Orthopedics

CME Review Article 

Prevention of VTE Following Total Hip and Knee Arthroplasty in Hemophilia Patients

Matthew I. Stein, MD; Justin Park, MD; Stephen Raterman, MD

Abstract

The often debilitating condition of hemophilic arthropathy is treated with elective total joint arthroplasty. Little has been published addressing the role of thromboembolic prophylaxis in the hemophilic patient population following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Although the American College of Chest Physicians and the American Academy of Orthopaedic Surgeons have set guidelines for thromboembolic prophylaxis in the general population, no such standard of care is in place for hemophilic patients. While the risk of thrombosis in hemophilic patients following THA and TKA is thought to be lower, cases have been reported of pulmonary embolism and deep vein thrombosis (DVT) in hemophilic patients.

Abstract

The often debilitating condition of hemophilic arthropathy is treated with elective total joint arthroplasty. Little has been published addressing the role of thromboembolic prophylaxis in the hemophilic patient population following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Although the American College of Chest Physicians and the American Academy of Orthopaedic Surgeons have set guidelines for thromboembolic prophylaxis in the general population, no such standard of care is in place for hemophilic patients. While the risk of thrombosis in hemophilic patients following THA and TKA is thought to be lower, cases have been reported of pulmonary embolism and deep vein thrombosis (DVT) in hemophilic patients.

Drs Stein and Raterman are from Department of Orthopedic Surgery and Sports Medicine, University of South Florida, Tampa, Florida; and Dr Park is from the Hospital for Joint Disease, Division of Orthopedic Surgery, New York University Hospital for Joint Diseases, New York, New York.

The material presented in any Vindico Medical Education continuing education activity does not necessarily reflect the views and opinions of ORTHOPEDICS or Vindico Medical Education. Neither ORTHOPEDICS nor Vindico Medical Education nor the authors endorse or recommend any techniques, commercial products, or manufacturers. The authors may discuss the use of materials and/or products that have not yet been approved by the US Food and Drug Administration. All readers and continuing education participants should verify all information before treating patients or using any product.

Correspondence should be addressed to: Matthew I. Stein, MD, Department of Orthopedic Surgery and Sports Medicine, University of South Florida, Tampa, FL 33613.

Hemophilic arthropathy is an unfortunately frequent manifestation of severe hemophilia, and one that can often lead to debilitating pain, restricted range of motion, and significant functional decline.1 For many years, this condition presented a therapeutic dilemma for the orthopedic surgeon, as patients with such a bleeding tendency were not candidates for elective total joint arthroplasty. However, with the advancement of the hematologic care of hemophilic patients over the past several years, primarily through the use of factor replacement therapy, hemophilic arthropathy can now be effectively treated surgically. More specifically, total joint arthroplasty in this patient population has repeatedly showed beneficial outcomes, improving the quality of life with diminished postoperative bleeding episodes.1–3

The number of hemophilic patients undergoing TKA or THA will continue to grow in the near future. Operating surgeons will have the same management dilemmas with hemophilic patients in regards to postoperative deep vein thrombisis (DVT) prophylaxis as they do when performing total joint arthroplasty in the general population. Unfortunately, currently no guidelines exist that address thromboembolic prophylaxis in hemophilic patients, and no literature to date has been published addressing the potential need for postoperative thromboembolic prophylaxis following THA and TKA. This review article summarizes the incidence of postoperative thrombosis in both the general and hemophilic population, outlines the current recommendations for postoperative thromboembolic prophylaxis following TKA and THA, and highlights the need for standard thromboembolic prophylactic guidelines in the hemophilic patient population.

Incidence of DVT Following TKA and THA

General Population

Elective TKA and THA carry with them a high risk of postoperative thromboembolic disease, a serious and potentially fatal complication. In the general population, this risk has been extensively studied and prophylactic guidelines have been set to best prevent such complications.

