RESUMO
BACKGROUND: Congenital thrombotic thrombocytopenic purpura (TTP) results from severe hereditary deficiency of ADAMTS13. The efficacy and safety of recombinant ADAMTS13 and standard therapy (plasma-derived products) administered as routine prophylaxis or on-demand treatment in patients with congenital TTP is not known. METHODS: In this phase 3, open-label, crossover trial, we randomly assigned patients in a 1:1 ratio to two 6-month periods of prophylaxis with recombinant ADAMTS13 (40 IU per kilogram of body weight, administered intravenously) or standard therapy, followed by the alternate treatment; thereafter, all the patients received recombinant ADAMTS13 for an additional 6 months. The trigger for this interim analysis was trial completion by at least 30 patients. The primary outcome was acute TTP events. Manifestations of TTP, safety, and pharmacokinetics were assessed. Patients who had an acute TTP event could receive on-demand treatment. RESULTS: A total of 48 patients underwent randomization; 32 completed the trial. No acute TTP event occurred during prophylaxis with recombinant ADAMTS13, whereas 1 patient had an acute TTP event during prophylaxis with standard therapy (mean annualized event rate, 0.05). Thrombocytopenia was the most frequent TTP manifestation (annualized event rate, 0.74 with recombinant ADAMTS13 and 1.73 with standard therapy). Adverse events occurred in 71% of the patients with recombinant ADAMTS13 and in 84% with standard therapy. Adverse events that were considered by investigators to be related to the trial drug occurred in 9% of the patients with recombinant ADAMTS13 and in 48% with standard therapy. Trial-drug interruption or discontinuation due to adverse events occurred in no patients with recombinant ADAMTS13 and in 8 patients with standard therapy. No neutralizing antibodies developed during recombinant ADAMTS13 treatment. The mean maximum ADAMTS13 activity after recombinant ADAMTS13 treatment was 101%, as compared with 19% after standard therapy. CONCLUSIONS: During prophylaxis with recombinant ADAMTS13 in patients with congenital TTP, ADAMTS13 activity reached approximately 100% of normal levels, adverse events were generally mild or moderate in severity, and TTP events and manifestations were rare. (Funded by Takeda Development Center Americas and Baxalta Innovations; ClinicalTrials.gov number, NCT03393975.).
Assuntos
Proteína ADAMTS13 , Púrpura Trombocitopênica Trombótica , Proteínas Recombinantes , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Proteína ADAMTS13/administração & dosagem , Proteína ADAMTS13/efeitos adversos , Proteína ADAMTS13/deficiência , Proteína ADAMTS13/genética , Estudos Cross-Over , Púrpura Trombocitopênica Trombótica/congênito , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Púrpura Trombocitopênica Trombótica/genética , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Pré-EscolarRESUMO
In patients with immune thrombotic thrombocytopenic purpura (iTTP), autoantibodies against the metalloprotease ADAMTS13 lead to catastrophic microvascular thrombosis. However, the potential benefits of recombinant human ADAMTS13 (rADAMTS13) in patients with iTTP remain unknown. Here, we report the clinical use of rADAMTS13, which resulted in the rapid suppression of disease activity and complete recovery in a critically ill patient whose condition had proved to be refractory to all available treatments. We also show that rADAMTS13 causes immune complex formation, which saturates the autoantibody and may promote its clearance. Our data support the role of rADAMTS13 as a novel adjunctive therapy in patients with iTTP.
