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Oral surgery in patients with hereditary bleeding disorders
Medicine; Pathology
0ral surgery in patients with hereditary bleeding disorders
G. R a m s t r 6 m 1, M. Blomb~ick 2, N. E g b e r g 2, H. J o h n s s o n 3, B. L j u n g b e r g 3, S. S c h u l m a n 3 Departments of 1Oral and Jaw Diseases, 2Clinical Chemistry and Blood Coagulation, and 3Medicine, Karelinska Hospital, Stockholm, Sweden
A survey of treatment in the Stockholm area (1974-1985) G. Ramstr6m, M. Blombdck, N. Egberg, H. Johnsson, B. Ljungberg and S. Schulman: Oral surgery in patients with hereditary bleeding disorders. A survey o f treatment in the Stockholm area (1974-1985). Int.J. Oral Maxillofac. Surg. 1989; 18: 320 322. Abstract. The results on the oral surgical management of patients with coagulation disorders at the Karolinska Hospital, Stockholm, during the period 1974-1985 have been compiled and compared with those obtained during the period 1965-1973. The present study included 380 tooth extractions performed in 250 treatment sessions in 107 patients. The incidence of postoperative bleeding and duration of hospitalization were reduced during the period of investigation.
In the late sixties there was still a substantial risk of protracted and uncontrollable hemorrhage in patients with coagulopathies following complicated, as well as simple tooth extractions 2'8. During the last 20 years the prognosis after performing extensive oral surgery in such patients, has improved significantly2~,8,12-15. The major factors contributing to the improvement of hemostatic control are: 1) coagulation factor concentrates; 2) antifibrinolytic substances to control the local fibrinolysis; 3) antibiotics to reduce the local bacterial infection, which stimulates local fibrinolysisS; 4) local measures to reduce hemorrhage, i.e. local hemostatics, suturing of a mucoperiosteal flap or an acrylic splintS,6,8,13. These measures have gradually been introduced over the last 25 years at t h e Karolinska Hospital and 3 periods with different treatment protocols can be distinguished. During treatment period 1 (1965 1969), only factor concentrate and/or plasma was used. During treatment period 2 (1969-1971), antifibrinolytic agents and antibiotics were added, whereas during treatment period 3 (1972-1973) local hemostatic measures were introduced additionally. In 1975 RAMSTROM & BLOMB~.CK reported their experiences with these 3 treatment protocols (Table 1)8. The present report covers the time period 1974-1985 when the patients were treated mainly accord-
ing to the protocol of period 3. The aim of this study was to investigate whether the clinical results reported in 1975 were still the same or had even improved.
Key words: hemophilia; von Willebrand's disease; tooth extraction; fibrinolytic inhibitors. Accepted for publication 24 August 1989
were included, as were 1 patient with Aldrich's syndrome and 1 with a severe form of thrombasthenia Glanzmann. Operative procedure
Material and methods
The material comprised 107 patients treated at the Department of Oral and Jaw Diseases at the Karolinska Hospital during 1974-1985. Definitions of patient material
Severe forms of Hemophilia A or B: <0.01 IU/ml of coagulation F VIII:C or F IX respectively; moderate forms: 0.01-0.05 IU/ml. Severe form of yon Willebrand's disease (type III): prolonged bleeding time, FVIII:C <0.05 IU/ml; von Willebrand factor antigen (vWF:Ag) <0.12 IU/ml, and v W F functional activity (Ristocetin cofactor activity) < 0.08 U/ml. I N types I and II the limits for functional vWF activity were arbitrarily set <0.08, 0.09-0.20 and 0.21-0.50 U/ml for severe, moderate and mild forms, respectively. All patients with the severe form and most patients with the moderate form had a prolonged bleeding time. The distribution of the patient material as to these disorders is given in Table 2. Three patients with factor X deficiency (0.05-0.10 U/ml), 4 with factor X I deficiency (0.05-0.10 U/ml) and 1 with factor X I I deficiency ( < 0.05 U/ml)
