LETTERS TO THE EDITORS 11 Bleakley CM, Davison GW. Cryotherapy and inflammation: evidence beyond the cardinal signs. Phys Ther Rev 2010; 15: 430–5. 12 Loeser JD. Common Pain Problems: Guide to Practical Management. Darien, CT: Health Communications Inc, 1998: 11–3. 13 d’Young AI. Domiciliary application of CryoCuff in severe haemophilia: qualitative questionnaire and clinical audit. Haemophilia 2008; 14: 823–7.
14 Low J, Reed A. Electrotherapy Explained: Principles and Practice. Oxford: Butterworth & Heineman, 2000: 258–61. 15 Lavelle BE, Snyder M. Differential conduction of cold through barriers. J Adv Nur 1985; 10: 55–61. 16 Johnston TD, Chen Y, Reed RL, II. Functional equivalence of hypothermia to specific clotting factor deficiencies. J Trauma 1994; 37: 413–7.
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17 Palmieri RM et al. Peripheral ankle cooling and core body temperature. J Athl Train 2006; 41: 185–8. 18 Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al. Guidelines for the management of hemophilia. Hemophilia 2013; 19: e1–47. 19 Pennes Harry H. Analysis of tissue and arterial blood temperatures in the resting human forearm. J Appl Physiol 1948; 1: 93–122.
Ankle joint-preserving surgery in a patient with severe haemophilia and Noonan syndrome: case report and literature review M . H O R I S B E R G E R , * A . B A R G , * M . W I E W I O R S K I , * A . E . A N D E R S O N † and V. VALDERRABANO* *Orthopaedic Department University Hospital of Basel, Basel, Switzerland; and †Department of Orthopaedics, Harold K. Dunn Orthopaedic Research Laboratory University of Utah, Salt Lake City, UT, USA
Severe haemophilia with recurrent joint bleeding may cause secondary ankle osteoarthritis [1]. Common radiographic findings of haemophilic arthropathy include subchondral cysts, osteoporosis, enlarged epiphyses, irregular subchondral surface, narrowing of the joint space and gross joint deformities [2]. Haemophilic pseudotumour occurs in approximately 2% of patients with severe haemophilia [3]. In the current literature, numerous treatment options have been described for various stages of haemophilic ankle arthropathy [4,5]. Ankle arthrodesis has been considered the standard treatment option in patients with haemophilic end-stage ankle arthropathy [6]. In the last two decades, total ankle replacement has become a feasible treatment option [7]. However, in patients with asymmetric ankle osteoarthritis and a concomitant deformity, where a substantial part of the tibiotalar joint remains preserved, procedures that sacrifice the native joint may not be an ideal treatment option. In patients with posttraumatic ankle osteoarthritis, promising short- and midterm results have been reported in those who underwent supramalleolar realignment surgery [8]. However, there is a paucity of literature to address Correspondence: Monika Horisberger, MD, Alexej Barg, MD, Orthopaedic Department, University Hospital of Basel, Spitalstrasse 21, CH-4031 Basel, Switzerland. Tel.: +41 (0)61 318 7169; fax: +41 (0)61 265 7800; e-mail: [email protected]; [email protected] Accepted after revision 18 October 2014 DOI: 10.1111/hae.12583 © 2014 John Wiley & Sons Ltd
the use of supramalleolar realignment surgery in patients with bleeding disorders. Herein, we describe the successful orthopaedic management of a patient with severe haemophilia A and Noonan syndrome treated by debridement of cysts, filling with allograft and allomatrix, and bilateral hindfoot osteotomies. In addition to describing our experience, we also provide a review of the current literature on realignment surgery for ankle haemophilic arthropathy. A 29-year-old man with severe haemophilia A (FVIII:C < 1.0) and Noonan syndrome presented to our clinic. His Noonan syndrome [9] was noted to be of autosomal dominant genetic origin, also occurring in three out of six of his siblings. The patient showed characteristic signs of Noonan syndrome, including short body height (158 cm) with associated disproportionality, a ventricular septum defect with stenosis of the pulmonal valve, and