Thrombosis Research 135 (2015) 109–113

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Regular Article

Incidence of symptomatic venous thromboembolism in patients with hemophilia undergoing joint replacement surgery: A retrospective study Juliana Perez Botero a, Daniel B. Spoon b, Mrinal S. Patnaik a, Aneel A. Ashrani a, Robert T. Trousdale c, Rajiv K. Pruthi a,⁎ a b c

Division of Hematology, Mayo Clinic, Rochester, Minnesota, United States Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, United States Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, United States

a r t i c l e

i n f o

Article history: Received 31 August 2014 Received in revised form 6 November 2014 Accepted 11 November 2014 Available online 18 November 2014 Keywords: Blood coagulation disorders Blood coagulation factors Embolism Thrombosis

a b s t r a c t Introduction: Venous thromboembolism (VTE) is a recognized complication after joint replacement surgery, and prophylaxis is routinely used in patients without bleeding disorders. However, for patients with hemophilia, pharmacologic prophylaxis is highly variable and controversial because of the inherent bleeding risk. Aim: To review our institutional experience with outcomes of total knee or hip arthroplasty with regard to symptomatic VTE and use of VTE prophylaxis in patients with hemophilia and without inhibitors. Methods: We reviewed records of 42 consecutive patients with hemophilia A or B who underwent 71 hip or knee replacements over a 39-year period. We also reviewed the literature to estimate the incidence of VTE after arthroplasty in the hemophilia population. Results: All patients used compression stockings for up to 6 weeks after surgery; additionally, 6 cases (10.5%; 57 with available data) used sequential intermittent compression devices and 2 (2.8%) postoperatively received low-molecular-weight heparin. One patient (1.4%) who received low-molecular-weight heparin had a symptomatic, lower-extremity, deep venous thrombosis 10 days after hip replacement for traumatic fracture. None of the other 70 surgical cases had symptomatic VTE within 3 months after the procedure. Analysis of pooled data from published series of hemophilia patients undergoing arthroplasty showed an estimated incidence of symptomatic VTE of 0.5%. Conclusion: Our study suggests that in patients with hemophilia, joint replacement surgery can be performed safely without routine pharmacologic VTE prophylaxis and without increasing risk of thromboembolic events. Pharmacologic VTE prophylaxis may be considered in select patients with known additional risk factors for VTE. © 2014 Elsevier Ltd. All rights reserved.

Introduction Deep venous thrombosis (DVT) and pulmonary embolism (venous thromboembolism [VTE]) are well-recognized complications after major surgery, particularly orthopedic procedures such as total knee arthroplasty (TKA) and total hip arthroplasty (THA). In the general population, the cumulative rate of symptomatic VTE up to 35 days after major orthopedic surgery has been estimated to be 4.3% without prophylaxis and 1.8% with the use of postoperative low-molecular-weight heparin (LMWH) corresponding to a risk reduction greater than 50%. The rates

Abbreviations: DVT, deep venous thrombosis; CI, confidence interval; LMWH, lowmolecular-weight heparin; POD, postoperative day; THA, total hip arthroplasty; TKA, total knee arthroplasty; VTE, venous thromboembolism. ⁎ Corresponding author at: Division of Hematology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, United States. Tel.: +1 507 284 2677; fax: +1 507 284 8286. E-mail address: [email protected] (R.K. Pruthi).

http://dx.doi.org/10.1016/j.thromres.2014.11.010 0049-3848/© 2014 Elsevier Ltd. All rights reserved.

of asymptomatic, radiologically (Doppler and/or venography) detected VTE are much higher. Thus, providing thromboprophylaxis (pharmacologic, nonpharmacologic, or both) is the standard of care [1]. In patients with hemophilia, recurrent hemarthroses result in hemophilic arthropathy and eventual need for TKA or THA [2,3]; these procedures increasingly are being performed, given improved surgical techniques and availability of coagulation factor concentrates [4]. However, correction of the hemostatic defect through perioperative use of coagulation factor concentrates theoretically increases their risk of VTE such that it is similar to the risk in the general population. The concern for bleeding complications in this population has led to varying practice in providing VTE prophylaxis [5], and the lack of controlled trials preclude development of evidence-based recommendations. Herein, we review our institutional experience with outcomes of TKA and THA in patients with hemophilia and without inhibitors. We also review the literature to estimate the incidence of VTE after arthroplasty in the hemophilia population.

