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Management of von Willebrand's disease with desmopressin
J Oral Maxillofac 46:31X314.
Surg
1966
Management of von Willebrand’s with Desmopressin JAMES E. ROYER, LCDR DC USN* AND WILLIAM
Report of Two Cases Case 1 A 35-year-old white woman was referred by her periodontist for removal of five teeth. Her history revealed that she had been hospitalized 10 years earlier following removal of a molar tooth and required a blood transfusion. Screening laboratory examinations were normal except for a prolonged bleeding time of 15 minutes. Specific factor assays were normal except for a reduced factor VIII axis of 25% consistent with Type I von Willebrand’s disease. Thirty minutes after infusing a trial dose of 21 pg of DDAVP (0.3 &kg) in 50 ml of normal saline solution, a blood sample was drawn and the factor VIII assay rose to 90%. The patient was then scheduled for outpatient ambulatory surgery the following week. The same amount of DDAVP was infused over 20 minutes and teeth nos. 5, 14,
* Head Oral and Maxillofacial Surgery, Naval Hospital Roosevelt Roads, Puerto Rico. t Head Oral and Maxillofacial Surgery, Naval Hospital, San Diego, California. The opinions or assertions expressed in this paper are those of the authors and are not to be construed as offkial or as necessarily reflecting the views of the Department of the Navy or the Naval Service at large. Address correspondence and reprint requests to LCDR Royer: US Naval Hospital, Box 3007. FPO Miami, FL 34051-8150. Association
of Oral and Maxillofacial
S. BATES, CAPT DC USNt
vascular endothelial cells.6 Studies indicate that it is the release of these endogenous stores. not synthesis, that is the mechanism.437 Current recommendations call for the intravenous infusion of 0.3 kg/kg of desmopressin, diluted in 50 ml of normal saline solutions, over 15 to 30 minutes.8 This infusion results in a rapid rise of F VIII : C, with maximum levels at about 90 to 120 minutes, and persistent activity for 6 or more hours. A delay of 24 to 48 hours is needed to re-establish the original response.* This further supports release-of-stores concept. Von Willebrand’s disease is comprised of five types. The most common and classical form (Type I) consists of a quantitative deficiency of von Willebrand’s factor and responds well to DDAVP therapy. Types II A, B, and C have qualitatively abnormal forms of von Willebrand’s factor. In the fifth type, pseudo-von Willebrand’s disease, an intrinsic platelet abnormality exists. Each subtype is characterized by deficient platelet aggregation due to an abnormal interaction of platelet and von Willebrand’s factor. DDAVP has been reported to increase platelet aggregation in both Type II B and pseudo-von Willebrand’s disease, and to cause thrombocytopenia.‘Oq” It is therefore contraindicated in these two subsets of the disease. The following case reports illustrate the effective use of DDAVP in oral surgery.
The hereditary bleeding disorders hemophillia A and von Willebrand’s disease are both characterized by inadequate levels of factor VIII coagulant activity (F VIII : C). Patients with von Willebrand’s disease have additional deficiencies in von Willebrand’s factor (F VIII : VWF), a property of blood plasma that allows normal platelet function and includes factor VIII-related antigen (F VIII : RAg) and ristocetin cofactor (F VIII : RCof).