Wikman, Agneta Taune; Kekomaki, Riitta; Kanhai, Humphrey H H; Oepkes, Dick; Husebekk, Anne; Westgren, Magnus

    2013-01-01

    Objective To characterise pregnancies where the fetus or neonate was diagnosed with fetal and neonatal alloimmune thrombocytopenia (FNAIT) and suffered from intracranial haemorrhage (ICH), with special focus on time of bleeding onset. Design Observational cohort study of all recorded cases of ICH caused by FNAIT from the international No IntraCranial Haemorrhage (NOICH) registry during the period 2001–2010. Setting 13 tertiary referral centres from nine countries across the world. Participants 37 mothers and 43 children of FNAIT pregnancies complicated by fetal or neonatal ICH identified from the NOICH registry was included if FNAIT diagnosis and ICH was confirmed. Primary and secondary outcome measures Gestational age at onset of ICH, type of ICH and clinical outcome of ICH were the primary outcome measures. General maternal and neonatal characteristics of pregnancies complicated by fetal/neonatal ICH were secondary outcome measures. Results From a total of 592 FNAIT cases in the registry, 43 confirmed cases of ICH due to FNAIT were included in the study. The majority of bleedings (23/43, 54%) occurred before 28 gestational weeks and often affected the first born child (27/43, 63%). One-third (35%) of the children died within 4 days after delivery. 23 (53%) children survived with severe neurological disabilities and only 5 (12%) were alive and well at time of discharge. Antenatal treatment was not given in most (91%) cases of fetal/neonatal ICH. Conclusions ICH caused by FNAIT often occurs during second trimester and the clinical outcome is poor. In order to prevent ICH caused by FNAIT, at-risk pregnancies must be identified and prevention and/or interventions should start early in the second trimester. PMID:23524102

  8. Co-stimulation with LPS or Poly I:C markedly enhances the anti-platelet immune response and severity of fetal and neonatal alloimmune thrombocytopenia.

    PubMed

    Li, Conglei; Chen, Pingguo; Vadasz, Brian; Ma, Li; Zhou, Hui; Lang, Sean; Freedman, John; Ni, Heyu

    2013-12-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening bleeding disorder caused by maternal antibodies against fetal/neonatal platelets. FNAIT is also linked with miscarriages, although the incidence and mechanisms of fetal death have not been well studied. IntegrinαIIbβ3 (GPIIbIIIa) and the GPIbα complex are major glycoproteins expressed on platelets and are also major antigens targeted in autoimmune thrombocytopenia (ITP), but reported cases of anti-GPIb-mediated FNAIT are rare. Bacterial and viral infections have been causally linked with the pathogenesis of immune-mediated thrombocytopenia (ITP); however, it is unknown whether these infections contribute to the severity of FNAIT. Here, immune responses against platelet antigens were examined by transfusing wild-type (WT) mouse platelets into β3-/- or GPIbα-/- mice. To mimic bacterial or viral infections, lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (Poly I:C) were injected intraperitoneally following platelet transfusions. The FNAIT model was established by breeding the immunised female mice with WT male mice. We demonstrated for the first time that the platelet GPIbα has lower immunogenicity compared to β3 integrin. Interestingly, co-stimulation with LPS or Poly I:C markedly enhanced the immune response against platelet GPIbα and caused severe pathology of FNAIT (i.e. miscarriages). LPS or Poly I:C also enhanced the immune response against platelet β3 integrin. Our data suggest that bacterial and viral infections facilitate the anti-platelet GPIbα response, which may lead to a severe non-classical FNAIT (i.e. miscarriage but not neonatal bleeding) that has not been adequately reported in humans.

  9. Coupled regulation of interleukin-12 receptor beta-1 of CD8+ central memory and CCR7-negative memory T cells in an early alloimmunity in liver transplant recipients

    PubMed Central

    Egawa, H; Ozawa, K; Takada, Y; Teramukai, S; Mori, A; Ogawa, K; Kaido, T; Fujimoto, Y; Kawaguchi, Y; Hatano, E; Sato, H; Ono, M; Takai, K; Tanaka, K; Uemoto, S

    2010-01-01

    This study investigated how CD8+ T cell subsets respond to allo- and infectious immunity after living donor liver transplantation (LDLT). Early alloimmunity: 56 recipients were classified into three types according to the post-transplant course; type I demonstrated uneventful post-transplant course, type II developed severe sepsis leading to multiple organ dysfunction syndrome or retransplantation and type III with acute rejection. In 23 type I recipients, the interleukin (IL)-12 receptor beta-1 (Rβ1)+ cells of central memory T cells (Il-12Rβ1+ TCM) were increased above the pretransplant level. In 16 type II recipients, IL-12Rβ1+ TCM was decreased markedly below the pretransplant level on postoperative day (POD) 5. In 17 type III recipients, IL-12Rβ1+ TCM was decreased for a more prolonged period until POD 10. Along with down-regulation of IL-12Rβ1+ TCM, the IL-12Rβ1+ cells of CCR7-negative subsets (CNS) as well as perforin, interferon (IFN)-γ and tumour necrosis factor (TNF)-α decreased gradually, resulting in the down-regulation of effectors and cytotoxicity. The down-regulation of IL-12Rβ1+ TCM was suggested to be due to the recruitment of alloantigen-primed T cells into the graft, and then their entry into the secondary lymphoid organ, resulting in graft destruction. Infectious immunity: immunocompetent memory T cells with the capacity to enhance effectors and cytotoxicity were generated in response to post-transplant infection along with both up-regulation of the IL-12Rβ1+ TCM and an increase in the CNS showing the highest level of IL-12Rβ1+ cells. In conclusion, this work demonstrated that the IL-12Rβ1+ cells of TCM and CNS are regulated in a tightly coupled manner and that expression levels of IL-12Rβ1+ TCM play a crucial role in controlling allo- and infectious immunity. PMID:20345976

  10. 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

  11. Henoch-Schönlein Purpura with Adalimumab Therapy for Ulcerative Colitis: A Case Report and Review of the Literature

    PubMed Central

    Donet, Jean A.; Cho-Vega, Jeong Hee; Sussman, Daniel A.; Deshpande, Amar R.

    2016-01-01

    Tumor necrosis factor-α (TNFα) inhibitor therapy has signified an important milestone in the fight against many rheumatological disorders and inflammatory bowel disease (IBD). Cutaneous adverse events caused by this class of medications are well known but relatively uncommon. Most reactions are mild and rarely warrant treatment withdrawal. Henoch-Schönlein purpura (HSP) is a disease with cutaneous vasculitis, arthritis, and gastrointestinal and renal involvement that is usually seen in children, though the worst complications are typically seen in adults. We present a case of HSP complicating adalimumab treatment in a patient with ulcerative colitis who had achieved endoscopic remission. We review similar cases reported in the literature and discuss the consequences of these autoimmune diseases. PMID:27529048

  12. 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.

  13. 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. PMID:24899338

  14. Henoch-Schönlein Purpura with Adalimumab Therapy for Ulcerative Colitis: A Case Report and Review of the Literature.

    PubMed

    LaConti, Joseph J; Donet, Jean A; Cho-Vega, Jeong Hee; Sussman, Daniel A; Ascherman, Dana; Deshpande, Amar R

    2016-01-01

    Tumor necrosis factor-α (TNFα) inhibitor therapy has signified an important milestone in the fight against many rheumatological disorders and inflammatory bowel disease (IBD). Cutaneous adverse events caused by this class of medications are well known but relatively uncommon. Most reactions are mild and rarely warrant treatment withdrawal. Henoch-Schönlein purpura (HSP) is a disease with cutaneous vasculitis, arthritis, and gastrointestinal and renal involvement that is usually seen in children, though the worst complications are typically seen in adults. We present a case of HSP complicating adalimumab treatment in a patient with ulcerative colitis who had achieved endoscopic remission. We review similar cases reported in the literature and discuss the consequences of these autoimmune diseases. PMID:27529048

  15. 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.

  16. 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.

  17. [Case of Henoch-Schönlein purpura nephritis successfully treated with tonsillectomy and steroid pulse therapy].

    PubMed

    Iwamoto, Mari; Wakabayashi, Mai; Hanada, Shigeru; Kobayashi, Namiko; Hata, Toshihiko; Ando, Ryoichi

    2009-01-01

    A 30-year-old Japanese man was admitted to our hospital because of fever, sore throat, abdominal pain, purpura skin lesion of the lower legs, and macrohematuria. On admission, his urine was positive (++) for protein; the sediment contained 100 red blood cells per high-power field, and the daily proteinuria level was 1.7 g. Renal biopsy was performed, and we diagnosed Henoch-Schönlein purpura nephritis (HSPN). Six months after the renal biopsy, the patient underwent a tonsillectomy. The pathological diagnosis of the resected tonsils was chronic tonsillitis. After tonsillectomy, the daily proteinuria had decreased to 0.1 g and the sediment contained only 10-19 red blood cells per high-power field. High-dose methylprednisolone therapy (500 mg/day for 3 days for three courses) was started two weeks after the tonsillectomy, followed by oral prednisolone at the initial dose of 30 mg on alternate days. The oral prednisolone was tapered gradually over 1 year. Antiplatelet drug (dipyridamole, 300 mg/day) and angiotensin II receptor antagonist (olmesartan, 10 mg/day) were also administered. This combination therapy resulted in a significant decrease in proteinuria and disappearance of microhematuria. The patient finally achieved clinical remission. Recent reports have shown that in patients with IgA nephropathy, combined tonsillectomy and methylprednisolone pulse therapy have an effect on clinical remission. In addition, it has been suggested that HSPN and IgA nephropathy represent a spectrum of clinical presentations of similar disorders. The result of this case indicated that this combination therapy had a favorable effect on clinical remission in adult patients with HSPN. PMID:19601558

  18. 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.

  19. 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...

  20. Haematology and neurology

    PubMed Central

    Austin, Steven; Cohen, Hannah; Losseff, Nick

    2007-01-01

    This review aims to update the reader on advances in the understanding of haematological conditions that may arise in neurological practice. Thrombophilia, antiphospholipid antibody syndrome, thrombotic thrombocytopenic purpura, sickle cell and clonal disorders associated with neuropathy are discussed. PMID:17369588

  1. Helicobacter pylori-associated immune thrombocytopenia.

    PubMed

    Franchini, Massimo; Veneri, Dino

    2006-03-01

    Idiopatic thrombocytopenic purpura (ITP), a disorder characterized by autoantibody-mediated platelet destruction, may be primary or secondary to various illnesses including lymphoproliferative, autoimmune, or infectious diseases. There are increasing data on the association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura and the significant increase in platelet count after bacterial eradication. The aim of this review is to consider the studies so far published on Helicobacter pylori infection and idiopathic thrombocytopenic purpura in order to evaluate a possible pathogenic correlation between these two conditions. A review of the literature data show that Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura is effective in increasing platelet count in approximately half of the cases. However, since the studies so far published are few, sometimes controversial and involve small series of patients, further controlled studies on larger numbers of patients with longer follow-up are needed to confirm these preliminary findings.

  2. 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.

  3. 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

  4. Autoimmune progesterone dermatitis: Case report with history of urticaria, petechiae and palpable pinpoint purpura triggered by medical abortion.

