Management of hereditary angioedema with C1‐inhibitor concentrate during two successive pregnancies

Abstract

Hereditary angioedema (HAE) is characterized by recurrent edema attacks in various organs causing discomfort and pain [1]. Managing and preventing recurrent attacks in patients with HAE is a clinical challenge that becomes considerably more complicated during pregnancy. The present report describes the management of a patient with type I HAE over the course of two pregnancies. The patient provided consent for publication.The patient had been diagnosed with type I HAE at 15 years of age and the disease was controlled with danazol. At 33 years of age the patient expressed an interest in trying to conceive, and danazol was discontinued. After conception, the patient experienced an increased frequency and severity of HAE attacks, occurring every 5-7 days in her first and second trimesters. The majority of these attacks were abdominal, causing severe pain and vomiting. These attacks were successfully managed in the emergency department with an intravenous infusion of 1500-2000 U of purified C1 esterase inhibitor (Berinert; CSL Behring, King of Prussia, PA, USA), analgesics, and antiemetics. The patient was hospitalized twice during the first trimester and once during the second trimester owing to persistent abdominal symptoms that did not completely resolve with management in the emergency department. In the third trimester, the patient started receiving 1500 U of C1 inhibitor (C1-INH) every 5 days as prophylactic therapy and had no further HAE attacks. At term, the patient was treated with a prophylactic dose of C1-INH given prior to induction for a vaginal delivery of a healthy male neonate weighing 2780 g that was HAE-negative on further testing. After delivery, the patient was restarted on danazol 100 mg twice daily for prevention of HAE attacks and thus was unable to breastfeed.Two years after her first delivery, the patient discussed with her physicians and planned for a second pregnancy. She discontinued danazol and initiated C1-INH prophylactic therapy (initially 500 U weekly and then increased to 1000 U weekly). A portacath catheter was inserted to facilitate recurrent intravenous administration of C1-INH. Once she became pregnant, the patient developed weekly HAE attacks despite prophylactic C1-INH infusions. On 5 separate occasions the patient attended the emergency department for treatment with C1-INH (1500-2000 U), analgesics, and antiemetics. This increase in her disease activity resulted in her prophylactic regimen being changed from 1000 U twice weekly, to 1500 U twice weekly, to a maximum dose of 2000 U twice weekly by the end of the first trimester (Table 1). The titration of the C1-INH dose resulted in a gradual decline in frequency and severity of HAE attacks, decreasing to every 2-3 weeks by the third trimester without any emergency department treatment needed. At delivery, the patient was treated with 1000 U of C1-INH prior to induction of labor, and vaginally delivered an HAE-positive male neonate weighing 2550 g without complication. After delivery, the patient breastfed for 24 hours before res...

Hereditary Angioedema Attack in Utero and Treatment of the Mother and Fetus

“…15,16 In these studies, all women delivered infants at full term without complications, and the treatment was generally safe and well tolerated. Further supportive information has come from treatment with plasma-derived C1-INH products during pregnancy for acute HAE attacks 9,23,24 and HAE prophylaxis 25,26 and short-term perinatal prophylaxis. 9,25 Although no controlled studies have been conducted comparing HAE treatment regimens during pregnancy, international guidelines recommend C1-INH concentrate as first-line treatment for acute HAE attacks during pregnancy on the basis of its safety profile.…”

Management of hereditary angioedema in pregnant women: a review

“…However, it has only been tested in isolated cases of nC1-INH-HAE and yielded variable results 3,4,19,20. There are several reports in which pdhC1INH has been proven to be safe and effective during pregnancy and breast-feeding for long-term prophylaxis, short-term prophylaxis, and acute therapy in patients with C1-INH-HAE,10,42,43,65–69 although no controlled studies have been conducted during pregnancy. It is recommended as the first-line therapy during pregnancy and lactation in C1-INH-HAE for all these indications 10,42,43…”

“…The long-term prophylactic pdhC1INH dosage and intervals between doses should be determined on a case-by-case basis, taking into account clinical disease severity9,10,70 and can vary from 500 U once a week to 2,000 U twice a week 65,69. A notable case has been published in which a pregnancy was successfully managed in a patient with severe C1-INH-HAE who was first treated with on-demand pdhC1INH and long-term prophylaxis with tranexamic acid and subsequently with both on-demand and long-term prophylaxis with pdhC1INH 71…”

“…pdhC1INH therapy has been shown effective in C1-INH-HAE2,9,42,43,54,58,59,65–69 and there are some data indicating that it may also be effective in nC1-INH-HAE3,19,20,50 and it is the optimal treatment in pregnant and lactating patients with both types of HAE. Therefore, intravenous pdhC1INH home self-administration programs and training should be considered for these patients 43.…”

Perioperative Management for Patients with Hereditary Angioedema

“…A 2009–2010 survey of United States physicians reported that 84% of physicians administered short-term procedural prophylaxis with 35% prescribing FFP, 30% prescribing C1-INH, and 19% prescribing high-dose attenuated androgens. 43 Of the respondents, 16% of United States physicians reported that they do not prescribe short-term procedural prophylaxis, suggesting increased need for awareness and need for education of treatment options. 38 , 42 , 44 …”