Perioperative Management of Bleeding and Transfusion

Introduction

Transfusion therapy is necessary and can be lifesaving in surgical patients. However, despite being the standard of care for blood loss and anemia, it has never undergone the rigorous, randomized testing required of a new therapeutic agent, including assessment of adverse events and risk assessment. Since the outbreak of acquired immunodeficiency syndrome (AIDS) in the 1980s, it has become apparent that the full extent of the risk of allogeneic transfusion therapy is unknown. In the 2000s, the British National CJD Surveillance Unit identified 48 individuals who received a blood component from 15 donors who later developed variant Creutzfeldt-Jakob disease (vCJD). One of these individuals developed symptoms 6.5 years after a transfusion of packed red blood cells (PRBCs) from an asymptomatic donor and died of vCJD in December 2003. A decade later, investigators in Brazil described two patients who tested positive for Zika virus after receiving platelet transfusions. The donor was asymptomatic at the time of donation, but later was confirmed to be infected with Zika virus after developing rash, retro-orbital pain, and bilateral knee pain. Considering these risks, it becomes apparent that alternatives to transfusion must be developed in combination with blood conservation measures. The goal of these measures should be to limit transfusion to clinical scenarios in which allogeneic blood product administration is clearly necessary to maintain adequate oxygen delivery and reduce mortality.

Patient Blood Management and Preoperative Evaluation

Patient blood management (PBM) is a process designed to optimize the risk-to-benefit ratio of allogeneic blood component administration and improve patient outcomes. According to the Society for the Advancement of Blood Management, the four pillars of PBM include interdisciplinary blood conservation strategies, management of anemia, optimization of perioperative coagulation, and patient-centered decision making. PBM requires an integrated program of preparation, reduction of blood loss, and elimination of unnecessary allogeneic transfusion. Although the benefit to patient outcome and cost reduction has been documented in the literature, implementation of an effective PBM program is challenging. In order to realize the benefits of PBM, infrastructure necessary for the diagnosis and treatment of anemia in the preoperative period prior to major elective surgery is essential.

When the concept of PBM is simplified, the major components of the program are geared toward preventing clinically significant levels of anemia in the perioperative period. While autologous predonation of PRBC has been recommended in the past for noncardiac surgical procedures with significant intraoperative blood loss such as total joint replacement and spine surgery, the cost and questionable efficacy of this technique has resulted in decreased utilization. Autologous predonation can result in lower hemoglobin at the time of surgery, off-setting any potential benefit. Predonation is also subject to the risk of clerical error and results in significant wastage of predonated units.

Preoperative anemia is an independent risk factor for mortality in both cardiac surgery and major noncardiac surgery. Without adequate red blood cell mass prior to a major operation, intraoperative blood conservation strategies are limited and allogeneic blood transfusion is almost assured. In a national audit of patients undergoing elective orthopedic surgery in the United States, 35% of patients had hemoglobin levels < 13 g/dL at the time of preadmission testing with one-third of these patients testing positive for iron deficiency. Treatment of reversible causes of anemia requires assessment up to 28 days prior to surgery with delay of elective cases for anemia treatment in order to optimize outcome. Without the ability to input, assess, and treat patients more than 7 days prior to major surgery, an opportunity to avoid unnecessary transfusion and limit cost is missed. In conjunction with plans for early input into enhanced recovery pathway programs as part of an expanded Preoperative Evaluation Clinic, anemia detection and treatment as well as preparation for intraoperative and postoperative PBM are recommended. If done comprehensively, cost-savings from this approach will be realized for the institution, patients will avoid allogeneic transfusion, and excess utilization of the blood supply will be curtailed.

Preoperative Assessment of Bleeding Risk

Common Disease States Associated with Excessive Bleeding

Hepatic Insufficiency

Patients with hepatic failure have an increased risk of perioperative hemorrhage as a result of factor deficiency and portal venous obstruction. In the event of portal venous obstruction, development of esophageal varices and potential venous engorgement around the operative field can produce enhanced blood loss. Deficiencies of liver-dependent factors, including factors II, VII, IX, and X, result in a coagulopathy most frequently characterized by prolongation of the prothrombin time (PT). Vitamin K may be indicated in the preoperative period if malnutrition is a component of the coagulopathy in a patient with liver failure. On the other hand, factor deficiency resulting from inadequate hepatic synthesis is likely to be unresponsive to vitamin K, and direct repletion of clotting factors with fresh frozen plasma (FFP) or prothrombin complex concentrate may be necessary to prevent life-threatening hemorrhage. However, patients with hepatic insufficiency also have anticoagulant deficiency and conventional repletion of factors can easily lead to overcorrection and thrombotic complications.

Accelerated fibrinolysis probably also plays a role in the coagulopathy seen in patients with liver failure. This acceleration is evidenced by D-dimer levels that are normal or slightly elevated in severe liver disease. One mechanism for the increased fibrinolysis in patients with chronic liver failure is the reduced clearance of tissue plasminogen activator (t-PA). Another potential mechanism is related to decreased synthesis of hepatic regulating plasma proteins. Alpha-2-antiplasmin is a hepatically synthesized enzyme that may be deficient in liver failure resulting in increased plasmin activity. Alpha-2-antiplasmin inhibits plasmin-mediated fibrinolysis by rapidly inactivating circulating plasmin and by crosslinking to fibrin, making clots that are resistant to plasmin degradation. Although plasminogen (the precursor to plasmin) and alpha-2-antiplasmin are both synthesized in the liver, alpha-2-antiplasmin is present in lower concentrations than plasminogen and may be depleted even when plasminogen is not. Another liver-synthesized molecule, fibrinogen, may also become depleted in liver failure and may merit measurement. Despite that, pure fibrinogen deficiency is uncommon.

Platelet count is often low in liver failure as a result of either splenic sequestration or increased consumption. Nevertheless, the hemostatic effect of platelets may still be clinically near-normal because of elevated levels of von Willebrand Factor (vWF). The synthesis of ADAMTS13, a vWF-cleaving protease, is decreased in liver failure thus leading to higher than normal vWF activity and platelet adhesion.

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