Coagulation and Blood Management
William G. Hamilton, MD, FAAOS
Sean E. Slaven, MD
Dr. Hamilton or an immediate family member has received royalties from DePuy, a Johnson & Johnson Company and Total Joint Orthopedics; is a member of a speakers’ bureau or has made paid presentations on behalf of DePuy, a Johnson & Johnson Company; serves as a paid consultant to or is an employee of DePuy, a Johnson & Johnson Company and Total Joint Orthopedics; and has received research or institutional support from Biomet, DePuy, a Johnson & Johnson Company, and Inova Health Care Services. Neither Dr. Slaven nor any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this chapter.
ABSTRACT
Venous thromboembolism represents a significant and potentially life-threatening condition, and patients undergoing major orthopaedic surgery are at elevated risk. Mechanical and pharmacologic prophylaxis can be implemented to mitigate the risk of thromboembolism, but must be carefully selected and managed to reduce the risk of bleeding and other complications. The American Academy of Orthopaedic Surgeons and the American College of Chest Physicians have issued clinical practice guidelines for management of thromboprophylaxis in orthopaedic patients.
Limiting allogeneic blood transfusion is beneficial to reduce complications, limit costs, reduce length of stay, and improve the overall patient experience. The use of tranexamic acid has resulted in a decreased transfusion rate with a favorable safety profile. It is important to review preoperative, intraoperative, and postoperative blood management protocols to fur-ther reduce the use of allogeneic blood transfusion.
Keywords: anticoagulation; blood transfusion; tranexamic acid; venous thromboembolism
Introduction
Knowledge of coagulation and blood management is important in orthopaedic surgery, because orthopaedic patients can have substantial intraoperative blood loss along with morbidity and mortality associated with venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism. Orthopaedic surgeons must balance prophylaxis against VTE with the risk of bleeding, postoperative hematoma, and wound drainage. Several modalities exist to regulate the coagulation pathway and achieve a low rate of VTE while limiting blood loss and the need for allogeneic blood transfusion.
VTE in the Orthopaedic Patient
Patients undergoing orthopaedic surgery are at significant risk for development of VTE, particularly those undergoing major orthopaedic procedures such as total hip arthroplasty (THA), total knee arthroplasty (TKA), hip fracture surgery, and surgery for trauma.1,2,3 Although spinal cord injury and orthopaedic oncology conditions are less common, affected patients are also at increased risk of VTE.4,5 Orthopaedic patients are at increased risk for VTE for several reasons, including increased age and medical comorbidity profile, difficulty ambulating leading to immobility, tourniquet use, and venous injury as a result of the trauma of surgery.6,7
Historically, published rates of asymptomatic VTE are as high as 30% in patients who underwent THA and TKA and who were screened using ultrasonography; however, the rates of symptomatic VTE are significantly lower and of greater clinical significance.1,8 Rates of symptomatic VTE in patients who underwent THA and TKA and who received VTE chemoprophylaxis are approximately 1% and have decreased substantially over the past several decades.2,9 Improvements in surgical and anesthetic techniques to allow for less tissue damage, improved pain control, and accelerated postoperative ambulation and recovery have contributed to lower rates of VTE. This decreasing rate of VTE and corresponding drop in mortality from VTE has led to updates in consensus VTE prophylaxis guidelines.
Coagulation Cascade
The goal of the coagulation cascade is to form a clot composed of platelets, fibrin, and red blood cells to achieve hemostasis. Coagulation begins following injury to the endothelium, which exposes the subendothelial matrix containing collagen and von Willebrand factor, which bind to and partially activate platelets. Following binding, platelets release adenosine diphosphate, which binds to P2Y1 and P2Y12, leading to platelet aggregation. P2Y12 is the target of clopidogrel, a common antiplatelet medication. Platelets secrete several other substances, including serotonin, fibrinogen, platelet-derived growth factor, and thromboxane A2, which lead to further platelet recruitment and aggregation.
The clotting process is propagated by the initiation of the coagulation cascade, which occurs via the extrinsic and intrinsic pathways (Figure 1). Both pathways converge in the activation of factor X to factor Xa, which converts prothrombin to thrombin. Thrombin both potently activates platelets and converts soluble fibrinogen to insoluble fibrin, enabling stable clot formation.