Assuntos
Proteína ADAMTS13 , Púrpura Trombocitopênica Trombótica , Feminino , Humanos , Proteína ADAMTS13/imunologia , Proteína ADAMTS13/uso terapêutico , Complexo Antígeno-Anticorpo/sangue , Complexo Antígeno-Anticorpo/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Púrpura Trombocitopênica Trombótica/imunologia , Púrpura Trombocitopênica Trombótica/terapia , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/uso terapêutico , Adulto , Negro ou Afro-Americano , Troca Plasmática , Resultado do TratamentoRESUMO
ABSTRACT: Caplacizumab prevents the interaction between von Willebrand factor and platelets and is used to treat immune thrombotic thrombocytopenic purpura (iTTP). Its administration has been associated with a delay in ADAMTS13 activity restoration after plasma exchange (PEX) suspension. We analyzed the outcomes of 113 iTTP episodes, 75 of which were treated with caplacizumab, in 108 patients from the Spanish Registry of Thrombotic Thrombocytopenic Purpura. Caplacizumab shortened the time to platelet count normalization and reduced PEX requirement, exacerbations, and relapses. There was no difference in the time to achieve ADAMTS13 activity ≥20% after PEX end between caplacizumab-treated and nontreated episodes (median [interquartile range], 14.5 [7.7-27.2] vs 13.0 [8.0-29.0] days, P = .653). However, considering the 36 episodes in which caplacizumab was started ≤3 days after iTTP diagnosis, the time for ADAMTS13 restoration from PEX end was higher than in those episodes in which caplacizumab was started >3 days after iTTP diagnosis (20.0 [12.0-43.0] vs 11.0 [3.5-20.0] days, P = .003) or than in non-caplacizumab-treated episodes (P = .033). This finding could be related to a significantly shorter duration of PEX in early caplacizumab-treated episodes than in late caplacizumab-treated episodes (5.5 [4.0-9.0] vs 15.0 [11.0-21.5] days, P < .001) or non-caplacizumab-treated episodes (11.0 [6.0-26.0] days, P < .001). There were no differences in time to ADAMTS-13 restoration from PEX start (28.0 [17.2-47.5], 27.0 [19.0-37.5] and 29.5 [15.2-45.0] days in early caplacizumab-treated, late caplacizumab-treated and non-caplacizumab-treated episodes). Early administered caplacizumab does not prevent the requirement for immunosuppression but has beneficial effects by shortening PEX requirement without major safety concerns.
Assuntos
Proteína ADAMTS13 , Troca Plasmática , Púrpura Trombocitopênica Trombótica , Anticorpos de Domínio Único , Humanos , Proteína ADAMTS13/sangue , Proteína ADAMTS13/metabolismo , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Púrpura Trombocitopênica Trombótica/terapia , Masculino , Feminino , Anticorpos de Domínio Único/uso terapêutico , Adulto , Pessoa de Meia-Idade , Contagem de Plaquetas , Doença Aguda , Resultado do Tratamento , IdosoRESUMO
ABSTRACT: Thrombotic thrombocytopenic purpura (TTP), a rare but fatal disease if untreated, is due to alteration in von Willebrand factor cleavage resulting in capillary microthrombus formation and ischemic organ damage. Interleukin-1 (IL-1) has been shown to drive sterile inflammation after ischemia and could play an essential contribution to postischemic organ damage in TTP. Our objectives were to evaluate IL-1 involvement during TTP and to test the efficacy of the recombinant IL-1 receptor antagonist, anakinra, in a murine TTP model. We retrospectively measured plasma IL-1 concentrations in patients with TTP and controls. Patients with TTP exhibited elevated plasma IL-1α and -1ß concentrations, which correlated with disease course and survival. In a mouse model of TTP, we administered anakinra (IL-1 inhibitor) or placebo for 5 days and evaluated the efficacy of this treatment. Anakinra significantly reduced mortality of mice (P < .001). Anakinra significantly decreased TTP-induced cardiac damage as assessed by blood troponin concentrations, evaluation of left ventricular function by echocardiography, [18F]fluorodeoxyglucose positron emission tomography of myocardial glucose metabolism, and cardiac histology. Anakinra also significantly reduced brain TTP-induced damage evaluated through blood PS100b concentrations, nuclear imaging, and histology. We finally showed that IL-1α and -1ß trigger endothelial degranulation in vitro, leading to the release of von Willebrand factor. In conclusion, anakinra significantly reduced TTP mortality in a preclinical model of the disease by inhibiting both endothelial degranulation and postischemic inflammation, supporting further evaluations in humans.