‘,’ Traditionally, inadequate hemostasis has been treated with transfusions of cryoprecipitate, fresh frozen plasma, or commercially prepared factor VIII concentrate. Unfortunately, these treatments have substantial sequelae, including the possibility of causing hepatitis, AIDS, hemolytic anemia, formation of factor inhibitors, and allergic reactions from blood component products.3 Mannucci and coworkers4 found that administration of DDAVP (I-desamino-8-d-arginine vasopressin, desmopressin) to patients with hemophilia A and von Willebrand’s disease resulted in a fourto six-fold elevation of F VIII : C and F VIII : VWF in patients with mild to moderate disease (concentrations of F VIII : C greater than 5% of normal). Preoperative intravenous infusion of desmopressin has been also used for epistaxis, menorrhagia; tonsillectomy, tympanoplasty, herniorrhaphy, thoracotomy, and neurosurgery.5 Desmopressin has been recently licensed in the United States for these uses. The mechanism of action by which the hormone elevates F VIII : C and von Willebrand’s factor is unclear. Both are in part synthesized and stored in
0 1988 American
Disease
Sur-
geons 0278-2391188 $0.00 + .25
313
314
AGROMEGALY
15, 18, and 19 were removed. The five extraction sites clotted normally and the patient experienced no postoperative hemorrhage. Case 2
Discussion
PROCNATHISM
by appropriate
fluid
References Wintrobe MM, Lee CR. Boggs DR, et al: Clinical Hematology. Philadelphia, Lea & Febiger. 1981. p 1169-75 DW. Robinson AG: Desmopressin. Ann Intern Med 103:228, 1985 Sherris JC, et al: Medical Microbiology-An Introduction to Infectious Disease. New York. Elsevier, 1984, p 406411. 646 Mannucci PM, Ruggeri ZM. Paretti Fl. et al: IDeamino-8-D-arginine vasopressin: A new pharmacological approach to the management of haemophila and von Willebrand’s disease. Lancet 869. 1977 Kobrinsky NL, Israels ED, Gerrard JM, et al: Shortening of bleeding time by I-deamino-8-D-arginine vasopressin in various bleeding disorder. Lancet 1145, 1984 McCarrol DR. Ruggeri ZM, Montgomery RR: The effect of DDAVP on plasma levels of von Willebrand antigen II in normal individuals and patients with von Willebrand’s disease. Blood 63:532. 1984 Garcia VV, Coppola R. Mannucci PM: The role of the spleen in regulating the plasma levels of factor VIII-von Willebrand’s factor after DDAVP. Blood 60:1402, 1984 Mannucci PM, Canciani MT, Rota et al: Response of factor Vllhvon Willebrand’s factor to DDAVP in healthy subjects and patients with hemophilla A and von Willebrand‘s disease. Br J Haematol 47:%3. 1981 Mannucci PM. Abera M. Nilsson IN, et al: Mechanism of plasminogen activator and factor VIII increase after vasoactive drugs. Br J Haematol 30:81, 1975 Holmberg L. Nilsson IM, Borge L, et al: Platelet aggregation induced by 1-desamino-8-d-arginine vasopressin (DDAVP) in Type II B von Willebrand’s disease. N Engl J Med 309:816, 1983 Talcahashi H, Nagayama R. Hattori A, et al: Platelet aggregation induced by DDAVP in platelet type von Willebrand’s disease. N Engl J Med 310:722, 1983
2. Richardson
3.
4.
5.
6.
7.
8.
The use of DDAVP in these distinct clotting disorders is the major clinical advantage to the newly released form of desmopressin for parental administration. Consultation with hematology, factor level assays, and determination of the response of the factor to desmopressin should be accomplished before attempting a surgical procedure. The only side effect is the risk of water retention and hypona-
MANDIBULAR
tremia. which can be prevented restriction.
I.
A 22-year-old white man was referred for removal of four third molars and an impacted maxillary left canine. He had a history of von Willebrand’s disease and received cryoprecipitate before an appendectomy 8 years ago. Screening laboratory examinations were within normal limits except for a bleeding time of 7.5 minutes and a PTT of 46 seconds. Evaluation by a hematologist and further hematologic studies revealed a F VIII : C of 12.5%, F VIII : RAg of 18%, and a F VIII RCoP of 25% (normal for each of these three is 50 to lOO%), consistent with von Willebrand’s syndrome. The patients response 60 minutes after a 0.3 &kg test dose of DDAVP revealed a F VIII : C of 65%, F VIII : RAg of 63%, and a F VIII RCoP of 70%. One week later, the four third molars and impacted canine were removed without postoperative hemorrhage.
WITH ASYMMETRIC
9.
10.
II.
