SÁBADO, 26 NOVEMBRO

Mesa Redonda – Anemia e Coagulopatias

Anemia and Von Willebrand Disease: From bench to bedside

14:30 – 15:00

Moderadores

Manuel Campos e Miguel Galvão

Palestrante

Fernanda Leite

von Willebrand disease (VWD) is considered the most common inherited bleeding disorder, with a variable prevalence depending on diagnosis setting: in population-based studies as 0.6% to 1.3% and in specialized centers to which symptomatic patients with VWD are referred of 0.005%-0.01%1.This fact may be explained since symptoms are often mild and a significant majority of patients remain undiagnosed.

Clinically, the leading symptom in VWD is bleeding, chiefly of mucosal origin, e.g. epistaxis, gingival or gastrointestinal bleeding and menorrhagia. Among women, menorrhagia is the bleeding most common occurring in 62% of the cases2. Menorrhagia is associated with significant morbidity including symptomatic iron deficiency anemia, psychological stress, reduced quality of life and increased health care costs3.Anemia may result from bleeding episodes due to quantitative and/or qualitative defects of von Willebrand factor (VWF), a multimeric glycoprotein synthesized by endothelial cells and megakaryocytes that mediates platelet adhesion/aggregation and stabilizes factor VIII (FVIII) in the circulation. In the most serious forms of VWD, characterized by reduced levels of VWF activity measured as ristocetin cofactor (VWF:RCo<10 U dL-1) and of FVIII:C (<20 UdL-1), joint and muscle bleeding resembling that seen in mild or moderate hemophilia A may also be observed. The complex structure of the protein and the wide range of plasma levels encountered in the population make laboratory assessment and diagnosis a challenging issue. A plasma VWF level of 30 IU/dL has been suggested as a threshold to distinguish patients with a bleeding tendency from healthy subjects with low-borderline plasma levels of VWF4.

The International Society on Thrombosis and Haemostasis Scientific and Standardization Committee on VWF adopted a simplified classification of VWD5. A more complex genetic based taxonomy does not impact on standardized bleeding assessment tool5. The standard clinical assessment tools score the occurrence of symptoms and their severity as part of VWD diagnosis6,7, determine if there is more bleeding than in normal population, justifying diagnosis of a bleeding disorder, and quantify the extent of symptoms, indicating situations requiring clinical intervention.

The goal of treatment is to correct abnormal platelet adhesion due to low or defective VWF and abnormal intrinsic coagulation due to low FVIII. Strategies for treatment vary by type and severity. The main therapeutic approaches available include desmopressin acetate (l-deamino-8-D-arginine vasopressin, DDAVP), which releases endogenous VWF from endothelial cells, use of antifibrinolytics and exogenous VWF contained in VWF/FVIII plasma-derived concentrates to replace the VWF protein that is missing and/or abnormal.

Based on clinical cases, the diagnosis and management of VWD will be discussed in specific populations including children and pregnant addressing regular prophylaxis vs on demand treatment.

 

References

[1] Federici AB, Bucciarelli P, Castaman G, et al. The bleeding score predicts clinical outcomes and replacement therapy in adults with von Willebrand disease. Blood 2014; 123:4037-4044.

[2] Ragni MV, Machin N, Malec LM, et al. Von Willebrand factor for menorrhagia: a survey and literature review. Haemophilia 2016; 22:397-402.

[3] Kadir RA, Edlund M, von Mackensen S. The impact of menstrual disorders on quality of life in women with inherited bleeding disorders. Haemophilia 2010; 16:832–839.

[4] Nichols WL, Hultin MB, James AH, et al. von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA). Haemophilia 2008; 14:171-232.

[5] Laffan MA, Lester W, O’Donnell JS, et al. The diagnosis and management of von Willebrand disease: a United Kingdom Haemophilia Centre Doctors Organization guideline approved by the British Committee for Standards in Haematology. Br J Haematol 2014; 167:453-465.

[6] Rodeghiero F, Tosetto A, Abshire T, et al. on behalf of ISTH/SSC joint VWF and Perinatal/Pediatric Hemostasis Subcommittees Working Group. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost 2010; 8:2063-2065.

[7] Rydz N, James PD. The evolution andvalue of bleeding assessment tools. J Thromb Haemost 2012; 10: 2223–2229.

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