A total of 380 teeth and retained roots were extracted (including 1 preprosthetic operation) in 250 treatment sessions. Ninety-one of the extracted teeth consisted of 3rd molars, 63 of which were impacted or partially impacted. In these cases and in 49 other cases a mucoperiosteal flap was reflected. All extractions were performed by the same surgeon. In all cases except 1 patient, in whom intubation anesthesia was used, the extractions and/or operations were carried out using local anesthesia (Xylocain-Exadrin® 2%, Astra, Sweden). No hematomas were seen after the injections. In m o s t cases (203 of 250 treatment sessions) the gingiva was sutured over the alveolus. Whenever acrylic splints were used (32 treatment sessions), they were prepared according to the Omnivac method. As local hemostatic agent Thrombase Dentaire (Laboratories ISH, France) or Surgicel (Johnson & Johnson, USA) was used. A treatment session is defined as the time from the start of treatment or of hospitalization until the postoperative course had been uneventful for 5-7 days. One treatment session could include one or more extractions. In 181
Oral surgery in hemophiliacs Table 1. Excerpts from the results of Ramst6m & Btomb/ick8
Period
No. extr. teeth
No. sess. with postop. bleed/Total no. No./no. %
Hemophilia A severe form
1 2 3
6 26 12
7.5 3.7 2.6
3260 1592 438
3/3 5/13 2/6
100 38 33
Hemophilia A moderate form
1 2 3
37 18 5
3.0 1.6 0.6
974 456 100
7/9 0/3 0/2
78 0 0
Hemophilia A mild form
1 2 3
31 22 20
3.0 0.8 0
802 93 0
8/11 4/9 1/11
73 44 9
Hosp. No. factor days/tooth units/tooth
sessions l tooth, in 49 sessions 2 teeth, in 19 sessions 3-10 teeth and in one treatment session 17 teeth were extracted.
tution therapy. M i n o r hemorrhage, which could be controlled by suturing or an acrylic splint, was not regarded as postoperative bleeding.
Replacement therapy and other medical treatment
Results
The results are summarized in Table 2. The amounts of concentrates given per extracted t o o t h were generally higher during the studied period than previously. M o s t of the patients were treated as outpatients. The number o f days in hospital per t o o t h was reduced from 0.9 to 0.2. The frequency of postoperative bleeding was reduced from 10% to 2.7% of the treatment sessions. Bleeding in the case with mild hemophilia A (Table 2) occurred 2 days after surgical removal of a canine tooth with a fractured root. In 11 patients, 4 with mild hemophilia, minor hemorrhages occurred which stopped by using a splint only. Factor VIII:C inhibitors were registered in 2 patients with hemophilia A. In one case extractions were done at
The following factor concentrates were used: for hemophilia A Hemophil, Travenol (USA), A H F and Octonativ, Kabi (Sweden); for hemophilia B Preconativ, Kabi, and for von Willebrand's disease A H F , Kabi. In patients with severe hemophilia and severe yon Willebrand's disease a single substitution dose was given immediately before surgery. The given a m o u n t was calculated to yield a plasma concentration of 0.08-0.10 I U / ml for hemophiliacs and of 0.15-0.20 I U / m l in von Willebrand patients. Treatment with Cyklokapron ® (1 g 3 times daily), and Penicillin V (1 g twice daily), both given orally, was started 1 h prior to surgery and continued for 1 week postoperatively. Postoperative bleeding was defined as a bleeding requiring additional substi-
321
two sessions. The first time, when the inhibitor titer was low, he was treated with 600 units of Factor VIII concentrate and tranexamic acid p.o., whereas at the second session he received Autoplex (Travenol), 50 U / k g bw and tranexamic acid p.o. and locally. The other patient had a low inhibitor titer and was treated with 500 I U F VIII:C concentrate and tranexamic acid. One patient with severe von Willebrand's disease had a low titer of antibody against von Willebrand factor. In 2 sessions a primary tooth was extracted using tranexamic acid p.o. only. In 8 patients with a deficiency of factors X, XI or XII a total of 26 teeth were extracted in 20 treatment sessions. They were only given antifibrinolytics and antibiotics and no postoperative bleedings were recorded. One patient with a severe form of thrombasthenia G l a n z m a n n and 1 patient with Aldrich syndrome were treated with platelet concentrates and tranexamic acid before extraction. In these patients 4 teeth were extracted in 4 treatment sessions. There were no significant postoperative bleedings in these patients.
