Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point-of-care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors and editors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

Choose from the list below to learn more about subscriptions for a:


Subscribers log in here


Xerocytosis

INTRODUCTION

Xerocytosis (also called dessicocytosis) is defined by the presence in the peripheral smear of hyperchromic erythrocytes (picture 1). The hyperchromia (and elevated mean cell hemoglobin concentration) are indicative of marked dehydration of the red cells [1].

Most of these syndromes are rare hereditary disorders, which involve unidentified abnormalities in the mechanisms controlling cell water and cation content [2]. However, a variable percentage of dehydrated cells may be present in several other hematologic disorders, such as sickle cell disease and hemoglobin C disease. These will be described here.

PATHOPHYSIOLOGY

Since the red cell is freely permeable to water, dehydrated cells require the loss of cell solutes, which then induce osmotic water loss. (See "Control of red blood cell hydration".) Xerocytosis is characterized by a reduction of cell content of potassium, the main intracellular cation. This may be associated with a slight increase in cell sodium content, but the total cation content of the red cell is significantly lower than in normal controls.

The dehydrated cells are more resistant to lysis when incubated in hypotonic solutions. This decrease in osmotic fragility is due to the small baseline cell size. On the other hand, xerocytes exhibit a characteristic increase in cell rigidity and reduction in cell deformability. These changes are thought to play an important role in the hemolysis resulting from premature destruction of xerocytes. In vitro, these membrane deformability changes can be reversed by rehydrating xerocytes and decreasing the mean cell hemoglobin concentration (MCHC) to normal values [3].

Syndromes with hereditary xerocytosis cannot readily be distinguished from hereditary stomatocytosis. (See "Stomatocytosis".) Several intermediate forms of disease exist between the classic overhydrated stomatocytosis (hydrocytosis) and classic xerocytosis.

           

