Haematin Therapy: ( Haem Arginate )

So far we have concentrated on treating the acute attack by correcting any factors that may have precipitated it, and providing adequate supportive therapy while the attack spontaneously resolves. It is also possible to treat the underlying disease process more directly by administering the end product of the deranged pathway as intravenous haematin. In the liver, it is thought to supplement the depleted intracellular 'free haem pool', thus repressing the activity of the initial and rate-controlling enzyme of haem biosynthesis, ALA synthase, and reducing the overproduction of porphyrins and precursors formed prior to the enzyme block. In an acute attack of porphyria, the intravenous administration of haematin consistently reduces both the plasma concentration and the urinary excretion of porphyrin precursors. Its effect may be supplemented with inhibitors of the haem degradative enzyme, Haem oxygenase, such as Tin protoporphyrin.
The clinical response to the therapy is more difficult to assess. In a disease characterised by spontaneous relapses and remissions, it is difficult to be sure whether improvement is the result of therapy or just the natural course of the disease. Our current impression is that haematin does curtail the clinical attack, and we frequently employ it.

No major side-effects have been reported with haematin when used in the standard doses. Phlebitis, around the injection site, occurs in a few patients. This can be prevented by injecting the solution into a large peripheral vein or via a central venous line, or by administering the haematin, with human albumin solution, to which it will bind. During haematin therapy, there is a mild disturbance of coagulation, with prolongation of the prothrombin and partial thromboplastin times, and a slight reduction in the platelet count. This reverts to normal on completion of the haematin course, and has only very rarely resulted in haemorrhagic complications. As mentioned above coagulation indices and the platelet count should be monitored during therapy and haematin should not be used with anticoagulant therapy.

Transient acute renal failure has been reported in one patient who received a bolus intravenous injection of 1000 mg of haematin. Yet, no renal complications have occurred with the standard recommended dosages, and even patients with renal insufficiency appear to tolerate haematin well, although it is probably wise to reduce the dosage slightly as an added precaution.
A commercially available haematin preparations is: NORMOSANG ( Haem Arginate - Leiras)