Immune Thrombocytopenia Induced by Sintilimab in Lung Cancer: A Case Report and Literature Review / 中国肺癌杂志

Immune checkpoint inhibitors (ICIs) show unique advantages in the treatment of lung cancer, making the treatment of lung cancer enter the era of immunotherapy, but ICIs will also have adverse reactions, and the incidence of immune-induced hematological toxicity is not very high. Immunotherapy-induced thrombocytopenia is a rare adverse event.We report one case of thrombocytopenia induced by ICIs and review the literature on thrombocytopenia associated with ICIs and discuss the clinical features, possible mechanisms, and optimal treatment. 
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Protocolo estadual para atendimento de casos suspeitos ou confirmados de síndrome de trombose com trombocitopenia (STT) associada à vacinação com vacinas de vetor de adenovírus não replicante contra a covid-19 / State protocol for the care of suspected or confirmed cases of thrombosis syndrome with thrombocytopenia (STT) associated with vaccination with non-replicating adenovirus vector vaccines against covid-19

Os efeitos generalizados exercidos pela pandemia da doença do Coronavírus 2019 (COVID-19) obrigaram governos e instituições de saúde mundiais a deslocar recursos para a contenção da crise sanitária e a desenvolver métodos para reduzi-los. As vacinas foram elencadas como principal método para conter a pandemia, com mais de um bilhão de doses administradas em todo o mundo. Entre as vacinas produzidas até o momento para combate ao vírus causador, SARS-CoV-2, estão as vacinas de vetores de adenovírus da Oxford-AstraZeneca (AZD1222) e a da Johnson & Johnson (Ad26.COV2.S). Após a implementação da vacinação em massa da população mundial, relatou-se um distúrbio pró-trombótico extremamente raro associado a ambas vacinas com trombocitopenia concomitante e desenvolvimento de anticorpos antiplaquetários fator 4 (anti-PF4). Esta desordem foi denominada inicialmente como Síndrome da Trombose com Trombocitopenia (STT) e posteriormente como Trombose Trombocitopênica Imune induzida por Vacina (TTIV). Os primeiros casos de trombose relacionados à vacinação para o SARS-CoV-2 começaram a ser reportados no final de fevereiro de 2021. Os relatos levaram à abertura de uma investigação pelas Agências do Reino Unido de Regulação de Produtos de Saúde e Medicina (MHRA) e Europeia de Medicina (EMA), as quais anunciaram em 11 de março de 2021 que não havia uma associação identificada. Entretanto, três grupos de cientistas da Noruega, Alemanha e Reino Unido reportaram, na semana seguinte, um caso de trombose localizada no seio venoso cerebral com trombocitopenia e anticorpos antiplaquetários fator 4 em um indivíduo que havia recebido a vacina da Oxford-AstraZeneca. Após maiores investigações, em 7 de abril de 2021, MHRA e EMA anunciaram a nova Síndrome de Trombose com Trombocitopenia e anticorpos antiplaquetários fator 4. Em 11 de novembro de 2021, houve a elaboração de uma definição de caso para STT, realizada pelo Brighton Collaboration, a qual engloba 5 critérios: (1) evidência de trombocitopenia sem exposição recente à heparina; (2) presença de trombose ou tromboembolismo confirmado por exame de imagem, procedimento cirúrgico, exame patológico ou dor de cabeça persistente com elevação de D-dímero (sugerindo trombose de seio venoso cerebral); (3) sintomas clínicos de trombose (Quadro 1); (4) exames de imagem e achados laboratoriais que confirmem o diagnóstico de trombose ou tromboembolismo; (5) achados laboratoriais que confirmem o diagnóstico de anticorpos de ativação plaquetária mediados por trombose, como enzima-imunoensaio (EIA) positivo para anti-PF4 e teste funcional positivo de ativação plaquetária com adição de PF4.

