Luis Becker, Juan Del Castillo, Matthias Pumberger, Nicolás Cancela.

Response/Recommendation: Routine venous thromboembolism (VTE) prophylaxis in patients undergoing upper extremity osteosynthesis under local or regional anesthesia is not needed.  VTE prophylaxis should be considered in patients at high risk of VTE and those undergoing surgery under general anesthesia that lasts over 90 minutes.

Strength of recommendation: Limited.

Rationale: Upper-extremity deep vein thrombosis (UEDVT) has a very low overall incidence of 0.4 to 1 in 10,000 persons^1–4.  Upper extremity thrombosis is divided into primary (20%) and secondary (80%) causes.  Among these, idiopathic thrombosis, effort-related thrombosis (Paget-Schroetter syndrome), or venous thoracic-outlet syndrome due to compression of the subclavian vein resulting from abnormalities of one or more structures at the costoclavicular junction represents the cause of primary thrombosis.  The more common secondary thrombosis of the upper extremity results from catheter- or pacemaker-associated thrombosis, cancer-associated thrombosis, hormone-induced coagulation abnormalities, and surgery or trauma to the upper extremity^2,5.  Pulmonary embolism (PE), post-thrombotic syndrome, and thrombosis recurrence have been described as serious complications associated with UEDVT^2,5,6.  However, UEDVT has a significantly lower risk of PE compared to lower extremity venous thrombosis^6–9.  UEDVT occur more frequently in association with central catheters and in association with malignancies and are less associated with immobilization^3,4,9.  Very few studies report the incidence of deep venous thrombosis due to upper extremity osteosynthesis.  In a report by Levy et al., among 300 patients with UEDVT, 31% of patients had developed thrombosis of upper extremity as a result of surgery or trauma⁷.  In another study comprising of 3,357 patients undergoing upper extremity orthopedic procedures, only six patients (0.0018%) developed postoperative VTE, and five out of six patients had a strong history of prior VTE¹⁰.  Calotta et al., analyzing registry 24,494 patients in a registry database reported an incidence of 0.3% of upper extremity DVT in patients undergoing open reduction and internal fixation of distal radius fractures¹¹.  The risk factors identified for upper extremity deep venous thrombosis (DVT) in the latter study were history of congestive heart failure and use of estrogen¹¹.  In another study by Mino et al., on 1,857 patients undergoing general surgery, the incidence of postoperative thrombosis of the upper extremity was 1.13%, with all, but one, patient developing the DVT in association with central catheter¹².  In contrast, Blom et al., reporting on an association between upper extremity surgery and UEDVT in two patients in a subcohort of 179 patients out of the MEGA study selected due to UEDVT, resulting in the odds ratio of 11.8 compared to a control cohort of 2,398 patients, in which three patients underwent upper extremity surgery within three months before index date^13,14.  In addition, Hoxie et al., reported an occurrence of pulmonary embolism in 5.6% of surgically treated patients with a proximal humerus fracture (4 hemiarthroplasty, 3 open reduction internal fixation [ORIF])¹⁵.  In contrast, Widmer et al., found no thromboembolic events in 50 patients, receiving VTE prophylaxis, after proximal humerus fracture¹⁶.  In addition to the aforementioned studies, there are sporadic case reports of the occurrence of UEDVT and PE and upper extremity fracture or osteosynthesis^17–23.  Two reviews around the topic of the need for thromboprophylaxis of upper limb surgery were identified.  The article by Roberts and Warwick summarizes the literature and guidelines regarding prophylaxis for thrombosis in hand, wrist, and elbow surgery^24,25.  They recommend risk assessment for DVT in patients with prolonged elbow or forearm surgery and found that history of active cancer or cancer treatment, age over 60 years, admission to intensive care unit, dehydration, history of VTE, obesity, history of one or more significant medical co-morbidities, family history of VTE, use of hormone replacement therapy or estrogen-containing contraceptives, varicose veins with phlebitis to be predisposing factors for upper extremity VTE.  The authors recommended that VTE prophylaxis be considered for patients at high-risk population and patients undergoing upper extremity osteosynthesis under local or regional anesthesia were considered to be at low-risk^24,25.  The other review article by Anakwe et al., also discussed the topic of thromboprophylaxis in patients undergoing elective upper extremity osteosynthesis²⁶.  They also recommended an approach that involved risk assessment and administration of chemoprophylaxis for high-risk patients and mechanical prophylaxis for others, unless contraindicated²⁶.  Evidence on which form of mechanical or chemical thromboprophylaxis should be chosen in case of upper limb osteosynthesis does not exist.  However, some organizational guidelines have been proposed.  The National Institute for Health and Care Excellence (NICE) Guidelines has produced guidelines that are stated below²⁷:

• 1.11.15 Be aware that VTE prophylaxis is generally not needed if giving local or regional anaesthetic for upper limb surgery. [2018].
• 1.11.16 Consider VTE prophylaxis for people undergoing upper limb surgery if the person’s total time under general anaesthetic is over 90 minutes or where their operation is likely to make it difficult for them to mobilize. [2018].