unilateral cryptorchism. Details regarding association between Noonan syndrome and bleeding disorders are described in the current literature [10]. The patient’s haemophilia A was diagnosed when he was 2 months old, receiving factor substitution since then. He had a history of recurrent intraarticular bleeding in both ankles (in the last 12 months four and three episodes in the right and left ankle respectively). The patient presented in our orthopaedic outpatient clinic with bilateral ankle and hindfoot pain with the right side being more symptomatic. Clinically he had peritalar instability with supramalleolar varus malalignment of the ankle in combination with inframalleolar valgus malalignment of the heel (Figs 1a Haemophilia (2015), 21, e70--e121
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and 2a). His ability to walk was severely limited by pain and malalignment to less than 100 m. He reported pain as 10/10 on the visual analogue scale. The total range of motion of the right and left ankle joints was 20° and 15° respectively. The American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score was 65 out of a maximum of 100 points. Radiographs demonstrated gross bilateral cysts of the distal tibia with the medial distal tibial angle on the right and left side being 65.5° and 77.0° respectively. Computed tomography revealed extensive cystic lesions, especially on the right side (Figs 1b and 2b). On the right side, a large cyst left a cortical defect of approximately 3 9 4 cm on the medial aspect of the distal tibia, including the whole medial malleolus; only the periosteum covered this cyst. A thin rim of subchondral bone persisted on the medial malleolus and the tibial plafond. Scintigraphy showed metabolic enhancement in the area of the bilateral cystic lesions, but no bone activity was noted in other regions. The preoperative Pettersson score on the right and left side was 10 and 9 points respectively. The patient underwent bilateral surgical treatment, with an interval of 2 years between procedures. We started with the right side first as it was more symp-
(a)
(b)
tomatic and determined to be an immediate risk for fracture. An intravenous ‘single-shot’ antibiotic prophylaxis was administered preoperatively using cefuroxime 1.5 g (ZINACEFâ; Glaxo Smith Kline AG, Muenchenbuchsee, Switzerland). A medial longitudinal incision was made over the distal tibial and medial malleolus and the gross cyst was exposed. Following debridement and irrigation of the cyst, the defect was filled with 27 and 15 cm3 of bone allograft on the right and left side respectively. To correct the supramalleolar varus malalignment, a medial open wedge osteotomy was performed [8]. The distal tibia was then stabilized with a medial T-shaped 3.5-mm LCP plate, on the right side a medial shift of the distal fragment had to be added to improve lower leg axis and an additional ventral 3.5-mm LCP was used to increase initial stability. Supramalleolar alignment correction resulted in a lateral shift of the heel on the right side. Therefore, we also performed medial displacement calcaneal osteotomy that was fixed in place with two 6.5-mm cannulated screws. The patient was preoperatively seen and evaluated in the Department of Haematology at the University Hospital of Basel. Preoperative preparation included analysis of, and screening for, clotting factors and
(c)
Fig. 1. (a) Radiograph and (b) computed tomography of the left ankle show a cyst located in the meta-diaphyseal region and varus alignment of the distal tibia (white arrows). (c) Postoperative radiograph of the left ankle demonstrates consolidation of the osteotomy and allograft as well as residual varus alignment of the distal tibia at 2 years postoperative.
(a)
(b)
(c)
Fig. 2. (a) Radiograph and (b) computed tomography of the right ankle show a very large cyst that occupies the entire medial malleolus and nearly the entire distal epi- and metaphysis (white arrows). (c) Postoperative radiographs of the right ankle demonstrate consolidation of osteotomy and allograft at 6-month follow-up.