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Materials and Methods

VTE Outcomes

This study was approved by the Mayo Clinic Institutional Review Board. Nine patients in this series have been reported previously, 1 in a case report [6] and 8 in a case series describing factor concentrate boluses vs continuous infusions for elective surgery [7].

One patient with mild hemophilia B (baseline factor IX activity 10%) underwent THA for traumatic hip fracture and received postoperative enoxaparin 30 mg twice daily from postoperative day (POD) 1 through 6 when he was discharged from the hospital. Factor IX replacement was continued at 4000 daily. Symptomatic DVT (deep femoral vein) was diagnosed by compression venous duplex ultrasound on POD 10. Enoxaparin dose was increased to 90 mg every 12 hours and concurrent FIX replacement (3000 units once daily) was continued for 5 days with resolution of the clot by ultrasound. Both factor replacement and anticoagulation were discontinued. As previously described [6], this patient was later found to be heterozygous for factor V Leiden, he had a BMI of 33 and no clinical evidence of postoperative infection, antiphospholipid syndrome or heparin induced thrombocytopenia. The incidence of symptomatic VTE in our series was 1 of 71 cases (1.4%) 95% CI [0, 4.13%].

Study Population, Setting, and Design In this retrospective cohort study, we reviewed the institutional medical records of all patients with hemophilia A or B, enrolled in the Comprehensive Hemophilia Center at Mayo Clinic (Rochester, Minnesota), who underwent arthroplasty from January 1, 1974, through July 31, 2013. Criteria for diagnosis and classification of severity of hemophilia conformed to the recommendations of the Scientific Standardization Committee of the International Society on Thrombosis and Haemostasis [8]. Measurements

Estimate of VTE Incidence We (J.P.B., D.B.S., M.S.P., and R.K.P.) abstracted patient data, including age at surgery, type and severity of hemophilia, the joint and type of surgery (primary vs revision arthroplasty), and the operating surgeon’s name. We also recorded the type of factor replacement, the daily factor levels, and use (or lack thereof) of VTE prophylaxis (pharmacologic or nonpharmacologic). Operative reports, progress notes, hospital summaries, and subsequent visit notes were reviewed to determine occurrence of symptomatic VTE (DVT and pulmonary embolism) during hospitalization and for up to 3 months postoperatively. Statistical Analysis This was a retrospective cohort study. Data were entered into a spreadsheet (Excel; Microsoft Corp) from which sums, medians, ranges and the incidence of VTE were established. Literature Review We searched PubMed using the medical subject headings hemophilia A, hemophilia B, and joint replacement. All articles written in English were reviewed. We excluded reports of single cases and series that included only patients with inhibitors. All case series reporting hip or knee replacements (or both) were included in the final review. Results Patient Characteristics During the study period, 42 patients underwent 71 joint arthroplasties. Thirty-eight patients had hemophilia A and 4 had hemophilia B. Twenty-two patients (52%) had severe hemophilia, 8 (19%) had moderate hemophilia, and 12 (29%) had mild hemophilia. Thirty-nine procedures (55%) were TKA and 32 (45%) were THA. Fifty-two procedures (73%) were primary arthroplasties and the remaining 19 (27%) were revisions. The mean age at surgery was 43.2 years (range, 15–74 years). Eleven orthopedic surgeons performed the procedures. VTE Prophylaxis, Factor Concentrate Infusions, and Factor Activity Details of VTE prophylaxis, factor replacement therapy, and factor activity are shown in Table 1. The average number of days of factor replacement was 11.78 (range, 4–25 days). The median and range for the maximum daily factor activity levels are presented in the Figure. Maximum daily factor levels were recorded both on the day of surgery and when available in the postoperative period throughout hospitalization(Fig. 1).

