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Von Willebrand's disease in the year 2003: towards the complete identification of gene defects for correct diagnosis and treatment.
Haematologica 2003; 88(1):94-108H

Abstract

BACKGROUND

Von Willebrand's disease (VWD) is an autosomally inherited bleeding disorder caused by a deficiency or abnormality of von Willebrand factor (VWF). VWF is a multimeric adhesive protein which plays an important role in primary hemostasis by promoting platelet adhesion to the subendothelium at sites of vascular injury and platelet-platelet interactions in high shear-rate conditions. It is also the carrier of factor VIII (FVIII), thus indirectly contributing to the coagulation process. VWD has a prevalence of about 1% in the general population, but the figure for clinically relevant cases is lower (about 100/million inhabitants). Bleeding manifestations are heterogeneous: mucosal bleeding is typical of all VWD cases but hemarthrosis and hematomas may also be present when FVIII levels are low.

INFORMATION SOURCES

Most cases appear to have a partial quantitative deficiency of VWF (type 1 VWD) with variable bleeding tendency, whereas qualitative variants (type 2 VWD), due to a dysfunctional VWF, are clinically more homogeneous. Type 3 VWD is rare and the patients have a moderate to severe bleeding diathesis because of the virtual absence of VWF, and a recessive pattern of inheritance. The diagnosis of VWD, especially type I, may be difficult, because the laboratory phenotype is highly heterogeneous and is confounded by the fact that factors outside the VWF gene (e.g., blood group) influence VWF levels. An array of tests is usually required to characterize the VWD types of the disorder and establish the best treatment modality.

CONCLUSIONS

The aim of treatment is to correct the dual defect of hemostasis, i.e. abnormal coagulation expressed by low levels of FVIII and abnormal platelet adhesion expressed by the prolonged bleeding time (BT). Desmopressin (DDAVP) is the treatment of choice for type 1 VWD because it corrects the FVIII/VWF levels and the prolonged BT in the majority of cases. In type 3 and in severe forms of type 1 and 2 VWD, DDAVP is not effective and for these patients plasma virally-inactivated concentrates containing FVIII and VWF are the mainstay of treatment. These concentrates are clinically effective and safe, although they do not always correct the BT.

Authors+Show Affiliations

Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital and University of Milan, Italy.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

12551832

Citation

Castaman, Giancarlo, et al. "Von Willebrand's Disease in the Year 2003: Towards the Complete Identification of Gene Defects for Correct Diagnosis and Treatment." Haematologica, vol. 88, no. 1, 2003, pp. 94-108.
Castaman G, Federici AB, Rodeghiero F, et al. Von Willebrand's disease in the year 2003: towards the complete identification of gene defects for correct diagnosis and treatment. Haematologica. 2003;88(1):94-108.
Castaman, G., Federici, A. B., Rodeghiero, F., & Mannucci, P. M. (2003). Von Willebrand's disease in the year 2003: towards the complete identification of gene defects for correct diagnosis and treatment. Haematologica, 88(1), pp. 94-108.
Castaman G, et al. Von Willebrand's Disease in the Year 2003: Towards the Complete Identification of Gene Defects for Correct Diagnosis and Treatment. Haematologica. 2003;88(1):94-108. PubMed PMID: 12551832.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Von Willebrand's disease in the year 2003: towards the complete identification of gene defects for correct diagnosis and treatment. AU - Castaman,Giancarlo, AU - Federici,Augusto B, AU - Rodeghiero,Francesco, AU - Mannucci,Pier Mannuccio, PY - 2003/1/29/pubmed PY - 2003/6/12/medline PY - 2003/1/29/entrez SP - 94 EP - 108 JF - Haematologica JO - Haematologica VL - 88 IS - 1 N2 - BACKGROUND: Von Willebrand's disease (VWD) is an autosomally inherited bleeding disorder caused by a deficiency or abnormality of von Willebrand factor (VWF). VWF is a multimeric adhesive protein which plays an important role in primary hemostasis by promoting platelet adhesion to the subendothelium at sites of vascular injury and platelet-platelet interactions in high shear-rate conditions. It is also the carrier of factor VIII (FVIII), thus indirectly contributing to the coagulation process. VWD has a prevalence of about 1% in the general population, but the figure for clinically relevant cases is lower (about 100/million inhabitants). Bleeding manifestations are heterogeneous: mucosal bleeding is typical of all VWD cases but hemarthrosis and hematomas may also be present when FVIII levels are low. INFORMATION SOURCES: Most cases appear to have a partial quantitative deficiency of VWF (type 1 VWD) with variable bleeding tendency, whereas qualitative variants (type 2 VWD), due to a dysfunctional VWF, are clinically more homogeneous. Type 3 VWD is rare and the patients have a moderate to severe bleeding diathesis because of the virtual absence of VWF, and a recessive pattern of inheritance. The diagnosis of VWD, especially type I, may be difficult, because the laboratory phenotype is highly heterogeneous and is confounded by the fact that factors outside the VWF gene (e.g., blood group) influence VWF levels. An array of tests is usually required to characterize the VWD types of the disorder and establish the best treatment modality. CONCLUSIONS: The aim of treatment is to correct the dual defect of hemostasis, i.e. abnormal coagulation expressed by low levels of FVIII and abnormal platelet adhesion expressed by the prolonged bleeding time (BT). Desmopressin (DDAVP) is the treatment of choice for type 1 VWD because it corrects the FVIII/VWF levels and the prolonged BT in the majority of cases. In type 3 and in severe forms of type 1 and 2 VWD, DDAVP is not effective and for these patients plasma virally-inactivated concentrates containing FVIII and VWF are the mainstay of treatment. These concentrates are clinically effective and safe, although they do not always correct the BT. SN - 0390-6078 UR - https://www.unboundmedicine.com/medline/citation/12551832/Von_Willebrand's_disease_in_the_year_2003:_towards_the_complete_identification_of_gene_defects_for_correct_diagnosis_and_treatment_ L2 - http://www.haematologica.org/cgi/pmidlookup?view=long&pmid=12551832 DB - PRIME DP - Unbound Medicine ER -