Surgery in Von Willebrand's Disease INGA MARIE NILSSON, M.D., SVEN-ERIK BERGENTZ, M.D., S. ANDERS LARSSON, M.D.
Fifty-eight major surgical procedures were performed in 38 patients with von Willebrand's disease (VWD), one of the most common of the inheritable hemorrhagic disorders. Specific treatment with fraction 1-0, (AHF-Kabi) in addition to a fibrinolytic inhibitor, was given to all patients. The effect of the treatment was checked by measuring the Duke bleeding time and factor VIII:C level. A marked difference between hemophilia and VWD from a surgical point of view is demonstrated. While most of the surgery in hemophiliacs is performed for severe joint deformities, contractures and blood cysts, surgery in VWD is mostly general surgery, often necessitated by massive hemorrhages from mucous membranes.
WILLEBRAND'S DISEASE (VWD), also called the Aland bleeding disease, is one of the most common of the inheritable hemorrhagic disorders. It was first recognized little more than 50 years ago by Erik von Willebrand. At that time the diagnosis was made on the basis of a prolonged bleeding time and an autosomal inheritance pattern. Almost 20 years later it was found that VWD was also characterized by decreased factor VIII activity.21 In 1957 and 1959 Nilsson and coworkers'9.20 showed that infusion of the then novel concentrate, human fraction I 08 to patients with VWD corrected the bleeding time and caused a prolonged increase in factor VIII activity. The same results were obtained whether fraction 1-0 was prepared from normal plasma or plasma from patients with severe hemophilia A. These findings were confirmed by several others and at that time it was concluded that the impaired hemostasis in VWD was due to lack of a plasma factor, the von Willebrand factor. It has been shown by several investigators that the platelets as such are normal in number and function.2024 Infusion of platelets has no effect on the bleeding symptoms in VWD. Recent advances in factor VIII biochemistry have shed new light on VWD. It has been well established that the von Willebrand factor is identical with a high molecular weight plasma protein, the factor VIII reV ON
Reprint requests: Sven-Erik Bergentz, Department of SurgeryMalmo General Hospital, 214 01 Malmo, Sweden. Supported by grants from the Swedish Medical Research Council
(B-79-19X-00087-15B); (B79-17X-00759-14C). Submitted for publication: March 12, 1979.
From the Coagulation Laboratory, and the Department of Surgery, Malmo General Hospital, University of Lund, Malmo, Sweden
lated protein. This protein can be measured quantitatively in plasma as factor VIII related antigen (VIIIR: Ag).2fi32 The von Willebrand factor is present not only in plasma, but also in platelets and in the vessel wall. The factor is necessary for a normal bleeding time, for adhesion of platelets to subendothelium, normalization of the glass bead retention of platelets and for aggregation of platelets with the antibiotic ristocetin.24 In Sweden about 1000 cases of VWD are known, corresponding to a prevalence of 10 in 100,000 inhabitants. The corresponding figure for hemophilia in Sweden is seven in 100,000. The most characteristic clinical feature of VWD is an increased tendency to bleeding from mucous membranes. In most cases the disease is inherited by an autosomal and dominant gene but in some cases with unusual clinical severity of the disease the transmission appears to be autosomal recessive.1'.24 Generally, the cases are classified as mild or severe according to clinical symptoms and the laboratory data. At least four genetic variants of VWD have now been distinguished.18 In the classical and most common form, type I, there is a quantitative defect of the factor VIII protein complex, i.e. the von Willebrand factor, and all activities associated with the protein are decreased. In the other types various qualitative molecular defects exist. Patients with type II have a structurally abnormal factor VIII related protein and the electrophoretic mobility of the protein is abnormally anodic. The different variants have identical clinical symptoms. Surgery in patients with VWD results, in about 60% of the cases, in severe, intra- and postoperative hemorrhage, unless specific treatment is given.30 In severe VWD this operative bleeding may be fatal. (For review see Silwer.30) The discovery that VWD is due to lack of a plasma factor has, since 1957, made it possible to give specific treatment of the condition with fraction 1-0. It has later
