1-desamino-8-arginine-vasopressin corrects the hemostatic defects in type 2B von Willebrand's disease

McKeown, Laurie P.; Connaghan, G.; Wilson, Olga; Hansmann, Kristin; Merryman, Paula K.; Gralnick, Harvey R.

doi:10.1002/(sici)1096-8652(199602)51:2<158::aid-ajh11>3.0.co;2-e

Cited by 32 publications

(19 citation statements)

References 28 publications

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“…Desmopressin is usually contraindicated for use in VWD type 2B patients, but it has been used safely in several patients with a mildly reduced platelet count. 11,[23][24][25][26] In contrast, replacement therapy is preferred for VWD type 2B patients that manifest severe thrombocytopenia, eventually in combination with platelet transfusion. Alternatively, agents blocking VWF-platelet interactions may be used to correct desmopresininduced thrombocytopenia.…”

Section: Discussionmentioning

confidence: 99%

Accelerated uptake of VWF/platelet complexes in macrophages contributes to VWD type 2B–associated thrombocytopenia

Casari

et al. 2013

Blood

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Key Points• Adsorption of VWF type 2B mutants to platelets induces thrombocytopenia in VWD type 2B mice.• VWF/platelet complexes are phagocytosed by macrophages in liver and spleen.Von Willebrand disease (VWD) type 2B is characterized by mutations causing enhanced binding of von Willebrand factor (VWF) to platelets. Bleeding tendency is associated with heterogeneous clinical manifestations, including moderate to severe thrombocytopenia. The underlying mechanism of the thrombocytopenia has remained unclear. Here, a mouse model of VWD type 2B was used to investigate pathways contributing to thrombocytopenia. Immunohistochemical analysis of blood smears revealed that mutant VWF was exclusively detected on platelets of thrombocytopenic VWD type 2B mice, suggesting that thrombocytopenic VWD type 2B mice were elevated two-to threefold upon chemical macrophage depletion. Colocalization of platelets with CD68-positive Kupffer cells and CD168-positive marginal macrophages in liver and spleen, respectively, confirmed the involvement of macrophages in the removal of VWF/platelet complexes. Significantly more platelets were found in liver and spleen of VWD type 2B mice compared with control mice. Finally, platelet survival was significantly shorter in VWD type 2B mice compared with control mice, providing a rationale for lower platelet counts in VWD type 2B mice. In conclusion, our data indicate that VWF type 2B binds to platelets and that this is a signal for clearance by macrophages, which could contribute to the thrombocytopenia in patients with VWD type 2B. (Blood. 2013;122(16):2893-2902

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Section: Discussionmentioning

confidence: 99%

Accelerated uptake of VWF/platelet complexes in macrophages contributes to VWD type 2B–associated thrombocytopenia

Casari

et al. 2013

Blood

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“…23 Thrombocytopenia can easily develop in patients with type 2B VWD after desmopressin use, and this disease represents a classic contraindication to the use of desmopressin; however, some patients with type 2B VWD have had a therapeutic response to desmopressin without developing thrombotic complications. 24 Therefore, desmopressin should be used in patients with type 2B VWD only under the guidance of a haematologist.…”

Section: Adverse Effects Precautions and Contraindicationsmentioning

confidence: 99%

How do you treat bleeding disorders with desmopressin?

Özgönenel

Rajpurkar

Lusher

2007

Postgraduate Medical Journal

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Desmopressin is an analog of vasopressin that exerts a substantial haemostatic effect by inducing the release of von Willebrand factor from its storage sites in endothelial cells. It has proved useful in treating or preventing bleeding episodes in patients with von Willebrand disease, haemophilia A and platelet function defects. Its efficacy in achieving a satisfactory level of haemostasis has reduced the use of blood products to treat bleeding episodes. Clinicians need to become familiar with the use of this drug that has become a home medication for many patients with inherited bleeding disorders.

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“…The three patients with type 2B vWD were treated with CFC since DDAVP is generally contraindicated because of the risk of platelet aggregation and thrombocytopenia [18], but this remains controversial [19].…”

Section: Discussionmentioning

confidence: 99%

Audit of clinical management of von Willebrand disease during 1997 at a single institution and review of treatment patterns between 1980 and 1997

Nitu-Whalley¹,

Miners²,

Lee³

1999

Haemophilia

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In 1997 the UK Haemophilia Centre Directors Organization published the guidelines for diagnosis and management of von Willebrand disease (vWD). The guidelines stated that desmopressin (DDAVP) should be used in type 1 and type 2N vWD, that it might be useful in other types 2 vWD and that it is ineffective in type 3 vWD. If patients are unresponsive to DDAVP or if it is contraindicated, the treatment of choice is clotting factor concentrates (CFC). In the light of these guidelines, we audited our practice for 1997. Furthermore, we undertook a retrospective review of the changing patterns of treatment of vWD between 1980 and 1997. During 1997, 10 patients with vWD received DDAVP and another 30 patients were treated with CFC (a total of 1.2 million IU): Haemate P (Centeon, Germany) and/or 8Y (BPL, Elstree, UK). Few patients had clear contraindications to DDAVP, but several patients with type 1 and 2 vWD received CFC on the basis of age or reduced levels of von Willebrand factor - where DDAVP was considered suboptimal for adequate haemostasis. However, this assumption was made without a preliminary test dose to assess the response to DDAVP. The analysis of treatment of vWD for the past 17 years showed that cryoprecipitate was discontinued from use in the early 1990s and that both DDAVP and CFC usage has been on the increase. In conclusion, the audit illustrated a general good adherence to guidelines but it highlighted the need for a DDAVP test before using CFC.

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1-desamino-8-arginine-vasopressin corrects the hemostatic defects in type 2B von Willebrand's disease

Cited by 32 publications

References 28 publications

Accelerated uptake of VWF/platelet complexes in macrophages contributes to VWD type 2B–associated thrombocytopenia

Accelerated uptake of VWF/platelet complexes in macrophages contributes to VWD type 2B–associated thrombocytopenia

How do you treat bleeding disorders with desmopressin?

Audit of clinical management of von Willebrand disease during 1997 at a single institution and review of treatment patterns between 1980 and 1997

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