Relatório de recomendação para adoção de um protocolo estadual para atendimento de casos suspeitos ou confirmados de síndrome de trombose com trombocitopenia (STT) associada à vacinação com as vacinas de vetor de adenovírus não replicante contra a covid-19 em Santa Catarina / Recommendation report for the adoption of a state protocol for the care of suspected or confirmed cases of thrombosis syndrome with thrombocytopenia (STT) associated with vaccination with non-replicating adenovirus vector vaccines against covid-19 in Santa Catarina

Este relatório refere-se à análise crítica dos documentos apresentados pelo CRIE/DIVE/SES/SC para a elaboração de um Protocolo Estadual de atendimento para casos de Síndrome de Trombose com Trombocitopenia (STT) associada à vacinação com vacinas de vetor de adenovírus não replicante contra a COVID-19, baseados na Nota Técnica CGPNI/DEIDT/SVS/MS nº 933/2021. Na Nota Técnica emitida pelo Ministério da Saúde consta uma breve contextualização, a investigação da STT, protocolo de investigação laboratorial, manejo clínico de casos e definição de casos para investigação de STT. O documento enviado pelo CRIE/DIVE/SES/SC intitulado "Fluxograma de Atendimento TTS" apresentou os dados da nota supracitada resumidos com a adição de um fluxograma de atendimento hospitalar. Este relatório visa avaliar e emitir um parecer técnico embasado em evidências científicas sobre a disponibilização dos medicamentos Imunoglobulina Humana intravenosa (IGHIV) e Rivaroxabana para o tratamento de STT, fluxo de aces o aos medicamentos e avaliação do impacto orçamentário, para posterior elaboração de um Protocolo Estadual para esta síndrome, destinado aos profissionais da saúde, pacientes e gestores do estado de Santa Catarina.

Problemas Relacionados à Trombocitopenia em Pacientes com Fibrilação Atrial Concomitante que Necessitam de Prevenção Antitrombótica: Um Estudo de Coorte Retrospectivo / Thrombocytopenia-Related Problems in Patients with Concomitant Atrial Fibrillation Requiring Antithrombotic Prevention: A Retrospective Cohort Study

Resumo Baixas doses de edoxabana e enoxaparina sódica foram objeto de uma comparação retrospectiva implementada com a técnica do escore de propensão a fim de mitigar os efeitos das diferenças nas características clínicas basais de duas coortes e minimizar o risco de viés. Posteriormente, usando um modelo de riscos proporcionais de Cox, avaliou-se a associação de cada tipo de terapia com o risco do composto de morte por todas as causas, acidente vascular cerebral/ataque isquêmico transitório, hospitalizações e ocorrência de sangramentos maiores. Para essa análise, um valor de p < 0,05 foi considerado estatisticamente significante. A terapia com enoxaparina e cirrose hepática como causadora de trombocitopenia estiveram associadas ao aumento do risco do endpoint composto (enoxaparina: hazard ratio (HR): 3,31; IC 95%: 1,54 a 7,13; p = 0,0023; cirrose hepática, HR: 1,04; 95% CI: 1,002 a 1,089; p = 0,0410). Por outro lado, a terapia com edoxabana mostrou-se significativamente associada à diminuição do risco do endpoint composto (HR: 0,071; 95% CI: 0,013 a 0,373; p = 0,0019). Com base nessa análise retrospectiva, o edoxaban em doses baixas seria uma ferramenta farmacológica segura e eficaz para a profilaxia de eventos cardioembólicos em pacientes com FA e trombocitopenia.