In an attempt to quantify the incidence of VTE in this patient population, we undertook a detailed review of 35 published studies, including 1 prospective study. The available data on outcomes after joint replacement surgery in patients with hemophilia are shown in Table 2. In aggregate, 8 of 843 patients (0.9%) 95% CI [0.26, 1.54%] had VTE (total number of THA and TKA procedures, 1,107). When combining all available published reports and our cohort (without doublecounting the 8 patients reported previously), the approximate incidence of symptomatic VTE in the hemophilia population undergoing THA or TKA was 6/1,170 (0.5%), 95% CI [0.1, 0.9%]. Three of the reported thromboses were diagnosed by surveillance ultrasound in the only prospective study published [39]. Two of the 5 cases of symptomatic VTE (DVT and pulmonary embolism, 1 each) occurred in patients with hemophilia B who received intermediatepurity factor IX concentrate, which is associated with a high thrombotic risk [2]; one with a below-the-knee DVT was managed conservatively, and the patient with pulmonary embolism received unfractionated heparin while continuing the postoperative replacement regimen concentrate. Kelley et al. [34] reported 1 symptomatic VTE after a THA, and Chevalier et al. [36] reported 2 symptomatic calf vein thromboses that were managed with elastic compression.

Table 1 VTE Prophylaxis, Perioperative Factor Replacement, and Plasma Factor Activity (N = 71). Characteristic Use of VTE prophylaxis, No. (%) Compression stockingsa SCIDb SCID + low-molecular weight heparinc Type of factor replacement Cryoprecipitate Cryoprecipitate + plasma-derived factor VIII Plasma-derived factor VIII Plasma-derived factor IX Recombinant factor VIII Recombinant factor IX Form of factor replacement (n = 59)d Bolus infusion Continuous infusion Preoperative peak factor activity, median (range), %

Value 71 (100) 6/57 (10.5) 2 (2.8) 12 (16.9) 3 (4.2) 25 (35.2) 2 (2.8) 27 (38.0) 2 (2.8) 25 (42.4) 34 (57.6) 97.5 (59–318)

Abbreviation: SCID, sequential intermittent compression device (knee high); VTE, venous thromboembolism. a Knee-high stockings were used during hospitalization and until 4–6 weeks postoperatively. b Use of devise not documented for 14 cases. c Both patients had traumatic hip fracture. d Does not include patients receiving cryoprecipitate.

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Fig. 1. Median and range of plasma factor activity in the perioperative period. (source file of figure uploaded).

Discussion Before the 1980s, in the absence of VTE prophylaxis, the incidence of symptomatic VTE after THA and TKA ranged from 15% to 30% in patients without bleeding disorders. Notable changes in management such as early ambulation, shortened length of hospitalization, and improved surgical techniques have lowered the incidence of VTE; however, estimates of VTE incidence without pharmacologic prophylaxis are not available because of the lack of contemporary placebo-controlled trials. Contemporary surgical series suggest that in aggregate, symptomatic VTE with LMWH prophylaxis affects approximately 1.15% of patients, with an upper estimate of 2.7% [41], and a point estimate of around 1.8%. [1]. The routine use of pharmacologic VTE prophylaxis in patients with hemophilia remains controversial, and practices vary greatly among different centers. A survey of European hemophilia treatment centers suggests that pharmacologic VTE prophylaxis is used by greater than half of respondents [42]. A recent survey of US treatment centers [5] revealed that 67% of respondents believed that patients with hemophilia undergoing joint replacement had high enough VTE risk to warrant some type of VTE prophylaxis, but only 37% indicated that they routinely provide prophylaxis for this purpose. Thirty percent of respondents believed in high risk of VTE but provided prophylaxis only for select patients (eg, a high-risk patient with coagulation factor levels N 100%) [43]. Prophylaxis measures included compression stockings (32%), sequential intermittent compression devices (35%), and pharmacologic agents (33%) such as LMWH, warfarin, unfractionated heparin fondaparinux, and aspirin (in decreasing order of frequency). The exact incidence of VTE after total joint arthroplasty in patients with hemophilia is unknown, and no clinical trial comparing the use of pharmacologic prophylaxis vs placebo has been performed or is likely to be performed. Thus, until more evidence is available, hemophilia centers base their practices on current state of knowledge and expert opinion. In our cohort of 71 joint arthroplasties, all patients received compression stockings and 2 patients received LMWH VTE prophylaxis (after THA for hip fracture), but the use of sequential intermittent compression devices was documented in only 10.5% of procedures. The incidence of symptomatic VTE was 1 in 71 (1.4%), which is lower than rates reported in the literature for patients without bleeding disorders undergoing the same surgical procedure in the absence of VTE prophylaxis [1]. The absence of thromboembolic complications in the other 70 operative cases coincides with reports from other large series [2,4, 37]. Our current practice is to use knee-high compression stockings in