Assuntos
Proteína Antagonista do Receptor de Interleucina 1 , Púrpura Trombocitopênica Trombótica , Animais , Masculino , Camundongos , Proteína ADAMTS13/metabolismo , Modelos Animais de Doenças , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Interleucina-1alfa/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/sangue , Camundongos Endogâmicos C57BL , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Púrpura Trombocitopênica Trombótica/patologia , Púrpura Trombocitopênica Trombótica/mortalidade , Estudos Retrospectivos , Fator de von Willebrand/metabolismo , Fator de von Willebrand/antagonistas & inibidoresRESUMO
Pregnancy is a potential trigger of acute thrombotic thrombocytopenic purpura (TTP). The management of pregnancy-associated immune-mediated TTP (iTTP) can be challenging, especially when it is refractory to standard treatment. Caplacizumab, a nanobody to von Willebrand factor (VWF) blocking its A1 domain, is a valuable new therapeutic option. Its use is, however, not approved during pregnancy and breastfeeding. We describe the successful off-label administration of caplacizumab during pregnancy and delivery in a patient with refractory iTTP. The favourable outcome without significant thrombotic or haemorrhagic complications indicates that caplacizumab may be an effective and safe treatment option in refractory iTTP during pregnancy.
Assuntos
Complicações Hematológicas na Gravidez , Púrpura Trombocitopênica Trombótica , Anticorpos de Domínio Único , Humanos , Gravidez , Feminino , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Púrpura Trombocitopênica Trombótica/imunologia , Anticorpos de Domínio Único/uso terapêutico , Adulto , Complicações Hematológicas na Gravidez/tratamento farmacológico , Fator de von Willebrand/antagonistas & inibidoresRESUMO
Acquired thrombotic thrombocytopenic (aTTP) purpura is a life-threatening condition that can lead to devastating thromboembolic events. Recently, caplacizumab has been shown to rapidly restore platelet numbers and reduce the risk of severe end-organ damage when added to plasma exchanges (PEXs) and immunosuppression (IST). Here, we report the outcomes in 3 children with aTTP who were treated with caplacizumab in combination with PEXs and IST. In all 3 patients, platelet count increased to >15,000/mm 3 in 24 h and normalized on day 4, whereas normalization of ADAMTS13 activity >50% and elimination of the inhibitor was achieved after 18 to 89 days. Epistaxis was observed in 2 patients and was the only side effect related to caplacizumab. Caplacizumab is a promising agent for first-line treatment of children with aTTP.
Assuntos
Púrpura Trombocitopênica Trombótica , Anticorpos de Domínio Único , Criança , Humanos , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Troca Plasmática , Fator de von Willebrand , Terapia de Imunossupressão , Proteína ADAMTS13RESUMO
INTRODUCTION: Immune thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening disorder. Caplacizumab has been the latest drug incorporated into the initial treatment of acute episodes, allowing for faster platelet recovery and a decrease in refractoriness, exacerbation, thromboembolic events, and mortality. However, caplacizumab is also associated with a bleeding risk and higher treatment costs, which prevent many centers from using it universally. AREAS COVERED: Studies that included iTTP and/or caplacizumab to date were selected for this review using PubMed and MEDLINE platforms. We describe outcomes in the pre-caplacizumab era and after it, highlighting the benefits and risks of its use early in frontline, and also pointing out special situations that require careful management. EXPERT OPINION: It is clear that the availability of caplacizumab has significantly and favorably impacted the management of iTTP patients. Whether this improvement is cost-effective still remains uncertain, and data on long-term sequelae and different healthcare systems will help to clarify this point. In addition, evidence of the bleeding/thrombotic risk of iTTP patients under this drug needs to be better addressed in future studies.