Discussion
The present study covers many years and during this period some changes in the general management of hemophilia have been introduced. For instance, the a m o u n t of factor concentrates administered prophylactically has increased dramatically. The concentrates also contain larger amounts of active factor, i.e. 500 or 1,000 I U F VIII:C per bottle, in comparison with previous concen-
Table 2. Number of patients, treatment sessions, extracted teeth, days in hospital, factor units transfused and postoperative bleeding. Comparison between earlier study period 3 (A) and present study (B) No. extr. teeth A B
No. days in hospital/ extr. tooth (mean) A B
No. and % of treatment sessions with postop. bleeding 1 A % B %
Coagulation disorder A severe A moderate A mild
6 2 8
15 14 21
6 2 11
22 26 53
12 5 20
32 62 63
2.6 0.6 -
0.9 0.3 _2
438 100 0
710 232 _2
2 0 1
33 0 9
1 3 1
5 12 2
B severe B moderate B mild
4 1
12 3 1
5 3
21 12 1
6 3
32 23 2
3.5 0
0.1
500 0
640 239 0
1 0
20 0
0 0 0
0 0 0
vW severe vW mild
7
6 25
13
12 79
18
31 105
-
0
0.55 0
139 0
0
0
1 0
8 0
28
97
40
226
64
350
0.9
0.2
-
-
4
10
6
2.7
Total
No. treatmerit sessions A B
Factor units/extracted tooth (mean) A B
No. patients A B
1.5
0
z Bleedings requiring substitution therapy. 2 One patient with hemophilia A mild form was hospitalized for 5 days after a postoperative bleeding. He was given 540 units of factor VIII.
322
R a m s t r 6 m et al.
trates. Therefore, the patients, and especially children, often received m o r e concentrate than required to increase their level to 0.08-0.10 IU/ml. Postoperative bleedings in hemophilia A patients were reduced from 16 to 5% as compared with the previous study. This could partly be due to the higher doses of concentrates used and to a better local management o f the patients. M o r e patients were subjected to extensive surgery than in the previous study. However, the extent o f the operation does not seem to affect the tendency to postoperative bleeding, provided that postoperative complications, such as infections or bone-sequesters, do not occur. With our present policy, and in spite of the more extensive surgery, the m e a n hospital stay has been reduced from 2.1 days to 0.5 days per tooth in patients with severe and moderate hemophilia A (Table 2). Our results show that oral surgery in patients with serious coagulation disorders can be performed with the same predictable success as in patients with normal hemostasis. In patients with mild hemophilia A and von Willebrand's disease the need for factor concentrates can be further minimized by the use of desmopressin, a synthetic analogue of vasopressin, which increases the level of the factor VIII:Cv W F complex 3,16. This drug can also be used in certain forms of platelet dysfunctions, since it may normalize an abnormal bleeding time 1°. Several reports 1,2,4,5,s,9'15 have shown that by the use of antifibrinolytic agents the need for substitution therapy in hemophilia patients is dramatically reduced. This is further confirmed in our s t u d y . SINDET-PEDERSEN 11 and STAJCIC 12 have demonstrated that m o u t h rinsing with fibrinolytic inhibitors can further reduce the frequency of hemorrhages and the quantity of substitution ther-