Haemophilia (2015), 21, e70--e121
© 2014 John Wiley & Sons Ltd
LETTERS TO THE EDITORS
antibodies. The perioperative haematological management included an initial bolus of recombinant FVIII at a dose calculated as: [(100% patient’s baseline factor activity level) 9 weight in kg 9 0.5]. The initial bolus of FVIII was followed by continuous infusion of 5 units kg1 h1. Measurements of FVIII levels were performed postoperatively and daily thereafter. When necessary, the infusion dose was adjusted to maintain serum levels of at least 80% of normal. Once wound healing was apparent, and before discharging the patient, we converted the continuous infusion to daily bolus dosing. The hospitalization duration was 14 and 10 days for the surgery on the right and left side respectively. The length of clotting factor replacement after discharge from the hospital was 30 days following surgery for both right and left sides. There were no intra- or perioperative complications. A blood transfusion was not necessary for either surgery. Complete wound healing occurred within 2 weeks of the surgery, free of adverse events on both sides. The operated lower leg was immobilized using a stable walker for 12 weeks with partial weight bearing. Osseous healing at the site of osteotomies occurred at 9 and 4 months on the right and left side respectively. The AOFAS hindfoot score was 69 points at latest follow-up: 56 and 79 months for the right and left side respectively. Weight-bearing radiographs at the latest follow-up showed good consolidation, no evidence of recurrence of the cysts, and improved hindfoot alignment with the medial distal tibial angle being 79.5° and 74.5° on the right and left side respectively (Figs 1c and 2c). Radiographs at latest follow-up also did not demonstrate continued narrowing of the joint space, indicating that haemophilic arthropathy was not progressive following surgery. The patient’s pain was markedly improved at the latest follow-up, with a rating of 2 and 3 points on the visual analogue scale for the right and left sides respectively. Pettersson scores of 6 and 7 points also demonstrated improvement for the right and left sides respectively. In addition, there were no recurrent bleeding episodes over a period of 12 months. Finally, total range of motion of the right and left ankle increased to 25° and 18° respectively. In our patient, joint-preserving surgery that included debridement/filling of cysts and hindfoot realignment surgery resulted in good functional outcome. Specifically, substantial pain relief, functional improvement and preservation of ankle mobility were noted. Also, the patient did not demonstrate continued narrowing of the joint space, which indicated that surgery may
References 1 Rodriguez-Merchan EC. The haemophilic ankle. Haemophilia 2006; 12: 337–44.
© 2014 John Wiley & Sons Ltd
e107
have halted the progression of arthrosis. To our knowledge, there is only one report that addressed the outcome of the supramalleolar osteotomy for haemophilic arthropathy [11]. Pearce et al. [11] reported the results of the supramalleolar varisation osteotomy on seven ankles (six patients). There were no intra- or perioperative complications. All osteotomies were united within 6 weeks postoperatively. The mean follow-up in the study by Pearce was 9.4 years ranging from 2 to 12.5 years. All patients in this cohort experienced substantial pain relief, with a reduction from 2 to 0.8 on the visual analogue scale [11]. Intraoperative, perioperative and postoperative complications associated with supramalleolar osteotomies can occur. Issues with wound healing and infection are noted to have a prevalence that may exceed 20% [8,12]. One of the more serious postoperative complications is delayed union or non-union at the supramalleolar osteotomy, which has a prevalence that may reach 22% [8,12]. Finally, supramalleolar osteotomy may not delay or completely halt degeneration of cartilage: in approximately 25% of cases, patients experience continued progression of painful ankle osteoarthritis [8,12]. In these cases, non-preserving procedures such as ankle arthrodesis or total ankle replacement should be considered. In this case report, we describe the successful management of patient with bilateral haemophilic ankle arthropathy with concomitant varus deformity and gross tibial cysts. We believe it is critical to consider the biomechanics and alignment of both ankles in patients who present with concomitant supramalleolar and inframalleolar deformity. Of course, the success of the orthopaedic treatment in patients with bleeding disorders will depend on careful management by an experienced, multidisciplinary team that includes experts in haematology.
Disclosures The authors stated that they had no interests which might be perceived as posing a conflict of bias.
Author contributions MH examined the patient, collected the data, analysed the radiographs, and wrote the initial manuscript draft. AB performed literature review and wrote the initial manuscript draft. AEA ensured the accuracy of data collection and reviewed the manuscript drafts. VV performed surgical treatment, ensured the accuracy of data collection, reviewed the initial draft, and was supervising author. All the authors have reviewed and authorized the submission of the present manuscript.
2 Rodriguez-Merchan EC. Common orthopaedic problems in haemophilia. Haemophilia 1999; 5(Suppl. 1): 53–60. 3 Sagarra M, Lucas M, De La TE et al. Successful surgical treatment of haemophilic
pseudotumour, filling the defect with hydroxyapatite. Haemophilia 2000; 6: 55–6. 4 Panotopoulos J, Hanslik-Schnabel B, Wanivenhaus A, Trieb K. Outcome of surgical
Haemophilia (2015), 21, e70--e121
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concepts in haemophilic arthropathy of the hindfoot. Haemophilia 2005; 11: 468–71. 5 Pasta G, Forsyth A, Merchan CR et al. Orthopaedic management of haemophilia arthropathy of the ankle. Haemophilia 2008; 14(Suppl. 3): 170–6. 6 Bluth BE, Fong YJ, Houman JJ, Silva M, Luck JV Jr. Ankle fusion in patients with haemophilia. Haemophilia 2013; 19: 432–7. 7 Barg A, Elsner A, Hefti D, Hintermann B. Haemophilic arthropathy of the ankle trea-
ted by total ankle replacement: a case series. Haemophilia 2010; 16: 647–55. 8 Barg A, Pagenstert GI, Horisberger M et al. Supramalleolar osteotomies for degenerative joint disease of the ankle joint: indication, technique and results. Int Orthop 2013; 37: 1683–95. 9 Tartaglia M, Gelb BD, Zenker M. Noonan syndrome and clinically related disorders. Best Pract Res Clin Endocrinol Metab 2011; 25: 161–79.