Abstract Low-dose edoxaban and enoxaparin sodium have been the subject of a retrospective comparison implemented with the propensity score technique in order to mitigate the effects of the differences in the basal clinical features of two cohorts and minimize the risk of bias. Subsequently, using a Cox proportional-hazards model, the association of each type of therapy with the risk of the composite of all-cause death, stroke/transient ischemic attack, hospitalizations and major bleeding events was assessed. For this analysis, a p-value < 0.05 was considered statistically significant. Therapy with enoxaparin and liver cirrhosis as causing thrombocytopenia were associated with increased risk of the composite endpoint (enoxaparin: hazard ratio (HR): 3.31; 95% CI: 1.54 to 7.13; p = 0.0023; liver cirrhosis, HR: 1.04; 95% CI: 1.002 to 1.089; p = 0.0410). Conversely, edoxaban therapy was significantly associated with decreased risk of the composite endpoint (HR: 0.071; 95% CI: 0.013 to 0.373; p = 0.0019). Based on this retrospective analysis, edoxaban at low doses would appear as an effective and safe pharmacological tool for the prophylaxis of cardioembolic events in patients with AF and thrombocytopenia.

Diagnostic value of two immunoassays for detecting heparin/PF4 complex antibodies in heparin-induced thrombocytopenia / 中华血液学杂志

Objectives: To assess the diagnostic values of latex immunoturbidimetric assay (LIA) and particle immunofiltration assay (PIFA) for heparin-induced thrombocytopenia (HIT) . Methods: Samples from 94 patients with suspected HIT from May 2016 to July 2018 in our hospital were prospectively analyzed by the two immunoassays. Their medical records and further follow-up data were also collected and analyzed by our hematologists to make the 4Ts scores and confirm the diagnosis of HIT, respectively. Performance characteristics of the two immunoassays were assessed, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) . Their post-test probabilities (PTP) were also calculated based on the 4Ts score. Results: Among 94 cases, 15 (16.0%) had a positive HIT, including 6 of 37 (16.2%) with an intermediate, and 9 of 15 (60.0%) with a high 4Ts score. PIFA operating characteristics were: sensitivity 100.0% (15/15) , specificity 51.9% (41/80) , PPV 28.3% (15/53) , NPV 100.0% (41/41) . The positive PTP in intermediate and high 4Ts score group were 28.7% and 75.7%, respectively, while negative PTP were all 0. At manufacturers' cutoffs, LIA operating characteristics were: sensitivity 66.7% (10/15) , specificity 94.9% (75/79) , PPV 71.4% (10/14) and NPV 93.8% (75/80) . The positive and negative PTP in intermediate 4Ts score group were 71.8% and 6.3%, while 95.2% and 34.4% in high 4Ts score group, respectively. Receiver operating characteristic (ROC) analysis manifested that LIA was preferable than PIFA, and combining the 2 assays together was significantly better than single test. Conclusions: 4Ts score is still an important tool for the diagnosis of HIT. Combining clinical score with heparin/PF4 antibody assay can increase the accuracy of confirming or excluding HIT. Although PIFA is inferior to LIA in the diagnostic value, its user friendliness and 100% NPV have major advantages. Combining the 2 assays together can achieve a higher diagnostic value.

Vancomycin-induced severe thrombocytopenia in a young infant

Abstract Vancomycin is a first-line drug for treating methicillin-resistant Staphylococcus aureus. Thrombocytopenia is a rare adverse reaction to vancomycin treatment, and there are no reports of vancomycin-induced thrombocytopenia (VIT) in infants. We describe the case of a 3-month-old girl who was diagnosed with purulent meningitis. After 13 days of treatment with vancomycin, her platelet count reduced to 8 × 109/L. Vancomycin was discontinued, and intravenous methylprednisolone was administered. The platelet count returned to normal after 4 days. Patients, especially young children, receiving vancomycin for a long clinical course should undergo careful monitoring of laboratory indicators and blood tests.

