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\begin{document}

\title{Perioperative management of von Willebrand patients at the time of
implant placement: Case report}



\author[1]{Hiroyuki Takashima}%
\author[2]{Aiji Sato (Boku)}%
\author[1]{Hironori Miiyamoto}%
\author[1]{Shinichiro Kato}%
\author[1]{Shota Furuno}%
\author[1]{Yasuyuki Shibuya}%
\affil[1]{Nagoya City University Graduate School of Medical Sciences and Medical School}%
\affil[2]{Aichi Gakuin University School of Dentistry}%


\vspace{-1em}



  
  \date{May 25, 2024}


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\selectlanguage{english}
\begin{abstract}
von Willebrand disease is a hereditary disease associated with a
tendency to bleed and it is important to reduce the possibility of
bleeding in a procedure. This case describes the use of a hemostatic
factor, Factor VIII concentrate (Confact F\selectlanguage{ngerman}®), during a dental procedure
involving teeth extraction and implant placement.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Title:} Perioperative management of von Willebrand patients at
the time of implant placement: Case report

\textbf{Authors:} Hiroyuki Takashima D.D.S.\textsuperscript{1}, Aiji
Sato D.D.S., Ph.D.\textsuperscript{2} , Hironori Miyamoro D.D.S.,
Ph.D.\textsuperscript{1}, Shinichiro Kato D.D.S.,
Ph.D.\textsuperscript{1}, Shota Furuno D.D.S.\textsuperscript{1},
Yasuyuki Shibuya D.D.S., Ph.D.\textsuperscript{1},

\textbf{Institutional affiliations and address for each author}

\textsuperscript{1}Department of Oral and Maxillofacial Surgery, Nagoya
City University Graduate School of Medical Sciences

\textsuperscript{2}Department of Anesthesiology, Aichi Gakuin University
School of Dentistry

\textbf{Corresponding author}

Aiji Sato (Boku), Department of Anesthesiology, Aichi Gakuin University
School of Dentistry 2-11 Suemori-dori, Chikusaku, Nagoya 464-8651, Japan

Tel: +81-52-759-2102, Fax; +81-52-759-2102, Email:
bokuaiji@dpc.aichi-gakuin.ac.jp

\textbf{Key Clinical Message}

In the management of patients with type 1 VWD, supplementation with Con
Facto F\selectlanguage{ngerman}® as well as hemodynamic stabilization with appropriate analgesia
and sedation may be important to reduce the risk of bleeding.

\textbf{ABSTRACT}

von Willebrand disease is a hereditary disease associated with a
tendency to bleed and it is important to reduce the possibility of
bleeding in a procedure. This case describes the use of a hemostatic
factor, Factor VIII concentrate (Confact F®), during a dental procedure
involving teeth extraction and implant placement.

\textbf{Keywords:} , von Willebrand disease, a hemostatic factor, Factor
VIII concentrate (Confact F®)

\textbf{Introduction}

Eric von Willebrand first reported Von Willebrand disease (VWD) in
1926.\textsuperscript{1} It is a congenital condition that results in an
excessive tendency to bleed owing to the quantitative and qualitative
abnormalities of von Willebrand factor (VWF).\textsuperscript{2} In the
perioperative management of VWD patients, it is necessary to reduce
bleeding by preoperatively replenishing coagulation factors and
stabilizing hemodynamics during anesthesia. Herein, we report our
experience with a patient with VWD. We performed safe perioperative
hemostatic management under intravenous sedation by supplementing with
heat-treated factor VIII concentrate (Confact F\textsuperscript{®})
before extracting the teeth and placing implants. Written consent was
obtained from the patient for this report.

\textbf{Case Report}

The patient is a 57-year-old man (height, 173.5 cm; weight, 61.7 kg),
and the

remaining teeth in his lower jaw were 1, 2, and 3 on the right side and
1, 4, and 5 on the left side. The patient had chronic apical
periodontitis and severe periodontal disease. There was teeth movement,
and it was difficult to preserve them. We planned to extract these teeth
and place six implants (Figure 1).

