Prescription for a patient with type 1 von Willebrand disease who is about to undergo wisdom teeth extraction?

Here’s how readers responded to a You Make the Call question about a patient with type 1 von Willebrand disease who is about to undergo wisdom teeth extraction.

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I am surprised that a type 1 patient had no measurable activity levels. What are her antigen levels? I would usually arrange a DDAVP response trial and use 0.3 msg/kg and cap at 20 mpg. I would use s/c if she is a normal weight and IV if she is overweight. I would also makes sure she is lying flat and that if given IV that this is given over 45 minutes, if possible. Also vital signs need to be measured q 15 minutes, and the patient needs to fluid restrict to 800 mls for 24 hours. I would use tranexamic acid at 25 mg/kg by mouth every 6 to 8 hours for 24 hours past any signs of local oozing. I would aim for functional levels above 0. 4 U/l at the time of dental work.

Mary-Frances Scully, MRCP
St. John’s NL, Canada

This appears to be severe type 1 von Willebrand’s disease (perhaps type 3?).

For tooth extraction in this patient, I’ll agree with an initial dose of 40 IU/kg administered 30 to 40 minutes pre-extraction, but will also commence oral tranexamic acid the day before procedure or, alternatively, administer a calculated intravenous dose (e.g., tranexamic acid 1.0 g IV) shortly before commencement of extraction.

After the procedure, I’ll suggest continuing tranexamic acid mouth washes 4-6 x per day for the next 3 to 5 days.

Assuming recovery and half-life of the particular vWF concentrate is already known to be satisfactory for this particular patient, I may not necessarily administer further concentrate post-extraction, unless dictated by significant post extraction bleeding.

Patrick Mensah
Haemophilia Centre
Leicester Royal Infirmary
United Kingdom

This patient mostly likely has severe type 1 disease, possibly type 3 disease, with very little probability for a DDAVP response. We do not have a documented clinical response for this patient, nor do we know her bleeding history, how many teeth are expected to be extracted, or her response to antifibrinolytic products in the past. Given all this, replacement with von Willebrand factor (vWF) concentrate would be preferable. The goal would be to achieve a trough vWF activitiy and FVIII activity levels of >50 IU/dL. We would recommend factor replacement prior to the procedure and for up to 5 to 10 days after, pending appropriate healing and lack of re-bleeding. An antifibrinolytic, such as epsilon-aminocaproic acid or tranexamic acid, would also be appropriate to have on hand for any delayed bleeding, which can be given in combination with factor concentrate as a loading dose prior to surgery and then as needed for 7 to 10 days post-op.

Jenny Zhou, MD

I would consider a trial of desmopressin with measurement of vWD activity and FVIII. I would watch for urinary retention.

Franc Wallace, MD

It sounds like a rather severe type I vWD with undetectable levels of ristocetin cofactor. I wouldn´t rely on DDAVP except perhaps with a previous test that showed good and sustained levels of vWF. I would use purified plasma-derived concentrates of vWF/FVIII or recombinant vWF, which is not available in my country, Argentina.

Jorge Korin, MD

The decision should be based on her bleeding history as well. Otherwise, treat with vWF and maintain with Amicar initially every 8 hours x 3 days.

John Akabutu, MD

One loading dose of Humate-P pre-procedure.

Amicar elixir 5 gm swish and swallow QID beginning 1 to 2 hours pre-procedure.

Lawrence Rice, MD

I would prescribe 20 u/kg for more than 3 days and would relay to the dentist to suture the extraction place.

Jerome Voegeli, MD

I recommend 50 IU/kg of a plasma-derived vWF concentrate one hour prior to the procedure and 40 IU/kg once a day for three days after the procedure.

In addition, aminocaproic acid suspension swish and swallow every 6 hours for 5 to 7 days.

Miguel A. Escobar, MD
University of Texas Houston Health Science Center
Gulf States Hemophilia & Thrombophilia Center

I would say that the initial dose – if in vWF units – is appropriate. However, you also want the FVIII elevated, so you need a product that contains both FVIII and vWF to get the levels of both to adequate. Continuing Factor support for 2 days in the face of as needed antifibrinolytics may be appropriate, but I would not suggest using the antifibrinolytic “as needed.” Instead, I suggest topical antifibrinolytic 4 times daily for 7 to 10 days.

This patient has a very severe type 1 disease if the factor VIII is only 21 percent, and I would not suggest the course of therapy before knowing that the clinical history, vWF antigen, vWF activity, platelet count, and multimer were all consistent with that diagnosis.

Ken D. Friedman, MD

I find it unusual for a type 1 vWF patient to have no detectable vWF function. The treatment sounds reasonable.

Ian Rabinowitz, MD

Has this patient ever been tested for response to DDAVP?

If so – with good response – I usually manage with DDAVP, factor reserved if bleeding is not optimally controlled, plus anti-fibrinolytics for 5 to 7 days.

Anas Al-Janadi, MD
Michigan State University

I would do just that, except do the 3 days bid.

Robert Ellis, MD

40 u/kg one hour prior to procedure

Sandeep Maseru

40 mcg for 70 kg patient (I presume you are referring to DDAVP Rx.) needs to be tested first and is probably too much dose and increases risk of side effects of drug.

John J. McCarthy, MD

If the patient’s vWF activity (by ristocetin cofactor or collagen binding) is undetectable, she likely doesn’t have type I vWD. Our RCOF assay reports down to 13 percent, but our collagen binding reports down to 2 percent. Our vWF Ag reports down to 3 percent. According to NHLBI criteria, patients with less than 3 percent RCOF activity or antigen have type III vWD. However, type III vWD patients generally have FVIII levels <10 percent.

Overall, there needs to be more clarity as to the patient’s vWF labs and whether the type I diagnosis is correct. As DDAVP is less effective outside of type I vWD, any dosing decisions cannot be made before the subtype diagnosis is confirmed.

Geoffrey Wool, MD, PhD
University of Chicago

Lots of missing information – past hx, bleeding events, circumstances, tx Response to STIMATE or previous infusions.

My plan would be 40 mcg/kg Humate-P 1 hour prior to procedure, 20 mcg/kg Humate-P 24 and 72 hours or consider STIMATE 1 spritz both nostrils 24 and 72 hours with instructions about fluid restriction.

Thomas Hyde, MD

The question did not specify which type of factor was suggested to be given. Different factors have different amounts of vWF to Factor VIII ratios. Also, recombinant vWF must be given more than one hour before so that it will be loaded with Factor VIII endogenously. I use Humate-P mostly in this situation. She is so severe, I would give Humate-P 60 units/kg pre op. When she can swallow, I would give oral tranexamic acid 1300 PO TID for 5 to 10 days. It is much better tolerated than Amicar. On days 1 and 3, I would give Humate –P 50-60 units/kg. However, if bleeding and/or swelling seem to increase, I would also treat on days 2 and 5. There is no reason to give Humate-P q 8 hours since the T/2 is much longer than that and such a schedule will be difficult to actually put in place for most patients with vWD. I would ould prescribe tranexamic acid on the day the sutures are removed.

Sally Stabler, MD
University of Colorado School of Medicine