10 Briggs BJ, Dickerman JD. Bleeding disorders in Noonan syndrome. Pediatr Blood Cancer 2012; 58: 167–72. 11 Pearce MS, Smith MA, Savidge GF. Supramalleolar tibial osteotomy for haemophilic arthropathy of the ankle. J Bone Joint Surg Br 1994; 76: 947–50. 12 Barg A, Saltzman CL. Single-stage supramalleolar osteotomy for coronal plane deformity. Curr Rev Musculoskelet Med 2014; 7: 277–91.
Successful pregnancy under fibrinogen substitution in a woman with congenital afibrinogenaemia complicated by a postpartum venous thrombosis A . L E B R E T O N , * † A . C A S I N I , * R . A L H A Y E K , ‡ K . L . K O U T E I C H , § M . N E E R M A N - A R B E Z * ¶ and P. DE MOERLOOSE* *Division of Angiology and Haemostasis, University Hospitals and Faculty of Medicine, Geneva, Switzerland; †Haematology Department, CHU Clermont-Ferrand, Clermont-Ferrand, France; ‡Urology Department, Dubai Hospital; §Gynaecology Department, Saudi German Hospital, Dubai, United Arab Emirates; and ¶Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Pregnant women with congenital afibrinogenaemia are at risk of several obstetrical complications, from spontaneous abortion to placental abruption, including postpartum haemorrhage [1]. Only one venous thrombotic event has been reported in this setting [2]. We report a case of successful pregnancy in a woman with congenital afibrinogenaemia, treated with fibrinogen substitution therapy, but complicated by venous thromboembolism in the postpartum period. Subsequent thrombophilia testing revealed heterozygosity for the FV Leiden mutation. A review of the literature is also presented. The propositus is a primiparous 32-year-old Syrian woman with congenital afibrinogenaemia inherited through a consanguineous relationship. The diagnosis was confirmed by genotype analysis which revealed a homozygous frameshift mutation in exon 5 of FGA (c.1846 del A; p.Thr616HisfsX32). As previously described by our group, this mutation is the most C-terminal causative FGA mutation identified in afibrinogenaemic patients. The resulting aberrant Aa-chain is most likely synthesized in the liver, but is not effiCorrespondence: Philippe de Moerloose, Division of Angiology and Haemostasis, University Hospitals of Geneva, Geneva, Switzerland. Tel.: ++41 22 372 97 50; fax: ++41 22 372 98 91; e-mail: [email protected] Accepted after revision 16 October 2014 DOI: 10.1111/hae.12584 Haemophilia (2015), 21, e70--e121
ciently assembled and/or secreted into the circulation given the phenotype of afibrinogenaemia in homozygous individuals [3]. Her family history is characterized by a number of spontaneous abortions but without any bleeding symptoms, except after major surgical interventions. Venous thrombotic events were reported for several affected family members. Our patient had suffered a haemiparesis following a therapeutic lumbar puncture, performed to relieve increased intracranial pressure, secondary to cerebrospinal fluid hypersecretion when she was a teenager. Fibrinogen concentrate (Clottafactâ, generous gift from LFB, Courtaboeuf, France) was administered from the beginning of her first pregnancy, aiming at a trough plasma fibrinogen level of greater than 1 g L1 throughout pregnancy and 2 g L1 for elective caesarean section. Infusions of fibrinogen during pregnancy allowed prothrombin time (PT) and activated partial thromboplastin time to reach normal or limit normal ranges (Fig. 1). Delivery by elective caesarean section (secondary to a stagnation of the foetal weight) was uneventful at 35 weeks of gestation. During the postpartum period, the patient did not receive any postpartum thrombophylaxis but was treated with 1.5 g of fibrinogen concentrate 2 days after delivery. Ten days postpartum, the patient reported pain in the lower right leg, followed by dry cough and dyspnoea. Seventeen days postpartum, a chest CT-scan revealed a pulmonary embolus, and a distal deep venous thrombosis in the right leg on Doppler © 2014 John Wiley & Sons Ltd
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14 Low J, Reed A. Electrotherapy Explained: Principles and Practice. Oxford: Butterworth & Heineman, 2000: 258–61. 15 Lavelle BE, Snyder M. Differential conduction of cold through barriers. J Adv Nur 1985; 10: 55–61. 16 Johnston TD, Chen Y, Reed RL, II. Functional equivalence of hypothermia to specific clotting factor deficiencies. J Trauma 1994; 37: 413–7.
