Proteolysis of von Willebrand factor in therapeutic plasma concentrates

P. M. Mannucci, A. Lattuada, Z. M. Ruggeri

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Therapeutic plasma concentrates containing von Willebrand factor (vWF) lack the largest, most hemostatically active multimers. To evaluate whether this abnormality results from proteolysis during manufacturing, we have analyzed the subunit structure of vWF in several commercial products and found a marked reduction in the relative content of intact 225-kD subunit, paralleled by an increase in the proteolytic fragments normally present in plasma, particularly that of 176 kD. There was no heightened vWF fragmentation in blood-bank cryoprecipitate prepared from platelet-poor, single-donor plasma; in contrast, there was a marked degree of fragmentation in cryoprecipitate prepared from pooled plasmapheresis plasma representing the starting fraction for the production of commercial concentrates. In cryoprecipitate prepared experimentally from plasma containing varying numbers of platelets, the degradation of vWF was proportional to the platelet count, but was greatly diminished by adding protease inhibitors to the plasma. On the basis of these findings, we postulate that the loss of the largest vWF multimers in commercial products results from the use of poorly centrifuged plasmapheresis plasma containing an excessive number of residual platelets and leukocytes. These cells, lysing when plasma is frozen and thawed for the preparation of cryoprecipitate, may liberate proteolytic enzymes that cleave the vWF subunit and contribute to the degradation of the largest multimers. Our results should help devise new approaches for the preparation of more effective concentrates for the treatment of von Willebrand disease.

Original languageEnglish
Pages (from-to)3018-3027
Number of pages10
JournalBlood
Volume83
Issue number10
Publication statusPublished - May 15 1994

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Proteolysis
von Willebrand Factor
Plasmas
Platelets
Platelet Count
Plasmapheresis
Therapeutics
Degradation
von Willebrand Diseases
Blood Banks
Protease Inhibitors
Leukocyte Count
Blood
Peptide Hydrolases
Blood Platelets

ASJC Scopus subject areas

  • Hematology

Cite this

Mannucci, P. M., Lattuada, A., & Ruggeri, Z. M. (1994). Proteolysis of von Willebrand factor in therapeutic plasma concentrates. Blood, 83(10), 3018-3027.

Proteolysis of von Willebrand factor in therapeutic plasma concentrates. / Mannucci, P. M.; Lattuada, A.; Ruggeri, Z. M.

In: Blood, Vol. 83, No. 10, 15.05.1994, p. 3018-3027.

Research output: Contribution to journalArticle

Mannucci, PM, Lattuada, A & Ruggeri, ZM 1994, 'Proteolysis of von Willebrand factor in therapeutic plasma concentrates', Blood, vol. 83, no. 10, pp. 3018-3027.
Mannucci PM, Lattuada A, Ruggeri ZM. Proteolysis of von Willebrand factor in therapeutic plasma concentrates. Blood. 1994 May 15;83(10):3018-3027.
Mannucci, P. M. ; Lattuada, A. ; Ruggeri, Z. M. / Proteolysis of von Willebrand factor in therapeutic plasma concentrates. In: Blood. 1994 ; Vol. 83, No. 10. pp. 3018-3027.
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