    PubMed

    Mbonile, Lumuli

    2016-04-01

    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. PMID:27032848

  5. 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

  6. 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

  7. Clinico-pathological association of Henoch-Schoenlein purpura nephritis and IgA nephropathy in children

    PubMed Central

    Mao, Song; Xuan, Xiaoyan; Sha, Yugen; Zhao, Sanlong; Zhu, Chunhua; Zhang, Aihua; Huang, Songming

    2015-01-01

    Objective: Henoch-Schonlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) are similar syndromes. We aimed to determine whether the crescent formation/immunocomplex in glomeruli is associated with the differences of the biochemical indexes between HSPN and IgAN. Methods: We investigated the medical records of 137 HSPN cases and 41 IgAN cases from January 2009 to April 2014 in Nanjing Children’s Hospital of Nanjing Medical University. The clinical and pathological data were analyzed and compared between HSPN and IgAN. Results: HSPN patients had markedly higher levels of blood white blood cell (WBC), hemoglobulin (Hb) and platelet (PLT), lower levels of hematuria, blood nitrogen (BUN) and C4 compared with IgAN cases. Crescents formation and C3 deposition in the kidney did not affect these differences. Significantly lower levels of hematuria, blood IgG, IgM and C4 in HSPN compared with IgAN cases were observed among patients with IgG deposition. Markedly higher levels of WBC and Hb, lower levels of hematuria, creatinine (Cr), C4 in HSPN compared with IgAN cases were observed among patients with IgM deposition. No marked differences of the biochemical indexes were noted between HSPN and IgAN cases among patients with C1q deposition. Markedly higher levels of WBC and Hb, lower level of blood C4 in HSPN compared with IgAN cases were observed among patients with fibrogen deposition. Conclusions: The different levels of biochemical indexes at presentation between HSPN and IgAN may be associated with the deposition of IgG, IgM, C1q and fibrogen in the kidney. PMID:26045740

  8. 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.

  9. [Clinico-pathological features and outcome in adult patients with Henoch-Schönlein purpura nephritis].

    PubMed

    Tsuruta, Yuki; Takei, Takashi; Takano, Mari; Sawara, Yukako; Aoki, Akiko; Eguchi, Aya; Kojima, Chiari; Moriyama, Takahito; Itabashi, Mitsuyo; Sugiura, Hidekazu; Tsukada, Misao; Ogawa, Tetsuya; Yoshida, Takumi; Uchida, Keiko; Tsuchiya, Ken; Nitta, Kosaku

    2010-01-01

    We examined the data of 24 patients with Henoch-Schönlein purpura nephritis (HSPN) over a 5-year follow-up period. Proteinuria, sediment RBC and CRP significantly decreased between the time of diagnosis and the end of the 5-year period. In the steroid usage group (n = 16), proteinuria was significantly higher, and crescent formation was significant higher at the time of diagnosis than in the non-steroid usage group (n = 8). However, there was no significant difference in the decrease in eGFR from the baseline at the end of the 5-year period between the two groups. Furthermore, to clarify the factors influencing the risk of renal function deterioration, we divided the patients into two groups, the (delta eGFR/pre eGFR) <0.25 group (n = 13) and (delta eGFR/pre eGFR) >0.25 group (n = 11), and compared the clinico-pathophysiological characteristics between the two groups. In the (delta eGFR/pre eGFR) >0.25 group, the ratio of glomerular obsolescence at the time of diagnosis was significantly higher than in the (delta eGFR/pre eGFR) <0.25 group. Glomerular obsolescence was identified as an independent risk factor for renal function deterioration. In this study, the prognosis of HSPN was related to glomerular obsolescence rather than to the disease activity. It may be necessary to consider the decrease in nephrons, in accordance with non-immunological glomerular obsolescence, in addition to immunological treatment to clarify the prognosis. PMID:20166542

  10. Alloantibodies to glycoprotein La/LLa (anti-HPA-5a and -5b) and IIb/IIIa (anti-HPA1a, -3a and -4a) in Nigerian parous women.

    PubMed

    Jeremiah, Z A; Oburu, J E; Erhabor, O; Buseri, F I

    2011-01-01

    Human platelet antibodies are often implicated in conditions such as neonatal alloimmune thrombocytopenia (NAIT), idiopathic thrombocytopenic purpura (ITP) and platelet refractoriness; however, the frequency of such alloantibodies has not been reported in Nigeria and West Africa. A cross section of apparently healthy adult female staff at a tertiary health facility in the Niger Delta, Nigeria, was screened for alloantibodies to human platelet antigens (HPA) using the GTI PakPlus qualitative solid-phase enzyme-linked immunosorbent assay (ELISA) method. Among the 100 women screened, no anti-glycoprotein IIb/IIIa (anti-HPA-Ia,-3a and -4a) antibodies were detected; however, prevalence of anti-glycoprotein Ia/IIa (anti-HPA-5b) was 30% and pf anti-glycoprotein Ia/IIa (anti-HPA-5a) was 18%. Parity had a significant influence on the development to HPA antibodies (Fisher's Exact test: 11.683, P < 0.05; 13.577, P < 0.01). Platelet count did not have an influence on the development of antibodies (P > 0.05). Clearly, there is need to initiate platelet serology in this setting and also a need to educate women about the risk associated with frequent pregnancies. Furthermore, caution should be exercised when recruiting parous women as blood donors

  11. 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.

  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. [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.

  14. Transfusion of prion-filtered red cells does not increase the rate of alloimmunization or transfusion reactions in patients: results of the UK trial of prion-filtered versus standard red cells in surgical patients (PRISM A).

    PubMed

    Elebute, Modupe O; Choo, Louise; Mora, Ana; MacRury, Coral; Llewelyn, Charlotte; Purohit, Shilpi; Hicks, Vicky; Casey, Caroline; Malfroy, Moira; Deary, Alison; Reed, Tania; Meredith, Sarah; Manson, Lynn; Williamson, Lorna M

    2013-03-01

    This study, conducted for the UK Blood Transfusion Services (UKBTS), evaluated the clinical safety of red cells filtered through a CE-marked prion removal filter (P-Capt™). Patients requiring blood transfusion for elective procedures in nine UK hospitals were entered into a non-randomized open trial to assess development of red cell antibodies to standard red cell (RCC) or prion-filtered red cell concentrates (PF-RCC) at eight weeks and six months post-transfusion. Patients who received at least 1 unit of PF-RCC were compared with a control cohort given RCC only. About 917 PF-RCC and 1336 RCC units were transfused into 299 and 291 patients respectively. Twenty-six new red cell antibodies were detected post-transfusion in 10 patients in each arm, an overall alloimmunization rate of 4.4%. Neither the treatment arm [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.3, 2.5] nor number of units transfused (OR 0.95, 95% CI 0.8, 1.1) had a significant effect on the proportion of patients who developed new alloantibodies. No pan-reactive antibodies or antibodies specifically against PF-RCC were detected. There was no difference in transfusion reactions between arms, and no novel transfusion-related adverse events clearly attributable to PF-RCC were seen. These data suggest that prion filtration of red cells does not reduce overall transfusion safety. This finding requires confirmation in large populations of transfused patients.

  15. Absence of the Adaptor Protein PEA-15 Is Associated with Altered Pattern of Th Cytokines Production by Activated CD4+ T Lymphocytes In Vitro, and Defective Red Blood Cell Alloimmune Response In Vivo

    PubMed Central

    Kerbrat, Stéphane; Vingert, Benoit; Junier, Marie-Pierre; Castellano, Flavia; Renault-Mihara, François; Dos Reis Tavares, Silvina; Surenaud, Mathieu; Noizat-Pirenne, France; Boczkowski, Jorge; Guellaën, Georges; Chneiweiss, Hervé; Le Gouvello, Sabine

    2015-01-01

    TCR-dependent and costimulation signaling, cell division, and cytokine environment are major factors driving cytokines expression induced by CD4+ T cell activation. PEA-15 15 (Protein Enriched in Astrocyte / 15kDa) is an adaptor protein that regulates death receptor-induced apoptosis and proliferation signaling by binding to FADD and relocating ERK1/2 to the cytosol, respectively. By using PEA-15-deficient mice, we examined the role of PEA-15 in TCR-dependent cytokine production in CD4+ T cells. TCR-stimulated PEA-15-deficient CD4+ T cells exhibited defective progression through the cell cycle associated with impaired expression of cyclin E and phosphoRb, two ERK1/2-dependent proteins of the cell cycle. Accordingly, expression of the division cycle-dependent cytokines IL-2 and IFNγ, a Th1 cytokine, was reduced in stimulated PEA-15-deficient CD4+ T cells. This was associated with abnormal subcellular compartmentalization of activated ERK1/2 in PEA-15-deficient T cells. Furthermore, in vitro TCR-dependent differentiation of naive CD4+ CD62L+ PEA-15-deficient T cells was associated with a lower production of the Th2 cytokine, IL-4, whereas expression of the Th17-associated molecule IL4I1 was enhanced. Finally, a defective humoral response was shown in PEA-15-deficient mice in a model of red blood cell alloimmunization performed with Poly IC, a classical adjuvant of Th1 response in vivo. Collectively, our data suggest that PEA-15 contributes to the specification of the cytokine pattern of activated Th cells, thus highlighting a potential new target to interfere with T cell functional polarization and subsequent immune response. PMID:26317969

  16. Absence of the Adaptor Protein PEA-15 Is Associated with Altered Pattern of Th Cytokines Production by Activated CD4+ T Lymphocytes In Vitro, and Defective Red Blood Cell Alloimmune Response In Vivo.

    PubMed

    Kerbrat, Stéphane; Vingert, Benoit; Junier, Marie-Pierre; Castellano, Flavia; Renault-Mihara, François; Dos Reis Tavares, Silvina; Surenaud, Mathieu; Noizat-Pirenne, France; Boczkowski, Jorge; Guellaën, Georges; Chneiweiss, Hervé; Le Gouvello, Sabine

    2015-01-01

    TCR-dependent and costimulation signaling, cell division, and cytokine environment are major factors driving cytokines expression induced by CD4(+) T cell activation. PEA-15 15 (Protein Enriched in Astrocyte / 15 kDa) is an adaptor protein that regulates death receptor-induced apoptosis and proliferation signaling by binding to FADD and relocating ERK1/2 to the cytosol, respectively. By using PEA-15-deficient mice, we examined the role of PEA-15 in TCR-dependent cytokine production in CD4(+) T cells. TCR-stimulated PEA-15-deficient CD4(+) T cells exhibited defective progression through the cell cycle associated with impaired expression of cyclin E and phosphoRb, two ERK1/2-dependent proteins of the cell cycle. Accordingly, expression of the division cycle-dependent cytokines IL-2 and IFNγ, a Th1 cytokine, was reduced in stimulated PEA-15-deficient CD4(+) T cells. This was associated with abnormal subcellular compartmentalization of activated ERK1/2 in PEA-15-deficient T cells. Furthermore, in vitro TCR-dependent differentiation of naive CD4(+) CD62L(+) PEA-15-deficient T cells was associated with a lower production of the Th2 cytokine, IL-4, whereas expression of the Th17-associated molecule IL4I1 was enhanced. Finally, a defective humoral response was shown in PEA-15-deficient mice in a model of red blood cell alloimmunization performed with Poly IC, a classical adjuvant of Th1 response in vivo. Collectively, our data suggest that PEA-15 contributes to the specification of the cytokine pattern of activated Th cells, thus highlighting a potential new target to interfere with T cell functional polarization and subsequent immune response. PMID:26317969

