Dear Peter,

since the patient was diagnosed with vFD type I, the treatment choice is systemic administration (intravenous infusion) of desmopressin (DDAVP) with concomitant administration of tranexamic acid, combined with local application of fibrin sealent.

Taking into account the mechanisms of desmopressin actions we could understand this recomendation.

DDAVP, a synthetic analogue of the antidiuretic hormone vasopressin, induces increase in plasma levels of vWF and FVIII three to five fold above the baseline level by exocytosis of these factors from the Weibel-Palade bodies (WPB) in the endothelial cells. In this ways, DDAVP promotes the platelet adhesion to the subendothelium and platelet-platelet interactions as well as the coagulation process. In addition, DDAVP causes a co-secretion of tissue plasminogen activator (t-PA) from WPB. These effects of DDAVP could be explained by a direct action on the endothelium via activation of endothelial vasopressin V2 receptor and by activating cyclic adenosine monophosphate (cAMP)- mediated signaling. Also, several putative mechanisms or mediators for the action of DDAVP other than vWF have been posulated. In this respect, after DDAVP administration the significant increase of the expression of the endothelial-derived P-selectin (another major constituent of WPB) or a tissue factor (TF) suggests a role of other endothelial mediators, with a possible involvement of monocyte-dependent mechanisms (platelets activation by increasing the expression of P-selectin ligand on their membrane). Additionally, the formation of microparticles and generation of procoagulant activity following DDAVP stimulation has been described. It has been suggested that the final effect of DDAVP on platelets involves the facilitation of glycoprotein (Gp)IIb-IIIa ligand interactions through modification of the cytosceleton focal adhesion protein VASP. This molecular mechanism modulates platelets binding to fibrinogen and vWF. DDAVP is supposed to induce a release of other WPB constituents such as interleukin (IL)-8, CD63 and endothelin-1.

Considerable interindividual variations in response to DDAVP may account for some of the controversies on hemostatic benefits of DDAVP. Thus, the ability of DDAVP to improve the platelet function is unpredictable, and a test dose of a remedy is recommended to establish the individual patterns of biological response and to predict clinical efficacy during bleeding/invasive procedures/surgery.

In the assessment of individual response to desmopressin several days prior to the intervention, the patient should be administered a test dose of 0.3μg/kg DDAVP diluted in 100mL of isotonic saline and infused for 30 minutes.

Checking the response to DDAVP: carry out the activities of vWF and FVIII before and one hour after test drug administration. Also, bleeding time and PFA-100 test could be used.

Prophylactic treatment with DDAVP

Prophylactic treatment with DDAVP should be administered approximately 1hour before the planned intervention: 0.3µg/kg DDAVP diluted in 100mL of isotonic saline and infused for 30-40minutes. Tranexamic acid in dose 10mg/kg diluted in 100mL of isotonic saline and infused for 20-30 minutes before intervention. Causion: don’t mix DDAVP and tranexamic acid in the same vial.

Local measures: prior to fibrin sealent application, my advice (good clinical experience in surgical practice) is to apply tranexamic acid (500mg diluted in 20mL of isotonic saline) directly on the wound (part of solution), followed by tampon with tranexamic acid (the rest of prepared solution) for 10 minutes. After this pretreatment apply fibrin sealent.

Post-intervention treatment with repeated doses of DDAVP 12-24 hours (next 1-2 days) after the procedure should be considered until progression of wound healing.

Best wishes

Dragica

Dear Peter,

I will prefer vWF containing Factor VIII(plasma derived)  than desmopressin prior to the procedure. I will avoid systemic antifibrinolytics. Topical application of antifibrinolytics can be applied. And of course, after the procedure would encourage to keep ice cubes at the site.

If CBC is normal it should be done under cover of FFP and desmopressin.

Dear Peter, 

perhaps this is of interest to you where they used  "recombinant factor VIII. Four teeth extraction procedures were executed twice. Before extraction, bolus recombinant factor VIII (50 IU/kg) was administered intravenously followed by continuous infusion (5-10 IU/kg per h) for approximately 48 h. The factor VIII:C level increased from about 1 to 20-32% 30 min after bolus infusion. During continuous infusion (10 IU/kg/h), factor VIII:C was maintained at more than 10%"

It was though type 3 von Willebrand disease. 