Rare complications of multikinase inhibitor treatment

ABSTRACT Objective: The advent of multikinase inhibitor (MKI) therapy has led to a radical change in the treatment of patients with advanced thyroid carcinoma. The aim of this manuscript is to communicate rare adverse events that occurred in less than 5% of patients in clinical trials in a subset of patients treated in our hospital. Subjects and methods: Out of 760 patients with thyroid cancer followed up with in our Division of Endocrinology, 29 (3.8%) received treatment with MKIs. The median age at diagnosis of these patients was 53 years (range 20-70), and 75.9% of them were women. Sorafenib was prescribed as first-line treatment to 23 patients with differentiated thyroid cancer and as second-line treatment to one patient with advanced medullary thyroid cancer (MTC). Vandetanib was indicated as first-line treatment in 6 patients with MTC and lenvatinib as second-line treatment in two patients with progressive disease under sorafenib treatment. Results: During the follow-up of treatment (mean 13.7 ± 7 months, median 12 months, range 6-32), 5/29 (17.2%) patients presented rare adverse events. These rare adverse effects were: heart failure, thrombocytopenia, and squamous cell carcinoma during sorafenib therapy and squamous cell carcinoma and oophoritis with intestinal perforation during vandetanib treatment. Conclusions: About 3 to 5 years after the approval of MKI therapy, we learned that MKIs usually lead to adverse effects in the majority of patients. Although most of them are manageable, we still need to be aware of potentially serious and rare or unreported adverse effects that can be life-threatening.

Mielosupresión inducida por linezolid: un caso pediátrico / Myelosupression induced by linezolid: a pediatric case

El linezolid es un antibiótico de la familia de las oxazolidinonas, que actúa inhibiendo la síntesis proteica. Se emplea en infecciones graves por cocos Gram-positivos multirresistentes. Sus principales efectos secundarios son los gastrointestinales y, con menor frecuencia, la neuropatía periférica, la acidosis láctica y la mielosupresión. Se presenta el caso clínico de un niño de 12 años con diagnóstico de osteoartritis séptica de cadera derecha con osteomielitis femoral en tratamiento con linezolid, que presentó un cuadro de intolerancia digestiva, asociado a astenia y pérdida de peso. Presentaba, además, anemia normocítica, junto con leucopenia y trombopenia leves, con datos sugestivos de alteración de la hematopoyesis en el frotis sanguíneo, sugerente de toxicidad por fármacos. El cuadro se resolvió con la interrupción de la administración del fármaco. La mielosupresión reversible asociada a linezolid se relaciona con tratamientos prolongados (> 28 días), por lo que son necesarios los controles hematológicos periódicos durante ellos.

Linezolid is an antibiotic of oxazolidinones family that inhibits proteical synthesis. It is used in several Gram-positive multirresistent infections. Its more frequent side effects are gastrointestinal, followed by peripheral neuropathy and myelosuppression. We report the case of a 12-year-old boy diagnosed with septic osteoarthritis of the hip and femoral osteomyelitis, following treatment with linezolid, who complained about digestive intolerance and weight loss. He showed severe normocytic anemia and mild leukopenia and thrombocytopenia with data of hematopoiesis disorder in the blood smear that suggested drug toxicity. These findings reverted when the treatment was discontinued. Reversible myelosuppression associated with linezolid is related to long treatments (more than 28 days). So it is necessary to check the blood count during long treatments.

Rivaroxaban para el tratamiento de la trombocitopenia inducida por heparina: caso clínico / Treatment of heparin-induced thrombocytopenia with rivaroxaban: case report

Heparin-induced thrombocytopenia (HIT) is immune-mediated. It occurs more frequently with unfractionated heparin (UFH) than with low molecular weight heparins (LMWH). It is associated with thromboembolic rather than hemorrhagic events, as opposed to thrombocytopenia of other etiologies. The key in therapy is the cessation of heparin and the start of another anticoagulant. We report a 58 years old female with HIT secondary to the use of Enoxaparin who was successfully managed with Rivaroxaban. Our goal is to report a novel therapy and provide the evidence that supports its use.