every patient and sequential compression devices or pharmacologic prophylaxis in select cases. As described above, the only observed episode of VTE occurred in 1 patient who received LMWH after THA for a traumatic fracture; this person later was found to be heterozygous for factor V Leiden [6]. This observation is consistent with other reported cases of VTE in patients with hemophilia (non–catheter associated) who had strong risk factors for hypercoagulable states (e.g., active neoplasia, congenital thrombophilia, use of intermediate-purity factor IX before high-purity products were available, or use of bypass agents) [2,44–46]. Persistently elevated levels of FVIII have shown to be a risk factor for thrombosis in the general population [43]. Given the time span over which our retrospective study was conducted, perioperative factor replacement evolved from exclusive use of bolus infusion to continuous infusion. Automation in performance of factor assays permitted timely availability of daily AM FVIII:C results. Hence, as show in the figure, most of the widely fluctuating FVIII:C levels were attributable to bolus FVIII infusions, which were provided without the benefit of having a morning FVIII:C, in the early part of this study. Our current practice is to adjust the continuous infusion to maintain a peak FVIII level at 150% or below. Overall, in the absence of additional risk factors, we observed no increased risk for symptomatic DVT in our cohort. Several limitations in our study warrant further discussion. The retrospective nature of our study, heterogeneity in terms of type of factor replacement, dosing, and evolution of surgical technique preclude firm recommendations. Although documentation of the use of compression stockings was adequate, we confirmed this practice by interviewing emeritus and currently practicing orthopedic surgeons who performed the procedures. However, we were unable to confirm compliance with use of compression stockings after hospital dismissal. We were limited by the lack of consistent documentation of the use of sequential intermittent compression devices in all patients. Because routine Doppler ultrasounds were not performed, we cannot exclude asymptomatic VTE; however, the intent of our study was to delineate the incidence of symptomatic VTE. Limitations of our literature review include the inconsistent reporting and/or use of VTE prophylaxis. Although 9 reports addressed VTE prophylaxis in the Methods section, 3 indicated pharmacologic prophylaxis was not used without specifying whether nonpharmacologic prophylaxis was undertaken [4,34,37], 4 used compression stockings on all patients [2,36,39,40] and 2 administered LMWH to all patients [35,38]. Although 26 studies did not address thromboprophylaxis in the Methods section [7,9–33], it is reasonable to conclude the

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Table 2 Outcomes of Joint Replacement in Patients With Hemophilia (Select Publications). Study

Study Period

Patients, No.

Surgical Procedures, No.

Hemophilia Type

Type of Infusion

Thomboprophylaxis Discussed

Used

Luck et al. [9] Habermann et al. [10] Lachiewicz et al. [11]

1968-1989 1972-2002 1973-1982

51 13 14

67 15 24

1974-1982 1974-1988

15 15

19 23

Rana et al. [14]

1976-1986

7

8

Norian et al. [15] Small et al. [16] Karthaus and Novakova [17] Magone et al. [18] McCollough et al. [19] Teigland et al. [20] Kjaersgaard-Anderson et al. [21] Goldberg et al. [22] Unger et al. [23] Heeg et al. [24] Chiang et al. [25] Bae et al. [26] Wang et al. [27] Cohen et al. [28]

1976-1998 1977-1979 1978-1985

38 5 9

53 5 11

A A and severe vWD A (including patients with inhibitors) A A and B (including patients with inhibitors) A and B (including patients with inhibitors) A and B A and B A

Figgie et al. [12] Thomason et al. [13]

1978-1986 1979 1979-1987 1980-1987

7 8 15 9

9 10 15 13

1981 1984-1991 1984-1994 1985-2006 1989-2001 1987-2007 1989-1997

10 15 9 25 21 48 16

13 26 12 35 25 59 21

Fehily et al. [29] Sikkema et al. [30] Dingli et al. [7] Rodriguez-Merchan [31] Rahme et al. [32] Takedani [33] Kelley et al. [34]

1990-1999 1990-2007 1993-2001 1996-2005 1998-2009 2006-2009 1972-1990

8 22 8 30 14 17 27

9 27 8 35 20 28 34

Silva and Luck [4] Goddard et al. [2]

1975-2001 1983-2007

68 57

Legroux-Gerot et al. [35]