apy. Thus, the results obtained in the present study may further be improved, if m o u t h rinsing is combined with the principles as described above. The necessity of treating local infections with antibiotics has been shown s. The rationale behind this policy has been explained by PLOW 7, who demonstrated that proteases (elastase and cathepsin) released from neutrophils can cause fibrin degradation, which is not inhibited by tranexamic acid. Unsuccessful treatment o f infections, therefore, probably accounts for some postoperative bleeding in this study. In conclusion, this study has shown that the management of patients with hemostatic disorders, who have to undergo oral surgery, has improved over the last 11 years (1974-1985) c o m p a r e d with our previous study. This study has also confirmed the importance of managing the local fibrin degradation by the use of antifibrinolytic and bacteriostatic agents in addition to substitution therapy. References 1. BJORLING, NILSSONIM. Fibrinolytic activity in alveoli after tooth extraction. Odontol Revy 1968: 19: 197-204. 2. BJ(}RLIN G, NILSSON IM. Oralkirurgiska ingrepp p~t patienter med koagulopatier. III. Swed Dent J 1972: 65: 431-40. 3. GH1RARDINIA, CHISTOLINIA, FIR1NDELLI MC, et al. Clinical evaluation of subcutaneously administered DDAVP. Thromb Res 1988: 49: 363-72. 4. GIORDANO ND, WATKINS RS, RADIVOYVITCH M, GOODSITT E. Dental extractions in hemophilic patients on aminocaproic acid prophylaxis. Oral Surg 1968: 26: 160-6. 5. KANEDA T, SH1K1MORIM, WATANABEI, et al. The importance of local hemostatic procedures in dental extractions and oral mucosal bleeding of hemophiliac patients. Int J Oral Surg 1981: 10: 266-71. 6. PIZZON1 D, CORTELLAROM, MANNUCCI PM. Replacement therapy and local measures for dental extractions in hemo-
philiacs: a comparison of various schemes of treatment. VIIth Congr Wld Fed Haemophilia. Teheran 1971. Excerpta Med 1973: 252: 242-4. 7. PLOW EF. The major fibrinolytic proteases of human leucocytes. Biochim, Biophys Acta 1980: 630: 47-56. 8. RAMSTROMG, BLOMBACKM. Tooth extractions in hemophiliacs. Int J Oral Surg 1975: 4: 1-17. 9. REIDWO, LUCASON, FRANSISCOJ, GEISLER PH, ERSLEVAJ. The use of epsilonaminocaproic acid in the management of dental extractions in the hemophiliac. Am J Med Sci 1964: 84: 184-8. 10. SCHULMANS, JOHNSSONH, EGBERG N, BLOM~CK M. DDAVP induced correction of prolonged bleeding time in patients with congenital platelet function defects. Thromb Res 1987: 45: 165-74. 11. SINDET-PEDERSENS, STENBJERGS. Effect of local antifibrinolytic treatment with tranexamic acid in hemophiliacs undergoing oral surgery. J Oral Maxillofac Surg 1986: 44:703 7. 12. STAmlC Z. The combined local/systemic use of antifibrinolytics in hemophiliacs undergoing dental extractions. Int J Oral Surg 1985: 14: 339M5. 13. SZPIRGLASH. L'h6mostase locale dans les extractions dentaire chez l'h6mophile. Thromb Diath Haemorrh 1971: Supp143: 247-53. 14. VINCKXERF, VBRMY~ENJ. Dental extractions in hemophilia: Reflections in l0 years' experience. Oral Surg 1985: 59: 64. 15. WALSH P, RIZZA CR, MATTHEWSJM et al. Epsilon-aminocaproic acid therapy for dental extractions in haemophilia and Christmas disease; A double blind controlled trial. Br J Haematol 1971: 20: 463-75. 16. WILLIAMSONR, EGGLESTONDJ. DDAVP and EACA used for minor oral surgery in yon Willebrand disease. Aust Dent J 1988: 33: 32-6.