Trombocitopenia inducida por fármacos / Drug-induced thrombocytopenia

La trombocitopenia puede tener varias causas, como la utilización de determinados fármacos. Los mecanismos causantes de la trombocitopenia inducida por fármacos incluyen disminución en la producción (supresión medular) o incremento en la destrucción (por mecanismos inmunes). Adicionalmente, la seudotrombocitopenia es un efecto in vitro, que se distingue de una real trombocitopenia inducida por medicamentos. Los estudios epidemiológicos son pocos, difieren en la metodología utilizada y describen una incidencia de 10 casos por millón de habitantes por año. El mecanismo fundamental de la trombocitopenia inducida por fármacos no está completamente esclarecido, pero al menos se plantean seis posibles mecanismos: anticuerpos inducidos por haptenos, anticuerpos dependientes del fármaco, inhibidores del complejo GP IIb-IIIa, autoanticuerpos inducidos por la droga, complejos inmunes y trombocitopenia inducida por heparina. La diana para los anticuerpos dependientes del fármaco son las glucoproteínas de la membrana plaquetaria, como las glucoproteínas Ib/IX y GPIIb/IIIa. El diagnóstico de trombocitopenia inducida por fármacos puede consistir en la identificación de síntomas clínicos (hematomas, petequias, sangramientos), la cuidadosa evaluación de la relación causal con el fármaco sospechoso, las investigaciones generales de laboratorio (conteos en sangre total, extendidos de sangre periférica, para descartar seudotrombocitopenia) y las pruebas serológicas para plaquetas. La trombocitopenia inducida por fármacos es una reacción adversa a medicamentos relativamente raros cuyas sus consecuencias pueden ser graves.

Thrombocytopenia can have several causes, including the use of certain drugs. The mechanism behind drug-induced thrombocytopenia is either a decrease in platelet production (bone marrow suppression) or an increased destruction (immune-mediated thrombocytopenia). In addition, pseudothrombocytopenia, an in vitro effect, has to be distinguished from true drug-induced thrombocytopenia. A small number of epidemiological studies, differing largely in the methodology used, describe incidences in the magnitude of 10 cases per 1 000 000 inhabitants per year. The underlying mechanism of drug-induced immune thrombocytopenia is not completely clarified, but at least six different types of antibodies appear to play a role; hapten-induced antibody, drug-dependent antibody ("compound" or "conformational-dependent" antibody), GPIIb-IIIa inhibitors, drug-induced autoantibody, immune complex and heparin-induced thrombocytopenia. Targets for drug-dependent antibodies are glycoproteins on the cell membrane of the platelets, such as glycoprotein (GP) Ib/IX and GPIIb/IIIa. Diagnosis of drug-induced immune thrombocytopenia may consist of identifying clinical symptoms (bruising, petechiae, bleeding), a careful evaluation of the causal relationship of the suspected causative drug, general laboratory investigation, such as total blood count and peripheral blood smear (to rule out pseudothrombocytopenia), and platelet serology tests. Although drug-induced thrombocytopenia is a relatively rare adverse drug reaction, its consequences may be severe.

Trombocitopenia inducida por tamoxifeno y letrozol / Thrombocytopenia induced by tamoxifen and letrozole

El tamoxifeno y el letrozol son fármacos muy utilizados en el tratamiento del cáncer de mama. Está descrito que la trombocitopenia (recuento plaquetario inferior a 100.000/mm3) es un efecto secundario raro tras el tratamiento con tamoxifeno. Sin embargo, no es un efecto adverso conocido del letrozol. Presentamos dos casos clínicos en los que tras tratamientos prolongados con estos fármacos nos encontramos con que las pacientes desarrollan trombocitopenia. En ambos casos, este efecto adverso desaparece en pocas semanas tras la retirada del fármaco.

Letrozole and tamoxifen are drugs used in the treatment of breast cancer. It is reported that thrombocytopenia (less than 100,000 / mm3 platelet count) is a rare side effect of tamoxifen. However, it is not a known side effect of letrozole. We present two cases in which after prolonged treatment with these drugs we found that the patients develop thrombocytopenia. In both cases, this adverse effect disappears a few weeks after drugs were stopped.