Traditionally, the rate of DVT or pulmonary embolism (PE) following total joint arthroplasty has been estimated to be between 40% and 84% in patients undergoing TKA, and 45% and 57% in those undergoing THA.4–10 Kim and Kim11 found that in the absence of chemoprophylaxis, 41.6% of patients following unilateral TKA, and 41.8% of patients following bilateral TKA, were positive by venography for DVT. Similarly, Cordell-Smith et al12 found that the combined prevalence of DVT after THA and TKA in patients who did not receive chemoprophylaxis was 46.4%. Although the reported fatal outcomes associated with such complications is far lower, the morbidity related to the high rates of DVT following TKA and THA reinforces the elevated risk of thrombotic events accompanying total joint arthroplasty and the need for effective prophylactic measures.

Hemophilic Population

The rate of DVT or PE following elective THA and TKA in hemophilic patients, however, has been only minimally addressed. This is primarily due to the fact that hemophilic patients are more at risk for postoperative bleeding than clotting, but also likely because elective joint arthroplasty in this patient population is a relatively new therapeutic option. Although only few documented cases exist of DVT or PE following total joint arthroplasty in the hemophilic population, patients diagnosed with mild to severe hemophilia are still at risk for thrombotic events.

Several case reports have highlighted instances of DVT, both spontaneous and postoperative, in patients with diagnosed hemophilia.13,14 Included among these cases, is that of a fatal PE following major pelvic surgery in a hemophilic patient.15 Girolami et al16 reviewed all 27 cases of non-catheter associated venous thrombosis in hemophilic patients, and concluded that the most frequent risk factor for thrombosis in this patient population was the administration of factor replacement therapy. Additionally, 2 patients were found to have congenital prothrombotic risk factors along with the inherited diagnosis of hemophilia. Krause et al17 focused specifically on the incidence of DVT following TKA and THA, and found that, in 32 patients with hemophilia A receiving no postoperative chemoprophylaxis, there were no documented cases of venous thrombosis. Similarly, in 68 patients using no postoperative thromboprophylaxis, Silva and Luck18 identified only 1 nonfatal PE.

Standard DVT Prophylactic Regimen Following TKA and THA

General Population

Although extensive research and literature has been published on the most appropriate thromboembolic prophylaxis following TKA and THA, the exact regimen and duration of chemoprophylaxis remains controversial. According to the American College of Chest Physicians (ACCP) 2008 guidelines, patients undergoing THA should be prophylactically treated with either low-molecular-weight heparin (LMWH), fondaparinux, or a vitamin K antagonist with a target international normalized ratio of approximately 2.5. Similarly, for patients undergoing TKA, the ACCP recommends the routine use of LMWH, fondaparinux, or adjusted dose vitamin K antagonist. Additionally, the optimal use of intermittent pneumatic compression is an alternative option to anticoagulant thromboprophylaxis in TKA patients. It is important to recognize, as the source of much debate in the orthopedic community, that the ACCP specifically recommends against the use of aspirin, dextran, or venous foot pumps as the sole method of prophylaxis in both THA and TKA patients.19

However, questionremains regarding the effectiveness of treatment with anti-platelet agents in low-risk patients.20,21 The AAOS 2007 guidelines state that patients at standard risk of PE and major bleeding should be treated with aspirin, LMWH, synthetic pentassacharides, and warfarin. Those with elevated risk of PE, however, may not be treated with aspirin.22 Although the AAOS does not specifically designate risk factors in their recommendations, the risk-stratified recommendations of the AAOS has been further defined and frequently supported in orthopedic literature. Among the risk factors often cited are, a previous history of DVT/PE, family history of DVT/PE, history of hypercoagulable disorder, severe deep venous insufficiency, hormone replacement/birth control therapy, and severe heart disease or malignancy.23,24 Callaghan et al23 found no DVT-related deaths and a low rate of admission for thromboembolic events, with no readmissions for bleeding, in low-risk TKA patients treated with anti-platelet prophylaxis. Similarly, Dorr et al24 found that a multimodal, risk stratified, thromboprophylactic regimen including the use of anti-platelet agents, is consistent with protecting patients, while limiting adverse clinical outcomes secondary to thromboembolic, vascular, and bleeding complications.