  17. Potential of Serum and Urinary Matrix Metalloproteinase-9 Levels for the Early Detection of Renal Involvement in Children With Henoch-Schönlein Purpura

    PubMed Central

    Erol, Meltem; Yigit, Ozgul; Tasdemir, Mehmet; Bostan Gayret, Ozlem; Buke, Ovgu; Gunes, Aysegul; Hamilcikan, Sahin; Kasapcopur, Ozgur

    2016-01-01

    Background Matrix metalloproteinase-9 (MMP-9) is an enzyme implicated in the pathogenesis of renal diseases. Renal involvement is the principal cause of morbidity and mortality in children with Henoch-Schönlein purpura (HSP). Objectives The aim of this study was to evaluate whether serum and urinary MMP-9 levels are associated with renal involvement in HSP Patients and Methods We evaluated 40 children with HSP (patient group) and 27 healthy volunteer children (control group). The patient group was divided into two subgroups based on the presence or absence of nephritis. Nephritis was defined as the existence of hematuria and/or proteinuria. All anthropometric data, physical examination findings, blood pressure, and laboratory parameters were recorded. The serum and urine samples were analyzed to determine the MMP-9 levels three days after the initial phase of the disease. Results The mean age was 7.65 ± 3.41 (range 2 - 16) years in the patient group and 9.52 ± 3.91 (range 2 - 16) years in the control group. Henoch-Schonlein purpura nephritis (HSPN) was identified in eight patients. There was no significant difference in the serum MMP-9 levels between the HSPN subgroup and the controls (P > 0.05). However, there were significant differences in the urinary MMP-9 levels between the HSP subgroup and the control group (P < 0.05), with the urinary MMP-9 levels being significantly higher in patients in the HSP subgroup (P = 0.001). Further, the urinary MMP-9 levels were significantly higher in the patients with nephritis than in the patients without nephritis (P = 0.001) and the controls (P = 0.001). The optimal cut-off point (sensitivity; specificity) of the urinary MMP-9 level for the diagnosis of HSPN was 94.7 pg/mL. Conclusions The levels of MMP-9 in the urine were remarkably high in patients with HSPN. This non-invasive marker may therefore be an important indicator for the early diagnosis of nephritis in children with HSP.

  18. Aberrant glycosylation of IgA1 is inherited in both pediatric IgA nephropathy and Henoch-Schönlein purpura nephritis.

    PubMed

    Kiryluk, Krzysztof; Moldoveanu, Zina; Sanders, John T; Eison, T Matthew; Suzuki, Hitoshi; Julian, Bruce A; Novak, Jan; Gharavi, Ali G; Wyatt, Robert J

    2011-07-01

    Serum galactose-deficient immunoglobulin A1 (Gd-IgA1) is an inherited risk factor for adult IgA nephropathy (IgAN). In this paper, we determined the heritability of serum Gd-IgA1 levels in children with IgAN and Henoch-Schönlein purpura nephritis (HSPN), two disorders with clinical phenotypes sharing common pathogenic mechanisms. Serum Gd-IgA1 concentrations were quantified using a Helix aspersa-lectin-based enzyme-linked immunosorbent assay. As a group, 34 children with either disorder (20 with HSPN and 14 with IgAN) had significantly higher Gd-IgA1 levels compared with 51 age- and ethnicity-matched pediatric controls. Serum levels of Gd-IgA1 were also elevated in a large fraction of 54 first-degree relatives of pediatric IgAN and HSPN patients compared with 141 unrelated healthy adult controls. A unilineal transmission of the trait was found in 17, bilineal transmission in 1, and sporadic occurrence in 5 of 23 families when both parents and the patient were analyzed. There was a significant age-, gender-, and household-adjusted heritability of serum galactose-deficient IgA1 estimated at 76% in pediatric IgAN and at 64% in HSPN patients. Thus, serum galactose-deficient IgA1 levels are highly inherited in pediatric patients with IgAN and HSPN, providing support for another shared pathogenic link between these disorders.

  19. 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

  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. Risk of long term renal impairment and duration of follow up recommended for Henoch-Schönlein purpura with normal or minimal urinary findings: a systematic review

    PubMed Central

    Narchi, H

    2005-01-01

    Background: The duration of follow up to assess the risk of long term renal impairment in Henoch-Schönlein purpura (HSP) without nephritic or nephrotic syndrome or renal failure on diagnosis remains undetermined. Aims: To undertake a systematic review of the literature to assess whether the risk of long term renal impairment without renal involvement on diagnosis could be estimated and to determine the time period when renal involvement is very unlikely after the diagnosis of HSP. Methods: Search of studies of unselected children with HSP, and available information on urinary findings, renal involvement, and long term renal function follow up. Studies of selected children with HSP nephropathy at diagnosis were excluded. Results: Twelve studies of 1133 children were reviewed. The follow up period ranged from 6 weeks to 36 years. Proteinuria and/or haematuria, which occurred in 34.2%, of which only one fifth were in association with nephritic or nephrotic syndrome, developed in 85% of cases within 4 weeks of the diagnosis of HSP, in 91% within 6 weeks, and in 97% within 6 months. Permanent renal impairment never developed after normal urinalysis; it occurred in 1.6% of those with isolated urinary abnormalities, and in 19.5% of those who developed nephritic or nephrotic syndrome. Conclusion: No long term renal impairment occurred after normal urinalysis. Even if urinalysis is normal at presentation, the testing should be continued for six months. There is no need to follow up after the first six months those whose urinalysis remains normal. PMID:15871983

  2. Alloimmunity to RhD in humans.

    PubMed

    Urbaniak, S J

    2006-01-01

    The RhD protein is expressed only on human red blood cells (RBC), and is one of the most immunogenic of the blood groups. It is of clinical importance since the alloantibody (anti-D) can hemolyse D positive RBC after blood transfusion, or cause hemolytic disease of the newborn. The immunogenicity of D is better understood with the knowledge of the genetic basis of the protein(s) involved, the molecular orientation in the RBC membrane, and the nature of the cellular immune response to proteins. The adaptive humoral response consists of antigen presenting cells, T-cells and B-cells, which interact cooperatively to result in antibody against the antigen in question. The anti-D that B-cells produce is targeted against surface membrane determinants (B-cell epitopes) and are conformational i.e. non-contiguous amino acids. The antigen specific T-cells recognize short linear peptides in the context of MHC class II, and these T-cell epitopes can reside anywhere in the protein. Since the RhD protein in D-positive individuals differs by some 35 amino acids from the RhCcEe protein in D-negative individuals, the opportunity for generating immunogenic T-cell epitopes is much greater than that for alleles characterized by a single amino acid difference e.g. E and e. Multiple conformational B-cell epitopes are also created by the presence of several D-specific amino acids in extracellular loops on the red cells surface, which may stimulate several B-cell clones and develop a strong polyclonal antibody response. With greater understanding comes the possibility of manipulating the immune response to D in clinical situations.

  3. 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.

  4. May-Hegglin anomaly and pregnancy: a systematic review.

    PubMed

    Hussein, Brwa A; Gomez, Keith; Kadir, Rezan A

    2013-07-01

    May-Hegglin anomaly (MHA) is an autosomal dominant disorder, characterized by a variable degree of thrombocytopaenia, large platelets and inclusion bodies in white blood cells. Bleeding manifestations are generally mild, but severe bleeding episodes have been reported. This is a systematic review of literature for MHA during pregnancy. The review revealed 26 articles (25 case reports and one case series) including 75 pregnancies (five twin pregnancies) in 40 women. In 11 women, first presentation was incidental thrombocytopaenia during routine antenatal blood test. Of these, five women were misdiagnosed as idiopathic thrombocytopenic purpura (ITP), including three who underwent splenectomy for resistant ITP. Postpartum haemorrhage (PPH) and bleeding after miscarriage were presenting symptoms in two women. Antiplatelet antibody was found in three pregnancies. Only one of them required intervention with intravenous immunoglobulin (IVIG) to prevent neonatal alloimmune thrombocytopaenia. PPH was reported in four pregnancies; three were primary PPH, of which one had blood transfusion, one had platelet and cryoprecipitate transfusion and the third was managed conservatively. There was one secondary PPH that was treated conservatively. Neonatal outcome included 78 live neonates and two intrauterine fetal deaths. Thirty-four neonates had thrombocytopaenia and subsequently were diagnosed with MHA, three of them required platelet transfusion prophylactically as they developed very low platelet counts and one neonate with platelet count of 29 × 10 cells/l and received IVIG, as the mother had a positive antiplatelet antibody during pregnancy. No obvious bleeding complications were reported among the neonates. MHA can present challenges during pregnancy and be associated with adverse maternal and neonatal outcome because of bleeding complications. Joint management by obstetrician and haematologists is required to minimize these risks. PMID:23811802

  5. 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

  6. 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

  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. A Case of Microangiopathic Hemolytic Anemia after Myxoma Excision and Mitral Valve Repair Presenting as Hemolytic Uremic Syndrome

    PubMed Central

    Park, Young Joo; Kim, Sang Pil; Shin, Ho-Jin

    2016-01-01

    Microangiopathic hemolytic anemia occurs in a diverse group of disorders, including thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and prosthetic cardiac valves. Hemolytic anemia also occurs as a rare complication after mitral valve repair. In this report, we describe a case of microangiopathic hemolytic anemia following myxoma excision and mitral valve repair, which was presented as hemolytic uremic syndrome. PMID:27081450

  9. A Case of Microangiopathic Hemolytic Anemia after Myxoma Excision and Mitral Valve Repair Presenting as Hemolytic Uremic Syndrome.

    PubMed

    Park, Young Joo; Kim, Sang Pil; Shin, Ho-Jin; Choi, Jung Hyun

    2016-03-01

    Microangiopathic hemolytic anemia occurs in a diverse group of disorders, including thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and prosthetic cardiac valves. Hemolytic anemia also occurs as a rare complication after mitral valve repair. In this report, we describe a case of microangiopathic hemolytic anemia following myxoma excision and mitral valve repair, which was presented as hemolytic uremic syndrome. PMID:27081450

  10. [Autoimmune thrombocytopenia: diagnosis and treatment].

    PubMed

    Veneri, Dino; Franchini, Massimo

    2005-05-01

    Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by an isolated, persistent thrombocytopenia in absence of known causes. In this review, we briefly analyze the most important diagnostic criteria of this autoimmune disorder, with particular consideration to differential diagnosis (false thrombocytopenia, congenital thrombocytopenia, acquired thrombocytopenia, pregnancy-associated thrombocytopenia) and to therapeutic options.

  11. Unusual presentations of Salmonella Typhi infections in children.

    PubMed

    Mittal, Sumit; Saxena, Ajit; Garg, Pankaj

    2009-01-01

    We report on three children with Salmonella typhi presenting with fever and urticaria, thrombocytopenic purpura and meningitis. We suggest that clinicians should consider S. typhi infection as a diagnosis even when the presenting features are more typical of other illnesses. PMID:19211418

  12. 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

  13. 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.

  14. 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. PMID:27165395

  15. IgA nephropathy and Henoch-Schoenlein purpura nephritis: aberrant glycosylation of IgA1, formation of IgA1-containing immune complexes, and activation of mesangial cells.