Extrinsic Pathway
Endothelial injury exposes tissue factor in the subendothelial matrix, which binds circulating factor VIIa. This TA-VIIa complex then activates factor X to factor Xa, which binds with cofactor factor Va to form the prothrombinase complex, which converts prothrombin (factor II) to thrombin (factor IIa). Initial thrombin production enhances the coagulation cascade by fully activating platelets and providing activation of coagulation factors XI, VIII, and V. Thrombin converts soluble fibrinogen to insoluble fibrin and activates factor XIII to factor XIIIa, which cross-links the fibrin and contributes to stable clot formation.
 Figure 1 Coagulation cascade with intrinsic and extrinsic pathways. Pharmacologic agents are listed in red next to their targets. |
Intrinsic Pathway
Although the extrinsic pathway relies on the extrinsic exposure to tissue factor, the intrinsic pathway is composed entirely of factors already in circulation and initiates after exposure to a negatively charged surface, thus termed the contact activation pathway. The intrinsic pathway serves to propagate factor X activation, as well as provide for alternate means of activation because of a limited amount of tissue factor available and the presence of tissue factor pathway inhibitor. Intrinsic pathway activation begins with the autoactivation of factor XII upon contact with a negatively charged substance (ie, activated platelet membrane), forming factor XIIa. Factor XIIa activates factor XIa, which in turn activates factor IXa. Factor IXa combines with factor VIIIa to form a complex capable of activating factor Xa, thus converging with the extrinsic pathway and leading to subsequent thrombin activation as outlined previously. Clotting can be downregulated by the activity of protein C, which when activated binds to cofactor protein S and inhibits factor VIIIa and factor Va.
Several of the clotting factors in the cascade are vitamin K dependent, including prothrombin; factors VII, IX, and X; and anticoagulant proteins C and S. These factors undergo vitamin K-dependent gamma-carboxylation of glutamic acid residues, which allows for membrane binding and normal function. Vitamin K epoxide reductase is required to reduce the now oxidized vitamin K back to its active form. Warfarin exerts its anticoagulant effect by inhibiting vitamin K epoxide reductase function.
The fibrin clot formed during coagulation undergoes breakdown via fibrinolysis, a process mediated by plasmin. As the structural integrity of the endothelium returns, endothelial cells release tissue plasminogen activator, which converts plasminogen into active plasmin. Plasmin then cleaves the fibrin and dissolves the clot, releasing fibrin degradation products such as D-dimer, which can be measured and used clinically. Tranexamic acid (TXA) decreases blood loss by acting as an antifibrinolytic agent, binding to plasminogen and preventing activation to plasmin, preserving the fibrin structure of clots.
Types of VTE Prophylaxis
Mechanical
Mechanical forms of VTE prophylaxis include graduated compression stockings and intermittent pneumatic compression devices, which are noninvasive, and inferior vena cava (IVC) filters. Graduated compression stockings have no associated bleeding risk but are more frequently associated with skin complications.1 Intermittent pneumatic compression devices have been shown to reduce the risk of VTE when worn appropriately and are recommended as a prophylactic measure according to the American College of Chest Physicians (ACCP) guidelines.1 Intermittent pneumatic compression devices are often combined with chemoprophylaxis following major orthopaedic surgery; however, in patients at increased risk for bleeding, they can be used in isolation.1,10
IVC filter placement is an option in patients at high risk for pulmonary embolism that limits the risk of bleeding events from anticoagulation. The ACCP recommends against the use of IVC filters because of the risk of harm during placement or retrieval, low retrieval rate, unclear indications for placement, and limited efficacy, shown in a study with 90 patients with IVC filters predominantly receiving arthroplasty and spine surgery.1,11 However, a 2021 study of patients undergoing arthroplasty and with high risk for VTE demonstrated a reduced risk of pulmonary embolism in those who received IVC filters (n = 119) compared with those without filters (0.8% versus 5.5%, respectively) and a 100% retrieval rate without complications, indicating IVC filter placement may still be a reasonable option in high-risk individuals.12
Pharmacologic
A list of pharmacologic agents is presented in Table 1.
