Clinical and molecular predictors of thrombocytopenia and risk of bleeding in patients with von Willebrand disease type 2B: a cohort study of 67 patients

Federici, Augusto B.; Mannucci, Pier Mannuccio; Castaman, Giancarlo; Baronciani, Luciano; Bucciarelli, Paolo; Canciani, Maria Teresa; Pecci, Alessandro; Lenting, Peter J.; Groot, Philip G. de

doi:10.1182/blood-2008-04-152280

Cited by 231 publications

(324 citation statements)

References 39 publications

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“…The pathogenic change in the A1 domain in type 2B VWD causes VWF to more readily bind platelets, acting as a gain of function mutation, and resulting in increased uptake and destruction of the VWF‐platelet complex 12. In some cases the destruction of platelets in type 2B VWD can cause thrombocytopenia 13. The sequestration of the VWF‐platelet complexes also results in a loss of HMWM.…”

Section: Classification Of Von Willebrand Diseasementioning

confidence: 99%

Current issues in diagnosis and treatment of von Willebrand disease

Keesler

Flood

2018

Research and Practice in Thrombosis and Haemostasis

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Essentials Classification of VWD includes quantitative (types 1 and 3) and qualitative (type 2) variants.New assays of VWF‐platelet binding may improve accuracy in diagnosis.Collagen binding represents an additional function of VWF not measured by current tests.Treatment options for VWD include desmopressin, plasma‐derived, and recombinant VWF. Clinically, von Willebrand disease (VWD) presents as mucosal bleeding caused by a decreased quantity or quality of von Willebrand factor (VWF). Diagnosis of VWD requires careful consideration of patient specific factors, bleeding symptoms, and laboratory results. Patients with borderline low VWF levels remain challenging, given that low VWF is not necessarily a guarantee of bleeding, but is present in many patients with symptoms, and treatment of low VWF may improve bleeding. Laboratory diagnosis of VWD is complex and no single test can determine the presence or absence of functional VWF. Historically, VWF binding to platelet GPIbα was measured by the ristocetin cofactor assay (VWF:RCo); a new assay using platelet GPIbα in the absence of ristocetin (VWF:GPIbM) is gradually replacing the VWF:RCo due to improved accuracy in diagnosis. VWF binding to collagen is a separate function, and requires specific testing to determine if a collagen binding defect is present. Regardless of these laboratory complexities, clinicians can empirically treat VWD to alleviate bleeding symptoms by raising VWF levels through desmopressin or VWF concentrate. Recombinant VWF is now available, but clinicians may need to add an initial dose of FVIII when treating emergency bleeds.

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Section: Classification Of Von Willebrand Diseasementioning

confidence: 99%

Current issues in diagnosis and treatment of von Willebrand disease

Keesler

Flood

2018

Research and Practice in Thrombosis and Haemostasis

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“…15 Mild-to-moderate thrombocytopenia is present in about 40% of patients because of in vivo platelet clumping. 16 Thrombocytopenia may further aggravate the bleeding risk in these patients. 16 Type 2B should also be differentiated from an even rarer disorder, platelet-type VWD, in which the responsible mutation directly affects the GpIb gene, inducing a gain-of-function with increased affinity for normal plasma VWF.…”

Section: Type 2 Vwd: a Heterogeneous Disease Subgroupmentioning

confidence: 99%

“…16 Thrombocytopenia may further aggravate the bleeding risk in these patients. 16 Type 2B should also be differentiated from an even rarer disorder, platelet-type VWD, in which the responsible mutation directly affects the GpIb gene, inducing a gain-of-function with increased affinity for normal plasma VWF. Molecular analysis of the GpIb gene is required for correct diagnosis.…”

Section: Type 2 Vwd: a Heterogeneous Disease Subgroupmentioning

confidence: 99%

How I treat type 2 variant forms of von Willebrand disease

Tosetto

Castaman²

2015

Blood

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Type 2 von Willebrand disease (VWD) includes a wide range of qualitative abnormalities of von Willebrand factor structure and function resulting in a variable bleeding tendency. According to the current classification, 4 different subtypes can be identified, each with distinctive phenotypic and therapeutic characteristics. Current available laboratory methods allow a straightforward approach to VWD subtyping, and although the precise molecular characterization remains complex, it is not required for appropriate treatment of the vast majority of cases. Desmopressin can be useful only in a few type 2 cases compared with patients with actual quantitative deficiency (type 1), most often in variants with a nearly normal multimeric pattern (type 2M). However, since no laboratory test accurately predicts response to desmopressin, a trial test should always be performed in all type 2 VWD patients, with the exception of type 2B ones. Replacement therapy with plasma-derived von Willebrand factor-factor VIII concentrates represents the safe mainstay of treatment of all patients, particularly those not responding to desmopressin or requiring a sustained hemostatic correction because of major surgery or bleeding. A significant patient bleeding history correlates with increased bleeding risk and should be considered in tailoring the optimal antihemorrhagic prophylaxis in the individual patient.

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“…27 In type 2B, DDAVP is contraindicated because of the transient appearance or aggravation of thrombocytopenia leading to an increased risk of bleeding, although a few patients have clinically benefited from its use. 30,31 Patients with type 3 VWD are unresponsive to DDAVP. Tachycardia, headache and flushing are frequent, mild adverse-effects of DDAVP and can often be attenuated by slowing the rate of infusion or by using the subcutaneous route.…”

Section: Treatmentmentioning

confidence: 99%