- Email: [email protected]
Synovectomy in the treatment of hemophilic arthropathy
Synovectomy in the Treatment of Hemophilic Arthropathy By Barbara Dyszy-Laube, Wojciech Kaminski, lrena Gizycka. Danuta Kaminska, Joanna Sekowska-Zmuda, and Elzbieta Ludert
I
N POLAND THERE ARE approximately 3000 hemophiliacs, but in spite of this small number among the total population, these patients require frequent hospitalization, and treatment costs are very high. In hemophilia the lack of antihemophilic factor can be regarded as an intrinsic factor preventing coagulation; in addition, the low thromboplastic activity in the tissues of joints, particularly the knee joint, can be regarded as an extrinsic factor; and even when clotting has been encouraged by the administration of factor VIII in any form, fibrinolysis occurs quickly because there is a raised fibrinolytic activity in the joint especially when the synovial membrane is hypertrophic after numerous recurrent hemorrhages. PATHOLOGIC
CHANGES
Hemophilic arthropathy involving progressive destruction of the joint is one of the commonest lesions in hemophilia. From the time of the first intra-articular bleed the synovial membrane undergoes typical pathologic changes corresponding closely to the clinical and radiologic picture.1vz Stage I: Hypertrophy and angiomatow change. The synovial membrane is covered with a network of very fragile thin-vvalled varicose veins often forming plexuses. Cartilage at this stage is normal. The varicose plexuses have disapStage II: Hypertrophy and pigmentation. peared, the synovial membrane is thinner, and tobacco brown in color. The surface of the synovial membrane is more compact and partly villous. Marked deposition of iron is visible. The articular cartilage is rough. Stage Ill: Hypertrophy and fibrosis. The final fibrous involution of the synovial membrane has occurred with numerous islands of connective tissue. There is no remaining cartilage but only compact yellowish bone and the joint is ankylosed. These characteristics in stage I suggest that the slightest trauma is sufficient to cause bleeding. MATERIAL
AND METHODS
Since 1971 we have performed synovectomies in 14 cases of hemophilia using the techniques of Storti and his colleagues.1-8 The patients were boys aged 6-16 yrs; all of them had been confined to bed for several months before operation because of recurrent intra-articular hemorrhages with up to 20 bleeds
From the First Pediatric Clinic of the Medical Faculty and the First Pediatric Surgical Clinic of the Medical Faculty, Warsaw, Poland. Presented before the 20th International Congress of British Paediatric Surgeons, London, England, July 25-27,1973. Address for reprint requests: Irene Gizycka. Klinika Chirurgii Dzieciecej, Warszawa. ul. Litewska 16. Poland. o 1974 by Grune & Stratton, Inc. Journal of Pediatric Surgery, Vol. 9, No. 1 (February), 1974
123
DYSZY-LAUBE
124
ET AL.
Table 1. AHG Case No.
Age (vr)
13 2
8
Serum
Flbrinolytlc
Level
(% of normal
Degree
of
valuel
Arthropathy
Actiwty (r/g)
Thromboplastic Activny (%)
Results of Synovectomy
0
414
2
Excellent
0.3
459
4
Improved
3
9
0
369
3.5
Excellent
4
7
0.5
207
3.5
Improved
5
9
2
576
2
Improved
6
15
3
1080
4.5
Improved
7
13
2.2
270
2
Improved
8
7
0.1
666
4.5
Excellent
9
6
0
756
2
Excellent
10
8
0.7
900
2
11
8
2
12
10
1.8
Improved
13
9
0
Improved
14
18
0
Uncertain
Improved Improved
in a year. None of them had been able to continue at school and they were becoming increasingly severely handicapped. Substitutive treatment before, during, and after operation was provided by repeated administration of cryoprecipitate of antihemophilic factor in a dosage of 15 cc/kg/day. With increasing experience in management of hemophilic patients after synovectomy we have limited the course of antihemophilic factor to 5 days only including the day of operation. The plasma-derivative therapy was supplemented by intensive systemic and local antitibrinolytic therapy as follows: (1) At the end of operation 200,000 units of Frey’s parotid inhibitor (Trasylol) was introduced into the joint. (2) Epsilon-aminocaproic acid was given orally for 3 wk starting a day before the operation. The standard dosage was 0.3-0.4 g/kg/day in six divided doses.B RESULTS AND
DISCUSSION
Synovectomy must be viewed chiefly as a “hemostatic” procedure.7 It is indicated for recurrent hemarthrosis in the same joint causing impaired function. Synovectomy of the knee joint was performed upon 14 boys. All of them had repeated administration of antihemophilic factor. The plasma level of this factor was maintained at about 30% of normal value, which provided effective hemostasis. This therapy was always supplemented by local and systemic antifibrinolytic management. The follow-up in 14 patients is from several weeks up to 2 yr, and results of synovectomy are impressive in all. (1) There has been no bleeding into the affected joint after treatment. (2) All patients are mobilized and attending school. (3) The range of mobility of the knee joint is improved in all. Full extension of the knee is difficult to obtain, especially the last 5”) although this does not seriously impair function. In three patients in whom no improvement was achieved after 6 mo in traction, full extension was obtained after several days’ direct pressure on the knee by a sheet of soft material tied to the bed. Because of a persistent tendency to contracture in two boys, an orthopedic apparatus was applied which kept the knee extended during walking and allowed flexion in the sitting position.