The British Society for Surgery of the Hand (BSSH) has also proposed guidelines that are stated below (Table1)²⁸:

Table1. BSSH recommendations for prophylaxis in hand, wrist, and elbow surgery

Risk	Example	Recommendation
Low	LA, regional anaesthesia or <90 minutes GA	No prophylaxis
Moderate	>90 minutes GA (including elbow arthroplasty) and/or 1 risk factor	Mechanical prophylaxis until mobile
High	>90 minutes GA and >1 risk factor, prolonged post-operative immobility, or tumour surgery	Mechanical prophylaxis and consider pharmacological prophylaxis until mobile

The evidence for the use of thromboprophylaxis in upper extremity osteosynthesis is limited.  There is scarce but consistent evidence that VTE prophylaxis in patients undergoing upper extremity osteosynthesis under local or regional anesthesia is not necessary.  Instead, chemoprophylaxis should be reserved for patients undergoing upper extremity osteosynthesis under long general anesthesia (> 90 minutes), those at high-risk VTE (as discussed above), and patients who are likely to have difficulty with mobilization.  The potential benefits of chemoprophylaxis should always be weighed against the bleeding risk.

References:

1.         Muñoz FJ, Mismetti P, Poggio R, et al. Clinical outcome of patients with upper-extremity deep vein thrombosis: results from the RIETE Registry. Chest. 2008;133(1):143-148. doi:10.1378/chest.07-1432

2.         Kucher N. Deep-Vein Thrombosis of the Upper Extremities. New England Journal of Medicine. 2011;364(9):861-869. doi:10.1056/NEJMcp1008740

3.         Joffe HV, Kucher N, Tapson VF, Goldhaber SZ, Deep Vein Thrombosis (DVT) FREE Steering Committee. Upper-extremity deep vein thrombosis: a prospective registry of 592 patients. Circulation. 2004;110(12):1605-1611. doi:10.1161/01.CIR.0000142289.94369.D7

4.         Isma N, Svensson PJ, Gottsäter A, Lindblad B. Upper extremity deep venous thrombosis in the population-based Malmö thrombophilia study (MATS). Epidemiology, risk factors, recurrence risk, and mortality. Thromb Res. 2010;125(6):e335-338. doi:10.1016/j.thromres.2010.03.005

5.         Mai C, Hunt D. Upper-extremity deep venous thrombosis: a review. Am J Med. 2011;124(5):402-407. doi:10.1016/j.amjmed.2010.11.022

6.         Lee J-A, Zierler BK, Zierler RE. The risk factors and clinical outcomes of upper extremity deep vein thrombosis. Vasc Endovascular Surg. 2012;46(2):139-144. doi:10.1177/1538574411432145

7.         Levy MM, Albuquerque F, Pfeifer JD. Low incidence of pulmonary embolism associated with upper-extremity deep venous thrombosis. Ann Vasc Surg. 2012;26(7):964-972. doi:10.1016/j.avsg.2011.12.016

8.         Ploton G, Pistorius M-A, Raimbeau A, et al. A STROBE cohort study of 755 deep and superficial upper-extremity vein thrombosis. Medicine (Baltimore). 2020;99(6):e18996. doi:10.1097/MD.0000000000018996

9.         Rokosh RS, Ranganath N, Yau P, et al. High Prevalence and Mortality Associated with Upper Extremity Deep Venous Thrombosis in Hospitalized Patients at a Tertiary Care Center. Ann Vasc Surg. 2020;65:55-65. doi:10.1016/j.avsg.2019.10.055

10.       Hastie GR, Pederson A, Redfern D. Venous thromboembolism incidence in upper limb orthopedic surgery: do these procedures increase venous thromboembolism risk? J Shoulder Elbow Surg. 2014;23(10):1481-1484. doi:10.1016/j.jse.2014.01.044

11.       Calotta NA, Shores JT, Coon D. Upper-Extremity Venous Thromboembolism Following Operative Treatment of Distal Radius Fractures: An Uncommon but Dangerous Complication. J Hand Surg Am. Published online May 14, 2021:S0363-5023(21)00165-9. doi:10.1016/j.jhsa.2021.03.011