Although there has been extensive research on the subject, no universally agreed-upon protocol exists for the thromboembolic prophylaxis of patients undergoing TKA and THA. Similarly, extensive debate exists regarding the appropriate duration of thromboembolic prophylaxis in the postoperative period. Friedman25 reviewed the subject, and found that prophylaxis with LMWH for approximately 4 weeks following THA resulted in clinically significant reductions of DVT, but that no data exists to support extending thromboprophylaxis beyond 10 days following TKA.

Hemophilic Population

The extensive discussion regarding the proper prophylactic regimen in the general population reinforces the necessity of similar, gold-standard protocols in the hemophilic population. Currently, no documented standard of care exists for the appropriate thromboembolic prophylactic protocol in the hemophilic population following THA or TKA. However, guidelines suggested by the ACCP and AAOS, regarding patients at risk of bleeding, may apply. According to the ACCP 2008 guidelines, patients with a high risk of bleeding following THA or TKA are recommended to use mechanical thromboprophylaxis with a venous foot pump or intermittent pneumatic compression only.19 The AAOS, however, recommends that patients at standard risk of PE and elevated risk of major bleeding should be treated with aspirin, warfarin, or nothing.22

Theoretically, the factor replacement therapy required during the perioperative and postoperative period in a hemophilic patient restores these patients to a normal coagulation profile with only mildly increased bleeding risks. These disparate recommendations by the ACCP and AAOS only add more confusion to the subject regarding the most appropriate thromboembolic prophylaxis in this unique patient population. Furthermore, the literature addressing THA and TKA in hemophilic patients sporadically mentions the chosen method of thromboprophylaxis, with the majority reporting no diagnosed DVTs.1,26,27 In fact, a comprehensive review of total joint arthroplasty in hemophilia references DVT as a complication of THA, but fails to mention the chosen method of thromboembolic prophylaxis.28

However, several fairly extensive published case series report the method of thromboembolic prophylaxis and any corresponding thrombotic complications. Silva et al18 found 1 non-fatal PE in 90 primary TKAs on 68 hemophilic patients with no postoperative thromboprophylaxis. Innocenti et al29 studied 24 modular TKA performed in 20 hemophilic patients, with no postoperative thromboprophylaxis, that resulted in no DVTs. Similarly, Miles et al3 found no cases of thromboembolic disease when reviewing 34 THAs performed on hemophilic patients, with only mechanical postoperative thromboprophylaxis, and Rodriguez-Merchan30 diagnosed no DVTs in 35 primary TKAs with no chemical thromboembolic prophylaxis.

Summary and Recommendations

The role of prophylactic management of postoperative thromboembolism in the hemophilic population deserves more attention. While the debate continues regarding the optimal postoperative DVT prophylactic regimen in the general population following THA and TKA, extensive research regarding prophylactic protocols in hemophilic patients is needed before evidence-based recommendations can be made.

Although hemophilic patients are generally at high risk of bleeding, the treatment required to perform elective arthroplasty increases the hemophilic patient’s risk of thrombosis. In theory, the factor replacement therapy given to hemophilic patients, perioperatively and postoperatively, returns the patient to a relatively normal clotting function, thereby exposing them to similar postoperative risks to the general population. Girolami et al16 reported that factor replacement therapy is the most common predisposing element to thrombosis in hemophilic patients. It is this careful balance between hemorrhage and thromboembolism that makes consultation with a hematologist essential.

Complicating matters further are the contradicting recommendations of the ACCP and AAOS regarding patients at an increased risk of postoperative bleeding. While the ACCP calls for mechanical thromboprophylaxis only, the AAOS also supports the use of aspirin or warfarin.19,22 Furthermore, much of the literature addressing total joint arthroplasty in hemophilic patients fails to mention specific methods of thromboembolic prophylaxis. Although the incidence of thrombotic events in hemophilic patients following THA and TKA appears to be minimal, the relatively recent accepted use of total joint arthroplasty as a means of treating hemophilic arthropathy, has limited the capability of performing larger case series and randomized, controlled trials. As THA and TKA become more common in hemophilic patients, larger case series and randomized, controlled trials will be essential to determining the true incidence of DVT following TKA and THA in hemophilic patients, as well as comparing the effectiveness and need for mechanical or chemical thromboembolic prophylaxis.

