Surgeries often lead to some form of bleeding. However, severe bleeding leads to morbidity and mortality. An undetected pre-existing bleeding disorder or a coagulation abnormality may worsen this outcome. If pre-existing bleeding disorders and coagulation abnormalities occur at the same time, severe perioperative bleeding may occur. To mitigate this outcome, it is important to adopt effective techniques to manage severe perioperative bleeding. This paper argues that the identification of patients with the highest risk of perioperative bleeding is the first and most important step of managing perioperative bleeding.
This paper emphasizes on preventive care (preoperative evaluations) as the most desirable technique for managing perioperative bleeding because it is an inexpensive way to reduce incidences of perioperative bleeding. Moreover, preoperative evaluations have a high chance of reducing the indiscriminate use of allogeneic blood products.
Besides preoperative evaluations, this paper highlights pharmacological interventions (such as aprotinin and recombinant VIIa use) and the reduction of allogeneic blood exposures as other effective techniques that could manage perioperative bleeding. This paper presents these interventions after combining the findings of an extensive review of the haemostatic changes occurring in the perioperative period and the insights of previous researchers that explain the efficacy and shortcomings of every intervention.
Severe perioperative bleeding is among the leading causes of morbidity and death in post-surgical and intra-surgical procedures. Perioperative bleeding stems from perioperative procedures, which include pre-operative, intra-operative, and post-operative surgical procedures (Kozek-Langenecker & Afshari, 2013). The severity of perioperative bleeding depends on many factors. However, a patient’s coagulation status and the nature of a surgery top this list (Koh & Hunt, 2003). Therefore, it is possible to classify perioperative bleeding as a surgical or coagulopathic issue. Indeed, its occurrence largely depends on a combination of excessive surgical and coagulopathic bleeding (Kozek-Langenecker & Afshari, 2013).
It is important to manage severe perioperative bleeding because of its adverse effects on patients. Besides increased morbidity and mortality, perioperative bleeding may cause increased complications during surgery. Increased incidences of perioperative bleeding may also increase medical costs, litigation costs, and patient care costs (Kozek-Langenecker & Afshari, 2013). It is always important to avoid these negative effects of perioperative bleeding, as they limit a patient’s chance of full recovery.
Although perioperative bleeding may occur as an unexpected event, medical practitioners experience an increased pressure to reduce the number of patients who need blood transfusion (Koh & Hunt, 2003). This pressure hails from an increased awareness of the dangers of blood transfusion and its adverse effects on patients (the potential of perioperative bleeding).
This paper aims to increase the wealth of knowledge regarding the management of perioperative bleeding to reduce the adverse effects of the condition on patients. By improving the wealth of knowledge regarding the management of severe perioperative bleeding, this paper aims to reduce the adverse effects associated with blood transfusion, anemia, and bleeding (for patients undergoing surgery, or other invasive procedures that may cause severe blood loss). This study however presents a bias in evaluating the management of perioperative bleeding by focusing on high-risk surgeries such as cardiopulmonary bypass and orthotopic liver transplants. These high-risk surgeries present an interesting focus for this study because they explain the sources of new strategies for managing perioperative bleeding.
Cardiopulmonary Bypass (CBP)
Patients who undergo CBP are often under a high risk of experiencing haemostasis. The high risk of haemostasis often occurs because there is contact between blood and the bypass circuit (Koh & Hunt, 2003). The contact between blood and this artificial surface normally requires the use of heparin. The onset of bypass often affects the platelet count. Koh & Hunt (2003) say this process (onset of bypass) explains about 30% to 50% of the reduction in platelet count. This reduction in platelet count normally occurs because of haemodillution. Conversely, the haemodillution traces to the contact between blood and artificial surfaces during bypass.
Platelet dysfunction may also lead to the reduction of platelet count because of the release of “a-granules, and generation of platelet micro-particles due to platelet destruction in the CPB circuit because of abnormal shear stresses., abnormal platelet aggregation tests and prolonged bleeding time that corrects 1-h post-operatively” (p. 180). Through this assessment, there is a strong consensus that the severity of perioperative bleeding is often dependent on the length of bypass and the degree of hypothermia (Koh & Hunt, 2003).
Orthotopic Liver Transplant (OLT)
The presence of end-stage liver disease is often a serious factor in the management of severe perioperative bleeding. The presence of end-stage liver disease often causes major haemostatic problems. These problems may occur because of several reasons, but a reduced level of coagulation protein is a leading cause (Kozek-Langenecker & Afshari, 2013). Similarly, the production of physiological anticoagulants may also lead to haemostatic problems. Relative to this assertion, Koh & Hunt (2003) say, “Reduced destruction of t-PA results in increased fibrinolytic potential and thrombocytopenia with some qualitative platelet dysfunction” (p. 181).