Assuntos
Púrpura Trombocitopênica Idiopática , Púrpura Trombocitopênica Trombótica , Anticorpos de Domínio Único , Humanos , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Fator de von Willebrand , Troca Plasmática , Proteína ADAMTS13/uso terapêutico , Púrpura Trombocitopênica Idiopática/terapiaRESUMO
Immune-mediated thrombotic thrombocytopenia purpura (iTTP) is a rare microvascular disease characterized by severe disseminated microvascular thrombose-bleeding syndrome. Caplacizumab has been approved for the treatment of iTTP in combination with Plasma Exchange (PE) and immunosuppressive therapy, but its role in iTTP therapy remains uncertain. Therefore, we conducted a meta-analysis to investigate the safety and efficacy of caplacizumab for the treatment of patients with iTTP. We searched electronic databases (PubMed, Embase, Cochrane Library, and Scopus) and reference lists of relevant articles to find articles published from 2015 to 2022. The time to normalization of the platelet count of the group caplacizumab is shorter than the group placebo (SMDâ=â-0.72; 95% CI -0.88 to -0.56; P â<â0.05). Caplacizumab reduced the incidence of mortality (ORâ=â0.41; 95% CI 0.18-0.92; P â<â0.05), exacerbations (ORâ=â0.10; 95% CI 0.05-0.18; P â<â0.05), and recurrence (ORâ=â0.17; 95% CI 0.06-0.50; P â<â0.05). However, the bleeding events in the caplacizumab group were higher than those in the placebo group, especially severe bleeding events. There was no difference in ADAMTS13 activity and thromboembolic events between the two groups. Our analysis indicated that caplacizumab is effective and well tolerated for the treatment of iTTP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022362370.
Assuntos
Púrpura Trombocitopênica Trombótica , Anticorpos de Domínio Único , Humanos , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Púrpura Trombocitopênica Trombótica/terapia , Anticorpos de Domínio Único/uso terapêutico , Troca Plasmática/métodos , Resultado do TratamentoRESUMO
Apadamtase alfa (ADAMTS13, recombinant-krhn; ADZYNMA), a human recombinant form of a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13), is being developed by Takeda under license from KM biologics for thrombotic thrombocytopenic purpura (TTP) and sickle cell disease. On 9 November 2023, apadamtase alfa was approved in the USA for prophylactic and on-demand enzyme replacement therapy (ERT) in paediatric and adult patients with congenital TTP. Apadamtase alfa is under regulatory review for congenital TTP in the EU and Japan, and is under clinical development for immune-mediated TTP in several countries worldwide. Clinical development of apadamtase alfa for vaso-occlusive crisis related to sickle cell anaemia is underway in the USA. This article summarizes the milestones in the development of apadamtase alfa leading to this first approval in the USA for congenital TTP.
Assuntos
Proteína ADAMTS13 , Aprovação de Drogas , Púrpura Trombocitopênica Trombótica , Humanos , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Proteína ADAMTS13/metabolismo , Terapia de Reposição de Enzimas , Anemia Falciforme/tratamento farmacológico , Estados Unidos , Proteínas Recombinantes/uso terapêuticoRESUMO
ABSTRACT: While awaiting confirmatory results, empiric therapy for patients suspected to have immune thrombotic thrombocytopenic purpura (iTTP) provides benefits and also accrues risks and costs. Rapid assays for ADAMTS13 may be able to avoid the cost and risk exposure associated with empiric treatment. We conducted, to our knowledge, the first cost-effectiveness evaluation of testing strategies with rapid vs traditional ADAMTS13 assays in patients with intermediate- to high-risk PLASMIC scores, with and without caplacizumab use. We built a Markov cohort simulation with 4 clinical base-case analyses: (1) intermediate-risk PLASMIC score with caplacizumab; (2) intermediate-risk PLASMIC score without caplacizumab; (3) high-risk PLASMIC score with caplacizumab; and (4) high-risk PLASMIC score without caplacizumab. Each of these evaluated 3 testing strategies: (1) rapid assay (<1-hour turnaround); (2) in-house fluorescence resonance energy transfer (FRET)-based assay (24-hour turnaround); and (3) send-out FRET-based assay (72-hour turnaround). The primary outcome was the incremental net monetary benefit reported over a 3-day time horizon and across accepted willingness-to-pay thresholds in US dollars per quality-adjusted life-year (QALY). While accruing the same amount of QALYs, the rapid assay strategy saved up to $46 820 (95% CI, $41 961-$52 486) per patient tested. No parameter variation changed the outcome. In probabilistic sensitivity analyses, the rapid assay strategy was favored in 100% (3 base cases and scenario analyses) and 99% (1 base-case and scenario analysis) across 100 000 Monte Carlo iterations within each. Rapid ADAMTS13 testing for patients with intermediate- or high-risk PLASMIC scores yields significant per patient cost savings, achieved by reducing the costs associated with unnecessary therapeutic plasma exchange and caplacizumab therapy in patients without iTTP.
