Major Orthopedic Reconstructions in an Inhibitor Patient – A Case Report
U. Stumpf, C. Eberhardt, M. Krause, W. Miesbach, I. Scharrer and A. A. Kurth
Abstract
Inhibitors against FVIII or FIX in patients with hemophilia are a common and serious complication. Until recently elective surgery was associated with major bleeding despite of a substitution therapy. Only emergency medical care was done if necessary. We report about one patient with hemophilia A and inhibitors who underwent 3 major reconstructions of the right knee. Because of severe joint destruction due to hemophilic arthropathy a total knee replacement was necessary.
After half a year a periprosthetic fracture of the femur occurred. An open reduction and an internal fixation was performed. In the rehabilitation phase after the second operation a second fracture of both the hardware and the bone occurred. We were faced with the problem, that we had to remove the distal part of the femur and the joint replacement and reconstruct it with a mega-tumor prosthesis. This is to our knowledge the first patient with inhibitors undergoing such a complicated recon- struction of a limb. All operations were done under factor VIIa substitution. Even in this high risk patient the operations were done without any bleeding complications.
After a follow up of nine months after the last operation no complications like infections, recurrent bleedings, or limited range of motion were seen.
Introduction
Patients with hemophilia A (FVIII deficiency) or hemophilia B (FXI deficiency) who receive factor concentrates may develop antibodies (IgG) to factors and pre- vent their effectiveness. This development of FVIII inhibitors remains one of the most serious complications in the treatment of patients with hemophilia. The inci- dence of inhibitors is about 5–32 % [1]. New prospective studies confirmed that young children with severe hemophilia A are at highest risk of inhibitor develop- ment [1]. Until recently elective surgery was mostly associated with major bleeding despite a substitution therapy. Only emergency care was done if necessary.
Recombinant FVIIa (rFVIIa, NovoSeven) is a potentially effective hemostatic drug.
Its beneficial effect was demonstrated in hemophilia patients with inhibitors to FVIII or FIX in several trials [2, 3] and the use of rFVIIa in these patients is gene- rally perceived [4]. NovoSeven (rFVIIa) is a recombinant product, which contains no human derivates and no traces of FXIII or FIX. So no rise of inhibitor titres
I. Scharrer/W. Schramm (Ed.)
34thHemophilia Symposium Hamburg 2003
” Springer Medizin Verlag Heidelberg 2005
under this treatment must be expected. Recurrent spontaneous hemarthros results in significant joint damage and require surgical intervention. Contrary to some pre- dictions that the use of prophylaxis would eliminate orthopedic complications of hemophilia there will be a need for orthopedic surgery because of the more active living of the patients, which may result in more sports related injuries, and an aging population with an increase of degenerative arthritis.
Case Report
A 43-year-old male patient suffers from a severe hemophilia A with an inhibitor. He is HIV and HCV, HBV and HAV positive. He has a very active daily living with sports and motor-biking. He had to undergo three major reconstructions of the right knee within 8 months. As a result of recurrent hemarthros he developed a severe hemo- philic arthropathy over years involving several joints. He already got an arthrodesis of the right elbow in 1998 and of the left knee in 1999. His right knee showed pro- gressive loss of function with maximal limitation of range of motion and difficulties to walk. Based on this the indication for elective joint replacement was given. All fol- lowing substitutions of rFVIIa (NovoSeven)/ tranexamic acid (Anvitoff)/ Feiba were done in close interdisciplinary cooperation with the hemophilia ambulance of the University Hospital Frankfurt/Main (Prof. Scharrer). The first operation, the implan- tation of a cemented constrained hinge knee replacement, was done under substitu- tion in combination with Feiba (prothrombin complexes), NovoSeven (rVIIa) and Anvitoff (tranexamic acid). Postoperative course showed no further bleedings, no infections, and under physiotherapy full weight-baring after 6 weeks. A sufficient function of the knee with a flexion of 90° could be achieved. Only six months later a traumatic periprosthetic fracture of the right femur occurred. Under immediately started substitution with NovoSeven (rFVIIa) and Anvitoff (tranexamic acid) an osteosynthesis with LCDC-plate could be done. Five days after surgery the substitu- tion could be changed from Novo Seven/Anvitoff to Feiba. In the postoperative cour- se the patient was restricted to no weight bearing for eight weeks. The further mobi- lization was good, and no further complications like bleeding episodes or infections occurred. Two months after this second operation we were faced with another frac- ture of the right femur (secondary dislocated spiral femur fracture with loosening of the implanted osteosynthesis material of the femur fracture), which took place within the first weight-baring test of physiotherapy without trauma.