Orthopedic surgeons should recognize and have a basic understanding of the thromboembolic risks associated with operating on hemophilic patients. Given the lack of well studied and proven protocols regarding this topic, it is our experience that close consultation with a hematologist, along with individualizing treatment plans based on patient risk factors, is most successful in planning appropriate thromboembolic prophylaxis in this patient population. Obtaining a detailed family history to rule out co-inherited prothrombotic genetic variations that may predispose a hemophilic patient to thrombosis is also essential.31,32 Ultimately, it is up to the operating surgeon to weigh the risks and benefits of chemoprophylaxis and take into account the recommendations of the ACCP and AAOS to determine the appropriate prophylactic regimen for their hemophilic patients.

References

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  2. Ballal RD, Botteman MF, Foley I, Stephens JM, Wilke CT, Joshi AV. Economic evaluation of major knee surgery with recombinant activated factor VII in hemophilia patients with high titer inhibitors and advanced knee arthropathy: exploratory results via literature-based modeling [published online ahead of print January 29, 2008]. Curr Med Res Opin. 2008; 24(3):753–768. doi:10.1185/030079908X273048 [CrossRef]
  3. Miles J, Rodríguez-Merchán EC, Goddard NJ. The impact of haemophilia on the success of total hip arthroplasty [published online ahead of print November 22, 2007]. Haemophilia. 2008; 14(1):81–84.
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  5. Xing KH, Morrison G, Lim W, Douketis J, Odueyungbo A, Crowther M. Has the incidence of deep vein thrombosis in patients undergoing total hip/knee arthroplasty changed over time? A systematic review of randomized controlled trials [published online ahead of print July 11, 2008]. Thromb Res. 2008; 123(1)24–34. doi:10.1016/j.thromres.2008.05.005 [CrossRef]
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  8. Stulberg BN, Insall JN, Williams GW, Ghelman B. Deep-vein thrombosis following total knee replacement. An analysis of six hundred and thirty-eight arthroplasties. J Bone Joint Surg Am. 1984; 66(2):194–201.
  9. Lassen MR, Borris LC, Christiansen HM, et al. Prevention of thromboembolism in 190 hip arthroplasties. Comparison of LMW heparin and placebo. Acta Orthop Scand. 1991; 62(1):33–38. doi:10.3109/17453679108993088 [CrossRef]
  10. Turpie AG, Levine MN, Hirsh J, et al. A randomized controlled trial of low-molecular-weight heparin (enoxaparin) to prevent deep-vein thrombosis in patients undergoing elective hip surgery. N Engl J Med. 1986; 315(15):925–929. doi:10.1056/NEJM198610093151503 [CrossRef]
  11. Kim YH, Kim JS. Incidence and natural history of deep-vein thrombosis after total knee arthroplasty. A prospective, randomised study. J Bone Joint Surg Br. 2002; 84(4):566–570. doi:10.1302/0301-620X.84B4.12330 [CrossRef]
  12. Cordell-Smith JA, Williams SC, Harper WM, Gregg PJ. Lower limb arthroplasty complicated by deep venous thrombosis. Prevalence and subjective outcome. J Bone Joint Surg Br. 2004; 86(1):99–101.
  13. Dargaud Y, Cruchaudet BB, Lienhart A, Coppéré B, Ninet J, Négrier C. Spontaneous proximal deep vein thrombosis in a patient with severe haemophilia A. Blood Coagul Fibrinolysis. 2003; 14(4):407–409. doi:10.1097/00001721-200306000-00013 [CrossRef]
  14. Ettingshausen CE, Saguer IM, Kreuz W. Portal vein thrombosis in a patient with severe haemophilia A and F V G1691A mutation during continuous infusion of F VIII after intramural jejunal bleeding—successful thrombolysis under heparin therapy. Eur J Pediatr. 1999; 158(Suppl 3):S180–182. doi:10.1007/PL00014351 [CrossRef]
  15. Butcher JH, Pasi KJ. Fatal postoperative pulmonary embolism in mild haemophilia. Haemophilia. 2006; 12(2):179–182. doi:10.1111/j.1365-2516.2006.01183.x [CrossRef]