Usually, when surgeons connect the recipient’s liver with the donors (reperfusion), huge volumes of t-PA may increase in the patient’s systemic circulation (Kozek-Langenecker & Afshari, 2013). Antifibrinolytics treatment may help to treat this condition, but its treatment scope also stretches to the treatment of urokinase disease and prostatectomy. Studies on the occurrence of perioperative bleeding on orthotopic liver transplants and cardiopulmonary bypass (as mentioned above) have led to the formulation of different strategies for managing the condition. Preoperative evaluation is among these strategies
Newman & Fleisher (2007) say that the identification of patients who suffer the highest risk of perioperative bleeding is the first and most important step of managing perioperative bleeding. The importance of a preoperative operation stems from the fact that this is the main preventive method for managing severe perioperative bleeding. Its importance also stems from the fact that many preexisting and mild blood disorders normally remain dormant until they experience haemostatic stress, like surgery (Kozek-Langenecker & Afshari, 2013).
Medical practitioners may also fail to detect such blood disorders in pre-surgery medical tests, such as the clotting test. The main goal of a preoperative operation is therefore to prepare an accurate index of suspicion regarding patients who are most likely to suffer a high risk of bleeding during surgery.
Identifying patients who suffer a high risk of bleeding may involve many steps like the evaluation of a patient’s medical history, interviewing family members (to confirm the patient’s medical history), and conducting a laboratory test to evaluate a patient’s risk of perioperative bleeding (Newman & Fleisher, 2007). Based on these tests, issues that would alarm medical practitioners include histories of bleeding during surgery and records of a family member suffering from severe perioperative bleeding. Kozek-Langenecker & Afshari (2013) say patients who have a history of bleeding disorders should visit a hematologist for a thorough pre-operative assessment (to have a more detailed insight into the risks of surgery for such patients).
Conducting these tests and procedures is however insufficient in providing an accurate preoperative evaluation of a patient. To mitigate this inadequacy, it is imperative for medical practitioners to evaluate patients’ characteristics (as well) to ascertain their risks of suffering from blood transfusion complications. Relative to this assertion, Koh & Hunt (2003) say, “These characteristics include, but are not limited to, congenital or acquired conditions such as factor VIII deficiency, sickle cell anemia, idiopathic thrombocytopenic purpura, and liver disease” (p. 200).
Consultants and members of the American Society of Anesthesiologists (ASA) have also supported the assertions of Koh & Hunt (2003) by affirming that the same steps need to be included as important components of preoperative evaluation assessments. This statement affirms a previous assertion by CSL Behring (2013), which suggests that most patients who are likely to suffer from blood transfusion complications may have a liver disease, may be high-risk obstetric patients, have severe trauma, and possibly suffer from underlying bleeding disorders.
Unrelated medical literature suggests that medical practitioners may ascertain the importance and risk of blood transfusion through a laboratory test (Kozek-Langenecker & Afshari, 2013). Besides conducting interviews, evaluating a patient’s history, and conducting laboratory tests, Newman & Fleisher (2007) say that it is crucial to check for congenital or acquired blood disorders (from the patient) to assess a patient’s risk of experiencing perioperative bleeding. This process mainly involves the process of coagulation. For example, the use of vitamins and herbal supplements may affect this process. The use of drugs (like aprotinin, warfarin, aspirin, and non-steroidals) may also affect the same process (Kozek-Langenecker & Afshari, 2013).
The use of drugs and their resultant effects on surgery may however be mitigated by simple procedures like stopping the use of drugs a few days before surgery. For example, Newman & Fleisher (2007) say patients can stop Aspirin use two days before surgery to allow for the restoration of Cyclo-oxygenase inhibition, which increases the risk of perioperative bleeding. Patients can also stop the use of warfarin three days before the surgery to reduce the risk of perioperative bleeding (Koh & Hunt, 2003).
The nature of operative procedure to occur during surgery is also an important preoperative process that would influence the assessment of a patient’s risk of bleeding during surgery. For example, many surgical procedures are either low-risk or high risk. Newman & Fleisher (2007) say low-risk surgeries do not require patients to undergo severe laboratory coagulation screening tests before they undergo the surgery.
However, if patients should undergo high-risk or moderate-risk surgeries, Koh & Hunt (2003) say they need to undergo, “Prothrombin time (PT), activated partial thromboplastin time (APTT) and platelet count tests” (p. 179). Broadly, after the ascertainment of a patient’s preoperative condition, clinicians should inform them about the potential risks and benefits of blood transfusion during surgery.