HEMOPHILIC
ARTHROPATHY
125
The functional capacity of the treated knee depends directly upon the degree of destruction preoperatively. Because functional improvement is slow, final judgment can not be expressed for at least 1 yr after operation. In estimating prognosis, the extent of quadriceps atrophy before operation is very important. The more severe the atrophy the greater will be the necessity for prolonged and laborious physiotherapy. The fibrinolytic activity was estimated according to the method of Astrup and Albrechtsen.8pQThe plasminogen activator from pig’s heart was used as a standard. In all specimens the fibrinolytic activity was raised, being from 207 to 1085 units/g tissue; the normal values given by Astrup and Sjorlinlo vary from 25 to 185 units/g tissue. The thromboplastic activity of the synovial membrane was compared with the same activity of human brain. The results were very low, from 2% to 4.5%. Excision of tissu,: actively producing enzymes reduces the total amount of bleeding episodes in other locations than the joint operated upon. After synovectomy in only two cases was there limited bleeding into another joint. This fact has a considerable beneficial psychological effect on the patient allowing him to lead a normal life, continue his school education, and even join in limited sports. SUMMARY
Excised synovial membrane was examined for fibrinolytic and thromboplastic activity. Late results of synovectomy are uniformly satisfactory. Fourteen boys, 6-16 yr old, with hemophilic arthropathy of the knee, were treated by synovectomy. Excised synovial membrane was examined for fibrinolytic and thromboplastic activity. The results of synovectomy are satisfactory. Follow-up is from several weeks to 2 yr. REFERENCES 1. Jordan H: Hemophilic Arthropathies. Springfield, III., Thomas, 1958 2. Storti E, Traldi A, Tosatti E, et al: Synovectomy, a new approach to hemophilic arthropathy. Acta Haematol41:4, 1969 3. Boni M, Ceciliani L: La synoviectomia de1 ginocchio. LVII Congr. Sot. Ital. Ortoped. Traumatologia. Bologna, Oct. 2-5, 1972 4. Storti E, Traldi A, Tosatti E, et al: Synovectomy in hemophilic arthropathy. Schweitz Med Wochenschr 100:2005, 1970 5. Storti E, Ascari E, Magrini U: L’activite fibrinolytique dam la synoviale hemophilique. Recherches histochimiques. Schweiz Med. Wocheuschr 102:1614:1972 6. Dyszy-Laube B, Kaminski W, Gizycka I, et al: Synowektomia w leczeniu artropatii he-
mofilowych u dziechi. Mem. III Congr. of Pol Paed. Surg. Sot. Warsaw 1973 7. Storti E, Ascari E, Molinari E, et al: Artropatia emofilica. LVII Congr. Sot. Ital. Ortoped. Traumatologia. Bologna, Oct. 2-5, 1972 8. Astrup T, Albrechtsen OK: Estimation of the plasminogen activator and the tripsin inhibitor in animal and human tissues. Stand J Clin Lab Invest 9:233, 1957 9. Astrup T, Mtillertz S: The fibrin plate method for estimating fibrinolytic activity. Arch Biochem Biophys 40:346, 1952 10. Astrup T, Sjiirlin KE: Thromboplastic and fibrinolytic activity of human synovial membrane and fibrous capsular tissue. Proc Sot Exp Biol Med 97:852, 1958
I
N POLAND THERE ARE approximately 3000 hemophiliacs, but in spite of this small number among the total population, these patients require frequent hospitalization, and treatment costs are very high. In hemophilia the lack of antihemophilic factor can be regarded as an intrinsic factor preventing coagulation; in addition, the low thromboplastic activity in the tissues of joints, particularly the knee joint, can be regarded as an extrinsic factor; and even when clotting has been encouraged by the administration of factor VIII in any form, fibrinolysis occurs quickly because there is a raised fibrinolytic activity in the joint especially when the synovial membrane is hypertrophic after numerous recurrent hemorrhages. PATHOLOGIC
CHANGES
