Long-term Subcutaneous Protein C Replacement in Neonatal Severe Protein C Deficiency

Abstract

We describe here the case of a boy who presented 2 days after birth with purpura fulminans on his feet and scalp. Laboratory investigations revealed signs of disseminated intravascular coagulation. An underlying coagulation disorder was suspected, and therapy with recombinant tissue plasminogen activator, fresh-frozen plasma, and unfractionated heparin was started. On the basis of plasma protein C activity and antigen levels of 0.02 and 0.03 IU/mL, respectively, after administration of fresh-frozen plasma, a diagnosis of severe protein C deficiency was established, and therapy with intravenous protein C concentrate (Ceprotin [Baxter, Deerfield, IL]) was started. Because of difficulties with venous access, we switched to subcutaneous administration after 6 weeks. The precise dosing schedule for subcutaneously administered protein C concentrate is unknown. In the literature, a trough level of protein C activity at >0.25 IU/mL is recommended to prevent recurrent thrombosis. During 1 year of follow-up our patient frequently had protein C activity levels at <0.25 IU/mL. Clinically, however, there was no recurrent thrombosis, and we kept the dosage unchanged. This report highlights 2 important points: (1) subcutaneously administered protein C concentrate is effective in treating severe protein C deficiency; and (2) in accordance with previous studies, after the acute phase trough levels of protein C activity at >0.25 IU/mL may not be necessary to prevent recurrent thrombosis. However, further research on the dosing, efficacy, and safety of protein C concentrate for prophylaxis and treatment of severe protein C deficiency is needed.

Déficit de proteína C en un paciente con coagulación intravascular diseminada asociada a sepsis y trombosis venosa profunda

“…Mayor controversia existe en los pacientes con episodios únicos de trombosis, en quienes debe sopesarse el riesgo de recurrencia con los riesgos del tratamiento anticoagulante a largo plazo. [11][12][13][14] Numerosas comunicaciones bibliográficas describen las manifestaciones trombóticas en los pacientes con CID. [1][2][3][4][5] Asimismo, desde la publicación de Griffin y cols., en 1982, 14 numerosas publicaciones muestran la asociación entre el déficit de proteína C y la trombosis, y en los casos de déficit grave, con la púrpura fulminante y la CID en las primeras etapas de la vida.…”

“…[11][12][13][14] Numerosas comunicaciones bibliográficas describen las manifestaciones trombóticas en los pacientes con CID. [1][2][3][4][5] Asimismo, desde la publicación de Griffin y cols., en 1982, 14 numerosas publicaciones muestran la asociación entre el déficit de proteína C y la trombosis, y en los casos de déficit grave, con la púrpura fulminante y la CID en las primeras etapas de la vida. 15,16 En el caso presentado, la evaluación y el seguimiento del laboratorio de hemostasia permitieron el diagnóstico de trombofilia hereditaria, con seguimiento y eventual tratamiento a largo plazo.…”

Long-term Follow-up of Homozygote Protein C Deficiency After Multimodal Therapy

“…There have been 4 other reports of the successful use of the subcutaneous protein C administration. 2,[8][9][10] Laboratory assays are important in assisting management, and the use of multiple assays to provide additional information can be most useful. This case also supports liver transplant as a final therapy, which is both clinically effective and cost-effective.…”

“…Since 1998, of 20 published cases of homozygous protein C deficiency presenting with neonatal purpura fulminans worldwide, 2,6,7,9,[11][12][13][14][15][16][17][18] most have had a poor clinical outcome; 75% have complete blindness (n = 15), 33% have severe neurological impairment (n = 6), and 10% have died within the first few days of life (n = 2). Other major morbidities such as renal failure (n = 2), epilepsy (n = 1), and impaired growth and development (n = 4) have also been reported, with only 3 patients having escaped any major morbidity, because of very early and continuous treatment with protein C concentrate.…”

“…1 Further cases have been reported; however, it remains an extremely rare condition presenting with neonatal purpura fulminans, as well as ophthalmologic, neurological, or renal complications due to thrombosis, which often occur in utero. [2][3][4][5][6] The condition is associated with extremely high rates of morbidity and mortality with the optimal treatment being highly complex, poorly understood, and often limited by cost and product supply. 7 We present the case of a boy with homozygous protein C deficiency, successfully treated with a unique sequential multimodal therapy until liver transplantation at 3 years of age.…”