12.       Mino JS, Gutnick JR, Monteiro R, Anzlovar N, Siperstein AE. Line-associated thrombosis as the major cause of hospital-acquired deep vein thromboses: an analysis from National Surgical Quality Improvement Program data and a call to reassess prophylaxis strategies. Am J Surg. 2014;208(1):45-49. doi:10.1016/j.amjsurg.2013.08.046

13.       Blom JW, Doggen CJM, Osanto S, Rosendaal FR. Old and new risk factors for upper extremity deep venous thrombosis. J Thromb Haemost. 2005;3(11):2471-2478. doi:10.1111/j.1538-7836.2005.01625.x

14.       Blom JW, Doggen CJM, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA. 2005;293(6):715-722. doi:10.1001/jama.293.6.715

15.       Hoxie SC, Sperling JW, Cofield RH. Pulmonary embolism after operative treatment of proximal humeral fractures. J Shoulder Elbow Surg. 2007;16(6):782-783. doi:10.1016/j.jse.2006.12.004

16.       Widmer BJ, Bassora R, Warrender WJ, Abboud JA. Thromboembolic events are uncommon after open treatment of proximal humerus fractures using aspirin and compression devices. Clin Orthop Relat Res. 2011;469(12):3332-3336. doi:10.1007/s11999-011-1942-7

17.       Lv B, Xue F, Shen Y-C, Hu F-B, Pan M-M. Pulmonary thromboembolism after distal ulna and radius fractures surgery: A case report and a literature review. World J Clin Cases. 2021;9(1):197-203. doi:10.12998/wjcc.v9.i1.197

18.       Li Y, Wang Z, Sang X. Subclavian vein thrombosis and fatal pulmonary embolism after proximal humerus fracture surgery. J Orthop Surg (Hong Kong). 2019;27(1):2309499019832728. doi:10.1177/2309499019832728

19.       Igeta Y, Naito K, Sugiyama Y, Kaneko K, Obayashi O. Pulmonary thromboembolism after operation for bilateral open distal radius fractures: a case report. BMC Res Notes. 2014;7:36. doi:10.1186/1756-0500-7-36

20.       Strony J, Chang G, Krieg JC. Upper-Extremity Deep Venous Thrombosis following a Fracture of the Proximal Humerus: An Orthopaedic Case Report. Case Rep Orthop. 2019;2019:6863978. doi:10.1155/2019/6863978

21.       Sawyer GA, Hayda R. Upper-extremity deep venous thrombosis following humeral shaft fracture. Orthopedics. 2011;34(2):141. doi:10.3928/01477447-20101221-27

22.       Basat HC, Kalem M, Binnet MS, Demirtaş M. Pulmonary thromboembolism after surgical treatment of ulnar pseudoarthrosis: a case report. Acta Orthop Traumatol Turc. 2011;45(4):284-287. doi:10.3944/AOTT.2011.2426

23.       Jupiter JB, Ring D, Weitzel PP. Surgical treatment of redisplaced fractures of the distal radius in patients older than 60 years. J Hand Surg Am. 2002;27(4):714-723. doi:10.1053/jhsu.2002.34007

24.       Roberts DC, Warwick DJ. Venous thromboembolism following elbow, wrist and hand surgery: a review of the literature and prophylaxis guidelines. J Hand Surg Eur Vol. 2014;39(3):306-312. doi:10.1177/1753193412469131

25.       Roberts DC, Warwick DJ. Updated recommendations for venous thromboembolism prophylaxis in hand, wrist and elbow surgery. J Hand Surg Eur Vol. 2019;44(10):1107-1108. doi:10.1177/1753193419871665

26.       Anakwe RE, Middleton SD, Beresford-Cleary N, McEachan JE, Talwalkar SC. Preventing venous thromboembolism in elective upper limb surgery. J Shoulder Elbow Surg. 2013;22(3):432-438. doi:10.1016/j.jse.2012.10.033

27.       National Guideline Centre (UK). Venous Thromboembolism in over 16s: Reducing the Risk of Hospital-Acquired Deep Vein Thrombosis or Pulmonary Embolism. National Institute for Health and Care Excellence (UK); 2018. Accessed August 23, 2021. http://www.ncbi.nlm.nih.gov/books/NBK493720/

28.       Haque A, Patel MS, Siddiqui B, Wildin CJ, Dias JJ. Venous thromboembolic events in hand surgery. J Plast Surg Hand Surg. 2021;55(3):190-194. doi:10.1080/2000656X.2020.1856671