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17 Palmieri RM et al. Peripheral ankle cooling and core body temperature. J Athl Train 2006; 41: 185–8. 18 Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al. Guidelines for the management of hemophilia. Hemophilia 2013; 19: e1–47. 19 Pennes Harry H. Analysis of tissue and arterial blood temperatures in the resting human forearm. J Appl Physiol 1948; 1: 93–122.
Ankle joint-preserving surgery in a patient with severe haemophilia and Noonan syndrome: case report and literature review M . H O R I S B E R G E R , * A . B A R G , * M . W I E W I O R S K I , * A . E . A N D E R S O N † and V. VALDERRABANO* *Orthopaedic Department University Hospital of Basel, Basel, Switzerland; and †Department of Orthopaedics, Harold K. Dunn Orthopaedic Research Laboratory University of Utah, Salt Lake City, UT, USA
Severe haemophilia with recurrent joint bleeding may cause secondary ankle osteoarthritis [1]. Common radiographic findings of haemophilic arthropathy include subchondral cysts, osteoporosis, enlarged epiphyses, irregular subchondral surface, narrowing of the joint space and gross joint deformities [2]. Haemophilic pseudotumour occurs in approximately 2% of patients with severe haemophilia [3]. In the current literature, numerous treatment options have been described for various stages of haemophilic ankle arthropathy [4,5]. Ankle arthrodesis has been considered the standard treatment option in patients with haemophilic end-stage ankle arthropathy [6]. In the last two decades, total ankle replacement has become a feasible treatment option [7]. However, in patients with asymmetric ankle osteoarthritis and a concomitant deformity, where a substantial part of the tibiotalar joint remains preserved, procedures that sacrifice the native joint may not be an ideal treatment option. In patients with posttraumatic ankle osteoarthritis, promising short- and midterm results have been reported in those who underwent supramalleolar realignment surgery [8]. However, there is a paucity of literature to address Correspondence: Monika Horisberger, MD, Alexej Barg, MD, Orthopaedic Department, University Hospital of Basel, Spitalstrasse 21, CH-4031 Basel, Switzerland. Tel.: +41 (0)61 318 7169; fax: +41 (0)61 265 7800; e-mail: [email protected]; [email protected] Accepted after revision 18 October 2014 DOI: 10.1111/hae.12583 © 2014 John Wiley & Sons Ltd
the use of supramalleolar realignment surgery in patients with bleeding disorders. Herein, we describe the successful orthopaedic management of a patient with severe haemophilia A and Noonan syndrome treated by debridement of cysts, filling with allograft and allomatrix, and bilateral hindfoot osteotomies. In addition to describing our experience, we also provide a review of the current literature on realignment surgery for ankle haemophilic arthropathy. A 29-year-old man with severe haemophilia A (FVIII:C < 1.0) and Noonan syndrome presented to our clinic. His Noonan syndrome [9] was noted to be of autosomal dominant genetic origin, also occurring in three out of six of his siblings. The patient showed characteristic signs of Noonan syndrome, including short body height (158 cm) with associated disproportionality, a ventricular septum defect with stenosis of the pulmonal valve, and unilateral cryptorchism. Details regarding association between Noonan syndrome and bleeding disorders are described in the current literature [10]. The patient’s haemophilia A was diagnosed when he was 2 months old, receiving factor substitution since then. He had a history of recurrent intraarticular bleeding in both ankles (in the last 12 months four and three episodes in the right and left ankle respectively). The patient presented in our orthopaedic outpatient clinic with bilateral ankle and hindfoot pain with the right side being more symptomatic. Clinically he had peritalar instability with supramalleolar varus malalignment of the ankle in combination with inframalleolar valgus malalignment of the heel (Figs 1a Haemophilia (2015), 21, e70--e121
e106
LETTERS TO THE EDITORS
and 2a). His ability to walk was severely limited by pain and malalignment to less than 100 m. He reported pain as 10/10 on the visual analogue scale. The total range of motion of the right and left ankle joints was 20° and 15° respectively. The American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score was 65 out of a maximum of 100 points. Radiographs demonstrated gross bilateral cysts of the distal tibia with the medial distal tibial angle on the right and left side being 65.5° and 77.0° respectively. Computed tomography revealed extensive cystic lesions, especially on the right side (Figs 1b and 2b). On the right side, a large cyst left a cortical defect of approximately 3 9 4 cm on the medial aspect of the distal tibia, including the whole medial malleolus; only the periosteum covered this cyst. A thin rim of subchondral bone persisted on the medial malleolus and the tibial plafond. Scintigraphy showed metabolic enhancement in the area of the bilateral cystic lesions, but no bone activity was noted in other regions. The preoperative Pettersson score on the right and left side was 10 and 9 points respectively. The patient underwent bilateral surgical treatment, with an interval of 2 years between procedures. We started with the right side first as it was more symp-