0003-4932/79/1200/0746 $00.85 © J. B. Lippincott Company
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VON WILLEBRAND'S DISEASE
been shown that also cryoprecipitate can be used in the treatment of the disease.4 Only a few series have been published of surgery in patients with VWD receiving specific treatment. Most of the publications are case reports,14 but a few compilations have appeared. Dudley'1 presented 65 operated children with bleeding disorders, 15 of whom had VWD. Adelman2 presented 171 surgical procedures carried out in 41 patients with von Willebrand's disease. Silwer3P summarized the Swedish experiences using fraction 1-0 and/or fresh plasma. In 38 operations abnormal bleeding was observed in some cases, but there was no mortality. In Malmo 58 operations have been performed since 1956 in patients with VWD, and receiving specific substitution therapy. The purpose of this paper is to report our experience from a surgical and a hematological point of view. Materials and Methods Clinical Material
The clinical material consists of 38 patients undergoing a total of 58 surgical procedures (Table 1). All the patients come from the Swedish compilation of TABLE 1. Number and Type of Operative Procedure
Procedure General surgery gastric surgery cholecystectomy appendectomy intestinal obstruction breast cancer varicose veins inguinal hernia miscellaneous
Gynecology hysterectomy* tubal resection uterine prolaps miscellaneous Ear-nose-throat surgery otosclerosis chronic otitis
tonsillectomy miscellaneous
Orthopedic surgery Dupuytrens' contracture myoplasty of quadriceps femoral exostosis
Number of Patients 9 6 3 2 2 2 2 8
34
5 2 1 3
11
2 2 2 3
9
747 TABLE 2. Classification of VWD.
Severe VWD.
Severe bleeding symptoms Duke bleeding time increased (usually >20 min) Ivy bleeding time >30 min.
VIII:C VIIIR:Ag VIIIR:RCF
Mild VWD
Type I.
Type II.
1-20%
Fifty-eight major surgical procedures were performed in 38 patients with von Willebrand's disease (VWD), one of the most common of the inheritable hemorrhagic disorders. Specific treatment with fraction 1-0, (AHF-Kabi) in addition to a fibrinolytic inhibitor, was given to all patients. The effect of the treatment was checked by measuring the Duke bleeding time and factor VIII:C level. A marked difference between hemophilia and VWD from a surgical point of view is demonstrated. While most of the surgery in hemophiliacs is performed for severe joint deformities, contractures and blood cysts, surgery in VWD is mostly general surgery, often necessitated by massive hemorrhages from mucous membranes.
WILLEBRAND'S DISEASE (VWD), also called the Aland bleeding disease, is one of the most common of the inheritable hemorrhagic disorders. It was first recognized little more than 50 years ago by Erik von Willebrand. At that time the diagnosis was made on the basis of a prolonged bleeding time and an autosomal inheritance pattern. Almost 20 years later it was found that VWD was also characterized by decreased factor VIII activity.21 In 1957 and 1959 Nilsson and coworkers'9.20 showed that infusion of the then novel concentrate, human fraction I 08 to patients with VWD corrected the bleeding time and caused a prolonged increase in factor VIII activity. The same results were obtained whether fraction 1-0 was prepared from normal plasma or plasma from patients with severe hemophilia A. These findings were confirmed by several others and at that time it was concluded that the impaired hemostasis in VWD was due to lack of a plasma factor, the von Willebrand factor. It has been shown by several investigators that the platelets as such are normal in number and function.2024 Infusion of platelets has no effect on the bleeding symptoms in VWD. Recent advances in factor VIII biochemistry have shed new light on VWD. It has been well established that the von Willebrand factor is identical with a high molecular weight plasma protein, the factor VIII reV ON
Reprint requests: Sven-Erik Bergentz, Department of SurgeryMalmo General Hospital, 214 01 Malmo, Sweden. Supported by grants from the Swedish Medical Research Council
(B-79-19X-00087-15B); (B79-17X-00759-14C). Submitted for publication: March 12, 1979.