Assuntos
Proteína ADAMTS13 , Análise Custo-Benefício , Púrpura Trombocitopênica Trombótica , Anticorpos de Domínio Único , Humanos , Proteína ADAMTS13/sangue , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Anticorpos de Domínio Único/uso terapêutico , Cadeias de MarkovRESUMO
European real-world data indicate that front-line treatment with caplacizumab is associated with improved clinical outcomes compared with delayed caplacizumab treatment. The objective of the study was to describe the characteristics, treatment patterns, and outcomes in hospitalized patients with an immune-mediated thrombotic thrombocytopenic purpura (iTTP) episode treated with front-line versus delayed caplacizumab in the US. This retrospective cohort analysis of a US hospital database included adult patients (≥18 years) with an acute iTTP episode (a diagnosis of thrombotic microangiopathy and ≥1 therapeutic plasma exchange [TPE] procedure) from January 21, 2019, to February 28, 2021. Unadjusted baseline characteristics, treatment patterns, healthcare resource utilization, and costs were compared between patients who received front-line versus delayed (<2 vs ≥2 days after TPE initiation) caplacizumab treatment. Out of 39 patients, 16 (41.0%) received front-line and 23 (59.0%) received delayed treatment with caplacizumab. Baseline characteristics and symptoms were similar between the two groups. Patients who received front-line caplacizumab treatment had significantly fewer TPE administrations (median: 5.0 vs 12.0); and a significantly shorter hospital stay (median: 9.0 days vs 16.0 days) than patients receiving delayed caplacizumab therapy. Both of these were significantly lower in comparison of means (t-test P < .01). Median inpatient costs (inclusive of caplacizumab costs) were 54% higher in the delayed treated patients than in the front-line treated patients (median: $112â 711 vs $73â 318). TPE-specific cost was lower in the front-line treated cohort (median: $6 989 vs $10â 917). In conclusion, front-line treatment with caplacizumab had shorter hospitalizations, lower healthcare resource utilization, and lower costs than delayed caplacizumab treatment after TPE therapy.
Assuntos
Púrpura Trombocitopênica Idiopática , Púrpura Trombocitopênica Trombótica , Anticorpos de Domínio Único , Trombose , Adulto , Humanos , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Estudos Retrospectivos , Anticorpos de Domínio Único/efeitos adversos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Troca Plasmática , Trombose/tratamento farmacológico , Proteína ADAMTS13 , HospitaisRESUMO
RATIONALE: Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy caused by reduced activity of the von Willebrand factor-cleaving protease (ADAMTS13), which can be life-threatening. The patient reported in this case study also had concurrent Sjögren syndrome and renal impairment, presenting multiple symptoms and posing a great challenge in treatment. PATIENT CONCERNS: A 25-year-old woman in the postpartum period visited the hospital due to indifference in consciousness for more than 1 day following cesarean section 8 days prior. DIAGNOSIS: Notable decreases were observed in platelets, hemoglobin, creatinine, and ADAMTS13 levels. After a consultative examination by an ophthalmologist, she was diagnosed with retinal hemorrhage in the right eye and dry eye syndrome in both eyes. INTERVENTIONS: Having been diagnosed with TTP with Sjögren syndrome and renal impairment, she received repeated treatments with plasmapheresis combined with rituximab. OUTCOMES: Following treatment and during the follow-up period, the patient's platelet counts and bleeding symptoms significantly improved. LESSONS: TTP has a high mortality rate, and when combined with Sjögren syndrome and renal impairment, it poses an even greater challenge in treatment. However, after administering standard plasmapheresis combined with rituximab treatment, the treatment outcome is favorable.