A physician had suspected the presence of VWD when the patient was aged
21 years, but no detailed testing or treatment was performed. The family
history was not relevant and the patient was on no current medications.

In terms of preoperative chest findings, the chest X-ray was normal
(Figure 2) with a normal cardiothoracic ratio of 42\%, and there were no
particular issues. Blood test results are shown in Table 1. The platelet
count, a hemostatic factor, was 360,000/\selectlanguage{greek}µ\selectlanguage{english}l, the activated partial
thromboplastin time was 35.4 seconds, and the prothrombin time 11.7
seconds; all were within normal limits. However, coagulation factor VIII
was 49\%, and VWF activity was 24\%, indicating that the coagulation
factor was lower than normal. Based on detailed testing carried out by
our hospital's hematology department, the patient was diagnosed with
Type 1 VWD, in which there is a quantitative decrease in the VWF.

There was nothing of particular note in terms of family history.
Implants in the upper jaw had already been placed at a different
hospital, and there had been some difficulty stopping the bleeding when
the teeth were extracted. In this case, after consulting with the
hematology department, we decided that surgery would be possible by
transfusing heat-treated factor VIII concentrate (Confact
F\selectlanguage{ngerman}\textsuperscript{®}), which contains VWF. This transfusion was done to
prevent abnormal bleeding during surgery. Furthermore, considering the
risk of bleeding due to fluctuations in hemodynamics, with the patient's
consent, we planned to carry out tooth extraction and implant placement
under local anesthesia with intravenous sedation.

\textbf{Anesthetic Course}

One hour before entering the operating room, 1,500 units of Confact
F\textsuperscript{®} were transfused. In terms of transfusion volume,
although we planned to carry out implant placement, it was determined
that the amount of bleeding would not differ greatly from that of tooth
extraction alone, so we used 25 IU/kg, basing our calculations on those
published in the New England Journal of Medicine (Table
2).\textsuperscript{3} Immediately before surgery, we took another blood
sample. We confirmed that VWF activity was 127\% and that coagulation
factor VIII had increased to 104\%. We then proceeded with the surgery.
Considering that fluctuations in hemodynamics during surgery promote
bleeding, intravenous sedation was performed to stabilize circulation.
Oxygen (2 l/min) was administered transnasally, and cefmetazole sodium
(1 g) was administered preoperatively to prevent infection. During the
operation, we used midazolam iv and propofol (1\% Diprivan Injection
kit\textsuperscript{®}) target-controlled infusion for continuous
intravenous sedation. Also, 2\% Xylocaine Dental\textsuperscript{®} with
epinephrine 1:80,000 was used for local anesthesia. The operation time
was 3 hours and 37 minutes, the anesthesia time was 4 hours and 16
minutes, and blood loss was 405 ml. Although it was a little difficult
to stop bleeding during the operation, we completed the procedure with
no major problems. No postoperative complications, such as bleeding were
observed, and the prognosis was favorable. One week after the operation,
evaluation of the coagulation factor VIII and VWF activity revealed that
they had decreased to 48\% and 23\%, respectively, which were close to
their preoperative values (Table 3).

\textbf{Discussion}

VWD is a congenital bleeding disorder inherited in an autosomal dominant
manner. This condition consists of a quantitative or qualitative
abnormality in the VWF, a hemostatic factor that causes a temporary
hemostatic disorder. The VWF functions as an intrinsic coagulation
factor that mediates platelet adhesion to subepithelial connective
tissue and stabilizes binding to coagulation factor VIII.