(a)
(b)
tomatic and determined to be an immediate risk for fracture. An intravenous ‘single-shot’ antibiotic prophylaxis was administered preoperatively using cefuroxime 1.5 g (ZINACEFâ; Glaxo Smith Kline AG, Muenchenbuchsee, Switzerland). A medial longitudinal incision was made over the distal tibial and medial malleolus and the gross cyst was exposed. Following debridement and irrigation of the cyst, the defect was filled with 27 and 15 cm3 of bone allograft on the right and left side respectively. To correct the supramalleolar varus malalignment, a medial open wedge osteotomy was performed [8]. The distal tibia was then stabilized with a medial T-shaped 3.5-mm LCP plate, on the right side a medial shift of the distal fragment had to be added to improve lower leg axis and an additional ventral 3.5-mm LCP was used to increase initial stability. Supramalleolar alignment correction resulted in a lateral shift of the heel on the right side. Therefore, we also performed medial displacement calcaneal osteotomy that was fixed in place with two 6.5-mm cannulated screws. The patient was preoperatively seen and evaluated in the Department of Haematology at the University Hospital of Basel. Preoperative preparation included analysis of, and screening for, clotting factors and
(c)
Fig. 1. (a) Radiograph and (b) computed tomography of the left ankle show a cyst located in the meta-diaphyseal region and varus alignment of the distal tibia (white arrows). (c) Postoperative radiograph of the left ankle demonstrates consolidation of the osteotomy and allograft as well as residual varus alignment of the distal tibia at 2 years postoperative.
(a)
(b)
(c)
Fig. 2. (a) Radiograph and (b) computed tomography of the right ankle show a very large cyst that occupies the entire medial malleolus and nearly the entire distal epi- and metaphysis (white arrows). (c) Postoperative radiographs of the right ankle demonstrate consolidation of osteotomy and allograft at 6-month follow-up.
Haemophilia (2015), 21, e70--e121
© 2014 John Wiley & Sons Ltd
LETTERS TO THE EDITORS
antibodies. The perioperative haematological management included an initial bolus of recombinant FVIII at a dose calculated as: [(100% patient’s baseline factor activity level) 9 weight in kg 9 0.5]. The initial bolus of FVIII was followed by continuous infusion of 5 units kg1 h1. Measurements of FVIII levels were performed postoperatively and daily thereafter. When necessary, the infusion dose was adjusted to maintain serum levels of at least 80% of normal. Once wound healing was apparent, and before discharging the patient, we converted the continuous infusion to daily bolus dosing. The hospitalization duration was 14 and 10 days for the surgery on the right and left side respectively. The length of clotting factor replacement after discharge from the hospital was 30 days following surgery for both right and left sides. There were no intra- or perioperative complications. A blood transfusion was not necessary for either surgery. Complete wound healing occurred within 2 weeks of the surgery, free of adverse events on both sides. The operated lower leg was immobilized using a stable walker for 12 weeks with partial weight bearing. Osseous healing at the site of osteotomies occurred at 9 and 4 months on the right and left side respectively. The AOFAS hindfoot score was 69 points at latest follow-up: 56 and 79 months for the right and left side respectively. Weight-bearing radiographs at the latest follow-up showed good consolidation, no evidence of recurrence of the cysts, and improved hindfoot alignment with the medial distal tibial angle being 79.5° and 74.5° on the right and left side respectively (Figs 1c and 2c). Radiographs at latest follow-up also did not demonstrate continued narrowing of the joint space, indicating that haemophilic arthropathy was not progressive following surgery. The patient’s pain was markedly improved at the latest follow-up, with a rating of 2 and 3 points on the visual analogue scale for the right and left sides respectively. Pettersson scores of 6 and 7 points also demonstrated improvement for the right and left sides respectively. In addition, there were no recurrent bleeding episodes over a period of 12 months. Finally, total range of motion of the right and left ankle increased to 25° and 18° respectively. In our patient, joint-preserving surgery that included debridement/filling of cysts and hindfoot realignment surgery resulted in good functional outcome. Specifically, substantial pain relief, functional improvement and preservation of ankle mobility were noted. Also, the patient did not demonstrate continued narrowing of the joint space, which indicated that surgery may
References 1 Rodriguez-Merchan EC. The haemophilic ankle. Haemophilia 2006; 12: 337–44.