    PubMed

    Novak, Jan; Moldoveanu, Zina; Renfrow, Matthew B; Yanagihara, Takeshi; Suzuki, Hitoshi; Raska, Milan; Hall, Stacy; Brown, Rhubell; Huang, Wen-Qiang; Goepfert, Alice; Kilian, Mogens; Poulsen, Knud; Tomana, Milan; Wyatt, Robert J; Julian, Bruce A; Mestecky, Jiri

    2007-01-01

    IgA1 in the circulation and glomerular deposits of patients with IgA nephropathy (IgAN) is aberrantly glycosylated; the hinge-region O-linked glycans are galactose-deficient. The circulating IgA1 of patients with Henoch-Schoenlein purpura nephritis (HSPN) has a similar defect. This aberrancy exposes N-acetylgalactosamine-containing neoepitopes recognized by naturally occurring IgG or IgA1 antibodies resulting in formation of immune complexes. IgA1 contains up to six O-glycosylation sites per heavy chain; it is not known whether the glycosylation defect occurs randomly or preferentially at specific sites. We sought to define the aberrant glycosylation of a galactose-deficient IgA1 myeloma protein and analyze the formation of the immune complexes and their biological activities. Supplementation of serum or cord-blood serum with this IgA1 protein resulted in formation of new IgA1 complexes. These complexes stimulated proliferation of cultured human mesangial cells, as did the naturally-occurring IgA1-containing complexes from sera of patients with IgAN and HSPN. Uncomplexed IgA1 did not affect cellular proliferation. Using specific proteases, lectin Western blots, and mass spectrometry, we determined the O-glycosylation sites in the hinge region of the IgA1 myeloma protein and IgA1 proteins from sera of IgAN patients. The IgA1 myeloma protein had galactose-deficient sites at residues 228 and/or 230 and 232. These sites reacted with IgG specific to galactose-deficient IgA1. IgA1 from the IgAN patients had galactose-deficient O-glycans at the same residues. In summary, we identified the neoepitopes on IgA1 responsible for formation of the pathogenic immune complexes. These studies may lead to development of noninvasive diagnostic assays and future disease-specific therapy.

  16. Multiple tuberculous aneurysms of the aorta.

    PubMed

    Pierret, Charles; Tourtier, Jean-Pierre; Grand, Bertrand; Boddaert, Guillaume; Laurian, Claude; de Kerangal, Xavier

    2011-06-01

    Tuberculous aneurysms of the aorta are quite rare, but are exceptional when found in multiple locations. We report the case of multiple tuberculous aortic aneurysms of the thoracic and abdominal aorta in a 19-year-old female discovered when she consulted for thrombocytopenic purpura. The treatment for both locations included prolonged antituberculous therapy and surgical resection with cryopreserved aortic allograft patch for the reconstruction.

  17. A Case Report of an Elderly Woman With Thrombocytopenia and Bilateral Lung Infiltrates

    PubMed Central

    Hashmi, Hafiz Rizwan Talib; Venkatram, Sindhaghatta; Diaz-Fuentes, Gilda

    2015-01-01

    Abstract Etiologies for diffuse alveolar hemorrhage are wide and range from infectious to vasculitis and malignant processes. Idiopathic thrombocytopenic purpura is an autoimmune disorder characterized by persistent thrombocytopenia, with a relatively indolent course in young patients, but a more complicated progression and high associated mortality in the older patients. Diffuse alveolar hemorrhage, complicating idiopathic thrombocytopenic purpura, is a very uncommon association, with only 2 reported cases in the literature. We present a 69-year-old healthy woman presenting with petechial rash, progressive dyspnea, and bilateral alveolar infiltrates. She was found to have idiopathic thrombocytopenic purpura associated with diffuse alveolar hemorrhage. The patient had an excellent response to high doses of pulse steroids and immunoglobulins. A high index of suspicion for noninfectious pulmonary diseases should be considered in patients with autoimmune diseases presenting with pulmonary infiltrates and hypoxia. Flexible bronchoscopy with sequential lavage is a relatively safe procedure in patients with coagulopathy and should be attempted to detect and confirm the diagnosis; absence of hemoptysis should not preclude the diagnosis. PMID:26683938

  18. Ectopic expression of CCL19 impairs alloimmune response in mice

    PubMed Central

    Krautwald, Stefan; Ziegler, Ekkehard; Förster, Reinhold; Ohl, Lars; Amann, Kerstin; Kunzendorf, Ulrich

    2004-01-01

    Initiation of an antitumour immune response is characterized by a complex process of chemokine-mediated cell migration and cell–cell interactions. Overexpression of chemokine CCL19 in tumour cells has been shown to result in accelerated tumour rejection under certain experimental conditions, suggesting a novel approach in the therapy of neoplastic malignancies. To investigate CCL19-mediated modulations of cellular immune responses in vivo, we generated a chimeric CCL19-immunoglobulin G2b (IgG2b) Fc fusion protein, which binds to the chemokine receptor CCR7 comparable to native CCL19. CCL19-IgG2b possesses a long-lasting potent chemotactic activity as a result of the extended half-life of Fc fusion proteins. Stable overexpression of CCL19-IgG2b in BALB/c-derived J558L tumour cells fails to support tumour cell rejection following transplantation in syngeneic mice. Moreover, overexpression of CCL19-IgG2b hinders tumour rejection in allogeneic C57BL/6 mice. This phenomenon was accompanied by a six-fold increase of dendritic cells (DCs) isolated from CCL19-IgG2b-secreting tumours when compared to the number of DCs isolated from control parental J558L tumours. While mice bearing the allogeneic parental tumour showed an intense hypercellularity in the draining lymph nodes, no such response could be observed in the draining lymph nodes of mice carrying the CCL19-IgG2b-secreting tumour. We could demonstrate that overexpression of CCL19-IgG2b in tumour cells retains antigen-presenting cells in the tumour mass and prevents DCs from migrating into draining lymph nodes to present antigens and to activate T cells, resulting in an impaired immune response against the tumour. PMID:15147573

  19. Ectopic expression of CCL19 impairs alloimmune response in mice.

    PubMed

    Krautwald, Stefan; Ziegler, Ekkehard; Förster, Reinhold; Ohl, Lars; Amann, Kerstin; Kunzendorf, Ulrich

    2004-06-01

    Initiation of an antitumour immune response is characterized by a complex process of chemokine-mediated cell migration and cell-cell interactions. Overexpression of chemokine CCL19 in tumour cells has been shown to result in accelerated tumour rejection under certain experimental conditions, suggesting a novel approach in the therapy of neoplastic malignancies. To investigate CCL19-mediated modulations of cellular immune responses in vivo, we generated a chimeric CCL19-immunoglobulin G2b (IgG2b) Fc fusion protein, which binds to the chemokine receptor CCR7 comparable to native CCL19. CCL19-IgG2b possesses a long-lasting potent chemotactic activity as a result of the extended half-life of Fc fusion proteins. Stable overexpression of CCL19-IgG2b in BALB/c-derived J558L tumour cells fails to support tumour cell rejection following transplantation in syngeneic mice. Moreover, overexpression of CCL19-IgG2b hinders tumour rejection in allogeneic C57BL/6 mice. This phenomenon was accompanied by a six-fold increase of dendritic cells (DCs) isolated from CCL19-IgG2b-secreting tumours when compared to the number of DCs isolated from control parental J558L tumours. While mice bearing the allogeneic parental tumour showed an intense hypercellularity in the draining lymph nodes, no such response could be observed in the draining lymph nodes of mice carrying the CCL19-IgG2b-secreting tumour. We could demonstrate that overexpression of CCL19-IgG2b in tumour cells retains antigen-presenting cells in the tumour mass and prevents DCs from migrating into draining lymph nodes to present antigens and to activate T cells, resulting in an impaired immune response against the tumour. PMID:15147573

  20. [A child with neonatal allo-immune neutropenia].

    PubMed

    Markhorst, D G; Hack, W W; de Waal, F C; Kuypers, R

    1990-10-01

    A newborn child with neonatal neutropenia as a result of the presence of maternal IgG isoantibodies against neutrophil granulocyte blood group antigens is reported. Mechanism, diagnostics and therapy of the disease are discussed. The diagnosis not only has consequences for the child, but also for the mother and following pregnancies. A review of the most important causes of neonatal neutropenia is given.

  1. Immunoregulatory Effects of Everolimus on In Vitro Alloimmune Responses

    PubMed Central

    Levitsky, Josh; Miller, Joshua; Huang, Xuemei; Gallon, Lorenzo; Leventhal, Joseph R.; Mathew, James M.

    2016-01-01

    Everolimus (EVL) is a novel mTOR-inhibitor similar to sirolimus (SRL) that is used in organ transplant recipients, often in combination with tacrolimus (TAC) or mycophenolate (MPA). The current study aims to determine its effects on regulatory T cells. Increasing concentrations of EVL, MPA and TAC alone or in combination were added to MLRs of healthy volunteers. Lymphoproliferation by 3H-TdR incorporation and the percentage of newly generated CD4+CD127-CD25+FOXP3+ (total Treg) and CD4+CD127-CD25HighFOXP3+ (natural Treg) in CFSE labeled responder cells were assessed by flow cytometry. In comparison to medium controls, EVL and other agents dose-dependently inhibited 3H-TdR incorporation in HLA-2DR-matched and HLA-mismatched MLRs (n = 3–10). However, EVL significantly amplified newly generated total and natural Tregs in CFSE labeled responder cells (p<0.05) at all concentrations, while MPA and SRL did this only at sub-therapeutic concentrations and inhibited at therapeutic levels. In contrast, TAC inhibited newly generated Tregs at all concentrations. When tested in combination with TAC, EVL failed to reverse TAC inhibition of Treg generation. Combinations of EVL and low concentrations of MPA inhibited proliferation and amplified Treg generation in an additive manner when compared to medium controls or each drug tested alone (p<0.05). The relative tolerogenic effect from high to low was EVL > SRL> MPA > TAC. If the results from these in vitro studies are extrapolated to clinical transplantation, it would suggest EVL plus low concentrations of MPA may be the most tolerogenic combination. PMID:27275747

  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. Palpable purpura with an unexpected outcome.