Trombocitopenia inducida por heparina: Nuevas opciones terapéuticas / Heparin-induced thrombocytopenia. New therapeutical options

La trombocitopenia inducida por heparina (TIH) es una reacción adversa inmunológica mediada por la formación de anticuerpos contra el complejo heparina-factor plaquetario 4 (FP4), caracterizada por la presencia de trombocitopenia y la asociación paradojal de trombosis arterial o venosa. Es una complicación poco frecuente pero grave del uso de cualquier tipo de heparina. En tratados con procedimientos cardiovasculares como intervención coronaria percutánea y cirugía de revascularización cardiaca, la prevalencia de anticuerpos es significativamente mayor que en otros escenarios clínicos. El reconocimiento de las características clínicas y de laboratorio permite la suspensión inmediata de la heparina y la instauración de tratamiento anticoagulante alternativo, para evitar la progresión y formación de nuevos trombos y sus complicaciones. En la presente revisión se resumen las diferentes alternativas terapéuticas para la TIH, en particular los anticoagulantes orales directos (DOACS) como el dabigatran, rivaroxaban y apixaban que pueden proporcionar una nueva opción para el tratamiento de TIH.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction due to antibodies to a multimolecular complex of heparin and platelet factor 4 (PF4) characterized by moderate thrombocytopenia and paradoxical arterial or venous thrombosis. It is a relatively infrequent complication related to the administration of any type of heparin. In patients undergoing percutaneous coronary revascularization or coronary artery by-pass graft the prevalence of HIT is higher than in other clinical settings. Recognizing clinical and laboratory features of HIT allow immediate discontinuation of heparin and the use of alternative anticoagulants to avoid serious thrombotic complications. In this review, we summarize different therapeutic options for the treatment of HIT with special emphasis on direct oral anticoagulants (DOACS) such as dabigatran, rivaroxaban and apixaban. DOACS might represent a therapeutic alternative for HIT treatment.

Tratamiento exitoso con fondaparinux en trombocitopenia inducida por heparina y trombosis / Successful treatment with fondaparinux in heparin-induced thrombocytopenia and thrombosis

La trombocitopenia inducida por heparina (TIH) es una reacción adversa inmunológica caracterizada por trombocitopenia y la asociación paradojal de trombosis arterial o venosa. Es causada por la formación de anticuerpos IgG contra el complejo multimolecular de heparina-factor plaquetario 4 (FP4). Fondaparinux es un inhibidor selectivo del factor Xa que tiene escasa afinidad por el FP4 y posee un menor potencial para inducir una respuesta inmunológica, haciendo del mismo un agente potencialmente útil en el tratamiento de la TIH. Se presenta el caso de una mujer de 73 años con TIH asociada a fenómenos trombóticos arteriales y venosos, que recibió exitosamente fondaparinux, con normalización del recuento plaquetario y sin progresión trombótica.

Heparin induced thrombocytopenia (HIT) is an immune-mediated adverse reaction characterized by thrombocytopenia and paradoxical arterial or venous thrombosis, due to the formation IgG antibodies directed to a multimolecular complex of heparin-platelet factor 4 (PF4). Fondaparinux is a selective factor Xa inhibitor with little affinity for PF4 and thus less likely to induce an immune response, making fondaparinux a potentially useful drug for the treatment of HIT. Herein we report the case of a 73 years old woman with HIT associated with arterial and venous thrombosis that was successfully treated with fondaparinux, with normalization of the platelet countand without progression of thrombosis.