© 2014 John Wiley & Sons Ltd
e107
have halted the progression of arthrosis. To our knowledge, there is only one report that addressed the outcome of the supramalleolar osteotomy for haemophilic arthropathy [11]. Pearce et al. [11] reported the results of the supramalleolar varisation osteotomy on seven ankles (six patients). There were no intra- or perioperative complications. All osteotomies were united within 6 weeks postoperatively. The mean follow-up in the study by Pearce was 9.4 years ranging from 2 to 12.5 years. All patients in this cohort experienced substantial pain relief, with a reduction from 2 to 0.8 on the visual analogue scale [11]. Intraoperative, perioperative and postoperative complications associated with supramalleolar osteotomies can occur. Issues with wound healing and infection are noted to have a prevalence that may exceed 20% [8,12]. One of the more serious postoperative complications is delayed union or non-union at the supramalleolar osteotomy, which has a prevalence that may reach 22% [8,12]. Finally, supramalleolar osteotomy may not delay or completely halt degeneration of cartilage: in approximately 25% of cases, patients experience continued progression of painful ankle osteoarthritis [8,12]. In these cases, non-preserving procedures such as ankle arthrodesis or total ankle replacement should be considered. In this case report, we describe the successful management of patient with bilateral haemophilic ankle arthropathy with concomitant varus deformity and gross tibial cysts. We believe it is critical to consider the biomechanics and alignment of both ankles in patients who present with concomitant supramalleolar and inframalleolar deformity. Of course, the success of the orthopaedic treatment in patients with bleeding disorders will depend on careful management by an experienced, multidisciplinary team that includes experts in haematology.
Disclosures The authors stated that they had no interests which might be perceived as posing a conflict of bias.
Author contributions MH examined the patient, collected the data, analysed the radiographs, and wrote the initial manuscript draft. AB performed literature review and wrote the initial manuscript draft. AEA ensured the accuracy of data collection and reviewed the manuscript drafts. VV performed surgical treatment, ensured the accuracy of data collection, reviewed the initial draft, and was supervising author. All the authors have reviewed and authorized the submission of the present manuscript.
2 Rodriguez-Merchan EC. Common orthopaedic problems in haemophilia. Haemophilia 1999; 5(Suppl. 1): 53–60. 3 Sagarra M, Lucas M, De La TE et al. Successful surgical treatment of haemophilic
pseudotumour, filling the defect with hydroxyapatite. Haemophilia 2000; 6: 55–6. 4 Panotopoulos J, Hanslik-Schnabel B, Wanivenhaus A, Trieb K. Outcome of surgical
Haemophilia (2015), 21, e70--e121
e108
LETTERS TO THE EDITORS
concepts in haemophilic arthropathy of the hindfoot. Haemophilia 2005; 11: 468–71. 5 Pasta G, Forsyth A, Merchan CR et al. Orthopaedic management of haemophilia arthropathy of the ankle. Haemophilia 2008; 14(Suppl. 3): 170–6. 6 Bluth BE, Fong YJ, Houman JJ, Silva M, Luck JV Jr. Ankle fusion in patients with haemophilia. Haemophilia 2013; 19: 432–7. 7 Barg A, Elsner A, Hefti D, Hintermann B. Haemophilic arthropathy of the ankle trea-
ted by total ankle replacement: a case series. Haemophilia 2010; 16: 647–55. 8 Barg A, Pagenstert GI, Horisberger M et al. Supramalleolar osteotomies for degenerative joint disease of the ankle joint: indication, technique and results. Int Orthop 2013; 37: 1683–95. 9 Tartaglia M, Gelb BD, Zenker M. Noonan syndrome and clinically related disorders. Best Pract Res Clin Endocrinol Metab 2011; 25: 161–79.