Monitoring Haemostatic Changes
Monitoring haemostatic change is an important process for managing severe perioperative bleeding. However, scientists have rarely studied this process beyond the scope of cardiac surgeries and orthotopic liver transplants (Koh & Hunt, 2003). Monitoring haemostatic changes, as a management procedure for severe perioperative bleeding, occur because the stress induced by surgery often causes haemostatic changes. Increased levels of free tissue plasminogen activator also occur from surgical procedures, thereby causing hyperfibrinolysis, which may further cause haemostatic problems. Clinicians need to consider many factors here because haemostatic problems and haemostatic changes may occur in different ways.
For example, Koh & Hunt (2003) say, “Consumption of coagulation factors, platelets and physiological anticoagulants do occur from bleeding and haemodilution from crystalloid infusion, but rarely result in a fall” (p. 180). Low-risk surgeries may however lead to a reduction in platelet count, but an acute phase reaction may cause a change of this outcome. In sum, blood transfusion should not cause excessive bleeding, but because patients may have haemostatic abnormalities, patients may experience serious perioperative bleeding.
Blood-based interventions to manage perioperative bleeding always aim to stabilize the platelet count. The stabilization of platelet count always occurs through the introduction of fresh frozen plasma and cryoprecipitate into the patient’s blood circulation system. In the United Kingdom (UK), the UK blood transfusion guidelines govern this process (Kozek-Langenecker & Afshari, 2013). For example, one guideline, as outlined here, is the maintenance of platelet count above 50–100*10 (Kozek-Langenecker & Afshari, 2013).
Another guideline is the prolongation of the PT / APTT, below 1.5. Clinicians may easily realize this standard using a dose of 15ml/kg of fresh frozen plasma. Moreover, if the fibrinogen is low, clinicians should administer the same dose above 0.8–1.0 g/dl (Kozek-Langenecker & Afshari, 2013).
Aprotinin is a protcase inhibitor that may reduce perioperative bleeding (Koh & Hunt, 2003). It does so by inhibiting plasmin. When administered in high dosage, aprotinin could easily lead to bradykinin production (Koh & Hunt, 2003). Nonetheless, the main role of administering aprotinin is to suppress fibrinolytic activities. Segal & Hunt (2000) say this goal has another effect of preserving platelet membrane reduction (scientists have affirmed this effect since the use of aprotinin in 1987) (Koh & Hunt, 2003). Its extensive use, during the late eighties, stems from medical research, which affirmed the efficacy of aprotinin in cardiac surgeries (Koh & Hunt, 2003).
Similar studies have affirmed this result in non-cardiac surgeries because aprotinin reduces blood requirements. The reduction in blood requirement reduces perioperative bleeding by up to 75% (Koh & Hunt, 2003). When administered in high dosages, this result is even more impressive. Segal & Hunt (2000) say that the high efficacy levels of aprotinin led to its extensive use in serious cardiac surgeries.
Besides cardiac surgeries, medical researchers have also affirmed that aprotinin has a high efficacy level in reducing perioperative bleeding in liver transplants (Koh & Hunt, 2003). However, compared to the use of aprotinin in cardiac surgery, there have been fewer efforts by researchers to understand the full effect of using aprotinin in liver transplants. Nonetheless, broadly, the preliminary studies on the use of aprotinin in liver transplants show that it can reduce perioperative bleeding by up to 60% (when administered in high dosages) (Koh & Hunt, 2003). The same studies have shown that perioperative bleeding could reduce by up to 40% when clinicians administer aprotinin in low dosages (Koh & Hunt, 2003). These studies however show no significant differences in mortality rate when clinicians use aprotinin (Koh & Hunt, 2003).
There have also been no significant differences in thromboembolic phenomena. Albeit the use of aprotinin reduces perioperative bleeding, its extensive use can lead to severe allergic reactions. From this understanding, experts advise that medical practitioners should conduct prior tests to ascertain this risk (Koh & Hunt, 2003).
Recombinant VIIa (rFVIIa)
The use of recombinant VIIa to manage perioperative bleeding has been an exciting issue in the medical field. Recombinant VIIa has a significant power in managing perioperative bleeding because of its successes in treating severe haemophiliacs (the success of recombinant VIIa in treating severe haemophiliacs also informs its use in treating intractable post-surgical intra-abdominal haemorrhage) (Hendriks & Meijer, 2001). The ability of recombinant VIIa to treat severe haemophiliacs explains why there is increased optimism about the ability of recombinant VIIa to manage perioperative bleeding as well. Preliminary studies on the use of recombinant VIIa to manage perioperative bleeding have shown significant positive results (Koh & Hunt, 2003).
Similar studies to evaluate the efficacy of recombinant VIIa in surgeries involving liver transplants have also shown the same positive results (Koh & Hunt, 2003). However, because of limited sampling, these results are only indicative. Nonetheless, the indicative results show that recombinant VIIa could reduce perioperative bleeding by up to 25% (Hendriks & Meijer, 2001). Scientists have also explored the side effects of its use in the same studies and reported that some patients developed hepatic artery thrombosis after using the product (Hendriks & Meijer, 2001).
