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Case 37: Collapsed in the Corridor
Published in Layne Kerry, Janice Rymer, 100 Diagnostic Dilemmas in Clinical Medicine, 2017
Heme arginate, an inhibitor of aminolevulinic acid synthase, is used as the drug of choice to treat acute episodes. It acts to reduce the accumulation of δ-aminolevulinic acid that occurs in episodes of acute intermittent porphyria.
Disorders of haem metabolism: iron and the porphyrias
Published in Martin Andrew Crook, Clinical Biochemistry & Metabolic Medicine, 2013
The acute attack is marked by an increase in ALA and PBG production. In acute intermittent porphyria, this increase is due to the block imposed by an inherited deficiency of PBG deaminase; in hepatic coproporphyria and variegate porphyria, this enzyme becomes rate limiting and is unable to respond normally to the increased demand. The increase in urinary ALA and PBG concentrations is the hallmark of the acute porphyric attack and, in hereditary coproporphyria and variegate porphyria, is superimposed on all the other biochemical abnormalities. The accelerated activity of the pathway and the spontaneous conversion of the precursors to porphyrin lead to increased urinary porphyrin excretion. About 1 per cent of acute attacks are fatal. It is important to stop precipitating drugs and not to use medications that could evoke an attack. Convulsions may be treated with gabapentin or vigabatrin. Haem arginate, given by slow intravenous infusion, can result in a reduction in ALA and PBG concentrations and thus reduce some of the features of the acute attack, but not usually the neuropathy.
Acute pain and medical disorders
Published in Pamela E Macintyre, Suellen M Walker, David J Rowbotham, Clinical Pain Management, 2008
Disease modification, including the administration of intravenous heme arginate (Hematin) (3 mg/kg/daily, for four days),231[II], high-dose dextrose (usually via an intravenous infusion: 0.1–0.2 g/kg/h)228 or cimetidine232 early in an attack, may decrease the duration and severity of symptoms, including pain, by reducing ALA synthetase activity and the subsequent production of “neurotoxic” ALA and porphyrins. A central venous catheter is indicated when administering intravenous hematin or dextrose as both produce phlebitis. Large volumes of dextrose may exacerbate hyponatremia. Hematin may cause a coagulopathy and rarely fever, aches, malaise, renal impairment, or circulatory collapse. Administration of hematin in albumin reduces phlebitis and coagulopathy and may enhance the drug’s efficacy.228
Safety of haem arginate in overdose: report of an uneventful fourfold accidental overdose
Published in Clinical Toxicology, 2022
Nandesh C. Patel, Nicholas Wroe, Daniel McNally, Penny Stein, Sally M. Bradberry, Muhammad E. M. O. Elamin
A 22-year-old female with known AIP presented to the Emergency Department with lower abdominal pain, vomiting and bilateral elbow and knee pain. Examination revealed mild epigastric tenderness. Full blood count, renal and liver function, and C-reactive protein were normal. A diagnosis of an acute attack of porphyria was made and the patient received prophylactic tinzaparin, IV sodium chloride 0.9%, cyclizine and morphine. Following consultation with the National Acute Porphyria Service, treatment with intravenous haem arginate 210 mg (3 mg/kg, 69.9 kg) daily for four days was advised. On day 2, the patient accidentally received all 4 vials (total dose 1000 mg) of haem arginate in a single infusion. This was discovered 16 h later. The patient had developed no new symptoms or signs. Management advice was sought from the patient’s haematologist and the UK National Poisons Information Service (NPIS) who liaised with the manufacturer, Recordati Rare Diseases Ltd. On NPIS advice, the patient received 7 l of intravenous 0.9% saline and a single intravenous dose of 100 mls Human Albumin 20% over the following 48 h. Activated charcoal 25 g 2-hourly up to 200 g was prescribed; however only a single 25 g dose was tolerated. Full blood count, coagulation, renal and hepatic function were normal except bilirubin 38 µmol/L (0–21 µmol/L). An arterial blood gas revealed an elevated anion gap of 21 mmol/L and normal osmolar gap without metabolic acidosis, excluding propylene glycol toxicity. Blood tests including arterial blood gases were monitored for five days.
Neurological and neuropsychiatric manifestations of porphyria
Published in International Journal of Neuroscience, 2019
Yiji Suh, Jason Gandhi, Omar Seyam, Wendy Jiang, Gunjan Joshi, Noel L. Smith, Sardar Ali Khan
Acute treatment can be administered by hematin or heme arginate intake. By taking hematin or heme arginate, heme will be replenished in the body, causing an increase of ALAS function which reduces the creation of porphyrin precursors. A standard dosage of 3 mg/kg of intravenous infusion should be given daily for a duration of 4 days [65]. This method may reduce the length of acute attacks, but cannot guarantee a permanent treatment. After a 10 day hemin treatment, porphobilinogen levels within the urine may decrease to zero [17].
Givosiran for the treatment of acute hepatic porphyria
Published in Expert Review of Clinical Pharmacology, 2022
Currently available therapies for prevention of acute AIP attacks include hemin administration, carbohydrate loading, gonadotrophin-releasing hormone analogue administration to women with AIP who experience attacks related to the menstrual cycle, and liver and kidney transplantation [19]. Studies of hemin for treatment of acute AIP attacks and for prophylactic treatment to prevent attacks have shown variable results [26,27]. For patients with prodromal attack symptoms, hemin administration in an outpatient setting may help control symptoms and potentially prevent hospitalization, but patients who have already progressed to a full attack often require inpatient treatment [19]. Case studies of prophylactic treatment with weekly hemin have shown improvement in patients with AIP, as well as reduced treatment costs resulting from less frequent inpatient admissions [27]. There is continued discussion about the use of prophylactic hemin infusions. Nevertheless, many physicians use prophylaxis on an individualized basis in patients with four or more attacks per year, although infusions often must be administered at high frequency to be beneficial, as heme is metabolized rapidly by heme oxygenase [19,28]. Patients with AIP who receive repeated administrations of hemin (heme arginate) over many years can develop secondary iron overload and liver damage. Therefore, close monitoring of ferritin levels and vigilance for complications associated with iron overload are important considerations [29]. Other adverse events associated with hemin include acute and chronic complications (e.g. headache, phlebitis, and venous thrombosis), also related to the large-bore venous catheters needed for infusion [25,30–33]. Patients with AIP who have severe recurring attacks may be eligible for liver transplantation, but typically this is performed only in extreme cases because of morbidity and mortality risks [19]. Kidney transplantation can be an effective treatment in some patients who develop end-stage kidney disease with AIP [19]. Therefore, available therapies for prevention of attacks and disease progression, as well as for acute attack treatment in patients with AIP (and AHPs in general), are limited. Recent research has focused on targeting the genes and proteins leading to the toxic buildups associated with APAs.