Two Cases of Hypersensitivity Reactions Caused by Human Serum Albumin During Therapeutic Plasma Exchange

Iso-oncotic human serum albumin (HSA) is the primary replacement fluid of choice during therapeutic plasma exchange (TPE). Hypersensitivity reactions to HSA are rare, but require proper evaluation and management. In this article, we report two cases of hypersensitivity reactions to 5% HSA during TPE and discuss strategies to address this problem. The first case was a 60-year-old female patient, who was scheduled for TPE for treatment of recurrent focal segmental glomerulosclerosis after ABO-incompatible kidney transplantation. She developed a pruritic rash on her entire body during the first two sessions of TPE using 5% HSA. The third session was conducted using 500 mL normal saline, 1,000 mL 10% pentastarch, and 750 mL 5% HSA, where she eventually developed a pruritic rash when HSA was infused. There were no adverse events during the fourth and fifth session when fresh frozen plasma was used in place of HSA. The second case was a 50-year-old male patient diagnosed with optic neuritis, who was admitted for five sessions of TPE. The patient developed a pruritic rash on his entire body during the first session of TPE using 5% HSA. The patient experienced no adverse events during the following four sessions using fresh frozen plasma. Certain elements contained in HSA, such as albumin aggregates, prekallikrein activator, and caprylate-modified albumin, might be the reason for these hypersensitivity reactions. Careful selection of alternative replacement fluids is important to avoid premature termination of TPE procedures and secure optimal treatment options for patients.

Custo-efetividade do fator VII ativado recombinante (rFVIIa) e complexo protrombínico parcialmente ativado (CCPa) no tratamento sob demanda do sangramento leve/moderado de pacientes com hemofilia congênita complicada por inibidores sob a perspectiva do sistema público de saúde do Brasil / Cost-effectiveness of rFVIIa and CCPa in the on-demand treatment of congenital haemophilia with inhibitors in the Brazilian public setting

Objetivo: Fornecer evidências econômicas que suportem o uso do fator VII ativado recombinante (rFVIIa) em comparação ao complexo protrombínico parcialmente ativado (CCPa) para o tratamento do episódio de sangramento leve a moderado devido a hemofilia com anticorpos inibidores no Sistema Único de Saúde (SUS). Métodos: Estudos que investigaram a eficácia clínica dos tratamentos CCPa e rFVIIa indicam diferenças entre eles na capacidade de controlar os sangramentos. A análise de custo-efetividade foi desenvolvida com base em dois modelos de árvore de decisão propostos por You et al. (2009) e Jiménez-Yuste et al. (2013). O desfecho clínico foi o percentual de pacientes que controlam o sangramento e o desfecho econômico incluiu custos médicos diretos. O horizonte de tempo variou com a gravidade da hemorragia. Os custos unitários foram obtidos do Diário Oficial da União (1 µg de rFVIIa R$ 2,09 e 1U de CCPa R$ 2,28). No modelo de You foram considerados também custos com ácido tranexâmico e centro de tratamento, extraídos da CMED (Câmara de Regulação do Mercado de Medicamentos) e do SIGTAP (Sistema de Gerenciamento da Tabela de Procedimentos), respectivamente. Resultados: O modelo de You indicou maior percentual de pacientes que tiveram o sangramento controlado com rFVIIa comparado ao CCPa (89,2% vs. 75,1%) com menor custo de tratamento (R$ 18.921 vs. R$ 28.691). Considerando Jiménez-Yuste, o percentual de pacientes com sangramento controlado também é maior com rFVIIa (79,0% vs. 61,0%), com menor custo de tratamento (R$ 63.446 vs. R$ 68.952). Conclusão: O rFVIIa é uma alternativa cost-saving para o tratamento de pacientes com hemofilia congênita com inibidores comparado ao CCPa.

Objective: To provide economic evidences that support the use of recombinant activated factor VII (rFVIIa) in comparison to activated prothrombin complex concentrate (aPCC) for the treatment of episodes of mild to moderate bleeding due to haemophilia with inhibitors in Sistema Único de Saúde (SUS). Methods: Studies that explored the clinical efficacy of aPCC and rFVIIa treatments have shown differences between them in their capacity for controlling bleeding episodes. The cost-effectiveness analysis was developed based on two decision tree models proposed by You et al. (2009) and Jiménez-Yuste et al. (2013). The clinical outcome was the percentage of patients with controlled bleeding, and the economic outcome was direct medical costs. The time horizon varied according to hemorrhage severity. Drugs unit costs were obtained from the Diário Oficial da União (1 µg of rFVIIa R$ 2.09 and 1U of aPCC R$ 2.28). In You model, also considered the costs with tranexamic acid and treatment center, extracted from CMED (Câmara de Regulação do Mercado de Medicamentos) and SIGTAP (Sistema de Gerenciamento da Tabela de Procedimentos), respectively. Results: You model showed a higher percentage of patients that controlled bleeding with rFVIIa compared to aPCC (89.2% vs. 75.1%) and with lower treatment cost (R$ 18,921 vs. R$ 28,691). Considering Jiménez-Yuste, the percentage of patients that controlled bleeding was also greater with rFVIIa (79.0% vs. 61.0%) with lower treatment cost (R$ 63,446 vs. R$ 68,952). Conclusion: rFVIIa is a cost-saving alternative for the treatment of patients with congenital haemophilia with inhibitors compared to aPCC.

Fibrinolytic and factor XIII activity in subarachnoid hemorrhagge

The balance between fibrinolytic activity and coagulation mechanisms seems to play an important role in the rebleeding of a subarachnoid hemorrhage (SAH) due to aneurysmatic rupture. In the present paper we describe our findings in a group of patients (n10)with SAH. The plasmatic levels of fibrinogen and their degradation products (FDP), APTT, prothrombin activity and factor XIII were determined within 72 hours of initial bleeding, or of eventual rebleeding. Factor XIII activity in the first bleeding was 82.1+4 percent, while the levels of FDP were 3.8+1mug/ml. In patients presenting rebleeding (n4), Factor XIII activity was 67.3+4.5 percent the day it manifested, which is significantly less than the values previously observed (p<0.01), while the FDP level was 4.1+2mug/ml. The decrease of factor XIII activity suggests an important role as regards clot stability in rupture location. It is also possible to attribute a rebleeding predictive value to its activity reduction.