Prevention of relapse in patients with acquired thrombotic thrombocytopenic purpura undergoing elective surgery: a case series.

Essentials Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease. Surgery is a possible trigger of acute TTP episodes and no guidelines are available. Six patients with severe ADAMTS-13 deficiency during remission underwent elective surgery. Patients were prophylactically treated to restore ADAMTS-13 activity and no relapses occurred. SUMMARY: Background Severe ADAMTS-13 deficiency has been recognized as the main risk factor for recurrence of thrombotic thrombocytopenic purpura (TTP). Several conditions, including surgery, may influence the levels of ultra-large von Willebrand factor and ADAMTS-13, acting as a trigger for an acute TTP event. Objectives To report our experience of management of six patients with acquired TTP who underwent elective surgery after prophylactic treatment to restore ADAMTS-13 activity levels. Patients Six patients followed for acquired TTP with severe ADAMTS-13 deficiency during remission were candidates for seven elective surgeries (inguinal hernioplasty, cholecystectomy, laparoscopic hysterectomy, oophorectomy, parotidectomy and two total hip arthroplasties). Results Four patients were treated with prophylactic plasma exchange (PEX) therapy immediately before surgery. One patient was treated with PEX therapy before her first surgery and with preemptive rituximab once her second surgery was scheduled. Because rituximab increased ADAMTS-13 levels only partially, she required one PEX procedure the day before her second surgery. One patient was treated with azathioprine after rituximab failure, obtaining a progressive increase of ADAMTS-13 activity to more than 40%. This level allowed her to undergo total hip arthroplasty without additional treatment. All surgeries were successful and no complications or relapses occurred. Conclusions Six patients with acquired TTP underwent seven successful surgical procedures using prophylaxis to restore ADAMTS-13 activity. Further observational studies or randomized clinical trials are needed to confirm whether prophylactic PEX could be the key factor in preventing relapse.

Trombocitopenia inmune primaria aguda presentación clínica y manejo en pacientes pediátricos, Hospital Mario Catarino Rivas / Acute primary immune thrombocytopenia clinical presentation and management in pediatric patients, Hospital Mario Catarino Rivas

Antecedentes: La trombocitopenia inmune primaria, conocida como púrpura trombocito-pénica idiopática (PTI), es un trastorno autoin-mune adquirido que afecta adultos y niños. Objetivo: Caracterizar los pacientes pediátri-cos con PTI aguda mediante su identi cación y seguimiento en el Hospital Nacional Mario Catarino Rivas (HNMCR) entre 1 febrero del 2016 al 31 enero del 2017. Pacientes y Méto-dos: Estudio cuantitativo, diseño no experi-mental longitudinal ­ prospectivo, alcance descriptivo. La población es todo paciente menor de 18 años de edad, que acudió al HNMCR con PTI aguda. La muestra 47 pacien-tes. Excluidos pacientes previamente diagnos-ticados con PTI, con segundos episodios o recaídas, con patologías sobre agregadas. Información recopilada mediante un instru-mento tipo encuesta: situación demográ ca, área geográ ca y revisión del expediente clíni-co, los datos fueron analizados con el progra-ma EPIINFO y EXCEL. Resultados: En cuanto al grupo etario el 56% fueron menores de cinco años de edad, la distribución por sexos hubo predominio del sexo masculino. 81% de los niños fueron hospitalizados, el resto recibió manejo ambulatorio; sin embargo en el 100% se inició alguna terapia con resolución de la trombocitopenia a los 3 meses. Luego del seguimiento, el diagnóstico nal de los casos captados fue PTI aguda 58%(n=27), evolucio-naron a la cronicidad 20% (n=9), el 22% (n=10) abandonaron seguimiento. Conclusiones: La mayoría de los pacientes con PTI son admitidos al hospital, aunque su conteo de plaquetas no los ponga en riesgo claro de hemorragias espontáneas, por no haber guías de manejo en nuestro hospital...(AU)

Heparin-induced thrombocytopenia associated with thrombotic microangiopathy.