Article Successful use of recombinant factor VIII devoid of von Will...

Dear Peter,

since the patient was diagnosed with vFD type I, the treatment choice is systemic administration (intravenous infusion) of desmopressin (DDAVP) with concomitant administration of tranexamic acid, combined with local application of fibrin sealent.

Taking into account the mechanisms of desmopressin actions we could understand this recomendation.

DDAVP, a synthetic analogue of the antidiuretic hormone vasopressin, induces increase in plasma levels of vWF and FVIII three to five fold above the baseline level by exocytosis of these factors from the Weibel-Palade bodies (WPB) in the endothelial cells. In this ways, DDAVP promotes the platelet adhesion to the subendothelium and platelet-platelet interactions as well as the coagulation process. In addition, DDAVP causes a co-secretion of tissue plasminogen activator (t-PA) from WPB. These effects of DDAVP could be explained by a direct action on the endothelium via activation of endothelial vasopressin V2 receptor and by activating cyclic adenosine monophosphate (cAMP)- mediated signaling. Also, several putative mechanisms or mediators for the action of DDAVP other than vWF have been posulated. In this respect, after DDAVP administration the significant increase of the expression of the endothelial-derived P-selectin (another major constituent of WPB) or a tissue factor (TF) suggests a role of other endothelial mediators, with a possible involvement of monocyte-dependent mechanisms (platelets activation by increasing the expression of P-selectin ligand on their membrane). Additionally, the formation of microparticles and generation of procoagulant activity following DDAVP stimulation has been described. It has been suggested that the final effect of DDAVP on platelets involves the facilitation of glycoprotein (Gp)IIb-IIIa ligand interactions through modification of the cytosceleton focal adhesion protein VASP. This molecular mechanism modulates platelets binding to fibrinogen and vWF. DDAVP is supposed to induce a release of other WPB constituents such as interleukin (IL)-8, CD63 and endothelin-1.

Considerable interindividual variations in response to DDAVP may account for some of the controversies on hemostatic benefits of DDAVP. Thus, the ability of DDAVP to improve the platelet function is unpredictable, and a test dose of a remedy is recommended to establish the individual patterns of biological response and to predict clinical efficacy during bleeding/invasive procedures/surgery.

In the assessment of individual response to desmopressin several days prior to the intervention, the patient should be administered a test dose of 0.3μg/kg DDAVP diluted in 100mL of isotonic saline and infused for 30 minutes.

Checking the response to DDAVP: carry out the activities of vWF and FVIII before and one hour after test drug administration. Also, bleeding time and PFA-100 test could be used.

Prophylactic treatment with DDAVP

Prophylactic treatment with DDAVP should be administered approximately 1hour before the planned intervention: 0.3µg/kg DDAVP diluted in 100mL of isotonic saline and infused for 30-40minutes. Tranexamic acid in dose 10mg/kg diluted in 100mL of isotonic saline and infused for 20-30 minutes before intervention. Causion: don’t mix DDAVP and tranexamic acid in the same vial.

Local measures: prior to fibrin sealent application, my advice (good clinical experience in surgical practice) is to apply tranexamic acid (500mg diluted in 20mL of isotonic saline) directly on the wound (part of solution), followed by tampon with tranexamic acid (the rest of prepared solution) for 10 minutes. After this pretreatment apply fibrin sealent.

Post-intervention treatment with repeated doses of DDAVP 12-24 hours (next 1-2 days) after the procedure should be considered until progression of wound healing.

Best wishes

Dragica

Dental management of patients with vWD is generally similar to treatment of patients with an equivalent level of hemophilia A.Management of patients with type 3 vWD, marked by a complete absence of vWF, is similar to the management of patients with a severe form of hemophilia A.

Desmopressin acetate is usually the treatment of choice for patients with the mild to moderate form of vWD.

However, selection of the treatment is not clear-cut, because it depends on the type of vWD, the patient’s response to desmopressin acetate, and the decision of the hematologist.

Laboratory investigations are necessary prior to any dental procedures that are likely to cause bleeding. These tests include the aPTT, bleeding time, and factor VIII level in the plasma (vWF:Ag, RCoF, and factor VIII coagulant). The severe form of vWD requires replacement therapy with factor concentrate that is rich in vWF because there is no recombinant therapy for vWF .