Address: G6ran Ramstr6m Dept. of Oral and Jaw Diseases Karolinska Hospital S-10401 Stockholm Sweden
0ral surgery in patients with hereditary bleeding disorders
G. R a m s t r 6 m 1, M. Blomb~ick 2, N. E g b e r g 2, H. J o h n s s o n 3, B. L j u n g b e r g 3, S. S c h u l m a n 3 Departments of 1Oral and Jaw Diseases, 2Clinical Chemistry and Blood Coagulation, and 3Medicine, Karelinska Hospital, Stockholm, Sweden
A survey of treatment in the Stockholm area (1974-1985) G. Ramstr6m, M. Blombdck, N. Egberg, H. Johnsson, B. Ljungberg and S. Schulman: Oral surgery in patients with hereditary bleeding disorders. A survey o f treatment in the Stockholm area (1974-1985). Int.J. Oral Maxillofac. Surg. 1989; 18: 320 322. Abstract. The results on the oral surgical management of patients with coagulation disorders at the Karolinska Hospital, Stockholm, during the period 1974-1985 have been compiled and compared with those obtained during the period 1965-1973. The present study included 380 tooth extractions performed in 250 treatment sessions in 107 patients. The incidence of postoperative bleeding and duration of hospitalization were reduced during the period of investigation.
In the late sixties there was still a substantial risk of protracted and uncontrollable hemorrhage in patients with coagulopathies following complicated, as well as simple tooth extractions 2'8. During the last 20 years the prognosis after performing extensive oral surgery in such patients, has improved significantly2~,8,12-15. The major factors contributing to the improvement of hemostatic control are: 1) coagulation factor concentrates; 2) antifibrinolytic substances to control the local fibrinolysis; 3) antibiotics to reduce the local bacterial infection, which stimulates local fibrinolysisS; 4) local measures to reduce hemorrhage, i.e. local hemostatics, suturing of a mucoperiosteal flap or an acrylic splintS,6,8,13. These measures have gradually been introduced over the last 25 years at t h e Karolinska Hospital and 3 periods with different treatment protocols can be distinguished. During treatment period 1 (1965 1969), only factor concentrate and/or plasma was used. During treatment period 2 (1969-1971), antifibrinolytic agents and antibiotics were added, whereas during treatment period 3 (1972-1973) local hemostatic measures were introduced additionally. In 1975 RAMSTROM & BLOMB~.CK reported their experiences with these 3 treatment protocols (Table 1)8. The present report covers the time period 1974-1985 when the patients were treated mainly accord-
ing to the protocol of period 3. The aim of this study was to investigate whether the clinical results reported in 1975 were still the same or had even improved.
Key words: hemophilia; von Willebrand's disease; tooth extraction; fibrinolytic inhibitors. Accepted for publication 24 August 1989
were included, as were 1 patient with Aldrich's syndrome and 1 with a severe form of thrombasthenia Glanzmann. Operative procedure
Material and methods
The material comprised 107 patients treated at the Department of Oral and Jaw Diseases at the Karolinska Hospital during 1974-1985. Definitions of patient material
Severe forms of Hemophilia A or B: <0.01 IU/ml of coagulation F VIII:C or F IX respectively; moderate forms: 0.01-0.05 IU/ml. Severe form of yon Willebrand's disease (type III): prolonged bleeding time, FVIII:C <0.05 IU/ml; von Willebrand factor antigen (vWF:Ag) <0.12 IU/ml, and v W F functional activity (Ristocetin cofactor activity) < 0.08 U/ml. I N types I and II the limits for functional vWF activity were arbitrarily set <0.08, 0.09-0.20 and 0.21-0.50 U/ml for severe, moderate and mild forms, respectively. All patients with the severe form and most patients with the moderate form had a prolonged bleeding time. The distribution of the patient material as to these disorders is given in Table 2. Three patients with factor X deficiency (0.05-0.10 U/ml), 4 with factor X I deficiency (0.05-0.10 U/ml) and 1 with factor X I I deficiency ( < 0.05 U/ml)