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Mar 2014. | This topic last updated: Jan 15, 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. Gallagher PG, Forget BG, Lux SE. Disorders of the erythrocyte membrane. In: Hematology of Infancy and Childhood, Nathan DG, Orkin SH, Ginsburg D, Look TA (Eds), WB Saunders, Philadelphia 2003. p.560.
  2. Stewart GW. The hereditary stomatocytosis and allied conditions: inherited disorders Na and K transport. In: Red cell membrane transport in health and disease, Bernhardt I, Ellory JC (Eds), Springer Verlag, Berlin 2003. p.511.
  3. Clark MR, Mohandas N, Caggiano V, Shohet SB. Effects of abnormal cation transport on deformability of desiccytes. J Supramol Struct 1978; 8:521.
  4. Clark MR, Shohet SB, Gottfried EL. Hereditary hemolytic disease with increased red blood cell phosphatidylcholine and dehydration: one, two, or many disorders? Am J Hematol 1993; 42:25.
  5. Entezami M, Becker R, Menssen HD, et al. Xerocytosis with concomitant intrauterine ascites: first description and therapeutic approach. Blood 1996; 87:5392.
  6. Vicente-Gutiérrez MP, Castelló-Almazán I, Salvía-Roiges MD, et al. Nonimmune hydrops fetalis due to congenital xerocytosis. J Perinatol 2005; 25:63.
  7. Ogburn PL Jr, Ramin KD, Danilenko-Dixon D, et al. In utero erythrocyte transfusion for fetal xerocytosis associated with severe anemia and non-immune hydrops fetalis. Am J Obstet Gynecol 2001; 185:238.
  8. Wiley JS. Inherited red cell dehydration: a hemolytic syndrome in search of a name. Pathology 1984; 16:115.
  9. Platt OS, Lux SE, Nathan DG. Exercise-induced hemolysis in xerocytosis. Erythrocyte dehydration and shear sensitivity. J Clin Invest 1981; 68:631.
  10. Jokinen CH, Swaim WR, Nuttall FQ. A case of hereditary xerocytosis diagnosed as a result of suspected hypoglycemia and observed low glycohemoglobin. J Lab Clin Med 2004; 144:27.
  11. Glader BE, Fortier N, Albala MM, Nathan DG. Congenital hemolytic anemia associated with dehydrated erythrocytes and increased potassium loss. N Engl J Med 1974; 291:491.
  12. Fairbanks G, Dino JE, Snyder LM. Passive cation transport in hereditary xerocytosis. In: Erythrocyte Membranes 3: Recent clinical and experimental advances, Alan R Liss, New York 1984. p.205.
  13. Carella M, Stewart G, Ajetunmobi JF, et al. Genomewide search for dehydrated hereditary stomatocytosis (hereditary xerocytosis): mapping of locus to chromosome 16 (16q23-qter). Am J Hum Genet 1998; 63:810.
  14. Houston BL, Zelinski T, Israels SJ, et al. Refinement of the hereditary xerocytosis locus on chromosome 16q in a large Canadian kindred. Blood Cells Mol Dis 2011; 47:226.
  15. Iolascon A, Stewart GW, Ajetunmobi JF, et al. Familial pseudohyperkalemia maps to the same locus as dehydrated hereditary stomatocytosis (hereditary xerocytosis). Blood 1999; 93:3120.
  16. Zarychanski R, Schulz VP, Houston BL, et al. Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis. Blood 2012; 120:1908.
  17. Faucherre A, Kissa K, Nargeot J, et al. Piezo1 plays a role in erythrocyte volume homeostasis. Haematologica 2014; 99:70.
  18. Vives Corrons JL, Besson I, Aymerich M, et al. Hereditary xerocytosis: a report of six unrelated Spanish families with leaky red cell syndrome and increased heat stability of the erythrocyte membrane. Br J Haematol 1995; 90:817.
  19. Paterakis GS, Laoutaris NP, Alexia SV, et al. The effect of red cell shape on the measurement of red cell volume. A proposed method for the comparative assessment of this effect among various haematology analysers. Clin Lab Haematol 1994; 16:235.
  20. Grootenboer S, Schischmanoff PO, Cynober T, et al. A genetic syndrome associating dehydrated hereditary stomatocytosis, pseudohyperkalaemia and perinatal oedema. Br J Haematol 1998; 103:383.
  21. Grootenboer S, Schischmanoff PO, Laurendeau I, et al. Pleiotropic syndrome of dehydrated hereditary stomatocytosis, pseudohyperkalemia, and perinatal edema maps to 16q23-q24. Blood 2000; 96:2599.
  22. Innes DS, Sinard JH, Gilligan DM, et al. Exclusion of the stomatin, alpha-adducin and beta-adducin loci in a large kindred with dehydrated hereditary stomatocytosis. Am J Hematol 1999; 60:72.
  23. Gallagher PG, Smith BD. Dehydrated hereditary stomatocytosis is not linked to the hlK1 locus, a Gardos channel candidate, on chromosome 19q13.2. Blood 1999; 93:2134.
  24. Bruce LJ. Hereditary stomatocytosis and cation-leaky red cells--recent developments. Blood Cells Mol Dis 2009; 42:216.
  25. Miller DR, Rickles FR, Lichtman MA, et al. A new variant of hereditary hemolytic anemia with stomatocytosis and erythrocyte cation abnormality. Blood 1971; 38:184.
  26. Chailley B, Feo C, Garay R, et al. Evidence for imbalanced furosemide-sensitive Na+, K+ cotransport in hereditary stomatocytosis. Scand J Haematol 1981; 27:365.