    PubMed

    Friesgaard Christensen, Anne; Clemmensen, Ole; Junker, Peter

    2013-01-01

    Scurvy is a potentially lethal condition caused by inadequate vitamin C intake. Hypovitaminosis of vitamin C causes vessel fragility and follicular hyperkeratosis that can lead to palpable purpuric skin lesions. In this case report, we aim to remind readers that scurvy still occurs in Western countries and that the clinical presentation may resemble vasculitis. PMID:23956916

  4. Suspects in the tale of lupus-associated thrombocytopenia

    PubMed Central

    Ziakas, P D; Routsias, J G; Giannouli, S; Tasidou, A; Tzioufas, A G; Voulgarelis, M

    2006-01-01

    Immunologically mediated thrombocytopenia is a frequent clinical manifestation in patients with systemic lupus erythematosus (SLE). Autoantibodies targeting platelet membrane glucoproteins have a central role in peripheral platelet destruction. Autoantibodies against thrombopoietin are also present in about one-third of patients, but their pathogenetic role is obscure. Thirty-eight serum samples from SLE patients were tested for anti-platelet antibodies, anti-thrombopoietin antibodies and levels of circulating thrombopoietin. Bone marrow histology was also assessed. Thirty-nine per cent of sera displayed anti-thrombopoietin antibodies and 29% had circulating anti-platelet antibodies. Anti-thrombopoietin antibodies were associated with lower thrombopoietin concentrations, and lower mean platelet values in long-term follow-up. Anti-platelet antibodies were present in about 40% of thrombocytopenic and non-thrombocytopenic individuals but were absent in patients who had recovered from thrombocytopenia, supporting their pathogenetic role. Both autoantibodies were absent in control sera from patients with rheumatoid arthritis and primary Sjögren’s syndrome. Decreased bone marrow cellularity, normal or low number of hypolobulated, pyknotic megakaryocytes and stromal alterations were prominent findings in thrombocytopenic SLE patients, suggesting a defect in megakaryopoiesis. These findings were not evident in specimens from patients with idiopathic thrombocytopenic purpura who had increased megakaryocytes, normal cellularity and absence of stromal alterations. In conclusion, peripheral destruction due to platelet autoantibodies, anti-thrombopoetin antibodies, lower effective circulating thrombopoetin and impaired compensatory response due to bone marrow damage interact in SLE and thrombocytopenia ensues. PMID:16792676

  5. Plasmapheresis in Clinical Medicine

    PubMed Central

    Linker, Charles

    1983-01-01

    Large-volume plasma exchange can now be rapidly and safely done using cell separator technology. Significant depletion of immunoglobulins and immune complexes can be achieved by repeated intensive plasmapheresis, but sustained depletion of these constituents requires concomitant immunosuppressive therapy. Plasmapheresis appears to work in some disorders by removing pathogenic antibodies, but other mechanisms of action have been postulated. It is the treatment of choice for thrombotic thrombocytopenic purpura and for the hyperviscosity syndrome due to macroglobulinemia. Apheresis can be useful in the treatment of many other disorders, most notably myasthenia gravis, glomerulonephritis associated with hemoptysis (Goodpasture's syndrome), refractory systemic lupus erythematosus, cryoglobulinemia and immune cytopenic disorders. Images PMID:6601332

  6. Verotoxinogenic Citrobacter freundii associated with severe gastroenteritis and cases of haemolytic uraemic syndrome in a nursery school: green butter as the infection source.

    PubMed Central

    Tschape, H.; Prager, R.; Streckel, W.; Fruth, A.; Tietze, E.; Böhme, G.

    1995-01-01

    A summer outbreak of severe gastroenteritis followed by haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura in a nursery school and kindergarten is described. Sandwiches prepared with green butter made with contaminated parsley were the likely vehicle of infection. The parsley originated from an organic garden in which manure of pig origin was used instead of artificial fertilizers. Clonally identical verotoxinogenic Citrobacter freundii were found as causative agents of HUS and gastroenteritis and were also detected on the parsley. Images Fig. 1 Fig. 2 PMID:7781732

  7. Proportion of drug-related serious rare blood dyscrasias: estimates from the Berlin Case-Control Surveillance Study.

    PubMed

    Andersohn, Frank; Bronder, Elisabeth; Klimpel, Andreas; Garbe, Edeltraut

    2004-11-01

    Drugs are an important cause of serious rare blood dyscrasias. To estimate the proportion of drug-related cases, we used data from the ongoing Berlin Case-Control Surveillance Study. The analysis included a total of 171 cases. The number of cases in which a drug etiology was assessed as at least "possible" was n = 29 (97%) for acute agranulocytosis, n = 4 (0.21%) for aplastic anemia, n = 8 (26%) for immune hemolytic anemia, n = 20 (25%) for immune thrombocytopenia, and n = 2 (20%) for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. Our analysis suggests that a substantial fraction of blood dyscrasias may be attributable to drug therapy. PMID:15495238

  8. The nontreatment of childhood ITP (or "the art of medicine consists of amusing the patient until nature cures the disease").

    PubMed

    Bolton-Maggs, P H; Dickerhoff, R; Vora, A J

    2001-06-01

    The management of childhood acute idiopathic thrombocytopenic purpura is controversial, with recent guidelines highlighting the lack of suitable evidence upon which to base management decisions. Three European centers have used an expectant policy and results over the past decade demonstrate that this is safe and convenient for the majority of children. Adequate parental education about the condition from an experienced specialist is essential, together with open access for children should they develop any problems. A clinical stratification of such patients must be incorporated into any future trials, together with quality of life assessment to discover the impact of restrictions on lifestyle, particularly in adolescents with chronic ITP who may need a different approach.

  9. Bacillary angiomatosis in an HIV seronegative patient on systemic steroid therapy.

    PubMed

    Schwartz, R A; Gallardo, M A; Kapila, R; Gascón, P; Herscu, J; Siegel, I; Lambert, W C

    1996-12-01

    Bacillary angiomatosis is an unusual systemic vascular proliferation seen predominantly in patients with the acquired immunodeficiency syndrome. These vascular lesions are due to infection with a Bartonella species, most commonly B. henselae, but sometimes B. quintana. It is treatable and often curable, but without therapy may be life-threatening. Clinically, the disorder often resembles several different vascular disorders, particularly pyogenic granuloma and Kaposi's sarcoma. We now report a clinically typical patient with bacillary angiomatosis who was HIV seronegative, but who had idiopathic thrombocytopenic purpura, was status-post splenectomy and to whom long-term systemic prednisone had been administered.

  10. Spectrum of diseases associated with increased proportions or absolute numbers of peripheral blood natural killer cells.

    PubMed

    Okuno, S H; Tefferi, A; Hanson, C A; Katzmann, J A; Li, C Y; Witzig, T E

    1996-06-01

    In a retrospective review of 1501 lymphoid flow cytometric studies of peripheral blood, we identified an increased proportion of natural killer cells in 125 cases (8%), 49 (3%) of which had a concomitant increase in absolute number of natural killer cells. Of the latter, the most frequent associated disorder was chronic natural killer cell lymphocytosis. Substantial quantitative increases in natural killer cells were also observed in some patients with lymphoma, leukaemia, immune thrombocytopenic purpura, or myelodysplastic syndrome. Our study provides incidence figures and clinical associations of an increased number of natural killer cells in the peripheral blood.

  11. Guidelines for the use of fresh frozen plasma. British Committee for Standards in Haematology, Working Party of the Blood Transfusion Task Force.

    PubMed

    Contreras, M; Ala, F A; Greaves, M; Jones, J; Levin, M; Machin, S J; Morgan, C; Murphy, W; Napier, J A; Thomson, A R

    1992-03-01

    Fresh frozen plasma should only be used to treat bleeding episodes or prepare patients for surgery in certain defined situations. Definite indications for the use of FFP: 1. Replacement of single coagulation factor deficiencies, where a specific or combined factor concentrate is unavailable. 2. Immediate reversal or warfarin effect. 3. Acute disseminated intravascular coagulation (DIC). 4. Thrombotic thrombocytopenic purpura (TTP). Conditional uses: FFP only indicated in the presence of bleeding and disturbed coagulation: 1. Massive transfusion. 2. Liver disease. 3. cardiopulmonary bypass surgery. 4. Special paediatric indications. No justification for the use of FFP: 1. Hypovolaemia. 2. Plasma exchange procedures. 3. 'Formula' replacement. 4. Nutritional support. 5. Treatment of immunodeficiency states.

  12. Possible role for exchange plasmapheresis with fresh frozen plasma for maternal indications in selected cases of preeclampsia and eclampsia.

    PubMed

    Schwartz, M L

    1986-07-01

    A new case of a preeclamptic who developed the diagnostic criteria for the hemolytic uremic syndrome and who was treated with plasmapheresis is presented. Fourteen case reports of gravidas with preeclampsia treated by exchange plasmapheresis with fresh frozen plasma for maternal indications are reviewed. Only four cases had been reported as eclampsia or preeclampsia. The other cases had been reported as thrombotic thrombocytopenic purpura, the postpartum hemolytic uremic syndrome, or fatty liver of pregnancy. The possible role of plasmapheresis in treating very carefully selected cases of preeclampsia is discussed.

  13. Vaccinations and secondary immune thrombocytopenia with antiphospholipid antibodies by human papillomavirus vaccine.

    PubMed

    Bizjak, Mojca; Bruck, Or; Kanduc, Darja; Praprotnik, Sonja; Shoenfeld, Yehuda

    2016-04-01

    A 13-year-old girl developed immune thrombocytopenic purpura (ITP) and concomitant positive antiphospholipid antibodies (aPL) following vaccination with a quadrivalent human papillomavirus (HPV) vaccine. During the course of a disease, she developed clinical manifestation with bleeding and she was treated with intravenous immunoglobulins. Consequently, the number of her platelets remained critically low and she was put on corticosteroids and rituximab. Since then, her platelet count remain within the normal range, but her aPL are still present. PMID:27312165

  14. [Changes and progress in the treatment of TTP--protocols of therapeutic plasma infusion and plasma exchange--therapeutic results by the Japanese and Canadian Study Groups].

    PubMed

    Ito, K; Hattori, A; Hirosawa, S; Takamatsu, J; Kakishita, E; Fujimura, K

    1993-01-01

    Plasma exchange (PE) and plasma infusion (PI) are effective in the treatment of TTP (thrombotic thrombocytopenic purpura). Comparison of PE and PI in the treatment of TTP was carried out by the Canadian Apheresis Study Group, which reported that PE was superior to PI. The Japanese TTP Study Group made a therapeutic protocol in which a smaller volume of Fresh frozen plasma (FFP) was used in the treatment with PI. The efficacy of PE and PI was similar. The results suggest that the volume of FFP necessary for effective treatment is not very large.

  15. 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).

  16. Intravenous anti-D immune globulin-induced intravascular hemolysis in Epstein-Barr virus-related thrombocytopenia.

    PubMed

    Levendoglu-Tugal, O; Jayabose, S

    2001-10-01

    RhoD immune globulin intravenous (anti-D IGIV) increases platelet counts in patients who have not undergone splenectomy and are positive for RhoD with idiopathic thrombocytopenic purpura. After treatment, in most patients, anemia develops as a result of immune-mediated red cell destruction in the spleen. Although intravascular hemolysis (IVH) is not expected, life-threatening IVH has been recently reported by the Food and Drug Administration, and physicians are encouraged to report their experience with patients with idiopathic thrombocytopenic purpura in whom IVH develops after anti-D administration. Severe IVH was observed after treatment with anti-D IGIV in two adolescent girls with acute thrombocytopenia related to Epstein-Barr virus. They did not have hemolytic anemia before treatment. The authors believe that anti-D IGIV triggered an unusual virus-induced immune response causing hemolysis; therefore, anti-D IGIV should not be used in patients with Epstein-Barr virus-related thrombocytopenia, particularly during the acute phase of infection.