Hemophilic arthropathy involving progressive destruction of the joint is one of the commonest lesions in hemophilia. From the time of the first intra-articular bleed the synovial membrane undergoes typical pathologic changes corresponding closely to the clinical and radiologic picture.1vz Stage I: Hypertrophy and angiomatow change. The synovial membrane is covered with a network of very fragile thin-vvalled varicose veins often forming plexuses. Cartilage at this stage is normal. The varicose plexuses have disapStage II: Hypertrophy and pigmentation. peared, the synovial membrane is thinner, and tobacco brown in color. The surface of the synovial membrane is more compact and partly villous. Marked deposition of iron is visible. The articular cartilage is rough. Stage Ill: Hypertrophy and fibrosis. The final fibrous involution of the synovial membrane has occurred with numerous islands of connective tissue. There is no remaining cartilage but only compact yellowish bone and the joint is ankylosed. These characteristics in stage I suggest that the slightest trauma is sufficient to cause bleeding. MATERIAL
AND METHODS
Since 1971 we have performed synovectomies in 14 cases of hemophilia using the techniques of Storti and his colleagues.1-8 The patients were boys aged 6-16 yrs; all of them had been confined to bed for several months before operation because of recurrent intra-articular hemorrhages with up to 20 bleeds
From the First Pediatric Clinic of the Medical Faculty and the First Pediatric Surgical Clinic of the Medical Faculty, Warsaw, Poland. Presented before the 20th International Congress of British Paediatric Surgeons, London, England, July 25-27,1973. Address for reprint requests: Irene Gizycka. Klinika Chirurgii Dzieciecej, Warszawa. ul. Litewska 16. Poland. o 1974 by Grune & Stratton, Inc. Journal of Pediatric Surgery, Vol. 9, No. 1 (February), 1974
123
DYSZY-LAUBE
124
ET AL.
Table 1. AHG Case No.
Age (vr)
13 2
8
Serum
Flbrinolytlc
Level
(% of normal
Degree
of
valuel
Arthropathy
Actiwty (r/g)
Thromboplastic Activny (%)
Results of Synovectomy
0
414
2
Excellent
0.3
459
4
Improved
3
9
0
369
3.5
Excellent
4
7
0.5
207
3.5
Improved
5
9
2
576
2
Improved
6
15
3
1080
4.5
Improved
7
13
2.2
270
2
Improved
8
7
0.1
666
4.5
Excellent
9
6
0
756
2
Excellent
10
8
0.7
900
2
11
8
2
12
10
1.8
Improved
13
9
0
Improved
14
18
0
Uncertain
Improved Improved
in a year. None of them had been able to continue at school and they were becoming increasingly severely handicapped. Substitutive treatment before, during, and after operation was provided by repeated administration of cryoprecipitate of antihemophilic factor in a dosage of 15 cc/kg/day. With increasing experience in management of hemophilic patients after synovectomy we have limited the course of antihemophilic factor to 5 days only including the day of operation. The plasma-derivative therapy was supplemented by intensive systemic and local antitibrinolytic therapy as follows: (1) At the end of operation 200,000 units of Frey’s parotid inhibitor (Trasylol) was introduced into the joint. (2) Epsilon-aminocaproic acid was given orally for 3 wk starting a day before the operation. The standard dosage was 0.3-0.4 g/kg/day in six divided doses.B RESULTS AND
DISCUSSION
Synovectomy must be viewed chiefly as a “hemostatic” procedure.7 It is indicated for recurrent hemarthrosis in the same joint causing impaired function. Synovectomy of the knee joint was performed upon 14 boys. All of them had repeated administration of antihemophilic factor. The plasma level of this factor was maintained at about 30% of normal value, which provided effective hemostasis. This therapy was always supplemented by local and systemic antifibrinolytic management. The follow-up in 14 patients is from several weeks up to 2 yr, and results of synovectomy are impressive in all. (1) There has been no bleeding into the affected joint after treatment. (2) All patients are mobilized and attending school. (3) The range of mobility of the knee joint is improved in all. Full extension of the knee is difficult to obtain, especially the last 5”) although this does not seriously impair function. In three patients in whom no improvement was achieved after 6 mo in traction, full extension was obtained after several days’ direct pressure on the knee by a sheet of soft material tied to the bed. Because of a persistent tendency to contracture in two boys, an orthopedic apparatus was applied which kept the knee extended during walking and allowed flexion in the sitting position.
