The first clinical description of the disorder Paroxysmal Nocturnal Haemoglobinuria (PNH) was in the early 18th century. According to Charles J Parker, writing in the American Society for Hematology Education Program Book in December 2008.
Many physicians, researchers and biomedical experts have worked hard to unravel the pathobiology of PNH and it was the observations of Dr Thomas Hale Ham (1905-1987) that Complement mediates the lysis of erythrocytes in acidified serum that led to the establishment of the ‘Ham Test’ that became the standard method of diagnosing this rare but debilitating disorder until the 1990s. In the mid 1960’s Wendell Rosse and John Dacie demonstrated that the erythrocyte populations from patients with PNH were mosaics and that lysis only occurred in the complement – sensitive population of red cells.
Flow cytometry then became the standard diagnostic test which depended on the understanding of the absence or partial deficiency of the glycosylphosphatidylinositol-anchored proteins on the cell surface. Taroh Kinoshita and colleagues demonstrated that PNH is the result of mutations in the PIGA gene. The PNH phenotype is determined by the PIGA genotype and PNH is an oligoclonal disorder.Did you know that the first clinical description of the group of diseases we now call thalassaemia was made by the American paediatrician Thomas Cooley in 1925 in a single page of the Transactions of the American Pediatric Society?1 Cooley’s (1871-1945) anaemia, as it was called, described a series of cases of splenomegaly in children with anaemia and peculiar bone changes.
The first clinical description of the disorder Paroxysmal Nocturnal Haemoglobinuria (PNH) was in the early 18th century. According to Charles J Parker, writing in the American Society for Hematology Education Program Book in December 2008.
Many physicians, researchers and biomedical experts have worked hard to unravel the pathobiology of PNH and it was the observations of Dr Thomas Hale Ham (1905-1987) that Complement mediates the lysis of erythrocytes in acidified serum that led to the establishment of the ‘Ham Test’ that became the standard method of diagnosing this rare but debilitating disorder until the 1990s. In the mid 1960’s Wendell Rosse and John Dacie demonstrated that the erythrocyte populations from patients with PNH were mosaics and that lysis only occurred in the complement – sensitive population of red cells.
Flow cytometry then became the standard diagnostic test which depended on the understanding of the absence or partial deficiency of the glycosylphosphatidylinositol-anchored proteins on the cell surface. Taroh Kinoshita and colleagues demonstrated that PNH is the result of mutations in the PIGA gene. The PNH phenotype is determined by the PIGA genotype and PNH is an oligoclonal disorder.
From the patient’s perspective it was the development by Hillmen and colleagues of the use of a known drug Eculizumab which binds to C5 was a major breakthrough.
In spite of these major scientific and clinical advances the sad fact is that in many instances clinicians are unable to differentiate between haematuria and haemoglobinuria (the dip-stick will not differentiate), thus subjecting patients to unnecessary investigations. A simple microscopic examination of the urine will of course suffice. PNH is an excellent example of the phrase: ‘From the bedside to bench’.
Read more:
Parker CJ, Bessler M, Brodsky R A, Hillmen P. Pages: 92-123, American Society of Hematology Education Program Book, Dec 2008