  17. The efficacy of rituximab in the treatment of inhibitor-associated hemostatic disorders.

    PubMed

    Franchini, Massimo; Veneri, Dino; Lippi, Giuseppe; Stenner, Rachel

    2006-08-01

    Rituximab is a chimeric anti-CD20 monoclonal antibody active against normal and malignant B cells which has proven to be effective in the therapy of CD-20 positive lymphomas. Its B-cell cytotoxic action has also been exploited in many non-malignant autoimmune disorders in which it has been used with the aim of interfering with the production of pathologic antibodies. The present knowledge regarding the use of rituximab in antibody-associated disorders of hemostasis (i.e. idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, acquired hemophilia A, congenital hemophilia with inhibitors, acquired inhibitors against coagulation factors) is presented briefly in this review. The results suggest that rituximab can be useful in the treatment of disorders of hemostasis associated with inhibitor formation. Although collectively the number of patients treated is now quite substantial, most of the data are drawn from isolated case reports or descriptions of small, uncontrolled series. Large, prospective, randomized trials are, therefore, needed to confirm the positive, preliminary results.

  18. [Does Helicobacter pylori infection play a role in extragastric diseases?].

    PubMed

    de Korwin, Jean-Dominique

    2008-03-01

    Since the discovery of Helicobacter pylori (H. pylori), numerous studies have considered the possibility that it plays a role in different extragastric diseases. Most of these studies may be classified as epidemiological studies or investigations of H. pylori eradication, but there are also case reports and in vitro studies. This review reveals the limitations common to most of them. Idiopathic thrombocytopenic purpura is the disease for which the strongest association with H. pylori infection has been shown. Data are also accumulating about the role of H. pylori infection in idiopathic iron deficiency anemia and chronic idiopathic urticaria. Interesting results show that H. pylori infection affects atherosclerosis and is weakly associated with ischemic heart disease and stroke. Moreover, CagA-positive H. pylori strains may play a role in the natural history of atherosclerotic stroke. Recent studies suggest a link between H. pylori and Parkinson's disease. Preliminary data indicate that H. pylori infection impairs gastric ghrelin production and may influence nutritional status. The association between H. pylori infection and other extragastric diseases remains controversial. H. pylori infection may cause extragastric manifestations directly or indirectly, by various mechanisms including atrophic gastritis, the release of inflammatory mediators, molecular mimicry, and systemic immune response. Evidence suggests that anti-H. pylori therapy improves idiopathic thrombocytopenic purpura (significant increase of platelet count in half of the cases), iron-deficiency anemia, and chronic urticaria (30% remission rate), but the data from randomized controlled trials are insufficient to confirm these positive effects.

  19. [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.

  20. Human leukocyte antigens and alloimmunization in heart transplantation: an open debate.

    PubMed

    Picascia, Antonietta; Grimaldi, Vincenzo; Casamassimi, Amelia; De Pascale, Maria Rosaria; Schiano, Concetta; Napoli, Claudio

    2014-10-01

    Considerable advances in heart transplantation outcome have been achieved through the improvement of donor-recipient selection, better organ preservation, lower rates of perioperative mortality and the use of innovative immunosuppressive protocols. Nevertheless, long-term survival is still influenced by late complications. We support the introduction of HLA matching as an additional criterion in the heart allocation. Indeed, allosensitization is an important factor affecting heart transplantation and the presence of anti-HLA antibodies causes an increased risk of antibody-mediated rejection and graft failure. On the other hand, the rate of heart-immunized patients awaiting transplantation is steadily increasing due to the limited availability of organs and an increased use of ventricular assist devices. Significant benefits may result from virtual crossmatch approach that prevents transplantation in the presence of unacceptable donor antigens. A combination of both virtual crossmatch and a tailored desensitization therapy could be a good compromise for a favorable outcome in highly sensitized patients. Here, we discuss the unresolved issue on the clinical immunology of heart transplantation.

  1. Prophylactic rituximab after allogeneic transplantation decreases B-cell alloimmunity with low chronic GVHD incidence

    PubMed Central

    Arai, Sally; Sahaf, Bita; Narasimhan, Balasubramanian; Chen, George L.; Jones, Carol D.; Lowsky, Robert; Shizuru, Judith A.; Johnston, Laura J.; Laport, Ginna G.; Weng, Wen-Kai; Benjamin, Jonathan E.; Schaenman, Joanna; Brown, Janice; Ramirez, Jessica; Zehnder, James L.; Negrin, Robert S.

    2012-01-01

    B cells are involved in the pathogenesis of chronic GVHD (cGVHD). We hypothesized that prophylactic anti–B-cell therapy delivered 2 months after transplantation would decrease allogeneic donor B-cell immunity and possibly the incidence of cGVHD. Therefore, in the present study, patients with high-risk chronic lymphocytic leukemia (n = 22) and mantle-cell lymphoma (n = 13) received a total lymphoid irradiation of 80 cGy for 10 days and antithymocyte globulin 1.5 mg/kg/d for 5 days. Rituximab (375 mg/m2) was infused weekly on days 56, 63, 70, and 77 after transplantation. The incidence of acute GVHD was 6%. The cumulative incidence of cGVHD was 20%. Nonrelapse mortality was 3%. Rituximab treatment after allogeneic transplantation significantly reduced B-cell allogeneic immunity, with complete prevention of alloreactive H-Y Ab development in male patients with female donors (P = .01). Overall survival and freedom from progression at 4 years for chronic lymphocytic leukemia patients were 73% and 47%, respectively; for mantle-cell lymphoma patients, they were 69% and 53%, respectively. This study is registered at www.clinicaltrials.gov as NCT00186628. PMID:22563089

  2. Role of HLA antigens in Rh (D) alloimmunized pregnant women from Mumbai, Maharashtra, India.

    PubMed

    Kumar, U Shankar; Ghosh, K; Gupte, S S; Gupte, S C; Mohanty, D

    2002-03-01

    Immunogenetic studies in various diseases provide potential genetic markers. We have studied the incidence of HLA A, B, C, DR and DQ loci antigen in Rh (D) antigen isoimmunized mothers compared to those nonimmunized isoimmunized Rh negative mothers. Seventy six mothers who were immunized to Rh (D) antigen due to pregnancy (responders) and fifty four mothers who did not develop Rh (D) isoimmunization despite positive pregnancies (nonresponders) were selected for the study. Standard methods of serological HLA typing, ABO and Rh (D) groups, and screening for Rh D antibodies were used. 392 unrelated individuals from the population were compared as controls. In addition 45 unrelated individuals from the same population were typed for HLA DRB and DQB gene using PCR-SSP kits. The genotype frequencies of HLA A2, A3, A28, B13, B17, B35, B52, B60, Cw2, Cw6, DR4, and DQ3 were significantly increased, while the frequencies of the HLA A11, A29, A31, B7, B37, B51, Cw1 and DR9 were decreased in the responder women when compared to the non-responder women. HLA A30 (19) split antigen was not identified in immunized women while HLA A23 (9) split antigen was not identified in non immunized women. HLA A3, B17, Cw2 and DR4 showed a significant relative risk among the immunized responder women. When compared with Rh immunized women (responders) reported from USA, England and Hungary the phenotype frequencies of HLA A11, A24, A28, B5, B17, B40, DR2 and DR5 were increased while HLA A23, B8, B18, and DR6 were decreased in the Indian Rh immunized women. Two locus haplotype frequency analysis observed among the responders women revealed that among the significant haplotypes expressed A2-B5, B7-Cw1, DR2-DQ1 were highly significant haplotypes in positive linkage, while A1-B5, and A1-B7 were in significant negative linkage disequilibrium. The haplotype frequencies were

  3. Methods for the selection of platelet products for alloimmune-refractory patients.

    PubMed

    Kopko, Patricia M; Warner, Paul; Kresie, Lesley; Pancoska, Carol

    2015-02-01

    The ability to efficiently and accurately diagnose the cause(s) of platelet (PLT) refractoriness is paramount in providing effective PLT products for transfusion. Recent advances in methods for detecting and identifying alloantibodies against human leukocyte antigens (HLAs) and human PLT antigens, combined with accurate molecular techniques for HLA typing, have provided a framework for the development of clinical algorithms to support such patients. Alloantibodies may be detected and/or identified by several methods, including complement-dependent cytotoxicity, enzyme-linked immunosorbent assays (ELISA), and microbead-based assays using Luminex or flow cytometry. The primary difference in these assays is the sensitivity of detection and the range of antibody specificities that may be reliably identified. Direct PLT cross-matching to identify compatible PLTs can be accomplished by several methods, including solid-phase red cell adherence, modified antigen capture ELISA, and flow cytometry. A survey of blood centers and laboratories providing transfusion support has identified the heterogeneity of testing options available, areas of concern and need for improvement, and common obstacles in providing appropriate and timely support to immune-refractory PLT patients. Depending on the testing methods and the pool of HLA-typed PLT donors available, there are numerous options for developing suitable algorithms to provide effective support to immune-refractory PLT patients.

  4. [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.

  5. Intravenous and standard immune serum globulin preparations interfere with uptake of /sup 125/I-C3 onto sensitized erythrocytes and inhibit hemolytic complement activity

    SciTech Connect

    Berger, M.; Rosenkranz, P.; Brown, C.Y.

    1985-02-01

    Antibody-sensitized sheep erythrocytes were used as a model to determine the effects of therapeutic immune serum globulin (ISG) preparations on the ability of this particulate activator to fix C3 and initiate hemolysis. Both standard and intravenous forms of ISG inhibit uptake of /sup 125/I-C3, presumably by competing for the deposition of ''nascent'' C3b molecules onto the erythrocytes. Both forms of ISG also inhibit hemolytic activity of whole serum or purified complement components. The inhibition appears to be a specific property of IgG itself, since similar inhibition was not caused by equivalent concentrations of human serum albumin, and was not affected by the buffer in which the ISG was dissolved. Interference with C3 uptake onto antibody-sensitized platelets and/or inhibition of hemolytic complement activity could contribute to the efficacy of high dose intravenous ISG in idiopathic thrombocytopenic purpura.

  6. Chronic idiopathic thrombocytopenia treated with immunoglobulin.

    PubMed Central

    Mori, P G; Mancuso, G; del Principe, D; Duse, M; Miniero, R; Tovo, R; Bardare, M; Carnelli, V; de Mattia, D

    1983-01-01

    Twenty five children with chronic idiopathic thrombocytopenic purpura followed from 6-96 months in 7 Italian paediatric departments were treated with high dose immunoglobulin according to a multicentre protocol. Positive responses were observed in 20 of 25 patients (80%) and negative responses in 5 of 25 (20%). On previous steroid treatment 7 of 10 positive responders were steroid resistant and 13 of 15 were steroid dependent. Within four weeks of beginning treatment 16 of 20 patients (80%) relapsed, while 4 of 20 (20%) maintained normal platelet values after 4-12 months' follow up. Statistical analysis of the platelet count on day five of treatment enabled us to divide positive responders into three groups: good, intermediate, and poor. The possible mode of action and clinical application of high dose immunoglobulin are discussed. PMID:6685997

  7. [Current treatment of primary immune thrombocytopenia].

    PubMed

    Lozano, María L; Vicente, Vicente

    2014-05-01

    Primary immune thrombocytopenia, also termed immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by premature platelet destruction and impaired platelet production. Traditional treatment of ITP has predominantly consisted of immune suppression and/or modulation. However, the understanding of the immune mediated impairment of platelet production has led to the development of new treatments that target the thrombopoietin receptor, promoting formation of megakaryocytes and increasing platelet counts. Best practice for the management of ITP has not yet been established because data from comparative studies are lacking. While some disagreement might still remain among experts concerning therapy (when, who, and how should be treated), in recent years different evidence-based practice guidelines have been published to assist healthcare professionals in the diagnosis and treatment of ITP. This review describes the current treatment landscape of ITP.