Some cases of thrombotic microangiopathy (TMA) are refractory to plasma exchange therapy (PE) with persistence or recurrence of thrombocytopenia. We report two patients suffering from TMA of different aetiologies (associated with disseminated malignancy, typical haemolytic uraemic syndrome) with recurrent or persistent thrombocytopenia despite adequate therapy including PE. Since both patients were exposed to unfractionated heparin, heparin-induced thrombocytopenia (HIT) was suspected as a cause. Pretest probabilities for HIT were intermediate. ELISA for PF4/heparin antibodies was strongly positive in both cases, and HIT was confirmed by heparin-induced platelet activation assay. Anticoagulation with lepirudin was initiated, with subsequent rapid increase of the platelet count. TMA might represent a predisposition for HIT. This could be due to TMA-related platelet activation with increased PF4 release. In TMA patients exposed to heparin and with refractory or rapidly recurrent thrombocytopenia HIT should always be considered as a possible cause.

Macrophages activated by C-reactive protein through Fc gamma RI transfer suppression of immune thrombocytopenia.

C-reactive protein (CRP) is an acute-phase protein with therapeutic activity in mouse models of systemic lupus erythematosus and other inflammatory and autoimmune diseases. To determine the mechanism by which CRP suppresses immune complex disease, an adoptive transfer system was developed in a model of immune thrombocytopenic purpura (ITP). Injection of 200 microg of CRP 24 h before induction of ITP markedly decreased thrombocytopenia induced by anti-CD41. CRP-treated splenocytes also provided protection from ITP in adoptive transfer. Splenocytes from C57BL/6 mice were treated with 200 microg/ml CRP for 30 min, washed, and injected into mice 24 h before induction of ITP. Injection of 10(6) CRP-treated splenocytes protected mice from thrombocytopenia, as did i.v. Ig-treated but not BSA-treated splenocytes. The suppressive cell induced by CRP was found to be a macrophage by depletion, enrichment, and the use of purified bone marrow-derived macrophages. The induction of protection by CRP-treated cells was dependent on FcRgamma-chain and Syk activation, indicating an activating effect of CRP on the donor cell. Suppression of ITP by CRP-treated splenocytes required Fc gamma RI on the donor cell and Fc gamma RIIb in the recipient mice. These findings suggest that CRP generates suppressive macrophages through Fc gamma RI, which then act through an Fc gamma RIIb-dependent pathway in the recipient to decrease platelet clearance. These results provide insight into the mechanism of CRP regulatory activity in autoimmunity and suggest a potential new therapeutic approach to ITP.

A case report of neonatal alloimmune thrombocytopenic purpura: the importance of correct diagnosis for future pregnancies

CONTEXTO: Púrpura trombocitopênica neonatal aloimune (PTNA) é uma doença neonatal caracterizada por aloimunização materna contra as plaquetas fetais, que apresentam antígenos herdados do pai. Podem ocorrer hemorragias cerebrais, levando à morte ou a anomalias neurológicas permanentes. RELATO DE CASO: Mulher saudável, de 30 anos, deu à luz, por parto cesariano na 36ª semana de gestação, seu primeiro filho. Com 10 horas de vida, o recém-nascido apresentou petéquias e contagem de 8 x 103 plaquetas/µl no sangue periférico; foi medicado com imunoglobulina e recebeu alta após 18 dias de internação, com 100 x 103 plaquetas/µl. A causa da trombocitopenia não foi elucidada na época. Um ano depois, a criança morreu de neuroblastoma. Como os pais desejavam outro filho, foram encaminhados para investigação da trombocitopenia. Genotipagem plaquetária e pesquisa de anticorpos antiplaquetários foram realizadas, mostrando total falta de concordância entre os sistemas HPA-1 do pai (HPA-1a1a) e da mãe (HPA-1b1b) e anticorpos anti-HPA-1a no soro da mãe. Concluímos que o primeiro bebê nasceu com PTNA. Por isso, na segunda gravidez, a mãe foi tratada com diversas infusões de imunoglobulina intravenosa. Foi realizado cuidadoso monitoramento por ultra-som, com resultados normais para mãe e feto durante a gravidez. O segundo bebê nasceu por cesárea às 39 semanas, apresentando 92 x 103 plaquetas/µl seis horas após o nascimento. As plaquetas do recém-nascido foram genotipadas como HPA-1a1b e o soro da mãe novamente mostrou anticorpos anti-HPA-1a. Não houve hemorragia. A terapia de infusão de imunoglobulina foi efetiva na prevenção da PTNA no segundo filho.