HEMOPHILIC
ARTHROPATHY
125
The functional capacity of the treated knee depends directly upon the degree of destruction preoperatively. Because functional improvement is slow, final judgment can not be expressed for at least 1 yr after operation. In estimating prognosis, the extent of quadriceps atrophy before operation is very important. The more severe the atrophy the greater will be the necessity for prolonged and laborious physiotherapy. The fibrinolytic activity was estimated according to the method of Astrup and Albrechtsen.8pQThe plasminogen activator from pig’s heart was used as a standard. In all specimens the fibrinolytic activity was raised, being from 207 to 1085 units/g tissue; the normal values given by Astrup and Sjorlinlo vary from 25 to 185 units/g tissue. The thromboplastic activity of the synovial membrane was compared with the same activity of human brain. The results were very low, from 2% to 4.5%. Excision of tissu,: actively producing enzymes reduces the total amount of bleeding episodes in other locations than the joint operated upon. After synovectomy in only two cases was there limited bleeding into another joint. This fact has a considerable beneficial psychological effect on the patient allowing him to lead a normal life, continue his school education, and even join in limited sports. SUMMARY
Excised synovial membrane was examined for fibrinolytic and thromboplastic activity. Late results of synovectomy are uniformly satisfactory. Fourteen boys, 6-16 yr old, with hemophilic arthropathy of the knee, were treated by synovectomy. Excised synovial membrane was examined for fibrinolytic and thromboplastic activity. The results of synovectomy are satisfactory. Follow-up is from several weeks to 2 yr. REFERENCES 1. Jordan H: Hemophilic Arthropathies. Springfield, III., Thomas, 1958 2. Storti E, Traldi A, Tosatti E, et al: Synovectomy, a new approach to hemophilic arthropathy. Acta Haematol41:4, 1969 3. Boni M, Ceciliani L: La synoviectomia de1 ginocchio. LVII Congr. Sot. Ital. Ortoped. Traumatologia. Bologna, Oct. 2-5, 1972 4. Storti E, Traldi A, Tosatti E, et al: Synovectomy in hemophilic arthropathy. Schweitz Med Wochenschr 100:2005, 1970 5. Storti E, Ascari E, Magrini U: L’activite fibrinolytique dam la synoviale hemophilique. Recherches histochimiques. Schweiz Med. Wocheuschr 102:1614:1972 6. Dyszy-Laube B, Kaminski W, Gizycka I, et al: Synowektomia w leczeniu artropatii he-
mofilowych u dziechi. Mem. III Congr. of Pol Paed. Surg. Sot. Warsaw 1973 7. Storti E, Ascari E, Molinari E, et al: Artropatia emofilica. LVII Congr. Sot. Ital. Ortoped. Traumatologia. Bologna, Oct. 2-5, 1972 8. Astrup T, Albrechtsen OK: Estimation of the plasminogen activator and the tripsin inhibitor in animal and human tissues. Stand J Clin Lab Invest 9:233, 1957 9. Astrup T, Mtillertz S: The fibrin plate method for estimating fibrinolytic activity. Arch Biochem Biophys 40:346, 1952 10. Astrup T, Sjiirlin KE: Thromboplastic and fibrinolytic activity of human synovial membrane and fibrous capsular tissue. Proc Sot Exp Biol Med 97:852, 1958