  8. 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

  9. [Diagnostic and therapeutic guidelines of thrombotic microangiopathies of the Spanish Apheresis Group].

    PubMed

    Contreras, Enric; de la Rubia, Javier; Del Río-Garma, Julio; Díaz-Ricart, Maribel; García-Gala, José María; Lozano, Miguel

    2015-04-01

    Thrombotic microangiopathies (TMA) are disorders defined by the presence of a microangiopathic hemolytic anemia (with the characteristic hallmark of schistocytes in the peripheral blood smear), thrombocytopenia and organ malfunction of variable intensity. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are the most important forms of TMA and, without the adequate treatment, they are associated with high morbimortality. In recent years, significant advances in the knowledge of the pathophysiology of TMA have occurred. Those advances have allowed us to move from a syndromic diagnosis with a similar treatment to all entities to the search of etiologic diagnosis which would lead to a specific treatment, finally leading to a better outcome of the patient. This document pretends to summarize the current status of knowledge of the pathophysiology of TMA and the therapeutic options available, and to offer a diagnostic and therapeutic practical tool to the professionals caring for the patients.

  10. Acquired loss of red cell Kell antigens.

    PubMed

    Vengelen-Tyler, V; Gonzalez, B; Garratty, G; Kruppe, C; Johnson, C L; Mueller, K A; Marsh, W L

    1987-02-01

    A 19-year-old patient with a long history of idiopathic thrombocytopenic purpura developed a potent antibody against a high-incidence antigen in the Kell blood group system. The direct antiglobulin test on his red cells was negative. His cells exhibited profound depression of Kell blood group antigens, but antigens of other blood groups were normal. Transfusion of incompatible blood was well tolerated and differential agglutination tests, using selected Rh antisera, showed in vivo survival of the transfused red cells for more than 8 weeks. However, the transfused red cells also showed acquired loss of Kell antigens. Five months after the initial findings, Kell-related antibody disappeared and Kell antigens reappeared on his red cells. The patient's serum stored from the initial investigation now reacted with his freshly collected red cells. These data suggest that an environmental agent in the patient's plasma was responsible for the temporary loss of Kell antigens from red cells in his circulation.

  11. Desmopressin-induced Moschcowitz-like syndrome after treatment of uterine atonic bleeding in a 28-year-old pregnant woman: case report and overview of the literature.

    PubMed

    Dieterich, Max; Mann, Ellen; Wagner, Klaus F; Kramer-Steiner, Beate; Reimer, Toralf; Gerber, Bernd; Stubert, Johannes

    2011-12-01

    Here we report of a patient who developed a Moschcowitz-like syndrome following a desmopressin treatment of severe postpartum hemorrhage. The patient got an anaphylactic reaction after cervical ripening with dinoproston, leading to an emergency cesarean. A postpartum uterine atony with a blood loss more than 1500 ml resulted in a disseminated intravascular coagulation that was treated with mass transfusion of blood products, including platelets and factor VII. Desmopressin is used as rescue medication in situations of severe bleeding. It was given in this life-threatening situation and presumably triggered a Moschcowitz-like syndrome. Desmopressin exerts its haemostatic effect by releasing von Willebrand factor, which is elevated in pregnancy per se. This results in an increased risk of developing microthrombi, leading to a Moschcowitz-like syndrome. In conclusion, desmopressin should not be administered in pregnant patients owing to its potential risk of triggering the development of thrombotic-thrombocytopenic purpura. PMID:21921792

  12. 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

  13. 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. PMID:26606109

  14. 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

  15. Multiple myeloma developing in a patient with immune thrombocytopenia.

    PubMed

    Itoh, Toshio

    2016-05-01

    A female diagnosed as having immune thrombocytopenic purpura (ITP) was found to be simultaneously suffering from monoclonal gammopathy of undetermined significance (IgGλ). Urine Bence-Jones protein was negative. During the course, plasma cells accounted for 21.6% of the bone marrow. Based on these clinical features in our case, the second disease was diagnosed as multiple myeloma (MM). Both ITP and MM were successfully treated with corticosteroids, bortezomib, lenalidomide with dexamethasone and eltrombopag olamine. MM with ITP may show the following features: 1) the great majority are IgG types, 2) λ chain types show marked light chain predominance when these two diseases appear simultaneously, 3) κ chain types are predominant in the cases with MM followed by ITP, and 4) MM cases with ITP are more often seen in Japan. PMID:27263790

  16. False Positive B-Cells Crossmatch after Prior Rituximab Exposure of the Kidney Donor

    PubMed Central

    Desoutter, Judith; Apithy, Marie-Joëlle; Bartczak, Ségolène; Guillaume, Nicolas

    2016-01-01

    Crossmatching is essential prior to kidney transplantation to confirm compatibility between the donor and the recipient, particularly to prevent acute antibody-mediated rejection. An unexpected positive crossmatch may be obtained in recipients with an autoimmune disease or preexisting antibodies not detected by single-antigen bead array due to complement interference or who have been previously treated by desensitization protocols such as rituximab, antithymocyte globulin, or intravenous immunoglobulins. We report donor and recipient investigations that revealed unexpected positive B-cells crossmatch, probably due to donor cells, as the donor had received rituximab therapy shortly before organ harvesting, in a context of severe idiopathic thrombocytopenic purpura. We consequently detected unexpected Class II IgG complement-dependent cytotoxicity for all sera tested. Other laboratory investigations failed to elucidate the reasons for this recipient-related positivity. PMID:27239362

  17. Extragastrointestinal manifestations of Helicobacter pylori infection: facts or myth? A critical review.

    PubMed

    Tan, Huck-Joo; Goh, Khean-Lee

    2012-07-01

    Helicobacter pylori (H. pylori) infection is reported to be associated with many extragastrointestinal manifestations, such as hematological diseases [idiopathic thrombocytopenic purpura (ITP) and unexplained iron deficiency anemia (IDA)], cardiovascular diseases (ischemic heart diseases), neurological disorders (stroke, Parkinson's disease, Alzheimer's disease), obesity and skin disorders. Among these, the best evidence so far is in ITP and unexplained IDA, with high-quality studies showing the improvement of IDA and ITP after H. pylori eradication. The evidence of its association with coronary artery disease is weak and many of the results may be erroneous. The role of H. pylori infection in affecting serum leptin and ghrelin levels has attracted a lot of attention recently and available data to date have been conflicting. There have also been many uncontrolled, small sample studies suggesting an association between H. pylori infection and neurological disorders or chronic urticaria. However, more studies are required to clarify such proposed causal links. PMID:22713083

  18. A 40-year-old woman with multiple pulmonary nodules. Pulmonary hyalinizing granuloma.

    PubMed

    Ussavarungsi, Kamonpun; Khoor, Andras; Jolles, Howard I; Mira-Avendano, Isabel

    2014-12-01

    A 40-year-old woman (a nonsmoker) with history of idiopathic thrombocytopenic purpura and a platelet count > 90,000 cells/μL without specific medication was referred to pulmonary clinic for evaluation of multiple pulmonary nodules. The patient presented to an outside hospital with fatigue, lack of energy, and dyspnea on exertion for 2 years. She denied fever, cough, chest pain, or weight loss. An initial chest radiograph showed bilateral multiple pulmonary nodules. A chest CT scan revealed multiple nodular lesions, varying in size, in all lobes of both lungs. There was no mediastinal lymphadenopathy or pleural effusion. There was no significant hypermetabolic activity on a subsequent fluorodeoxyglucose PET scan/CT scan, and there had been no significant change. She underwent CT scan-guided percutaneous transthoracic biopsy and bronchoscopy with transbronchial biopsies, all of which were inconclusive. An open lung biopsy was considered. PMID:25451362

  19. 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

  20. [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.

  1. [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. PMID:27384637

  2. [Clinical application of reticulated platelet analysis using the matic-modified thiazole orange method and flow cytometry].

    PubMed

    Toba, K; Fuse, I; Koike, T; Tsuchiyama, J; Higuchi, W; Niikuni, K; Abe, T; Yano, T; Takahashi, M; Shibata, A; Aizawa, Y

    2000-11-01

    Reticulated platelet (RP) analysis using thiazole orange (TO) and a flow cytometer is a convenient and promising method for estimating platelet kinetics in patients with thrombocytopenia. Among many different modifications of the TO method, a novel protocol reported by Matic in 1998 seems to be superior because it allows RP analysis using a sample of whole blood very quickly and accurately. Therefore, we used this method to analyze platelet kinetics in patients with idiopathic thrombocytopenic purpura (ITP) and hemophagocytic syndrome (HPS), as well as patients with hematopoietic malignancies (HM) after intensive chemotherapy. The proportion of RP was increased in the patients with ITP and HPS, and furthermore showed a negative linear correlation with the platelet count. The change in the proportion of RP occurred about one week before the change in the circulating platelet count in the patients with HM after chemotherapy. This modification of the TO method by Matic is expected to become a standard protocol for RP analysis.

  3. Eosinophilic gastroenteritis associated with systemic lupus erythematosus.

    PubMed

    Barbie, David A; Mangi, Abeel A; Lauwers, Gregory Y

    2004-01-01

    Eosinophilic gastroenteritis is an uncommon disease with an obscure etiology, although associations with allergy, the idiopathic hypereosinophilic syndrome, and connective tissue disease have been reported. We present the case of a 37-year-old woman with a history of idiopathic thrombocytopenic purpura who presented with refractory nausea, vomiting, and abdominal pain. Imaging studies were significant for bowel wall thickening and ascites, while laboratory studies revealed a positive antinuclear antibody (ANA), a positive anti-double stranded (DS) DNA antibody, low complement, and proteinuria. Exploratory laparotomy with gastric and small bowel biopsies established the diagnosis of eosinophilic gastroenteritis. In addition, the patient met clinical criteria for the diagnosis of systemic lupus erythematosus. Previous studies have described eosinophilic gastroenteritis in patients with scleroderma, polymyositis, or dermatomyositis. This is the first report to our knowledge of an individual with eosinophilic gastroenteritis and systemic lupus erythematosus. PMID:15492606

  4. 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

  5. Audit of pediatric hematology-oncology outpatients in Kuala Lumpur.

    PubMed

    Menon, Bina Sharine; Juraida, Eni; Ibrahim, Hishamshah; Mohamed, Mahfuzah; Ho, Caroline; Khuzaiah, Raja

    2008-07-01

    The aims of this study were to determine the types of cancers and hematological disorders in patients attending a pediatric hematology-oncology clinic. This was a prospective study at the Pediatric Institute, General Hospital Kuala Lumpur, Malaysia from June 2005-November 2006. During the 18-month study, 803 patients attended the clinic, 730 had oncological problems and 73 had hematological problems. The age range was from 2 months to 28 years (median 6 years). The patients were Malay (66%), Chinese (23%), Indian (10%) and other races (1%). Of the oncological patients, 51% had either leukemia (n=293) or lymphoma (n=77). The other most common diagnoses were retinoblastoma, followed by Wilm's tumor and germ cell tumors. Six patients (0.8%) developed a second malignant neoplasm. Of the hematological patients, 60% had platelet disorders, most commonly chronic immune thrombocytopenic purpura. Twenty-four per cent had bone marrow failure and 16% had red cell disorders.