A case report of neonatal alloimmune thrombocytopenic purpura: the importance of correct diagnosis for future pregnancies.

CONTEXT: Neonatal alloimmune thrombocytopenic purpura (NAITP) is a neonatal disorder characterized by maternal alloimmunization against fetal platelet antigens inherited from the father. Intracranial hemorrhage leading to death or permanent neurological disability may occur in the fetus. CASE REPORT: A healthy 30-year-old woman gave birth to her first baby by cesarean after an uneventful 36-week pregnancy. Ten hours after birth, the infant presented severe petechiae, with platelet count of 8 x 10(3)/microl. The mother's platelet count was normal (180 x 10(3)/microl). The infant re ceived intravenous immunoglobulin and was discharged 18 days later, with platelet count of 100 x 10(3)/microl. The cause of thrombocytopenia was not elucidated at that time. One year later, the infant died of neuroblastoma. Since the parents wanted another child, they were referred for investigation of this thrombocytopenia. Platelet genotyping and platelet antibody screening were performed, showing total HPA-1 system mismatch between mother (HPA-1b1b) and father (HPA-1a1a), with anti-HPA-1a antibodies in the mother's serum. We concluded that the first baby was born with NAITP. Thus, in the second pregnancy, the mother was treated with several infusions of intravenous immunoglobulin. Careful ultrasound monitoring was performed, with normal results for mother and fetus throughout the pregnancy. The second baby was born by cesarean at 39 weeks, presenting 92 x 10(3) platelets/microl six hours after birth. The baby's platelets were genotyped as HPA-1a1b and the mother's serum again showed anti-HPA-1a antibodies. No clinical bleeding was observed. Intravenous immunoglobulin therapy was an effective treatment for preventing NAITP in the second baby.

Doenças hemorrágicas no atendimento odontológico em crianças / Hemorrhagic diseases in pediatric dentistry

O atendimento odontológico a pacientes com doenças hemorrágicas confere grande responsabilidade ao profissional, para a identificaçäo do problema e adequada atuaçäo, numa atitude multidisciplinar com os demais membros da equipe de saúde. Este aspecto é bem enfatizado na prática da Odontopediatria, em que o bebê ou criança pode estabelecer um primeiro contato sem o diagnóstico prévio de qualquer distúrbio na hemostasia. Por esta razäo, as autoras efetuaram uma revisäo da literatura sobre as patologias mais frequentes observadas, subordinadas ao tema abordado, com base em levantamento piloto das crianças atendidas no setor de Odontologia da Fundaçäo Hemope

Antenatal screening for HPA-1a by flow cytometry.

Pregnant women who attended antenatal clinics at King George V Hospital, the Birth Centre or were referred by obstetricians from February 19 July, 1996 were screened for the platelet antigen HPA-1a by flow cytometry. Forty out of 2,300 (1.7%) were found to be negative for this antigen. Of the 28 women followed throughout their pregnancy, none developed antibody to HPA-1a. Platelet counts performed on samples from 17 babies born to 17 of these mothers were all normal. This study proves the simplicity and rapidity of flow cytometry for platelet antigen screening. The results were comparable with the Solid Phase Red Cell Adherence (SPRCA) method and with PCR. The lack of a plentiful supply of specific antibody and the rarity of fetomaternal alloimmune thrombocytopenia (FMAIT) argue against the introduction of routine screening for maternal HPA-1a status at the present time.

Post-transfusion purpura due to HPA-1a immunization in a male patient: response to subsequent multiple HPA-1a-incompatible red-cell transfusions.

We report a male patient who developed post-transfusion purpura. Thrombocytopenia did not recur when intravenous IgG was given before the transfusion of platelet-depleted washed red-cell concentrates.

Molecular analysis of human platelet antigen system 1 antigen on single cells can be applied to preimplantation genetic diagnosis for prevention of alloimmune thrombocytopenia.