From the Coagulation Laboratory, and the Department of Surgery, Malmo General Hospital, University of Lund, Malmo, Sweden
lated protein. This protein can be measured quantitatively in plasma as factor VIII related antigen (VIIIR: Ag).2fi32 The von Willebrand factor is present not only in plasma, but also in platelets and in the vessel wall. The factor is necessary for a normal bleeding time, for adhesion of platelets to subendothelium, normalization of the glass bead retention of platelets and for aggregation of platelets with the antibiotic ristocetin.24 In Sweden about 1000 cases of VWD are known, corresponding to a prevalence of 10 in 100,000 inhabitants. The corresponding figure for hemophilia in Sweden is seven in 100,000. The most characteristic clinical feature of VWD is an increased tendency to bleeding from mucous membranes. In most cases the disease is inherited by an autosomal and dominant gene but in some cases with unusual clinical severity of the disease the transmission appears to be autosomal recessive.1'.24 Generally, the cases are classified as mild or severe according to clinical symptoms and the laboratory data. At least four genetic variants of VWD have now been distinguished.18 In the classical and most common form, type I, there is a quantitative defect of the factor VIII protein complex, i.e. the von Willebrand factor, and all activities associated with the protein are decreased. In the other types various qualitative molecular defects exist. Patients with type II have a structurally abnormal factor VIII related protein and the electrophoretic mobility of the protein is abnormally anodic. The different variants have identical clinical symptoms. Surgery in patients with VWD results, in about 60% of the cases, in severe, intra- and postoperative hemorrhage, unless specific treatment is given.30 In severe VWD this operative bleeding may be fatal. (For review see Silwer.30) The discovery that VWD is due to lack of a plasma factor has, since 1957, made it possible to give specific treatment of the condition with fraction 1-0. It has later
0003-4932/79/1200/0746 $00.85 © J. B. Lippincott Company
746
VOl. 190.o NO. 6
VON WILLEBRAND'S DISEASE
been shown that also cryoprecipitate can be used in the treatment of the disease.4 Only a few series have been published of surgery in patients with VWD receiving specific treatment. Most of the publications are case reports,14 but a few compilations have appeared. Dudley'1 presented 65 operated children with bleeding disorders, 15 of whom had VWD. Adelman2 presented 171 surgical procedures carried out in 41 patients with von Willebrand's disease. Silwer3P summarized the Swedish experiences using fraction 1-0 and/or fresh plasma. In 38 operations abnormal bleeding was observed in some cases, but there was no mortality. In Malmo 58 operations have been performed since 1956 in patients with VWD, and receiving specific substitution therapy. The purpose of this paper is to report our experience from a surgical and a hematological point of view. Materials and Methods Clinical Material
The clinical material consists of 38 patients undergoing a total of 58 surgical procedures (Table 1). All the patients come from the Swedish compilation of TABLE 1. Number and Type of Operative Procedure
Procedure General surgery gastric surgery cholecystectomy appendectomy intestinal obstruction breast cancer varicose veins inguinal hernia miscellaneous
Gynecology hysterectomy* tubal resection uterine prolaps miscellaneous Ear-nose-throat surgery otosclerosis chronic otitis
tonsillectomy miscellaneous
Orthopedic surgery Dupuytrens' contracture myoplasty of quadriceps femoral exostosis
Number of Patients 9 6 3 2 2 2 2 8
34
5 2 1 3
11
2 2 2 3
9
747 TABLE 2. Classification of VWD.
Severe VWD.
Severe bleeding symptoms Duke bleeding time increased (usually >20 min) Ivy bleeding time >30 min.
VIII:C VIIIR:Ag VIIIR:RCF
Mild VWD
Type I.
Type II.
1-20%