  16. Girolami A, Scandellari R, Zanon E, Sartori R, Girolami B. Non-catheter associated venous thrombosis in hemophilia A and B. A critical review of all reported cases. J Thromb Thrombolysis. 2006; 21(3):279–284. doi:10.1007/s11239-006-6556-7 [CrossRef]
  17. Krause M, Von Auer Ch., Kurth A, Bohm M, Hovy L, Scharrer I. (2007). Evaluation of thrombotic events in hemophiliacs undergoing major orthopedic surgery without thrombosis prophylaxis. Presented at: the 36th Hemophilia Symposium. ; Hamburg, Germany. ; March 1–4, 2005. .
  18. Silva M, Luck JV Jr, . Long-term results of primary total knee replacement in patients with hemophilia. J Bone Joint Surg Am. 2005; 87(1):85–91. doi:10.2106/JBJS.C.01609 [CrossRef]
  19. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008; 133(6 Suppl):381S–453S. doi:10.1378/chest.08-0656 [CrossRef]
  20. Eikelboom JW, Karthikeyan G, Fagel N, Hirsh J. American Association of Orthopedic Surgeons and American College of Chest Physicians Guidelines for Venous Thromboembolism Prevention in Hip and Knee Arthroplasty Differ: What are the Implications for Clinicians and Patients?Chest. 2009; 135(2):513–520. doi:10.1378/chest.08-2655 [CrossRef]
  21. Zimlich RH, Fulbright BM, Friedman RJ. Current status of anticoagulation therapy after total hip and total knee arthroplasty. J Am Acad Orthop Surg. 199; 64(2):54–62.
  22. American Academy of Orthopaedic Surgeons Clinical Guideline on Prevention of Symptomatic Pulmonary Embolism in Patients Undergoing Total Hip or Knee Arthroplasty. Adopted by the American Academy of Orthopedic Surgeons Board of Directors May 2007. Available at: www.aaos.org/research/guidelines/PE_guideline.pdf.
  23. Callaghan JJ, Warth LC, Hoballah JJ, Liu SS, Wells CW. Evaluation of deep venous thrombosis prophylaxis in low-risk patients undergoing total knee arthroplasty. J Arthroplasty. 2008; 23(6 Suppl 1):20–24. doi:10.1016/j.arth.2008.05.018 [CrossRef]
  24. Dorr LD, Gendelman V, Maheshwari AV, Boutary M, Wan Z, Long WT. Multimodal thromboprophylaxis for total hip and knee arthroplasty based on risk assessment. J Bone Joint Surg Am. 2007; 89(12):2648–2657. doi:10.2106/JBJS.F.00235 [CrossRef]
  25. Friedman RJ. Optimal duration of prophylaxis for venous thromboembolism following total hip arthroplasty and total knee arthroplasty. J Am Acad Orthop Surg. 2007; 15(3):148–155.
  26. Bae DK, Yoon KH, Kim HS, Song SJ. Total knee arthroplasty in hemophilic arthropathy of the knee. J Arthroplasty. 2005; 20(5):664–668. doi:10.1016/j.arth.2005.01.008 [CrossRef]
  27. Chiang CC, Chen PQ, Shen MC, Tsai W. Total knee arthroplasty for severe haemophilic arthropathy: long-term experience in Taiwan. Haemophilia. 2008; 14(4):828–834. doi:10.1111/j.1365-2516.2008.01693.x [CrossRef]
  28. Beeton K, Rodriguez-Merchan EC, Alltree J. Total joint arthroplasty in haemophilia. Haemophilia. 2000; 6(5):474–481. doi:10.1046/j.1365-2516.2000.00443.x [CrossRef]
  29. Innocenti M, Civinini R, Carulli C, Villano M, Linari S, Morfini M. A modular total knee arthroplasty in haemophilic arthropathy [published online ahead of print June 29, 2007]. Knee. 2007; 14(4):264–268. doi:10.1016/j.knee.2007.05.001 [CrossRef]
  30. Rodriguez-Merchan EC. Total knee replacement in haemophilic arthropathy. J Bone Joint Surg Br. 2007; 89(2):186–188. doi:10.1302/0301-620X.89B2.18682 [CrossRef]
  31. Dargaud Y, Meunier S, Negrier C. Haemophlia and thrombophilia: an unexpected association!Haemophilia. 2004; 10(4):319–326. doi:10.1111/j.1365-2516.2004.00906.x [CrossRef]
  32. Pruthi RK, Heit JA, Green MM, et al. Venous thromboembolism after hip fracture surgery in a patient with haemophilia B and factor V Arg506Gln (factor V Leiden). Haemophilia. 2000; 6(6):631–634. doi:10.1046/j.1365-2516.2000.00431.x [CrossRef]
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Instructions