A total of 380 teeth and retained roots were extracted (including 1 preprosthetic operation) in 250 treatment sessions. Ninety-one of the extracted teeth consisted of 3rd molars, 63 of which were impacted or partially impacted. In these cases and in 49 other cases a mucoperiosteal flap was reflected. All extractions were performed by the same surgeon. In all cases except 1 patient, in whom intubation anesthesia was used, the extractions and/or operations were carried out using local anesthesia (Xylocain-Exadrin® 2%, Astra, Sweden). No hematomas were seen after the injections. In m o s t cases (203 of 250 treatment sessions) the gingiva was sutured over the alveolus. Whenever acrylic splints were used (32 treatment sessions), they were prepared according to the Omnivac method. As local hemostatic agent Thrombase Dentaire (Laboratories ISH, France) or Surgicel (Johnson & Johnson, USA) was used. A treatment session is defined as the time from the start of treatment or of hospitalization until the postoperative course had been uneventful for 5-7 days. One treatment session could include one or more extractions. In 181
Oral surgery in hemophiliacs Table 1. Excerpts from the results of Ramst6m & Btomb/ick8
Period
No. extr. teeth
No. sess. with postop. bleed/Total no. No./no. %
Hemophilia A severe form
1 2 3
6 26 12
7.5 3.7 2.6
3260 1592 438
3/3 5/13 2/6
100 38 33
Hemophilia A moderate form
1 2 3
37 18 5
3.0 1.6 0.6
974 456 100
7/9 0/3 0/2
78 0 0
Hemophilia A mild form
1 2 3
31 22 20
3.0 0.8 0
802 93 0
8/11 4/9 1/11
73 44 9
Hosp. No. factor days/tooth units/tooth
sessions l tooth, in 49 sessions 2 teeth, in 19 sessions 3-10 teeth and in one treatment session 17 teeth were extracted.
tution therapy. M i n o r hemorrhage, which could be controlled by suturing or an acrylic splint, was not regarded as postoperative bleeding.
Replacement therapy and other medical treatment
Results
The results are summarized in Table 2. The amounts of concentrates given per extracted t o o t h were generally higher during the studied period than previously. M o s t of the patients were treated as outpatients. The number o f days in hospital per t o o t h was reduced from 0.9 to 0.2. The frequency of postoperative bleeding was reduced from 10% to 2.7% of the treatment sessions. Bleeding in the case with mild hemophilia A (Table 2) occurred 2 days after surgical removal of a canine tooth with a fractured root. In 11 patients, 4 with mild hemophilia, minor hemorrhages occurred which stopped by using a splint only. Factor VIII:C inhibitors were registered in 2 patients with hemophilia A. In one case extractions were done at
The following factor concentrates were used: for hemophilia A Hemophil, Travenol (USA), A H F and Octonativ, Kabi (Sweden); for hemophilia B Preconativ, Kabi, and for von Willebrand's disease A H F , Kabi. In patients with severe hemophilia and severe yon Willebrand's disease a single substitution dose was given immediately before surgery. The given a m o u n t was calculated to yield a plasma concentration of 0.08-0.10 I U / ml for hemophiliacs and of 0.15-0.20 I U / m l in von Willebrand patients. Treatment with Cyklokapron ® (1 g 3 times daily), and Penicillin V (1 g twice daily), both given orally, was started 1 h prior to surgery and continued for 1 week postoperatively. Postoperative bleeding was defined as a bleeding requiring additional substi-
321
two sessions. The first time, when the inhibitor titer was low, he was treated with 600 units of Factor VIII concentrate and tranexamic acid p.o., whereas at the second session he received Autoplex (Travenol), 50 U / k g bw and tranexamic acid p.o. and locally. The other patient had a low inhibitor titer and was treated with 500 I U F VIII:C concentrate and tranexamic acid. One patient with severe von Willebrand's disease had a low titer of antibody against von Willebrand factor. In 2 sessions a primary tooth was extracted using tranexamic acid p.o. only. In 8 patients with a deficiency of factors X, XI or XII a total of 26 teeth were extracted in 20 treatment sessions. They were only given antifibrinolytics and antibiotics and no postoperative bleedings were recorded. One patient with a severe form of thrombasthenia G l a n z m a n n and 1 patient with Aldrich syndrome were treated with platelet concentrates and tranexamic acid before extraction. In these patients 4 teeth were extracted in 4 treatment sessions. There were no significant postoperative bleedings in these patients.
