A 1 day old neonate presents with extreme jaundice at birth. A full blood count and chemistry profile are performed with the following results:
WBC 20.7 x 109/L, Hb 114 g/L, MCV 86.0 fL, MCH 28.5 pg and platelet count 243 x 109/L. Total bilirubin 403 µmol/L and conjugated bilirubin 283 µmol/L.
The blood film shows extreme poikilocytosis with micropoikilocytes, microspherocytes, triangular fragments, budding red cells and polychromasia. It is noted from the blood film, that the platelet count is falsely elevated and the MCV is very low for age. (The MCV range for a 1day old full term neonate is 101 – 117 fL). The extreme poikilocytosis is the major contributing factor to the very low MCV. A diagnosis of hereditary pyropoikilocytosis is made on the blood film.
Hereditary pyropoikilocytosis is an autosomal recessive disorder characterized by severe haemolytic anaemia with thermal instability of the red cells. It forms part of a group of haemolytic anaemias due to red cell membrane abnormalities. This group also includes hereditary elliptocytosis, Southeast Asian ovalocytosis and hereditary spherocytosis. Hereditary pyropoikilocytosis is found predominantly in Africans and African Americans but has also been seen in Caucasians and Arabs. The disease presents in the neonate with anaemia and jaundice and is diagnosed from the blood film that shows bizarre poikilocytes, micropoikilocytes, microspherocytes, triangular fragments and budding red cells. These red cell changes are caused by mechanical instability of the red cell skeleton due to defective binding of the spectrin chains. Erythrocyte spectrin maintains the cellular shape and provides structural support for the lipid bilayer of the red cell membrane. Disruption of the spectrin complex leads to disorders characterised by abnormally shaped red cells. Hereditary elliptocytosis is due to a gene mutation resulting in a qualitative spectrin abnormality. Hereditary pyropoikilocytosis co-inherits this qualitative spectrin abnormality as well as a second mutation that causes a quantitative spectrin deficiency. Thus hereditary elliptocytosis and hereditary pyropoikilocytosis are closely related disorders. Often one parent or a close relative of the child with hereditary pyropoikilocytosis will have hereditary elliptocytosis.
Thermal sensitivity and osmotic fragility tests may be performed to aid in the diagnosis of hereditary pyropoikilocytosis. In hereditary pyropoikilocytosis, the red cells demonstrate thermal autohaemolysis and increased osmotic fragility. The spectrin in normal red cells denatures at temperatures between 49ºC and 50ºC whereas in hereditary pyropoikilocytosis, the spectrin denatures at temperatures between 45ºC and 46ºC. Prolonged exposure at 37ºC will also induce fragmentation in hereditary pyropoikilocytosis.
The clinical course of hereditary pyropoikilocytosis is variable although the degree of haemolysis wanes with time. Splenectomy has been shown to improve the anaemia but has no effect on the abnormal red cell morphology.