10 Briggs BJ, Dickerman JD. Bleeding disorders in Noonan syndrome. Pediatr Blood Cancer 2012; 58: 167–72. 11 Pearce MS, Smith MA, Savidge GF. Supramalleolar tibial osteotomy for haemophilic arthropathy of the ankle. J Bone Joint Surg Br 1994; 76: 947–50. 12 Barg A, Saltzman CL. Single-stage supramalleolar osteotomy for coronal plane deformity. Curr Rev Musculoskelet Med 2014; 7: 277–91.
Successful pregnancy under fibrinogen substitution in a woman with congenital afibrinogenaemia complicated by a postpartum venous thrombosis A . L E B R E T O N , * † A . C A S I N I , * R . A L H A Y E K , ‡ K . L . K O U T E I C H , § M . N E E R M A N - A R B E Z * ¶ and P. DE MOERLOOSE* *Division of Angiology and Haemostasis, University Hospitals and Faculty of Medicine, Geneva, Switzerland; †Haematology Department, CHU Clermont-Ferrand, Clermont-Ferrand, France; ‡Urology Department, Dubai Hospital; §Gynaecology Department, Saudi German Hospital, Dubai, United Arab Emirates; and ¶Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Pregnant women with congenital afibrinogenaemia are at risk of several obstetrical complications, from spontaneous abortion to placental abruption, including postpartum haemorrhage [1]. Only one venous thrombotic event has been reported in this setting [2]. We report a case of successful pregnancy in a woman with congenital afibrinogenaemia, treated with fibrinogen substitution therapy, but complicated by venous thromboembolism in the postpartum period. Subsequent thrombophilia testing revealed heterozygosity for the FV Leiden mutation. A review of the literature is also presented. The propositus is a primiparous 32-year-old Syrian woman with congenital afibrinogenaemia inherited through a consanguineous relationship. The diagnosis was confirmed by genotype analysis which revealed a homozygous frameshift mutation in exon 5 of FGA (c.1846 del A; p.Thr616HisfsX32). As previously described by our group, this mutation is the most C-terminal causative FGA mutation identified in afibrinogenaemic patients. The resulting aberrant Aa-chain is most likely synthesized in the liver, but is not effiCorrespondence: Philippe de Moerloose, Division of Angiology and Haemostasis, University Hospitals of Geneva, Geneva, Switzerland. Tel.: ++41 22 372 97 50; fax: ++41 22 372 98 91; e-mail: [email protected] Accepted after revision 16 October 2014 DOI: 10.1111/hae.12584 Haemophilia (2015), 21, e70--e121
ciently assembled and/or secreted into the circulation given the phenotype of afibrinogenaemia in homozygous individuals [3]. Her family history is characterized by a number of spontaneous abortions but without any bleeding symptoms, except after major surgical interventions. Venous thrombotic events were reported for several affected family members. Our patient had suffered a haemiparesis following a therapeutic lumbar puncture, performed to relieve increased intracranial pressure, secondary to cerebrospinal fluid hypersecretion when she was a teenager. Fibrinogen concentrate (Clottafactâ, generous gift from LFB, Courtaboeuf, France) was administered from the beginning of her first pregnancy, aiming at a trough plasma fibrinogen level of greater than 1 g L1 throughout pregnancy and 2 g L1 for elective caesarean section. Infusions of fibrinogen during pregnancy allowed prothrombin time (PT) and activated partial thromboplastin time to reach normal or limit normal ranges (Fig. 1). Delivery by elective caesarean section (secondary to a stagnation of the foetal weight) was uneventful at 35 weeks of gestation. During the postpartum period, the patient did not receive any postpartum thrombophylaxis but was treated with 1.5 g of fibrinogen concentrate 2 days after delivery. Ten days postpartum, the patient reported pain in the lower right leg, followed by dry cough and dyspnoea. Seventeen days postpartum, a chest CT-scan revealed a pulmonary embolus, and a distal deep venous thrombosis in the right leg on Doppler © 2014 John Wiley & Sons Ltd
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