Discussion
The present study covers many years and during this period some changes in the general management of hemophilia have been introduced. For instance, the a m o u n t of factor concentrates administered prophylactically has increased dramatically. The concentrates also contain larger amounts of active factor, i.e. 500 or 1,000 I U F VIII:C per bottle, in comparison with previous concen-
Table 2. Number of patients, treatment sessions, extracted teeth, days in hospital, factor units transfused and postoperative bleeding. Comparison between earlier study period 3 (A) and present study (B) No. extr. teeth A B
No. days in hospital/ extr. tooth (mean) A B
No. and % of treatment sessions with postop. bleeding 1 A % B %
Coagulation disorder A severe A moderate A mild
6 2 8
15 14 21
6 2 11
22 26 53
12 5 20
32 62 63
2.6 0.6 -
0.9 0.3 _2
438 100 0
710 232 _2
2 0 1
33 0 9
1 3 1
5 12 2
B severe B moderate B mild
4 1
12 3 1
5 3
21 12 1
6 3
32 23 2
3.5 0
0.1
500 0
640 239 0
1 0
20 0
0 0 0
0 0 0
vW severe vW mild
7
6 25
13
12 79
18
31 105
-
0
0.55 0
139 0
0
0
1 0
8 0
28
97
40
226
64
350
0.9
0.2
-
-
4
10
6
2.7
Total
No. treatmerit sessions A B
Factor units/extracted tooth (mean) A B
No. patients A B
1.5
0
z Bleedings requiring substitution therapy. 2 One patient with hemophilia A mild form was hospitalized for 5 days after a postoperative bleeding. He was given 540 units of factor VIII.
322
R a m s t r 6 m et al.
trates. Therefore, the patients, and especially children, often received m o r e concentrate than required to increase their level to 0.08-0.10 IU/ml. Postoperative bleedings in hemophilia A patients were reduced from 16 to 5% as compared with the previous study. This could partly be due to the higher doses of concentrates used and to a better local management o f the patients. M o r e patients were subjected to extensive surgery than in the previous study. However, the extent o f the operation does not seem to affect the tendency to postoperative bleeding, provided that postoperative complications, such as infections or bone-sequesters, do not occur. With our present policy, and in spite of the more extensive surgery, the m e a n hospital stay has been reduced from 2.1 days to 0.5 days per tooth in patients with severe and moderate hemophilia A (Table 2). Our results show that oral surgery in patients with serious coagulation disorders can be performed with the same predictable success as in patients with normal hemostasis. In patients with mild hemophilia A and von Willebrand's disease the need for factor concentrates can be further minimized by the use of desmopressin, a synthetic analogue of vasopressin, which increases the level of the factor VIII:Cv W F complex 3,16. This drug can also be used in certain forms of platelet dysfunctions, since it may normalize an abnormal bleeding time 1°. Several reports 1,2,4,5,s,9'15 have shown that by the use of antifibrinolytic agents the need for substitution therapy in hemophilia patients is dramatically reduced. This is further confirmed in our s t u d y . SINDET-PEDERSEN 11 and STAJCIC 12 have demonstrated that m o u t h rinsing with fibrinolytic inhibitors can further reduce the frequency of hemorrhages and the quantity of substitution ther-