1986-1996

Chevalier et al. [36]

BI Not mentioned BIa and CI

Not mentioned Not mentioned Not mentioned

Unknown Unknown Unknown

0 0 0

Not mentioned CI

Not mentioned Not mentioned

Unknown Unknown

0 0

BIb

Not mentioned

Unknown

0

Not mentioned BI BI

Not mentioned Not mentioned Not mentioned

Unknown Unknown Unknown

0 0 0

A and B A and B A and vWD A

Not mentioned Not mentioned Not mentioned BI

Not mentioned Not mentioned Not mentioned Not mentioned

Unknown Unknown Unknown Unknown

0 0 0 0

A A A and B A and B A and B A and B A (including patients with inhibitors) A and B A and B A A and B A and B A A and B

BI Not mentioned BI A and B BI Not mentioned CIc

Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned

Unknown Unknown Unknown Unknown Unknown Unknown Unknown

0 0 0 0 0 0 0

Bolus and CI CI CI BId CI CI BI and CI

Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Not mentioned Yes

Unknown Unknown Unknown Unknown Unknown Unknown Not usede

90 70

A and B A and B (including patients with inhibitors)

Not mentioned BId

Yes Yes

12

17

A and B

CI

Yes

1992-2010

51

72

A and B

CI

Yes

Solimeno et al. [37]

1993-2007

92

116

BIg and CI

Yes

Schild et al. [38]

1995-2008

51

69

A and B (including patients with inhibitors) A and B

Not usedf Compression stockings (all patients) LMWH (all patients) Not usedf Compression stockings (all patients) Not usedf

0 0 0 0 0 0 1 DVT, symptomatic 0 2 (1 DVT and 1 DVT + PE)

CI

Yes

Hermans et al. [39]

2002-2008

17

24

A and B

CI

Yes

Feng et al. [40]

2003-2010

19

25

A

BI

Yes

LMWH (all patients) Not usedf Compression stockings (all patients) Not usedf Compression stockings (all patients)

Total VTE, No.

0 2 DVT

0 0 3 CVT, asymptomatic

0

Abbreviations: A, hemophilia A; B, hemophilia B; BI, bolus infusion; CI, continuous infusion; CVT, calf vein thrombosis; DVT, deep vein thrombosis; LMWH, low-molecular-weight heparin; PE, pulmonary embolism; VTE, venous thromboembolism; vWD, von Willebrand disease. a One patient with inhibitors received factor VIII and activated prothrombin complex concentrate. b One patient with inhibitors received factor VIII concentrate and prothrombin complex. c One patient with inhibitors received factor VIII and recombinant activated factor VII. d Two patients with factor VIII inhibitors received recombinant activated factor VII. e Authors stated that routine prophylaxis for DVT was not used because of underlying coagulopathy. f Authors stated that no antithrombotic (pharmacologic) prophylaxis was used. g Seven patients with inhibitors received recombinant activated factor VII by BI or CI.

pharmacologic thromboprophylaxis likely was not used; however, we cannot determine whether mechanical methods were used. Further limitations include the fact that the studies included patients undergoing THA and TKA over a 43-year period (1968–2010). In addition, although we attempted to minimize the effect of duplicate reports, it is

possible that we underestimated the actual incidence of VTE by an increase in the denominator. In conclusion, our experience and that of others suggest that in patients with hemophilia undergoing joint replacement surgery, the incidence of symptomatic VTE is low. The small numbers of patients and

