Insights into the Natural History of Paroxysmal Nocturnal Hemoglobinuria (PNH): Analysis of the Presenting Clinical, Haematological and Flow Cytometric Features of 705 Patients Leads to Improved Classification and Prediction of Clinical Course

Original Publication Date: 
Friday, January 31, 2014

Note: This review is based upon a presentation at the 2013 American Society of Hematology (ASH) Annual Meeting, December 7-10 in New Orleans, Louisiana.The full abstract may be reviewed on the ASH Annual Meeting Web site. Search by entering the title in the search box. The abstract number is referenced to access the full report.

Abstract # 3718

Stephen John Richards, Ph.D., Richard Kelly, M.D., Anita Hill, M.B.Ch.B., Ph.D., Anita Dickinson, M.Sc., Fiona Cullen, M.Sc., Jane Shingles, Ph.D., Matthew Cullen, M.Sc., and Peter Hillmen, M.B.Ch.B., Ph.D.

A group of researchers from Great Britain have collected blood cells from 705 patients (median age 45 years; slightly more males than females) with paroxysmal nocturnal hemoglobinuria (PNH) over the past 22 years.

This goal of this study was to use these specimens to better understand the natural history of PNH and develop an objective way to classify PNH. The most common conditions at diagnosis among the patients with PNH were aplastic anemia (58% of patients) and hemolytic anemia (36% of patients).

Key findings

  • At diagnosis, 61% of males and 47% of females had pancytopenia (low counts of red blood cells, white blood cells, and platelets).
  • Although more males (98%) than females (88%) had low red blood cell counts and hemoglobin concentrations, these differences were not statistically significant.
  • Patients with aplastic anemia had significantly lower white blood cell and platelet counts, but hemoglobin concentrations and red cell counts did not vary by disease type.
  • Only 10 of 154 patients with aplastic anemia developed hemolysis (premature destruction of red blood cells), and all of these patients had PNH clones (abnormal copies of cells) that were larger than 5%.
  • In 44% of patients with hemolysis when they entered the study, PNH white blood cell clones continued to grow. 

Conclusions

  • Pancytopenia is common in patients with PNH who have aplastic anemia or hemolytic anemia, and the two groups have similar levels of anemia.
  • Anemia seems to be less severe and female than male patients with PNH who have aplastic anemia or hemolytic anemia.
  • Bone marrow failure seems to be the main clinical characteristic of PNH in more than 95% of patients.
  • A PNH classification system based on the degree of aplasia (decreased or no production of blood cells in the bone marrow), hemolysis with or without thrombosis (clots in blood vessels), and PNH clone size could be a powerful predictor of disease course.
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