apy. Thus, the results obtained in the present study may further be improved, if m o u t h rinsing is combined with the principles as described above. The necessity of treating local infections with antibiotics has been shown s. The rationale behind this policy has been explained by PLOW 7, who demonstrated that proteases (elastase and cathepsin) released from neutrophils can cause fibrin degradation, which is not inhibited by tranexamic acid. Unsuccessful treatment o f infections, therefore, probably accounts for some postoperative bleeding in this study. In conclusion, this study has shown that the management of patients with hemostatic disorders, who have to undergo oral surgery, has improved over the last 11 years (1974-1985) c o m p a r e d with our previous study. This study has also confirmed the importance of managing the local fibrin degradation by the use of antifibrinolytic and bacteriostatic agents in addition to substitution therapy. References 1. BJORLING, NILSSONIM. Fibrinolytic activity in alveoli after tooth extraction. Odontol Revy 1968: 19: 197-204. 2. BJ(}RLIN G, NILSSON IM. Oralkirurgiska ingrepp p~t patienter med koagulopatier. III. Swed Dent J 1972: 65: 431-40. 3. GH1RARDINIA, CHISTOLINIA, FIR1NDELLI MC, et al. Clinical evaluation of subcutaneously administered DDAVP. Thromb Res 1988: 49: 363-72. 4. GIORDANO ND, WATKINS RS, RADIVOYVITCH M, GOODSITT E. Dental extractions in hemophilic patients on aminocaproic acid prophylaxis. Oral Surg 1968: 26: 160-6. 5. KANEDA T, SH1K1MORIM, WATANABEI, et al. The importance of local hemostatic procedures in dental extractions and oral mucosal bleeding of hemophiliac patients. Int J Oral Surg 1981: 10: 266-71. 6. PIZZON1 D, CORTELLAROM, MANNUCCI PM. Replacement therapy and local measures for dental extractions in hemo-
philiacs: a comparison of various schemes of treatment. VIIth Congr Wld Fed Haemophilia. Teheran 1971. Excerpta Med 1973: 252: 242-4. 7. PLOW EF. The major fibrinolytic proteases of human leucocytes. Biochim, Biophys Acta 1980: 630: 47-56. 8. RAMSTROMG, BLOMBACKM. Tooth extractions in hemophiliacs. Int J Oral Surg 1975: 4: 1-17. 9. REIDWO, LUCASON, FRANSISCOJ, GEISLER PH, ERSLEVAJ. The use of epsilonaminocaproic acid in the management of dental extractions in the hemophiliac. Am J Med Sci 1964: 84: 184-8. 10. SCHULMANS, JOHNSSONH, EGBERG N, BLOM~CK M. DDAVP induced correction of prolonged bleeding time in patients with congenital platelet function defects. Thromb Res 1987: 45: 165-74. 11. SINDET-PEDERSENS, STENBJERGS. Effect of local antifibrinolytic treatment with tranexamic acid in hemophiliacs undergoing oral surgery. J Oral Maxillofac Surg 1986: 44:703 7. 12. STAmlC Z. The combined local/systemic use of antifibrinolytics in hemophiliacs undergoing dental extractions. Int J Oral Surg 1985: 14: 339M5. 13. SZPIRGLASH. L'h6mostase locale dans les extractions dentaire chez l'h6mophile. Thromb Diath Haemorrh 1971: Supp143: 247-53. 14. VINCKXERF, VBRMY~ENJ. Dental extractions in hemophilia: Reflections in l0 years' experience. Oral Surg 1985: 59: 64. 15. WALSH P, RIZZA CR, MATTHEWSJM et al. Epsilon-aminocaproic acid therapy for dental extractions in haemophilia and Christmas disease; A double blind controlled trial. Br J Haematol 1971: 20: 463-75. 16. WILLIAMSONR, EGGLESTONDJ. DDAVP and EACA used for minor oral surgery in yon Willebrand disease. Aust Dent J 1988: 33: 32-6.
Address: G6ran Ramstr6m Dept. of Oral and Jaw Diseases Karolinska Hospital S-10401 Stockholm Sweden