Audit of the Use of Regular Haem Arginate Infusions in Patients with Acute Porphyria to Prevent Recurrent Symptoms

Abstract

The National Acute Porphyria Service (NAPS) provides acute care support and clinical advice for patients in England with active acute porphyria requiring haem arginate treatment and patients with recurrent acute attacks.This audit examined the benefits and complications of regular haem arginate treatment started with prophylactic intent to reduce the frequency of recurrent acute attacks in a group of patients managed through NAPS. We included 22 patients (21 female and 1 male) and returned information on diagnosis, indications for prophylactic infusions, frequency and dose, analgesia, activity and employment and complications including thromboembolic disease and iron overload.The median age at presentation with porphyria was 21 years (range 9-44), with acute abdominal pain as the predominant symptom. Patients had a median of 12 (1-400) attacks before starting prophylaxis and had received a median of 52 (0-1,350) doses of haem arginate. The median age at starting prophylaxis was 28 years (13-58) with a median delay of 4 years (0.5-37) between presentation and prophylaxis. The frequency of prophylactic haem arginate varied from 1 to 8 per month, and 67% patients were documented as having a reduction in pain frequency on prophylaxis. Only one patient developed clinically significant iron overload and required iron chelation, but the number of venous access devices required varied from 1 to 15, with each device lasting a median of 1.2 years before requiring replacement. Six patients stopped haem arginate and in three this was because their symptoms had improved. Prophylactic haem arginate appears to be beneficial in patients with recurrent acute porphyria symptoms, but maintaining central venous access may prove challenging.

Acute Porphyrias

“…Patients should be screened for iron overload when heme therapy is used frequently or for long periods (> 3 years). Fortunately, the incidence of iron overload, even among patients receiving prophylactic repeated infusions of heme, is low (23,24). Orthotopic liver transplantation should be considered in patients who have frequent, nearly continuous and unremitting attacks.…”

Phase I open label liver-directed gene therapy clinical trial for acute intermittent porphyria

“…The standard cut-off scores of BDI-II are: minimal depression (0-9), mild depression (10)(11)(12)(13)(14)(15)(16)(17)(18); moderate depression (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) and severe depression . The standard cutoff scores of BAI are low anxiety (0-21), moderate anxiety (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) and severe anxiety (36-63).…”

“…Thromboembolic disease and iron overload (a dose of 250 mg of heme arginate contains 22.7 mg of iron) are also side effects associated with repeated courses of this therapy (18). Even though prophylactic heme appears to be beneficial in patients with recurrent attacks, life-long exposure to drugs for the control of symptoms may cause considerable adverse events that greatly impair quality of life (16,17). Thus alternative therapies for severe AIP are needed.…”

“…Although heme represses ALAS, thus blocking heme biosynthesis, it also activates hemeoxygenase-1 (EC:1.14.99.3), which in turn promotes acute attack recurrences and the decline of the therapeutic efficacy (16,17). Thromboembolic disease and iron overload (a dose of 250 mg of heme arginate contains 22.7 mg of iron) are also side effects associated with repeated courses of this therapy (18).…”

Messenger RNA therapy for rare genetic metabolic diseases

“…AIP symptoms are invariably accompanied by excess accumulation and renal excretion of these two haem precursors. Current treatment is based on infusions of haem33 and opioid analgesics to relieve pain 34. However, reduction of ALA and PBG levels occurs 3 days after intravenous haem infusion (3–4 mg/kg/day), with pain and nausea typically resolving on day 4 35…”