Partial response to sorafenib treatment associated with transient grade 3 thrombocytopenia in a patient with locally advanced thyroid cancer

Advanced radioactive refractory and progressive or symptomatic differentiated thyroid carcinoma (DTC) is a rare condition. Sorafenib was recently approved for the treatment of these patients. We present the case of a 67 year old woman diagnosed with DTC who underwent a total thyroidectomy with central, lateral-compartment neck dissection and shaving of the trachea and esophagus due to tumor infiltration. A local recurrence was detected 14 months later requiring, additionally, two tracheal rings resection. The patient received a cumulative 131I dose of 650 mCi and developed dysphagia and dyspnea 63 months after initial surgery. A 18FGD-PET/CT showed progression of the local mass associated to hypermetabolic pulmonary nodules. Sorafenib 800 mg/day was then prescribed. A dose reduction to 400 mg/day was necessary due to grade 3 thrombocytopenia that appeared four months after drug prescription. Platelet count went to normal after this dose reduction. Five months after initiation of sorafenib, a partial response of the local mass with significant intra-tumoral necrosis was observed. We conclude that sorafenib is a valid option for locally advanced DTC and that the platelet count should be evaluated regularly because it seems that thrombocytopenia might be more frequently observed in DTC than in other types of tumors.

Association between IPTA Gene Polymorphisms and Hematological Abnormalities in Hepatitis C Virus-Infected Patients Receiving Combination Therapy

BACKGROUND/AIMS: Hematological abnormalities during hepatitis C virus (HCV) combination therapy with pegylated interferon alpha and ribavirin often necessitate dose reduction. Variants of the ITPA gene have been reported to protect against anemia during the early stages of HCV combination treatments but have also been associated with larger decreases in platelet counts. We aimed to identify the association between specific ITPA gene polymorphisms and hematological abnormalities in patients undergoing HCV combination therapy. METHODS: In this retrospective study, 175 patients treated with HCV combination therapy were enrolled at St. Martin De Porres Hospital in Taiwan between 2006 and 2012. Two single nucleotide polymorphisms (SNP) within or adjacent to the ITPA gene (rs1127354, rs6051702) were genotyped. We investigated the effect of ITPA gene variants on hematological abnormalities during the therapy. RESULTS: The ITPA rs1127354 minor variants were significantly associated with protection against anemia at week 4 (p=1.86 x 10(-6)) and with more severe decreases in platelet counts during HCV combination therapy. SNP rs6051702 was not associated with the hemoglobin decline to >3 g/dL at week 4 in our study (p=0.055). CONCLUSIONS: The ITPA SNP rs1127354 is a useful predictor of ribavirin-induced anemia in Taiwanese patients and may be related to more severe decreases in platelet counts during the early stage of HCV combination therapy.

Association between IPTA Gene Polymorphisms and Hematological Abnormalities in Hepatitis C Virus-Infected Patients Receiving Combination Therapy

BACKGROUND/AIMS: Hematological abnormalities during hepatitis C virus (HCV) combination therapy with pegylated interferon alpha and ribavirin often necessitate dose reduction. Variants of the ITPA gene have been reported to protect against anemia during the early stages of HCV combination treatments but have also been associated with larger decreases in platelet counts. We aimed to identify the association between specific ITPA gene polymorphisms and hematological abnormalities in patients undergoing HCV combination therapy. METHODS: In this retrospective study, 175 patients treated with HCV combination therapy were enrolled at St. Martin De Porres Hospital in Taiwan between 2006 and 2012. Two single nucleotide polymorphisms (SNP) within or adjacent to the ITPA gene (rs1127354, rs6051702) were genotyped. We investigated the effect of ITPA gene variants on hematological abnormalities during the therapy. RESULTS: The ITPA rs1127354 minor variants were significantly associated with protection against anemia at week 4 (p=1.86 x 10(-6)) and with more severe decreases in platelet counts during HCV combination therapy. SNP rs6051702 was not associated with the hemoglobin decline to >3 g/dL at week 4 in our study (p=0.055). CONCLUSIONS: The ITPA SNP rs1127354 is a useful predictor of ribavirin-induced anemia in Taiwanese patients and may be related to more severe decreases in platelet counts during the early stage of HCV combination therapy.