Aspirin
Aspirin acts by inhibiting platelets, specifically as a cyclooxygenase inhibitor targeting the production of thromboxane A2 and prostaglandin I2, which play a role in platelet aggregation and vasoconstriction. Aspirin is administered orally, with the typical dose for VTE prophylaxis of 81 mg twice daily or 325 mg twice daily, both of which have been shown to be effective. Aspirin has a half-life of only 20 minutes, but its effect on platelets is irreversible and lasts for the life of the platelets (approximately 10 days).13 Platelet function recovers at a rate of approximately 10% per day, and as little as 20% function may be necessary for relatively normal hemostatic function.13 Aspirin does not affect serum coagulation studies, but platelet function tests can be ordered to assess platelet function, although this is not routinely done in orthopaedic patients.
Aspirin is an attractive choice for VTE prophylaxis for several reasons. It is administered orally, requires no laboratory monitoring, is inexpensive, and has a good safety profile. Aspirin has been shown in multiple studies to be noninferior to other anticoagulants in preventing VTE and death after THA and TKA.14,15 A 2019 study demonstrated that using aspirin for VTE prophylaxis may significantly reduce mortality risk, specifically cardiac-related mortality, because of cardioprotective benefits not offered by other anticoagulants.16 Aspirin also has decreased rates of hematoma formation, wound drainage, and periprosthetic joint infection compared with other anticoagulants, which in addition to its efficacy may explain why it is the preferred VTE prophylaxis for 88% of members of the American Association of Hip and Knee Surgeons and has been consistently featured as an option in the American Academy of Orthopaedic Surgeons (AAOS) clinical practice guideline (CPG) titled Preventing Venous Thromboembolic Disease in Patients Undergoing Elective Hip and Knee Arthroplasty since 2007.10,14,17,18,19 Aspirin has recently been reported to be effective in higher risk groups, including those with cardiac and other medical comorbidities, patients with obesity, and revision arthroplasty.14,20,21
A limitation to VTE chemoprophylaxis with aspirin has been the lack of multicenter randomized controlled
trials (RCTs) to compare its efficacy with that of other anticoagulants. The Pulmonary Embolism Prevention, or PEP, trial included 13,356 patients with hip fracture and 4,088 patients who underwent elective arthroplasty and found a reduction in pulmonary embolism and DVT in the hip fracture group with aspirin compared with no treatment.22 This provided enough of an evidentiary basis for the American College of Chest Physicians to include aspirin as an acceptable form of VTE prophylaxis in its 2012 CPGs, bringing it in line with the 2011 AAOS CPGs.1,10 Additional multicenter RCTs are in progress, such as the PREVENTion of Clots in Orthopaedic Trauma (PREVENT CLOT) trial comparing aspirin with low-molecular-weight heparin (LMWH) in orthopaedic trauma patients and the Pulmonary Embolism Prevention after HiP and KneE Replacement (PEPPER) trial comparing aspirin with warfarin and rivaroxaban in patients undergoing arthroplasty.23,24 The results of these trials will provide valuable data on the suitability of aspirin for VTE prophylaxis in these populations.
trials (RCTs) to compare its efficacy with that of other anticoagulants. The Pulmonary Embolism Prevention, or PEP, trial included 13,356 patients with hip fracture and 4,088 patients who underwent elective arthroplasty and found a reduction in pulmonary embolism and DVT in the hip fracture group with aspirin compared with no treatment.22 This provided enough of an evidentiary basis for the American College of Chest Physicians to include aspirin as an acceptable form of VTE prophylaxis in its 2012 CPGs, bringing it in line with the 2011 AAOS CPGs.1,10 Additional multicenter RCTs are in progress, such as the PREVENTion of Clots in Orthopaedic Trauma (PREVENT CLOT) trial comparing aspirin with low-molecular-weight heparin (LMWH) in orthopaedic trauma patients and the Pulmonary Embolism Prevention after HiP and KneE Replacement (PEPPER) trial comparing aspirin with warfarin and rivaroxaban in patients undergoing arthroplasty.23,24 The results of these trials will provide valuable data on the suitability of aspirin for VTE prophylaxis in these populations.
Table 1 Venous Thromboembolic Prophylactic Agents | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Related posts:
Orthopaedic Patient Safety: Core Competencies and Communication Skills
Structure and Biology of Normal and Diseased Bone
Polytrauma Care
Rotator Cuff Disease, Calcific Tendinitis, Adhesive Capsulitis, Throwing Shoulder, and Instability
Ligament Injuries of the Wrist
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