A lack or decrease in these functions can cause bleeding. Under the
disease classification proposed by the International Society on
Thrombosis and Haemostasis, there are the following types of VWD: 1, 2A,
2B, 2M, 2N, and 3.\textsuperscript{4} Type 1 is the most common and
features a quantitative deficiency of the VWF but no functional
problems. It was previously reported that desmopressin (DDAVP) is
effective for hemostasis management in mild to moderate hemophilia and
VWD.\textsuperscript{5} Therefore, DDAVP was used in many cases
considering side effects such as the risk of infection from hepatitis
virus and AIDS. However, the increase in deficiency factor activity is
uncertain. Although it is used for short-term hemostasis, it has limited
application since it cannot be repeatedly or continuously used. The
improved viral inactivation accuracy of Confact
F\textsuperscript{®}improves the purity and safety of the drug, and the
risk of infection is said to be lower than before.\textsuperscript{6}
Although in this case, we planned to perform tooth extraction and
implant placement, it was determined that the amount of bleeding would
not differ greatly from carrying out tooth extraction alone, so for the
transfusion volume, we used 25 IU/kg, basing our calculations on those
published in the New England Journal of Medicine (Table 2). Although no
abnormal bleeding was observed during or after surgery, it was necessary
to pay attention to bleeding when carrying out implant placement.
Furthermore, stabilizing hemodynamics using appropriate analgesia and
sedation is also considered extremely important for reducing the risk of
bleeding.

\textbf{Conclusion}

In this case, we carried out safe perioperative management under
intravenous sedation combined with local anesthesia after preoperatively
supplementing with heat-treated factor VIII concentrate (Confact
F\textsuperscript{®}) when extracting teeth and placing implants for a
Type 1 VWD patient. Stabilizing hemodynamics using appropriate analgesia
and sedation is also considered important for reducing the risk of
bleeding.

\textbf{Acknowlegements}

Not applicable

\textbf{Funding}

None

\textbf{Conflict of interest}

The authors declare that we have no conflict of interest.

\textbf{Data availability statement}

Not applicable due to patient privacy concerns.

\textbf{Author's contributions}

All authors contributed to the case. Preoperative management and
anesthetic planning were performed by HT, SF and AS. Anesthetic
Management was performed by AS, SK and HM. The first draft of the
manuscript was written by AS and all authors commented on previous
versions of the manuscript. YS helped with the supervision of the
manuscript and development of the overall periopertative plan. All
authors read and approved the final manscript.

\textbf{Ethical approval}

Not applicable.

\textbf{Consent for publication}

The authors obtained written consent for publication from the patient.

\textbf{ORCID} Aiji Sato (Boku) 0000-0003-0182-2543

\textbf{References}

1. von Willebrand, EA. 1926. Hereditar Pseudohemophili, Finska
Lakaresallskpets Handlinger 68:87--112.

2. Nishi H, Miyauchi M, Takechi M, et al. 2007. Dental management for
von

Willebrand disease patients who had difficulty in communication.
Pediatric Oral and Maxillofacial Surgery. 1991;17:101-107.

3. Leebeek FW, Eikenboom JC. Von Willebrand's disease. New England
Journal

of Medicine. 2016;375:2067--2080.

4. Matsushita T. Hemophilia and von Willebrand disease---Focus on
replacement therapy. Journal of the Japanese Society of Internal
Medicine. 2009;98:58--68.

5. Yamamoto K, Matsuzuka Y, Morimoto Y, et al. Hemostatic effect of
DDAVP on tooth

extraction in patients with mild and moderate hemophilia A and von
Willebrand

disease. Japanese Journal of Oral and Maxillofacial Surgery.
1995;41:984-990.

6. Uda A, Jinno J, Kobayashi R, et al. Tooth extraction in sisters with
von Willebrand disease. Nihon University Journal of Oral Science.
2004;30:129-133.

\textbf{Figure Legends}

Figure1

The remaining teeth in his lower jaw were 1, 2, and 3 on the right side
and 1, 4, and 5 on the left side. The patient had chronic apical
periodontitis and severe periodontal disease.

Figure 2

The chest X-ray was normal with a normal cardiothoracic ratio of 42\%\selectlanguage{english}
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