CME Accreditation

This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Vindico Medical Education and Orthopedics. Vindico Medical Education is accredited by the ACCME to provide continuing medical education for physicians.

Vindico Medical Education designates this Journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

This CME activity is primarily targeted to orthopedic surgeons, hand surgeons, head and neck surgeons, trauma surgeons, physical medicine specialists, and rheumatologists. There is no specific background requirement for participants taking this activity.

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In accordance with the Accreditation Council for Continuing Medical Education’s Standards for Commercial Support, all CME providers are required to disclose to the activity audience the relevant financial relationships of the planners, teachers, and authors involved in the development of CME content. An individual has a relevant financial relationship if he or she has a financial relationship in any amount occurring in the last 12 months with a commercial interest whose products or services are discussed in the CME activity content over which the individual has control.

Drs Stein, Park, and Raterman have no relevant financial relationships to disclose. Dr D’Ambrosia, Editor-in-Chief, has no relevant financial relationships to disclose. The staff of ORTHOPEDICS have no relevant financial relationships to disclose.

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The audience is advised that this continuing medical education activity may contain references to unlabeled uses of FDA-approved products or to products not approved by the FDA for use in the United States. The faculty members have been made aware of their obligation to disclose such usage.

Educational Objectives

As a result of reading this article, physicians should be able to:

  1. Demonstrate how elective total joint arthroplasty has been shown to have good outcomes in hemophilic patients.

  2. Explain the impact of factor replacement therapy on thrombembolic events in hemophilic patients.

  3. Assess postoperative thromboembolism following total hip arthroplasty (THA) and total knee arthroplasty (TKA) in hemophilic patients.

  4. List the conflicting recommendations from the American Academy of Orthopaedic Surgeons and American College of Chest Physicians regarding appropriate deep vein thrombosis prophylaxis in patients at high risk of bleeding undergoing THA or TKA.

Authors

Drs Stein and Raterman are from Department of Orthopedic Surgery and Sports Medicine, University of South Florida, Tampa, Florida; and Dr Park is from the Hospital for Joint Disease, Division of Orthopedic Surgery, New York University Hospital for Joint Diseases, New York, New York.

The material presented in any Vindico Medical Education continuing education activity does not necessarily reflect the views and opinions of ORTHOPEDICS or Vindico Medical Education. Neither ORTHOPEDICS nor Vindico Medical Education nor the authors endorse or recommend any techniques, commercial products, or manufacturers. The authors may discuss the use of materials and/or products that have not yet been approved by the US Food and Drug Administration. All readers and continuing education participants should verify all information before treating patients or using any product.

Correspondence should be addressed to: Matthew I. Stein, MD, Department of Orthopedic Surgery and Sports Medicine, University of South Florida, Tampa, FL 33613.

10.3928/01477447-20110317-21

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