  6. Helicobacter pylori and extragastric diseases.

    PubMed

    Goni, Elisabetta; Franceschi, Francesco

    2016-09-01

    During the past year, many articles were published on the extragastric diseases related to Helicobacter pylori infection. This supports the theory that some microorganisms may cause diseases even far from the primary site of infection by interfering with different biologic processes. The role of H. pylori on idiopathic thrombocytopenic purpura, sideropenica anemia, and vitamin B12 deficiency is well known. On the other hand, there is a growing interest in the bacterium's association with cardiovascular, neurologic, hematologic, dermatologic, head and neck, and uro-gynecologic diseases, as well as diabetes mellitus and metabolic syndrome, with very promising results. This review has been aimed at summarizing the results of the most relevant studies published over the last year on this fascinating topic. PMID:27531539

  7. [Lupus nephropathy in childhood and familial lupus. Genetic study of a family].

    PubMed

    Gómez Campdera, F J; Yebra, M; Vicario, J L; Rodríguez, M; Rengel, M; Manzano, L; Martín Villa, J M; Gutiérrez, C

    1989-04-15

    We report a case of a 14 1/2-year-old boy who was diagnosed of systemic lupus erythematosus in the background of an acute nephritic syndrome, 3 1/2 years after being diagnosed of idiopathic thrombocytopenic purpura. The familial history suggested the presence of other cases of SLE, which were proven with relevant clinical and laboratory studies. A genetic study for disease markers was carried out and a correlation was found with haplotypes HLA A25, B18, BW6, DRX, and DQW; C2 deficiency was ruled out. We conclude that it is of paramount importance to rule out the existence of familial SLE in front of infantile SLE, particularly in boys, and we emphasize the necessity of keeping on further searching for genetic markers of the disease. PMID:2755225

  8. Acquired dysfunction due to the circulation of "exhausted" platelets.

    PubMed

    Pareti, F I; Capitanio, A; Mannucci, L; Ponticelli, C; Mannucci, P M

    1980-08-01

    An acquired platelet functional defect was found to be present in eight patients who presented with various clinical conditions--three with renal allograft rejection, three with the hemolytic uremic syndrome or thrombotic thrombocytopenic purpura, one with acute consumption coagulopathy due to an incompatible transfusion and one with systemic lupus erythematosus. They showed defective platelet aggregation and reduced levels of adenine nucleotides and serotonin with abnormal uptake and storage of the amine. The bleeding time was more prolonged than predicted from the platelet count. These abnormalities were strikingly similar to those occurring in patients with congenital storage pool deficiency. The acquired defect is thought to be related to the presence in the circulation of "exhausted" platelets following their in vivo exposure to inducers of the release reaction such as damaged endothelium, thrombin and immune complexes. The bleeding tendency of the underlying diseases might be aggravated by the impairment of platelet function. PMID:7405945

  9. 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.

  10. Cancer-associated thrombotic microangiopathy.

    PubMed

    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

  11. Splenic scintigraphy using Tc-99m-labeled heat-denatured red blood cells in pediatric patients: concise communication

    SciTech Connect

    Ehrlich, C.P.; Papanicolaou, N.; Treves, S.; Hurwitz, R.A.; Richards, P.

    1982-03-01

    Ten children underwent splenic imaging with heat-denatured red blood cells labeled with technetium-99m (Tc-99m DRBC). The presenting problems included the heterotaxia syndrome, recurrent idiopathic thrombocytopenic purpura following splenectomy, mass in the left posterior hemithorax, and blunt abdominal trauma. In nine patients, the presence or absence of splenic tissue was established. A splenic hematoma was identified in the tenth patient. All patients were initially scanned with Tc-99m sulfur colloid (Tc-99m SC), and were selected for Tc-99m DRBC scintigraphy only after the results of the SC scans failed to establish the clinical problem beyond doubt. The availability of kits containing stannous ions, essential for efficient and stable labeling of red blood cells with Tc-99m and requiring only a small volume of blood, make splenic scintigraphy in children a relatively simple and definitive diagnostic procedure, when identification of splenic tissue is of clinical importance.

  12. 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.

  13. An evaluation of a solid phase red cell adherence test for detecting platelet-associated IgG in immune thrombocytopenia.

    PubMed

    Jones, C D; Gould, L M; Lee, S

    1990-04-01

    A solid phase red cell adherence (SPRCA) test, designed for platelet cross-match testing, was evaluated to determine its efficacy in detecting platelet-associated IgG (PAIgG) in immune thrombocytopenic purpura (ITP). This new method was compared to the platelet suspension immunofluorescence (PSIF) test. Fifty-three patient samples were tested by both methods, including 17 for whom a clinical diagnosis of ITP had been made. The SPRCA method showed 65% sensitivity, whereas the PSIF method showed 53% sensitivity. The specificity for both was 100%. The SPRCA compared favorably to the PSIF test in sensitivity and cost effectiveness. The SPRCA test is rapid, easy to perform, and suitable for detecting PAIgG in ITP.

  14. [Shiga toxin and tetanus toxin as a potential biologic weapon].

    PubMed

    Toczyska, Izabela; Płusa, Tadeusz

    2015-09-01

    Toxins produced by the bacteria are of particular interest as potential cargo combat possible for use in a terrorist attack or war. Shiga toxin is usually produced by shiga toxigenic strains of Escherichia coli (STEC - shigatoxigenic Escherichia coli). To infection occurs mostly after eating contaminated beef. Clinical syndromes associated with Shiga toxin diarrhea, hemorrhagic colitis, hemolytic uremic syndrome (HUS - hemolytic uremic syndrome) or thrombotic thrombocytopenic purpura. Treatment is symptomatic. In HUS, in which mortality during an epidemic reaches 20%, extending the kidney injury dialysis may be necessary. Exposure to tetanus toxin produced by Clostridium tetani, resulting in the most generalized tetanus, characterized by increased muscle tension and painful contractions of individual muscle groups. In the treatment beyond symptomatic behavior (among others spasticity medications, anticonvulsants, muscle relaxants) is used tetanus antitoxin and antibiotics (metronidazole choice). A common complication is acute respiratory failure - then it is necessary to implement mechanical ventilation. PMID:26449578

  15. Flow-driven assembly of VWF fibres and webs in in vitro microvessels

    PubMed Central

    Zheng, Ying; Chen, Junmei; López, José A.

    2015-01-01

    Several systemic diseases, including thrombotic thrombocytopenic purpura, manifest much of their pathology through activation of endothelium and thrombotic occlusion of small blood vessels, often leading to multi-organ failure and death. Modelling these diseases is hampered by the complex three-dimensional architecture and flow patterns of the microvasculature. Here, we employ engineered microvessels of complex geometry to examine the pathological responses to endothelial activation. Our most striking finding is the capacity of endothelial-secreted von Willebrand factor (VWF) to assemble into thick bundles or complex meshes, depending on the vessel geometry and flow characteristics. Assembly is greatest in vessels of diameter ≤300 μm, with high shear stress or strong flow acceleration, and with sharp turns. VWF bundles and webs bind platelets, leukocytes and erythrocytes, obstructing blood flow and sometimes shearing passing erythrocytes. Our findings uncover the biophysical requirements for initiating microvascular thrombosis and suggest mechanisms for the onset and progression of microvascular diseases. PMID:26223854

  16. Complement in hemolytic anemia.

    PubMed

    Brodsky, Robert A

    2015-11-26

    Complement is increasingly being recognized as an important driver of human disease, including many hemolytic anemias. Paroxysmal nocturnal hemoglobinuria (PNH) cells are susceptible to hemolysis because of a loss of the complement regulatory proteins CD59 and CD55. Patients with atypical hemolytic uremic syndrome (aHUS) develop a thrombotic microangiopathy (TMA) that in most cases is attributable to mutations that lead to activation of the alternative pathway of complement. For optimal therapy, it is critical, but often difficult, to distinguish aHUS from other TMAs, such as thrombotic thrombocytopenic purpura; however, novel bioassays are being developed. In cold agglutinin disease (CAD), immunoglobulin M autoantibodies fix complement on the surface of red cells, resulting in extravascular hemolysis by the reticuloendothelial system. Drugs that inhibit complement activation are increasingly being used to treat these diseases. This article discusses the pathophysiology, diagnosis, and therapy for PNH, aHUS, and CAD.

  17. Complement in hemolytic anemia.

    PubMed

    Brodsky, Robert A

    2015-01-01

    Complement is increasingly being recognized as an important driver of human disease, including many hemolytic anemias. Paroxysmal nocturnal hemoglobinuria (PNH) cells are susceptible to hemolysis because of a loss of the complement regulatory proteins CD59 and CD55. Patients with atypical hemolytic uremic syndrome (aHUS) develop a thrombotic microangiopathy (TMA) that in most cases is attributable to mutations that lead to activation of the alternative pathway of complement. For optimal therapy, it is critical, but often difficult, to distinguish aHUS from other TMAs, such as thrombotic thrombocytopenic purpura; however, novel bioassays are being developed. In cold agglutinin disease (CAD), immunoglobulin M autoantibodies fix complement on the surface of red cells, resulting in extravascular hemolysis by the reticuloendothelial system. Drugs that inhibit complement activation are increasingly being used to treat these diseases. This article discusses the pathophysiology, diagnosis, and therapy for PNH, aHUS, and CAD.

  18. Platelet transfusions in platelet consumptive disorders are associated with arterial thrombosis and in-hospital mortality.

    PubMed

    Goel, Ruchika; Ness, Paul M; Takemoto, Clifford M; Krishnamurti, Lakshmanan; King, Karen E; Tobian, Aaron A R

    2015-02-26

    While platelets are primary mediators of hemostasis, there is emerging evidence to show that they may also mediate pathologic thrombogenesis. Little data are available on risks and benefits associated with platelet transfusions in thrombotic thrombocytopenic purpura (TTP), heparin-induced thrombocytopenia (HIT) and immune thrombocytopenic purpura (ITP). This study utilized the Nationwide Inpatient Sample to evaluate the current in-hospital platelet transfusion practices and their association with arterial/venous thrombosis, acute myocardial infarction (AMI), stroke, and in-hospital mortality over 5 years (2007-2011). Age and gender-adjusted odds ratios (adjOR) associated with platelet transfusions were calculated. There were 10 624 hospitalizations with TTP; 6332 with HIT and 79 980 with ITP. Platelet transfusions were reported in 10.1% TTP, 7.1% HIT, and 25.8% ITP admissions. Platelet transfusions in TTP were associated with higher odds of arterial thrombosis (adjOR = 5.8, 95%CI = 1.3-26.6), AMI (adjOR = 2.0, 95%CI = 1.2-3.3) and mortality (adjOR = 2.0,95%CI = 1.3-3.0), but not venous thrombosis. Platelet transfusions in HIT were associated with higher odds of arterial thrombosis (adjOR = 3.4, 95%CI = 1.2-9.5) and mortality (adjOR = 5.2, 95%CI = 2.6-10.5) but not venous thrombosis. Except for AMI, all relationships remained significant after adjusting for clinical severity and acuity. No associations were significant for ITP. Platelet transfusions are associated with higher odds of arterial thrombosis and mortality among TTP and HIT patients.

  19. 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.

  20. 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