Because of the large bone defect in the right distal femur we decided to implant a modular tumor prosthesis Type MUTARS (ImplantCast, Buxtehude, Germany).
For this application parts of the prosthesis were custom made. This prosthesis should replace the total right knee, bridge the bone defect of the distal femur (20 cm) and was anchored in the proximal 1/3 of the femur. During the time to manu- facture and deliver the implant the fracture was stabilized by an extension bandage with 5 kg and strict bed rest. The posttraumatic hematoma was controlled with a substitution of FEIBA (6000 IU 12h). Two days prior the third and largest operati- on, substitution was changed from Feiba to NovoSeven / Anvitoff to start surgery under optimal conditions. In this reconstruction of the right limb a bone defect of 56 U. Stumpf et al.
the distal femur of 24 cm had to be bridged. The proximal anchorage was achieved by outstanding of a part of the prosthesis between trochanter major and femur neck. During the implantation of the tibial part a fissure of the distal tibia occurred.
This was stabilized by cerclage-bandage. The resting holes of the trephine after the plate osteosynthesis in the femur were stabilized with cerclages, too. Intraoperative and postoperative hemostasis was secured with NovoSeven. Postoperative x-rays showed the properly positioned prosthesis and no further fracture of the remaining bone. Within the follow-up of the last nine months neither further bleeding episo- des, nor infections were seen. With regard to function a full range of motion was achieved. The rehabilitation started carefully: for the first eight weeks no weight- baring of the left leg was allowed, mobilization started with a wheel-chair. Weight- baring was slowly increased with scrutches, up to full weight-baring of the right limb was achieved. Flexion in the right knee within the first two weeks after surgery was only up to 60° allowed. Then flexion was carefully raised up to actually 90°.
Further x-ray controls showed no signs of loosening or fractures.
It is mandatory to reflect about the costs of such an outstanding procedure in an inhibitor patient. The substitutive therapy rFVIIa (NovoSeven) and Feiba: Knee prosthesis (Type Blauth): NovoSeven was € 1,015,004.52; LCDCP osteosynthesis:
€ 592,028.46 NovoSeven 444,847.66 €/Feiba 147,180.90 €). Implantation of MUTARS prosthesis right limb: 1,026,096.34 € (NovoSeven 879,292.02 €/Feiba 326,804.34 €).
The total reconstruction of the right limb with the necessary factor substitution was 2,813,129.32 €. Even in emergency situation we try to keep a close contact and give early information to the patients health insurance. In this special case all costs were reimbursed by the health insurance company.
Discussion
We conclude that it is possible to perform major reconstruction of a limb even in patients with hemophilia A and inhibitors. Under therapy with NovoSeven the Major Orthopedic Reconstructions in an Inhibitor Patient – A Case Report 57
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11.4.
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D-Dimere /µg/L)
Fig. 1. Course of d-dimers Feiba/NovoSeven/Feiba
bleedings are intraoperative under control even in operations with large wounds.
This is to our knowledge the first patient with inhibitors undergoing such a com- plicated reconstruction of a limb.
The incidence of infection after surgery is higher in patients with hemophilia, HIV and hepatitis C infection than in the general population. We are aware of this risk and avoided infection by combined antibiotic prophylaxis intra- and postope- rative. However, the benefits of this procedure are substantial and must be weighed against the risks.
Substitutive treatment is always a combination; successful hemostasis is not possible without adverse events: one of the adverse events of Feiba (prothrombin complexes) is the increase of d-dimers under treatment; tranexamic acid (Anvitoff) is used for inhibition of fibrinolysis under NovoSeven. The increasing of d-dimers level was in the expected range after such large operations, if it is getting too high due to the experience of our hemophilia center this was indication for us to reduce the units of Feiba per day.
After stabilizing the patient postoperatively we changed the therapy from NovoSeven to Feiba. The costs of such an procedure can not be judged disregarding the benefits of prevention of invalidity, the ability to return to work and the impro- vement of life quality.
References
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3. Lusher J et al. Recombinant Factor VIIa (NovoSeven) in the treatment of internal bleeding in patients with Factor VIII and IX inhibitors. Haemostasis 1996; 26 (suppl. 1): 124-130 4. Scharrer I. Recombinant factor VIIa for patients with inhibitors to factor VIII or IX or fac-
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