This outcome is however also indicative because the sample size used to come up with this finding was small. From these research limitations, it is important to conduct more research on the use of recombinant VIIa to manage perioperative bleeding because most of the findings presented here are anecdotal.
Reduction of Allogeneic Blood Exposure
A reduction in the allogeneic blood exposure is an important measure in the management of perioperative bleeding. A reduction in allogeneic blood exposure may occur from different processes including “preoperative autologous transfusion, intraoperative red cell salvage, acute normovolaemic dilution, controlled hypotension, pre-op erythropoietin, and transfusion trigger” (Koh & Hunt, 2003, p. 180). Despite the contribution of the above methods to reduce allogeneic blood exposure, there is still a lot of medical debate regarding the use of some of these methods to reduce allogeneic blood exposure.
For example, there is considerable debate regarding the ability of acute normovolaemic dilution to reduce allogeneic blood exposure (Koh & Hunt, 2003). The same contention also exists in the ability of intraoperative red cell salvage to reduce allogeneic blood exposure. Therefore, the above processes do not absolutely reduce allogeneic blood exposure, but as Newman & Fleisher (2007) argue, their combined result is likely to achieve this outcome (a reduction in allogeneic blood exposure). However, it is often difficult to justify the use of some of these measures because of their high inhibitive costs in managing perioperative bleeding.
From the analysis of preventive, pharmacological, and surgical techniques for managing perioperative bleeding, it is safe to say a multi-thronged approach is the best approach for preventing perioperative bleeding. The choice of management technique however depends on the nature of the surgery and the history of the patient. The nature of the surgery especially has a high influence on the choice of pharmacological method to use. For example, aprotinin is highly effective in reducing perioperative bleeding in cardiac surgeries. Recombinant VIIa is similarly highly effective in surgeries that involve liver transplants.
Based on the assessment of preoperative evaluations to determine a patient’s risk of bleeding during surgery, it is important to mention that the adoption of preventive measures to manage perioperative bleeding is the best approach in this analysis because it is an inexpensive way of reducing the incidences of perioperative bleeding. The adoption of preventive measures also has a high chance of reducing the indiscriminate use of allogeneic blood products. The use of surgical techniques to manage perioperative bleeding is therefore a secondary management technique. Preventive interventions should be the first line of action that most clinicians should pursue.
Significant gaps in research however limit our knowledge regarding the reliability of these techniques across different types of surgeries. For example, this paper identifies that there is inadequate research to understand the full impact of using recombinant VIIa in liver and cardiac surgeries. The focus on liver surgery and cardiac surgery appears to be at the center of most medical studies that focus on exploring ways of managing severe perioperative bleeding.
This narrow focus has its advantage and disadvantages. One advantage is the development of extensive knowledge regarding how to manage perioperative bleeding in cardiac and liver surgeries. However, a notable disadvantage is the lack of enough information regarding known perioperative management techniques beyond liver and cardiac surgeries. For example, this paper shows that there is little information regarding the efficacy of monitoring haemostatic changes to manager perioperative bleeding beyond cardiac and liver surgeries.
In sum, the management of perioperative bleeding is a highly dynamic process that medical practitioners should approach with extensive care. An understanding of the right type of intervention to use is especially important in managing this condition. The failure to do so may lead to reduced efficacies of available interventions, or the worsening of symptoms. Future research should however try to establish the real efficacies of each intervention, depending on the nature of the surgery. Preferably, there should be more research to investigate the efficacies of the above-mentioned techniques beyond the realms of cardiac surgeries and orthotopic liver transplants.
CSL Behring. (2013). Perioperative Bleeding & Bleeding in Critically Ill Patients. Retrieved from http://www.allaboutbleeding.com/hcp/perioperative-bleeding.aspx
Hendriks, H., & Meijer, K. (2001). Reduced transfusion requirements by recombinant factor VIIa in orthotopic liver transplantation: a pilot study. Transplantation, 71(3), 402–405.
Koh M., & Hunt, B. (2003). The management of perioperative bleeding. Blood Rev, 17(3), 179-85.
Kozek-Langenecker, S., & Afshari, A. (2013). Management of severe perioperative bleeding: Guidelines from the European Society of Anaesthesiology. European Journal of Anaesthesiology, 30(6), 270–382.
Newman, M., & Fleisher, L. (2007). Perioperative Medicine: Managing for Outcome. Sydney, Australia: Elsevier Health Sciences.
Segal, H., & Hunt, B. (2000). Aprotinin: pharmacological reduction of perioperative bleeding. Lancet, 355(5), 1289–1290.