Assuntos
Plasmaferese , Púrpura Trombocitopênica Trombótica , Rituximab , Síndrome de Sjogren , Humanos , Feminino , Síndrome de Sjogren/complicações , Síndrome de Sjogren/terapia , Plasmaferese/métodos , Adulto , Púrpura Trombocitopênica Trombótica/terapia , Púrpura Trombocitopênica Trombótica/complicações , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Rituximab/uso terapêutico , Rituximab/administração & dosagem , Terapia Combinada , Insuficiência Renal/terapia , Insuficiência Renal/etiologia , Fatores Imunológicos/uso terapêutico , Fatores Imunológicos/administração & dosagemRESUMO
ABSTRACT: For patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP), caplacizumab, a nanobody against von Willebrand factor A1 domain, has become crucial. Delayed normalization of ADAMTS13 activity during caplacizumab therapy has been identified. In a retrospective analysis, we compared platelet count, ADAMTS13 activity, its inhibitor, and anti-ADAMTS13 immunoglobulin G (IgG) levels in acute iTTP cases treated with caplacizumab (n = 14) or without it (n = 16). The median time from initial therapeutic plasma exchange (TPE) to the first rituximab administration was 12 days in the caplacizumab group (n = 11) and 10 days in the group without caplacizumab (n = 13). We evaluated ADAMTS13-related parameters at onset and once a week until day 28 after the first TPE. The number of days until the platelet counts reached ≥150 × 109/L was significantly shorter in the caplacizumab group than in the non-caplacizumab group. The median ADAMTS13 activity levels on days 14, 21, and 28 were significantly lower in the caplacizumab group. The median titers of the ADAMTS13 inhibitor and anti-ADAMTS13 IgG on the same days were significantly higher in the caplacizumab group. Furthermore, the median number of days from the first TPE until finally achieving an ADAMTS13 activity of ≥10% was significantly longer in the caplacizumab group than in the non-caplacizumab group (42 vs 23 days, P = .014). We observed delayed ADAMTS13 activity recovery and continued inhibitor and anti-ADAMTS13 IgG detection in patients with acute iTTP on caplacizumab, possibly because of the decreased number of TPEs and delayed frontline rituximab.
Assuntos
Proteína ADAMTS13 , Púrpura Trombocitopênica Trombótica , Anticorpos de Domínio Único , Humanos , Proteína ADAMTS13/metabolismo , Anticorpos de Domínio Único/uso terapêutico , Anticorpos de Domínio Único/farmacologia , Masculino , Feminino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Púrpura Trombocitopênica Trombótica/terapia , Estudos Retrospectivos , Adulto , Idoso , Imunoglobulina G/sangue , Contagem de Plaquetas , Japão , Rituximab/uso terapêutico , Rituximab/farmacologia , Resultado do Tratamento , Troca Plasmática , População do Leste AsiáticoRESUMO
Thrombotic thrombocytopenic purpura, an immune/non-immune thrombotic microangiopathy (TTP/TMA) is associated with high morbidity and mortality, even with appropriate treatment. In patients refractory to standard treatment with plasmapheresis there is no certainty about the best therapeutic strategy. This report shows our experience in eight refractory patients who survived after treatment with rituximab.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Rituximab/uso terapêutico , Recidiva , Estudos Retrospectivos , Rituximab/farmacocinéticaRESUMO
Thrombotic thrombocytopenic purpura presents as a multisystemic disease with thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological and renal involvement. We report a 24 years-old male presenting with purpura and a generalized seizure. His blood tests showed an hemolytic anemia, unconjungated hyperbilirubinemia, increased lactated dehydrogenase, thrombocytopenia and impairment of renal function. He was initially treated with daily plasmapheresis and steroids without improvement. Due to persistence of the disease, he was treated with two doses of intravenous vincristine in four days, with clinical and laboratory improvement. He was discharged 40 days after the last dose of vincristine, in good conditions.
Assuntos
Adulto , Humanos , Masculino , Fibrinolíticos/uso terapêutico , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Vincristina/uso terapêutico , Plasmaferese , Contagem de Plaquetas , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/diagnósticoRESUMO
Cerebellar disorders associated with HIV infection are usually caused by opportunistic infections, central nervous system lymphoma, and toxic effects of medicines, nutritional and metabolic disorders, and cerebrovascular disease. We present an unusual association of cerebellar degeneration and immune thrombocytopenic purpura in a 28-years-old woman HIV infected. An autoimmune aetiology is likely.
