The continuous release of free hemoglobin has been linked with the development of pulmonary hypertension (increased pressure over the pulmonary artery); this, in turn, leads to episodes of syncope (fainting), chest pain, and progressive breathlessness. Pulmonary hypertension eventually causes right ventricular heart failure, the symptoms of which are peripheral edema (fluid accumulation in the skin of the legs) and ascites (fluid accumulation in the abdominal cavity). Causes
They may be classified according to the means of hemolysis, being either intrinsic in cases where the cause is related to the red blood cell (RBC) itself, or extrinsic in cases where factors external to the RBC dominate. Intrinsic effects may include problems with RBC proteins or oxidative stress handling, whereas external factors include immune attack and microvascular angiopathies (RBCs are mechanically damaged in circulation). Intrinsic causes
Hereditary (inherited) hemolytic anemia can be due to :

Defects of red blood cell membrane production (as in hereditary spherocytosis and hereditary elliptocytosis). Defects in hemoglobin production (as in thalassemia, sickle-cell disease and congenital dyserythropoietic anemia). Defective red cell metabolism (as in glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency). Wilsons disease may infrequently present with hemolytic anemia without due to excessive inorganic copper in blood circulation, which destroys red blood cells (though the mechanism of hemolysis is still unclear). Extrinsic causes
Acquired hemolytic anemia may be caused by immune-mediated causes, drugs, and other miscellaneous causes.
Mitapivat, sold under the brand name Pyrukynd, is a medication used to treat hemolytic anemia. It is taken as the sulfate hydrate salt by mouth. Mitapivat is a pyruvate kinase activator.Mitapivat was approved for medical use in the United States in February 2022. Medical uses
Mitapivat is indicated for the treatment of hemolytic anemia in adults with pyruvate kinase deficiency. Pharmacology
Mechanism of action
Mitapivat binds to and activates pyruvate kinase, thereby enhancing glycolytic pathway activity, improving adenosine triphosphate (ATP) levels and reducing 2,3-diphosphoglycerate (2,3-DPG) levels. Mutations in pyruvate kinase cause deficiency in pyruvate kinase which prevents adequate red blood cell (RBC) glycolysis, leading to a buildup of the upstream glycolytic intermediate 2,3-DPG and deficiency in the pyruvate kinase product ATP. Society and culture
Legal status
On 15 September 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Pyrukynd, intended for the treatment of an inherited condition called pyruvate kinase deficiency. The applicant for this medicinal product is Agios Netherlands B.V.

Names
Mitapivat is the international nonproprietary name (INN). References
Further reading
Kung C, Hixon J, Kosinski PA, Cianchetta G, Histen G, Chen Y,  et al. (September 2017). "AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency". Blood. 130 (11): 1347–1356. doi:10.1182/blood-2016-11-753525. PMC 5609468. PMID 28760888. Rab MA, Van Oirschot BA, Kosinski PA, Hixon J, Johnson K, Chubukov V,  et al. (January 2021).