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lack of a control arm in our study preclude comparison to the general population. Routine use of mechanical VTE prophylaxis with pharmacologic VTE prophylaxis considered in select high risk patients is a reasonable approach. We suggest that future studies report the use of VTE prophylaxis (or lack thereof) and whether it was mechanical or pharmacologic. However, prospective studies (such as one currently ongoing [47]) may help clarify and possibly stratify patients with hemophilia at risk of VTE and standardize future clinical practice. Declaration of Interest The authors stated that they had no interests that might be perceived as posing a conflict or bias. Conflict of Interest None. Acknowledgment All listed authors (J.P.B., D.B.S., M.S.P., A.A.A., R.T.T., R.K.P.) designed the research study, performed the chart review, analyzed the data, and contributed to writing of the manuscript. In addition, we thank Robert D. McBane, MD; C. Christopher Hook, MD, Animesh Pardanani, MBBS, PhD; John A. Heit; William L. Nichols, Jr, MD; Michelle A. Elliott, MD; and Waldemar E. Wysokinski, MD, PhD, for assistance with clinical management of the patients and suggestions for manuscript preparation. References [1] Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, et al. American College of Chest Physicians. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012 Feb;141(2 Suppl.):e278S–325S. [2] Goddard NJ, Mann HA, Lee CA. Total knee replacement in patients with end-stage haemophilic arthropathy: 25-year results. J Bone Joint Surg (Br) 2010 Aug;92(8): 1085–9. [3] Goddard NJ, Rodriguez-Merchan EC, Wiedel JD. Total knee replacement in haemophilia. Haemophilia 2002 May;8(3):382–6. [4] Silva M, Luck Jr JV. Long-term results of primary total knee replacement in patients with hemophilia. J Bone Joint Surg Am 2005 Jan;87(1):85–91. [5] Pradhan SM, Key NS, Boggio L, Pruthi R. Venous thrombosis prophylaxis in haemophilics undergoing major orthopaedic surgery: a survey of haemophilia treatment centres. Haemophilia 2009 Nov;15(6):1337–8 [Epub 2009 Aug 21]. [6] Pruthi RK, Heit JA, Green MM, Emiliusen LM, Nichols WL, Wilke JL, et al. Venous thromboembolism after hip fracture surgery in a patient with haemophilia B and factor V Arg506Gln (factor V Leiden). Haemophilia 2000 Nov;6(6):631–4. [7] Dingli D, Gastineau DA, Gilchrist GS, Nichols WL, Wilke JL. Continuous factor VIII infusion therapy in patients with haemophilia A undergoing surgical procedures with plasma-derived or recombinant factor VIII concentrates. Haemophilia 2002 Sep; 8(5):629–34. [8] White II GC, Rosendaal F, Aledort LM, Lusher JM, Rothschild C, Ingerslev J, et al. Subcommittee. Definitions in hemophilia: recommendation of the scientific subcommittee on factor VIII and factor IX of the scientific and standardization committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 2001 Mar; 85(3):560. [9] Luck Jr JV, Kasper CK. Surgical management of advanced hemophilic arthropathy: an overview of 20 years’ experience. Clin Orthop Relat Res 1989 May;242:60–82. [10] Habermann B, Eberhardt C, Hovy L, Zichner L, Scharrer I, Kurth AA. Total hip replacement in patients with severe bleeding disorders: a 30 years single center experience. Int Orthop 2007 Feb;31(1):17–21 [Epub 2006 May 20]. [11] Lachiewicz PF, Inglis AE, Insall JN, Sculco TP, Hilgartner MW, Bussel JB. Total knee arthroplasty in hemophilia. J Bone Joint Surg Am 1985 Dec;67(9):1361–6. [12] Figgie MP, Goldberg VM, Figgie III HE, Heiple KG, Sobel M. Total knee arthroplasty for the treatment of chronic hemophilic arthropathy. Clin Orthop Relat Res 1989 Nov; 248:98–107. [13] Thomason III HC, Wilson FC, Lachiewicz PF, Kelley SS. Knee arthroplasty in hemophilic arthropathy. Clin Orthop Relat Res 1999 Mar;360:169–73. [14] Rana NA, Shapiro GR, Green D. Long-term follow-up of prosthetic joint replacement in hemophilia. Am J Hematol 1986 Dec;23(4):329–37. [15] Norian JM, Ries MD, Karp S, Hambleton J. Total knee arthroplasty in hemophilic arthropathy. J Bone Joint Surg Am 2002 Jul;84-A(7):1138–41. [16] Small M, Steven MM, Freeman PA, Lowe GD, Belch JJ, Forbes CD, et al. Total knee arthroplasty in haemophilic arthritis. J Bone Joint Surg (Br) 1983 Mar;65(2):163–5. [17] Karthaus RP, Novakova IR. Total knee replacement in haemophilic arthropathy. J Bone Joint Surg (Br) 1988 May;70(3):382–5.

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Incidence of symptomatic venous thromboembolism in patients with hemophilia undergoing joint replacement surgery: a retrospective study.

Venous thromboembolism (VTE) is a recognized complication after joint replacement surgery, and prophylaxis is routinely used in patients without bleed...
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