  27. Basu AP, Carey P, Cynober T, et al. Dehydrated hereditary stomatocytosis with transient perinatal ascites. Arch Dis Child Fetal Neonatal Ed 2003; 88:F438.
  28. Grootenboer-Mignot S, Crétien A, Laurendeau I, et al. Sub-lethal hydrops as a manifestation of dehydrated hereditary stomatocytosis in two consecutive pregnancies. Prenat Diagn 2003; 23:380.
  29. Stewart GW, Amess JA, Eber SW, et al. Thrombo-embolic disease after splenectomy for hereditary stomatocytosis. Br J Haematol 1996; 93:303.
  30. Jaïs X, Till SJ, Cynober T, et al. An extreme consequence of splenectomy in dehydrated hereditary stomatocytosis: gradual thrombo-embolic pulmonary hypertension and lung-heart transplantation. Hemoglobin 2003; 27:139.
  31. Syfuss PY, Ciupea A, Brahimi S, et al. Mild dehydrated hereditary stomatocytosis revealed by marked hepatosiderosis. Clin Lab Haematol 2006; 28:270.
  32. Jaffé ER, Gottfried EL. Hereditary nonspherocytic hemolytic disease associated with an altered phospholipid composition of the erythrocytes. J Clin Invest 1968; 47:1375.
  33. Wiley JS, Ellory JC, Shuman MA, et al. Characteristics of the membrane defect in the hereditary stomatocytosis syndrome. Blood 1975; 46:337.
  34. Shohet SB, Nathan DG, Livermore BM, et al. Hereditary hemolytic anemia associated with abnormal membrane lipid. II. Ion permeability and transport abnormalities. Blood 1973; 42:1.
  35. Shojania AM, Godin DV, Frohlich J. Hereditary high phosphatidylcholine hemolytic anemia: report of a new family and review of the literature. Clin Invest Med 1990; 13:313.
  36. Clark MR, Morrison CE, Shohet SB. Monovalent cation transport in irreversibly sickled cells. J Clin Invest 1978; 62:329.
  37. Bertles JF, Milner PF. Irreversibly sickled erythrocytes: a consequence of the heterogeneous distribution of hemoglobin types in sickle-cell anemia. J Clin Invest 1968; 47:1731.
  38. Billett HH, Kim K, Fabry ME, Nagel RL. The percentage of dense red cells does not predict incidence of sickle cell painful crisis. Blood 1986; 68:301.
  39. Serjeant GR, Serjeant BE, Milner PF. The irreversibly sickled cell; a determinant of haemolysis in sickle cell anaemia. Br J Haematol 1969; 17:527.
  40. Kaul DK, Chen D, Zhan J. Adhesion of sickle cells to vascular endothelium is critically dependent on changes in density and shape of the cells. Blood 1994; 83:3006.
  41. Kaul DK, Fabry ME, Nagel RL. Vaso-occlusion by sickle cells: evidence for selective trapping of dense red cells. Blood 1986; 68:1162.
  42. Ballas SK, Smith ED. Red blood cell changes during the evolution of the sickle cell painful crisis. Blood 1992; 79:2154.
  43. Lawrence C, Fabry ME, Nagel RL. Red cell distribution width parallels dense red cell disappearance during painful crises in sickle cell anemia. J Lab Clin Med 1985; 105:706.
  44. Fabry ME, Mears JG, Patel P, et al. Dense cells in sickle cell anemia: the effects of gene interaction. Blood 1984; 64:1042.
  45. Horiuchi K, Stephens MJ, Adachi K, et al. Image analysis studies of the degree of irreversible deformation of sickle cells in relation to cell density and Hb F level. Br J Haematol 1993; 85:356.
  46. Franco RS, Yasin Z, Lohmann JM, et al. The survival characteristics of dense sickle cells. Blood 2000; 96:3610.
  47. Gibson JS, Speake PF, Ellory JC. Differential oxygen sensitivity of the K+-Cl- cotransporter in normal and sickle human red blood cells. J Physiol 1998; 511 ( Pt 1):225.
  48. Brugnara C, de Franceschi L, Alper SL. Inhibition of Ca(2+)-dependent K+ transport and cell dehydration in sickle erythrocytes by clotrimazole and other imidazole derivatives. J Clin Invest 1993; 92:520.
  49. Olivieri O, Vitoux D, Galacteros F, et al. Hemoglobin variants and activity of the (K+Cl-) cotransport system in human erythrocytes. Blood 1992; 79:793.
  50. Brugnara C, Kopin AS, Bunn HF, Tosteson DC. Regulation of cation content and cell volume in hemoglobin erythrocytes from patients with homozygous hemoglobin C disease. J Clin Invest 1985; 75:1608.
  51. Brugnara C. Characteristics of the volume- and chloride-dependent K transport in human erythrocytes homozygous for hemoglobin C. J Membr Biol 1989; 111:69.
  52. Fabry ME, Romero JR, Suzuka SM, et al. Hemoglobin C in transgenic mice with full mouse globin knockouts [abstract]. Blood 1998; 92:330a.
  53. Romero JR, Suzuka SM, Nagel RL, Fabry ME. Expression of HbC and HbS, but not HbA, results in activation of K-Cl cotransport activity in transgenic mouse red cells. Blood 2004; 103:2384.
  54. Eyssette-Guerreau S, Bader-Meunier B, Garcon L, et al. Infantile pyknocytosis: a cause of haemolytic anaemia of the newborn. Br J Haematol 2006; 133:439.