J Oral Maxillofacsurg 46:314-320.1968
Treatment of an Asymmetric Mandibular Prognathism in an Acromegalic Patient AK10 MIZUNO, DMD, PHD(Jpn)* AND KATSUTOSHI Hyperpituitarism causes both giantism and acromegaly. Acromegaly, or adult hyperpituitarism, Received from the Department of Oral and Maxillofacial Surgery, Hamamatsu University School of Medicine, Hamamatsu City, Japan. * Associate Professor. t Chief and Professor. Address correspondence and reprint requests to Dr. Mizuno: Department of Oral and Maxillofacial Surgery, Hamamatsu University School of Medicine, 3608, Handa-cho, Hamamatsu 43131 Japan. 0 1988 American geons
Association
0278-2391188 $0.00 + .25
of Oral and Maxillofacial
MOTEGI,
MD, DMD, PHD(Jpn)t
is a relatively
rare disease caused by acidophilic adenoma or hypertrophy of the acidophilic cells of the pituitary. Signs and symptoms are severe enlargement of the skeleton, connective tissues, and internal organs. In this paper, a case of asymmetric prognathism of the mandible and macroglossia in an acromegalic patient due to pituitary adenoma is presented. Report of a Case
Sur-
In November, 1984, a 24-year-old man was referred to our clinic, complaining of masticatory disturbance and
Surg
1966
Management of von Willebrand’s with Desmopressin JAMES E. ROYER, LCDR DC USN* AND WILLIAM
Report of Two Cases Case 1 A 35-year-old white woman was referred by her periodontist for removal of five teeth. Her history revealed that she had been hospitalized 10 years earlier following removal of a molar tooth and required a blood transfusion. Screening laboratory examinations were normal except for a prolonged bleeding time of 15 minutes. Specific factor assays were normal except for a reduced factor VIII axis of 25% consistent with Type I von Willebrand’s disease. Thirty minutes after infusing a trial dose of 21 pg of DDAVP (0.3 &kg) in 50 ml of normal saline solution, a blood sample was drawn and the factor VIII assay rose to 90%. The patient was then scheduled for outpatient ambulatory surgery the following week. The same amount of DDAVP was infused over 20 minutes and teeth nos. 5, 14,
* Head Oral and Maxillofacial Surgery, Naval Hospital Roosevelt Roads, Puerto Rico. t Head Oral and Maxillofacial Surgery, Naval Hospital, San Diego, California. The opinions or assertions expressed in this paper are those of the authors and are not to be construed as offkial or as necessarily reflecting the views of the Department of the Navy or the Naval Service at large. Address correspondence and reprint requests to LCDR Royer: US Naval Hospital, Box 3007. FPO Miami, FL 34051-8150. Association
of Oral and Maxillofacial
S. BATES, CAPT DC USNt
vascular endothelial cells.6 Studies indicate that it is the release of these endogenous stores. not synthesis, that is the mechanism.437 Current recommendations call for the intravenous infusion of 0.3 kg/kg of desmopressin, diluted in 50 ml of normal saline solutions, over 15 to 30 minutes.8 This infusion results in a rapid rise of F VIII : C, with maximum levels at about 90 to 120 minutes, and persistent activity for 6 or more hours. A delay of 24 to 48 hours is needed to re-establish the original response.* This further supports release-of-stores concept. Von Willebrand’s disease is comprised of five types. The most common and classical form (Type I) consists of a quantitative deficiency of von Willebrand’s factor and responds well to DDAVP therapy. Types II A, B, and C have qualitatively abnormal forms of von Willebrand’s factor. In the fifth type, pseudo-von Willebrand’s disease, an intrinsic platelet abnormality exists. Each subtype is characterized by deficient platelet aggregation due to an abnormal interaction of platelet and von Willebrand’s factor. DDAVP has been reported to increase platelet aggregation in both Type II B and pseudo-von Willebrand’s disease, and to cause thrombocytopenia.‘Oq” It is therefore contraindicated in these two subsets of the disease. The following case reports illustrate the effective use of DDAVP in oral surgery.
The hereditary bleeding disorders hemophillia A and von Willebrand’s disease are both characterized by inadequate levels of factor VIII coagulant activity (F VIII : C). Patients with von Willebrand’s disease have additional deficiencies in von Willebrand’s factor (F VIII : VWF), a property of blood plasma that allows normal platelet function and includes factor VIII-related antigen (F VIII : RAg) and ristocetin cofactor (F VIII : RCof).‘,’ Traditionally, inadequate hemostasis has been treated with transfusions of cryoprecipitate, fresh frozen plasma, or commercially prepared factor VIII concentrate. Unfortunately, these treatments have substantial sequelae, including the possibility of causing hepatitis, AIDS, hemolytic anemia, formation of factor inhibitors, and allergic reactions from blood component products.3 Mannucci and coworkers4 found that administration of DDAVP (I-desamino-8-d-arginine vasopressin, desmopressin) to patients with hemophilia A and von Willebrand’s disease resulted in a fourto six-fold elevation of F VIII : C and F VIII : VWF in patients with mild to moderate disease (concentrations of F VIII : C greater than 5% of normal). Preoperative intravenous infusion of desmopressin has been also used for epistaxis, menorrhagia; tonsillectomy, tympanoplasty, herniorrhaphy, thoracotomy, and neurosurgery.5 Desmopressin has been recently licensed in the United States for these uses. The mechanism of action by which the hormone elevates F VIII : C and von Willebrand’s factor is unclear. Both are in part synthesized and stored in