Transtornos cerebelares associados a infecção pelo HIV são comumente causados por infecções oportunistas, linfoma do sistema nervoso central, efeitos tóxicos de medicamentos anti-retrovirais, alterações metabólicas e nutricionais, e doença cerebrovascular. Apresentamos um caso incomum de associação de degeneração cerebelar e púrpura trombocitopênica imunológica em um mulher de 28 anos infectada pelo HIV. Discutimos uma possível etiologia autoimune para justificar o quadro.
Assuntos
Adulto , Feminino , Humanos , Doenças Cerebelares/complicações , Infecções por HIV/complicações , HIV-1 , Doenças Neurodegenerativas/complicações , Púrpura Trombocitopênica Trombótica/complicações , Doenças Cerebelares/diagnóstico , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Imageamento por Ressonância Magnética , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/tratamento farmacológico , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/tratamento farmacológicoRESUMO
We report a 23 years old female who presented a second episode of thrombotic thrombocytopenic purpura (TTP). She was treated with fresh frozen plasma infusions and 14 plasma exchange (PE) sessions without response. Therefore a second-line therapy was started, associating a weekly cycle administration of vindesine (Vds) 2 mg/m2 and rituximab (R) 375 mg/m2. Five cycles of this association plus one cycle of R exclusively, were administered. After the third course, biological signs of improvement were observed and complete normalization of blood cell counts and other specific parameters was seen after 8 weeks. From the beginning of her second relapse we detected a severe deficit (<5%) in von Willebrand-cleaving factor (ADAMTS13) associated to the presence of ADAMTS13 inhibitors. The combined treatment induced an improvement in ADAMTS13 values without detectable inhibitors. After 21 months of follow-up the patient was well, without signs of relapse but ADAMTS13 values were still under normal, which may be an unfavorable prognostic factor. PE is the treatment of choice for acquired idiopathic TTP, but for refractory cases or TTP cases with severe ADAMTS13 values/high inhibitor titers, PE associated to an immunosuppressive treatment should be considered.
Assuntos
Adulto , Feminino , Humanos , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Vindesina/uso terapêutico , Proteínas ADAM/antagonistas & inibidores , Proteínas ADAM/química , Proteínas ADAM/metabolismo , Quimioterapia Combinada , Transfusão de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/imunologia , Recidiva , Resultado do Tratamento , Fator de von Willebrand/análiseRESUMO
Se revisa la presentación de 6 pacientes adultos con púrpura trombótica trombocitopénica (PTT), que fueron atendidos en el Servicio de Clínica Médica del Hospital Escuela de Corrientes durante un período de 11 años. La púrpura trombótica trombocitopénica es una anemia hemolítica microangiopática caracterizada por una pentada clínica típica: trombocitopenia, anemia hemolítica microangiopática, fallo renal, fiebre y manifestaciones neurológicas. Todos los pacientes presentaron trombocitopenia y anemia hemolítica microangiopática. El compromiso neurológico fue la segunda característica más frecuente. Todos los pacientes fueron tratados con plasmaféresis. Tres pacientes se recuperaron completamente y 3 fallecieron. El pilar del tratamiento es la transfusión de plasma y la plasmaféresis. Se hace hincapié en su implementación inmediata dada la alta mortalidad de esta patología.
Assuntos
Humanos , Masculino , Adolescente , Adulto , Feminino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Trombótica/terapia , Desintegrinas , Metaloendopeptidases , Plasmaferese/efeitos adversos , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/etiologia , Púrpura Trombocitopênica Trombótica/prevenção & controle , Púrpura Trombocitopênica Trombótica/tratamento farmacológicoRESUMO
La púrpura trombocitopénica trombótica y el síndrome hemolítico urémico en el adulto son expresiones distintas de una misma enfermedad. Su incidencia es muy baja, aproximadamente uno en un millón de habitantes, pero su mortalidad sin tratamiento adecuado es alta. Las manifestaciones clínicas son heterogéneas y se pueden confundir con las producidas por otras entidades. En este informe se presentan y discuten las características clínicas de nueve pacientes vistos en seis años en un hospital universitario de referencia y se enfatizan los hallazgos que deben hacer sospechar la existencia de la enfermedad.