OBJECTIVE: Our purpose was to develop a molecular assay to determine the human platelet antigen system 1 status on single nucleated cells, including human blastomeres. STUDY DESIGN: Eighty single cultured lymphoblasts of known human platelet antigen system 1 genotype and 24 media blanks were mixed in blinded fashion. Amplification of a 246 bp deoxyribonucleic acid fragment and subsequent Nci I restriction digestion were performed to distinguish human platelet antigen system 1a from 1b alleles. Specificity and sensitivity of the technique were determined. Eight blastomeres were also tested. RESULTS: Deoxyribonucleic acid amplification at the human platelet antigen system 1 locus was successful in 95% of the reactions. No media blanks showed amplified deoxyribonucleic acid. The diagnosis was correct in all homozygous human platelet antigen system 1a or 1b cells; three of 23 heterozygous cells amplified but failed to digest with Nci I. Overall specificity was 95%. All blastomeres successfully amplified. CONCLUSIONS: The human platelet antigen system 1 status determination is reliable from a single cell and can be used for preimplantation genetic diagnosis for the prevention of alloimmune thrombocytopenia.

Use of intravenous immunoglobulin in acquired immune deficiency syndrome.

Patients infected with the human immunodeficiency virus (HIV) may have an antibody deficiency and a deficiency of cellular immunity. Intravenous immunoglobulin (IVIG) preparations may benefit HIV-infected children and adults with recurrent bacterial infections at doses of 200 to 400 mg/kg every 2 to 4 weeks. In addition, IVIG (1 to 2 g/kg) is effective at raising platelet counts to hemostatic levels in HIV-infected patients with idiopathic thrombocytopenic purpura and life-threatening bleeding. Indirect evidence also suggests that IVIG may be effective in preventing Pneumocystis carinii pneumonia. Finally, recent studies suggest that specific anti-HIV antibody preparations may have a therapeutic role, either as immunoglobulin concentrates or as immunoadhesions and immunotoxins. However, further investigations are needed to exclude antibody enhancement of HIV infection by the Fc receptor or the complement receptor.

Prevention of chronic ITP?

The treatment of childhood ITP with IVIG has been widely used in acute or in previously treatment-dependent, chronic forms of the disease. We discuss propositions of a prospective multicenter study to evaluate the efficacy of IVIG to prevent the development of chronic ITP in childhood. The problems of such a study, i.e. evaluation criteria, number (about 10% of patients with acute ITP will develop the chronic form) and related topics are discussed.

Purpura trombocitopenica idiopatica en pacientes tratados en el Hospital San Juan de Dios, Bogota (1980-1985) / Idiopatic thrombocytopenic purpura in patientes treated in Hospital San Juan de Dios, Bogota (1980-1985)

Se revisaron todas las historias con diagnostico de prupura trombocitopenica idiopatica (PTI), de los pacientes que ingresaron al hospital San Juan de Dios de la ciudad de Bogota, durante el periodo comprendido entre el 1 de enero de 1980 y el 31 de diciembre de 1985; con el fin de identificar la forma de presentacion, incidencia, factores pronosticos y respuesta al tratamiento. Se encontraron 54 historias con diagnostico de PTI de las cuales 32 reunian los criterios establecidos para ser5 incluidas en el trabajo; 22 (68%) eran mujeres y 10 (31.5%) hombres. La edad promedio en las mujeres fue de 26.2 anos y de 27.7 para los hombres. Se encontraron antecedentes importantes en 11 pacientes. Los motivos de consulta mas comunes fueron: petequias 100%, equimosis 68.7%, gingivorragia 50% y epistaxis 53.1%. De los 32 pacientes hospitalizados, 4 (12.5%) mejoraron espontaneamente, 17 (60.7%) mejoraron al tratamiento con prednisona, 11 (39.3%) no respondieron a dicho tratamiento. a 7 de estos pacientes se les practico esplenectomia, 5 de los cuales habia recibido prednisona y azatioprina y 2 solamente prednisona. Todos mejoraron. Con base en estas observaciones se propone la realizacion de un estudio prospectivo en nuestro hospital, utilizando como modalidades terapeuticas: 1) corticoterapia, si no hay remision o se presentan exacerbaciones por mas de 6 meses estaria indicada la esplenectomia y por ultimo el uso de inmunosupresores en quienes sean refractarios a las 2 modalidades terapeuticas anteriores

Relapsing post-transfusion purpura. A preventable disease.

Post-transfusion purpura is an isoimmune disorder that can recur if unrecognized. A 56-year-old woman is described who had her third episode of post-transfusion purpura 17 years after her last exposure to the inciting antigen. Clinical and immunologic features are reviewed, and specific preventive measures are proposed.