0 1988 American
Disease
Sur-
geons 0278-2391188 $0.00 + .25
313
314
AGROMEGALY
15, 18, and 19 were removed. The five extraction sites clotted normally and the patient experienced no postoperative hemorrhage. Case 2
Discussion
PROCNATHISM
by appropriate
fluid
References Wintrobe MM, Lee CR. Boggs DR, et al: Clinical Hematology. Philadelphia, Lea & Febiger. 1981. p 1169-75 DW. Robinson AG: Desmopressin. Ann Intern Med 103:228, 1985 Sherris JC, et al: Medical Microbiology-An Introduction to Infectious Disease. New York. Elsevier, 1984, p 406411. 646 Mannucci PM, Ruggeri ZM. Paretti Fl. et al: IDeamino-8-D-arginine vasopressin: A new pharmacological approach to the management of haemophila and von Willebrand’s disease. Lancet 869. 1977 Kobrinsky NL, Israels ED, Gerrard JM, et al: Shortening of bleeding time by I-deamino-8-D-arginine vasopressin in various bleeding disorder. Lancet 1145, 1984 McCarrol DR. Ruggeri ZM, Montgomery RR: The effect of DDAVP on plasma levels of von Willebrand antigen II in normal individuals and patients with von Willebrand’s disease. Blood 63:532. 1984 Garcia VV, Coppola R. Mannucci PM: The role of the spleen in regulating the plasma levels of factor VIII-von Willebrand’s factor after DDAVP. Blood 60:1402, 1984 Mannucci PM, Canciani MT, Rota et al: Response of factor Vllhvon Willebrand’s factor to DDAVP in healthy subjects and patients with hemophilla A and von Willebrand‘s disease. Br J Haematol 47:%3. 1981 Mannucci PM. Abera M. Nilsson IN, et al: Mechanism of plasminogen activator and factor VIII increase after vasoactive drugs. Br J Haematol 30:81, 1975 Holmberg L. Nilsson IM, Borge L, et al: Platelet aggregation induced by 1-desamino-8-d-arginine vasopressin (DDAVP) in Type II B von Willebrand’s disease. N Engl J Med 309:816, 1983 Talcahashi H, Nagayama R. Hattori A, et al: Platelet aggregation induced by DDAVP in platelet type von Willebrand’s disease. N Engl J Med 310:722, 1983
2. Richardson
3.
4.
5.
6.
7.
8.
The use of DDAVP in these distinct clotting disorders is the major clinical advantage to the newly released form of desmopressin for parental administration. Consultation with hematology, factor level assays, and determination of the response of the factor to desmopressin should be accomplished before attempting a surgical procedure. The only side effect is the risk of water retention and hypona-
MANDIBULAR
tremia. which can be prevented restriction.
I.
A 22-year-old white man was referred for removal of four third molars and an impacted maxillary left canine. He had a history of von Willebrand’s disease and received cryoprecipitate before an appendectomy 8 years ago. Screening laboratory examinations were within normal limits except for a bleeding time of 7.5 minutes and a PTT of 46 seconds. Evaluation by a hematologist and further hematologic studies revealed a F VIII : C of 12.5%, F VIII : RAg of 18%, and a F VIII RCoP of 25% (normal for each of these three is 50 to lOO%), consistent with von Willebrand’s syndrome. The patients response 60 minutes after a 0.3 &kg test dose of DDAVP revealed a F VIII : C of 65%, F VIII : RAg of 63%, and a F VIII RCoP of 70%. One week later, the four third molars and impacted canine were removed without postoperative hemorrhage.
WITH ASYMMETRIC
9.
10.
II.
J Oral Maxillofacsurg 46:314-320.1968
Treatment of an Asymmetric Mandibular Prognathism in an Acromegalic Patient AK10 MIZUNO, DMD, PHD(Jpn)* AND KATSUTOSHI Hyperpituitarism causes both giantism and acromegaly. Acromegaly, or adult hyperpituitarism, Received from the Department of Oral and Maxillofacial Surgery, Hamamatsu University School of Medicine, Hamamatsu City, Japan. * Associate Professor. t Chief and Professor. Address correspondence and reprint requests to Dr. Mizuno: Department of Oral and Maxillofacial Surgery, Hamamatsu University School of Medicine, 3608, Handa-cho, Hamamatsu 43131 Japan. 0 1988 American geons
Association
0278-2391188 $0.00 + .25
of Oral and Maxillofacial
MOTEGI,
MD, DMD, PHD(Jpn)t
is a relatively
rare disease caused by acidophilic adenoma or hypertrophy of the acidophilic cells of the pituitary. Signs and symptoms are severe enlargement of the skeleton, connective tissues, and internal organs. In this paper, a case of asymmetric prognathism of the mandible and macroglossia in an acromegalic patient due to pituitary adenoma is presented. Report of a Case
Sur-
In November, 1984, a 24-year-old man was referred to our clinic, complaining of masticatory disturbance and